Post-traumatic bilateral vesicocutaneous fistula of thighs treated with buccal mucosa graft urethroplasty and cyanoacrylate glue instillation: a novel treatment for management of a complicated fistula

Post-traumatic vesicocutaneous fistula (VCF) is a rare variant of urinary fistulas. These fistulas may externally communicate to abdomen, perineum, buttocks, scrotum or very rarely thigh. These fistulas usually develop at a variable time duration after trauma and are usually preceded with thigh swelling or abscess formation followed by spontaneous rupture. We, hereby, report a case of VCF of bilateral thighs with associated penobulbar urethral stricture after road traffic accident which was managed with dual modality of buccal mucosa graft urethroplasty surgery and cyanoacrylate glue injection in the fistulous tracts. To the best of our knowledge, this is first report of bilateral VCFs communicating externally to thighs. In literature, very few cases of VCFs of thigh are reported and are rarely managed with adhesive glue application.

https://ift.tt/2xFonL8

Cushings reflex secondary to neck haematoma following thyroidectomy

Neck haematoma following thyroid surgery can present with respiratory distress which is generally attributed to airway obstruction. We recently had a 63-year-old female patient who underwent total thyroidectomy for toxic nodular goitre. However, within 4 hours of surgery, she developed sudden respiratory distress which was managed by prompt evacuation of the neck haematoma. Just before the haematoma evacuation, the patient had hypertension and bradycardia along with the distress. The arterial blood gas analysis sampled at that time was normal. Intraoperatively, the tracheal framework was found rigid and non-pliable. Considering the various clinical–biochemical findings observed, we think that the cause of the respiratory distress in the index case was transiently elevated intracranial pressure, secondary to bilateral internal jugular veins' compression. We hypothesise that in many patients with immediate postoperative neck haematoma, the Cushing's reflex would at least contribute partly, if not solely to the respiratory distress.

https://ift.tt/2DwRF3T

Three differently timed presentations of dermatomyositis associated with advanced ovarian cancer

Each of the three patients reported in this article presented with dermatomyositis at various stages of their advanced ovarian cancer. Dermatomyositis was the presenting feature and preceded the diagnosis of ovarian cancer by several months in one patient. In another patient, dermatomyositis occurred just prior to the scheduled third cycle of palliative chemotherapy after surgical debulking for stage 4 disease. The third patient presented with pathognomonic diagnostic features of dermatomyositis after ovarian cancer recurrence. Diagnosis was delayed in at least two of these patients; however, once appropriately diagnosed, each patient responded well to immunomodulatory treatment. In one patient, initiation of oral prednisolone seemed to correlate with a steady improvement in her proximal myopathy. A pulsed methylprednisolone approach was used in another patient with conversion to a tapering dose of oral prednisolone to good effect. In the patient in whom the most severe myopathy affecting bulbar muscle groups was demonstrated, an infusion of 5 days of intravenous immunoglobulin produced an eventual improvement in her steroid-refractory myopathy.

https://ift.tt/2xBDS6M

Hereditary Myelodysplastic Syndrome and Acute Myeloid Leukemia: Diagnosis, Questions, and Controversies

Abstract

Purpose of Review

To review the diagnosis of individuals with hereditary hematopoietic malignancies (HHMs) that predispose to myelodysplastic syndrome and acute myeloid leukemia, barriers to HHM diagnosis, and unaddressed questions and controversies within the HHM field.

Recent Findings

Pathogenic germline mutations in approximately a dozen genes predispose to HHMs, and many more genes are likely to be involved. Many of these HHM genes have only been identified recently. HHM phenotypes are diverse, but may be categorized as "purely" myeloid syndromes, syndromes with abnormal platelet number/function, and HHMs with additional organ system involvement. A number of questions remain unanswered in this emerging field, including the ideal diagnostic approach for patients at risk for HHMs, the optimal surveillance of unaffected carriers, and how to personalize care for individuals with HHMs.

Summary

The field of HHMs is evolving rapidly. Ongoing research in this area will eventually inform the care of patients with both somatic and hereditary cancer syndromes, but much work remains to be done.

https://ift.tt/2xP8gtx

Role of feasibility and pilot studies in randomised controlled trials: a cross-sectional study

Objectives

To assess the value of pilot and feasibility studies to randomised controlled trials (RCTs) funded by the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme. To explore the methodological components of pilot/feasibility studies and how they inform full RCTs.

Study design

Cross-sectional study.

Setting

Both groups included NIHR HTA programme funded studies in the period 1 January 2010–31 December 2014 (decision date). Group 1: stand-alone pilot/feasibility studies published in the HTA Journal or accepted for publication. Group 2: all funded RCT applications funded by the HTA programme, including reference to an internal and/or external pilot/feasibility study. The methodological components were assessed using an adapted framework from a previous study.

Main outcome measures

The proportion of stand-alone pilot and feasibility studies which recommended proceeding to full trial and what study elements were assessed. The proportion of 'HTA funded' trials which used internal and external pilot and feasibility studies to inform the design of the trial.

Results

Group 1 identified 15 stand-alone pilot/feasibility studies. Study elements most commonly assessed were testing recruitment (100% in both groups), feasibility (83%, 100%) and suggestions for further study/investigation (83%, 100%). Group 2 identified 161 'HTA funded' applications: 59 cited an external pilot/feasibility study where testing recruitment (50%, 73%) and feasibility (42%, 73%) were the most commonly reported study elements: 92 reported an internal pilot/feasibility study where testing recruitment (93%, 100%) and feasibility (44%, 92%) were the most common study elements reported.

Conclusions

'HTA funded' research which includes pilot and feasibility studies assesses a variety of study elements. Pilot and feasibility studies serve an important role when determining the most appropriate trial design. However, how they are reported and in what context requires caution when interpreting the findings and delivering a definitive trial.

https://ift.tt/2MZdE2Y

Cross-sectional associations of sedentary behaviour and physical activity on depression in Japanese older adults: an isotemporal substitution approach

Objectives

Reducing sedentary behaviour (SB) and increasing physical activity (PA) have been shown to be associated with decreased depression. However, there are yet few studies examining the potential benefits on older adults' depression, when SB is replaced with PA. This study aimed to examine the associations of objectively assessed SB, light-intensity PA (LPA) and moderate-to-vigorous PA (MVPA) with depression among a sample of Japanese older adults, and to explore impacts of substituting SB with PA on older adults' depression.

Design

Cross-sectional analysis.

Setting

General community.

Participants

A total of 276 older adults aged 65–85 years living in Japan.

Main outcome measures

Three behaviours including the average daily time spent in SB (≤1.5 METs); LPA (>1.5 to <3.0 METs) and MVPA (≥3.0 METs) per day were calculated by accelerometers. Depression was assessed using the Japanese version of the 15-item Geriatric Depression Scale (GDS-15).

Results

Less SB (β=0.129, 95% CI 0.015 to 0.243) and more LPA (β=–0.138, 95% CI –0.265 to –0.011) were found to be significantly and negatively associated with the GDS-15 score in the single-activity model. The isotemporal substitution model found that replacing only 30 min per day of SB with the same amount of LPA to be significantly and negatively associated with the GDS-15 score (β=–0.131, 95% CI –0.260 to –0.002).

Conclusions

These findings indicated that substituting even small amounts of SB with LPA may contribute to less depression in older adults. Potential favourable effects can be observed for replacing only 30 min per day of SB with LPA.

https://ift.tt/2QTVhj0

Drug-susceptible tuberculosis treatment success and associated factors in Ethiopia from 2005 to 2017: a systematic review and meta-analysis

Objectives

The main aim of this study was to assess the overall tuberculosis (TB) treatment success in Ethiopia and to identify potential factors for poor TB treatment outcome.

Design

A systematic review and meta-analysis of published literature was conducted. Original studies were identified through a computerised systematic search using PubMed, Google Scholar and Science Direct databases. Heterogeneity across studies was assessed using Cochran's Q test and I² statistic. Pooled estimates of treatment success were computed using the random-effects model with 95% CI using Stata V.14 software.

Results

A total of 230 articles were identified in the systematic search. Of these 34 observational studies were eligible for systematic review and meta-analysis. It was found that 117 750 patients reported treatment outcomes. Treatment outcomes were assessed by World Health Organization (WHO) standard definitions of TB treatment outcome. The overall pooled TB treatment success rate in Ethiopia was 86% (with 95% CI 83%_88%). TB treatment success rate for each region showed that, Addis Ababa (93%), Oromia (84%), Amhara (86%), Southern Nations (83%), Tigray (85%) and Afar (86%). Mainly old age, HIV co-infection, retreatment cases and rural residence were the most frequently identified factors associated with poor TB treatment outcome.

Conclusion

The result of this study revealed that the overall TB treatment success rate in Ethiopia was below the threshold suggested by WHO (90%). There was also a discrepancy in TB treatment success rate among different regions of Ethiopia. In addition to these, HIV co-infection, older age, retreatment cases and rural residence were associated with poor treatment outcome. In order to further improve the treatment success rate, it is strategic to give special consideration for regions which had low TB treatment success and patients with TB with HIV co-infection, older age, rural residence and retreatment cases.

https://ift.tt/2MZcZP2

Ambulatory blood pressure monitoring in children suffering from orthostatic hypertension

It is particularly important to utilize appropriate blood pressure measurement methods to evaluate the changes of orthostatic hypertension (OHT) for children, and this study was designed to analyze the blood p...

https://ift.tt/2NHaPc6

Multielements determination and metal transfer investigation in herb medicine Bupleuri Radix by inductively coupled plasma‐mass spectrometry

Food Science &Nutrition, EarlyView.


https://ift.tt/2zulCgS

Cancers, Vol. 10, Pages 354: Anticancer Activity of Cynomorium coccineum

Cancers, Vol. 10, Pages 354: Anticancer Activity of Cynomorium coccineum

Cancers doi: 10.3390/cancers10100354

Authors: Mouna Sdiri Xiangmin Li William W. Du Safia El-Bok Yi-Zhen Xie Mossadok Ben-Attia Burton B. Yang

The extensive applications of Cynomorium species and their rich bioactive secondary metabolites have inspired many pharmacological investigations. Previous research has been conducted to examine the biological activities and numerous interesting pharmaceutical activities have been reported. However, the antitumor activities of these species are unclear. To understand the potential anticancer activity, we screened Cynomorium coccineum and Cynomorium songaricum using three different extracts of each species. In this study, the selected extracts were evaluated for their ability to decrease survival rates of five different cancer cell lines. We compared the cytotoxicity of the three different extracts to the anticancer drug vinblastine and one of the most well-known medicinal mushrooms Amaurederma rude. We found that the water and alcohol extracts of C. coccineum at the very low concentrations possessed very high capacity in decreasing the cancer cells viability with a potential inhibition of tumorigenesis. Based on these primitive data, we subsequently tested the ethanol and the water extracts of C. coccineum, respectively in in vitro and in vivo assays. Cell cycle progression and induction of programmed cell death were investigated at both biological and molecular levels to understand the mechanism of the antitumor inhibitory action of the C. coccineum. The in vitro experiments showed that the treated cancer cells formed fewer and smaller colonies than the untreated cells. Cell cycle progression was inhibited, and the ethanol extract of C. coccineum at a low concentration induced accumulation of cells in the G1 phase. We also found that the C. coccineum&rsquo;s extracts suppressed viability of two murine cancer cell lines. In the in vivo experiments, we injected mice with murine cancer cell line B16, followed by peritoneal injection of the water extract. The treatment prolonged mouse survival significantly. The tumors grew at a slower rate than the control. Down-regulation of c-myc expression appeared to be associated with these effects. Further investigation showed that treatment with C. coccineum induced the overexpression of the tumor suppressor Foxo3 and other molecules involved in inducing autophagy. These results showed that the C. coccineum extract exerts its antiproliferative activity through the induction of cell death pathway. Thus, the Cynomorium plants appear to be a promising source of new antineoplastic compounds.

https://ift.tt/2zulnCu

Hemoglobin Concentration in Children at Different Altitudes in Peru: Proposal for [Hb] Correction for Altitude to Diagnose Anemia and Polycythemia

High Altitude Medicine &Biology, Ahead of Print.


https://ift.tt/2IhV0CO

Intermittent Hypoxia–Hyperoxia Conditioning Improves Cardiorespiratory Fitness in Older Comorbid Cardiac Outpatients Without Hematological Changes: A Randomized Controlled Trial

High Altitude Medicine &Biology, Ahead of Print.


https://ift.tt/2zuNXUk

Treatment patterns and outcomes for patients with advanced melanoma in US oncology clinical practices

Future Oncology, Ahead of Print.


https://ift.tt/2Q9X5Dv

Ponatinib in the treatment of chronic myeloid leukemia and philadelphia chromosome positive acute lymphoblastic leukemia

Future Oncology, Ahead of Print.


https://ift.tt/2OfdfOv

DNA as a self-antigen: nature and regulation

Chetna Soni | Boris Reizis

https://ift.tt/2Q8eQ5R

A Case Study of Genomic Instability in an Industrial Strain of Saccharomyces cerevisiae

The Saccharomyces cerevisiae strain JAY270/PE2 is a highly efficient biocatalyst used in the production of bioethanol from sugarcane feedstock. This strain is heterothallic and diploid, and its genome is characterized by abundant structural and nucleotide polymorphisms between homologous chromosomes. One of the reasons it is favored by many distilleries is that its cells do not normally aggregate, a trait that facilitates cell recycling during batch-fed fermentations. However, long-term propagation makes the yeast population vulnerable to the effects of genomic instability, which may trigger the appearance of undesirable phenotypes such as cellular aggregation. In pure cultures of JAY270, we identified the recurrent appearance of mutants displaying a mother-daughter cell separation defect resulting in rough colonies in agar media and fast sedimentation in liquid culture. We investigated the genetic basis of the colony morphology phenotype and found that JAY270 is heterozygous for a frameshift mutation in the ACE2 gene (ACE2/ace2-A7), which encodes a transcriptional regulator of mother-daughter cell separation. All spontaneous rough colony JAY270-derived isolates analyzed carried copy-neutral loss-of-heterozygosity (LOH) at the region of chromosome XII where ACE2 is located (ace2-A7/ace2-A7). We specifically measured LOH rates at the ACE2 locus, and at three additional chromosomal regions in JAY270 and in a conventional homozygous diploid laboratory strain. This direct comparison showed that LOH rates at all sites were quite similar between the two strain backgrounds. In this case study of genomic instability in an industrial strain, we showed that the JAY270 genome is dynamic and that structural changes to its chromosomes can lead to new phenotypes. However, our analysis also indicated that the inherent level of genomic instability in this industrial strain is normal relative to a laboratory strain. Our work provides an important frame of reference to contextualize the interpretation of instability processes observed in the complex genomes of industrial yeast strains.

https://ift.tt/2NKz9Kg

HO Endonuclease-Initiated Recombination in Yeast Meiosis Fails To Promote Homologous Centromere Pairing and Is Not Constrained To Utilize the Dmc1 Recombinase

Crossover recombination during meiosis is accompanied by a dramatic chromosome reorganization. In Saccharomyces cerevisiae, the onset of meiotic recombination by the Spo11 transesterase leads to stable pairwise associations between previously unassociated homologous centromeres followed by the intimate alignment of homologous axes via synaptonemal complex (SC) assembly. However, the molecular relationship between recombination and global meiotic chromosome reorganization remains poorly understood. In budding yeast, one question is why SC assembly initiates earliest at centromere regions while the DNA double strand breaks (DSBs) that initiate recombination occur genome-wide. We targeted the site-specific HO endonuclease to various positions on S. cerevisiae's longest chromosome in order to ask whether a meiotic DSB's proximity to the centromere influences its capacity to promote homologous centromere pairing and SC assembly. We show that repair of an HO-mediated DSB does not promote homologous centromere pairing nor any extent of SC assembly in spo11 meiotic nuclei, regardless of its proximity to the centromere. DSBs induced en masse by phleomycin exposure likewise do not promote homologous centromere pairing nor robust SC assembly. Interestingly, in contrast to Spo11, HO-initiated interhomolog recombination is not affected by loss of the meiotic kinase, Mek1, and is not constrained to use the meiosis-specific Dmc1 recombinase. These results strengthen the previously proposed idea that (at least some) Spo11 DSBs may be specialized in activating mechanisms that both 1) reinforce homologous chromosome alignment via homologous centromere pairing and SC assembly, and 2) establish Dmc1 as the primary strand exchange enzyme.

https://ift.tt/2OM3Vi6

Evidence of Zip1 Promoting Sister Kinetochore Mono-orientation During Meiosis in Budding Yeast

Halving of the genome during meiosis I is achieved as the homologous chromosomes move to the opposite spindle poles whereas the sister chromatids stay together and move to the same pole. This requires that the sister kinetochores should take a side-by-side orientation in order to connect to the microtubules emanating from the same pole. Factors that constrain sister kinetochores to adopt such orientation are therefore crucial to achieve reductional chromosome segregation in meiosis I. In budding yeast, a protein complex, known as monopolin, is involved in conjoining of the sister kinetochores and thus facilitates their binding to the microtubules from the same pole. In this study, we report Zip1, a synaptonemal complex component, as another factor that might help the sister kinetochores to take the side-by-side orientation and promote their mono-orientation on the meiosis I spindle. From our results, we propose that the localization of Zip1 at the centromere may provide an additional constraining factor that promotes monopolin to cross-link the sister kinetochores enabling them to mono-orient.

https://ift.tt/2NJ7wkv

De novo PHACTR1 mutations in West syndrome and their pathophysiological effects

Abstract

Trio-based whole exome sequencing identified two de novo heterozygous missense mutations [c.1449T > C/p.(Leu500Pro) and c.1436A > T/p.(Asn479Ile)] in PHACTR1, encoding a molecule critical for the regulation of protein phosphatase 1 (PP1) and the actin cytoskeleton, in unrelated Japanese individuals with West syndrome (infantile spasms with intellectual disability). We then examined the role of Phactr1 in the development of mouse cerebral cortex and the pathophysiological significance of these two mutations and others [c.1561C > T/p.(Arg521Cys) and c.1553T > A/p.(Ile518Asn)], which had been reported in undiagnosed patients with intellectual disability. Immunoprecipitation analyses revealed that actin-binding activity of PHACTR1 was impaired by the p.Leu500Pro, p.Asn479Ile and p.Ile518Asn mutations while the p.Arg521Cys mutation exhibited impaired binding to PP1. Acute knockdown of mouse Phactr1 using in utero electroporation caused defects in cortical neuron migration during corticogenesis, which were rescued by an RNAi-resistant PHACTR1 but not by the four mutants. Experiments using knockdown combined with expression mutants, aimed to mimic the effects of the heterozygous mutations under conditions of haploinsufficiency, suggested a dominant negative effect of the mutant allele. As for dendritic development in vivo, only the p.Arg521Cys mutant was determined to have dominant negative effects, because the three other mutants appeared to be degraded with these experimental conditions. Electrophysiological analyses revealed abnormal synaptic properties in Phactr1-deficient excitatory cortical neurons. Our data show that the PHACTR1 mutations may cause morphological and functional defects in cortical neurons during brain development, which is likely to be related to the pathophysiology of West syndrome and other neurodevelopmental disorders.

https://ift.tt/2QWExYx

Hypoxia Induces the Acquisition of Cancer Stem-like Phenotype Via Upregulation and Activation of Signal Transducer and Activator of Transcription-3 (STAT3) in MDA-MB-231, a Triple Negative Breast Cancer Cell Line

Abstract

The finding that hypoxia can induce cancer stemness in various experimental models is in agreement with the conceptual basis of cancer cell plasticity. Here, we aimed to gain insights into the molecular basis of hypoxia-induced cancer cell plasticity in triple negative breast cancer (TNBC). To achieve this goal, we employed our previously published in-vitro model of TNBC, in which a small subset of stem-like cells can be distinguished from the bulk cell population based on their responsiveness to a Sox2 reporter. In MDA-MB-231, a TNBC cell line, we observed that hypoxia significantly increased the expression of luciferase and green fluorescence protein (GFP), the readouts of the Sox2 reporter. Upon hypoxic challenge, the bulk, reporter unresponsive (RU) cells acquired stem-like features, as evidenced by the significant increases in the proportion of CD44^high/CD24^low cells, colony formation and resistance to cisplatin. Correlating with these phenotypic changes, RU cells exposed to hypoxia exhibited a substantial upregulation of the active/phosphorylated form of STAT3 (pSTAT3). This hypoxia-induced activation of STAT3 correlated with increased STAT3 transcriptional activity, as evidenced by increased STAT3-DNA binding and an altered gene expression profile. This hypoxia-induced STAT3 activation is biologically significant, since siRNA knockdown of STAT3 in RU cells significantly attenuated the hypoxia-induced acquisition of Sox2 activity and stem-like phenotypic features. In conclusion, our data have provided the proof-of-concept that STAT3 is a critical mediator in promoting the hypoxia-induced acquisition of cancer stemness in TNBC. Targeting STAT3 in TNBC may be useful in overcoming chemoresistance and decreasing the risk of disease relapse.

https://ift.tt/2NJ1JeL

Macrophage Activation Syndrome, Glomerulonephritis, Pericarditis, and Retinal Vasculitis as Initial Presentation of Systemic Lupus Erythematosus

Macrophage activation syndrome (MAS) is a rare manifestation of systemic lupus erythematosus (SLE) with potentially life-threatening consequences. To the best of our knowledge, this is the first case reported in literature for a constellation of MAS, glomerulonephritis, pericarditis, and retinal vasculitis as initial presentation of SLE. Despite extensive multisystem involvement of his disease, the patient responded well to initial steroid treatment, with mycophenolate mofetil successfully added as a steroid-sparing agent. Our case highlights the importance of multispecialty collaboration in the diagnosis and management of SLE with multisystem involvement.

https://ift.tt/2Q8i6OR

Harnessing Androgen-Receptor Pathway Activation for Targeted Alpha Particle Radioimmunotherapy of Breast Cancer

Purpose: The impact of androgen receptor (AR) activity in breast cancer (BCa) biology is unclear. We characterized and tested a novel therapy to an AR-governed target in BCa. Experimental Design: We evaluated the expression of prototypical AR-gene products human kallikrein 2 (hK2) and Prostate Specific Antigen (PSA) in BCa models. We screened 13 well-characterized BCa cell lines for hK2 and PSA production upon in-vitro hormone stimulation by testosterone (DHT). AR-positive lines were further evaluated by exposure to estrogen (17β-Estradiol) and the synthetic progestin D-Norgestrel. We then evaluated an anti-hK2 targeted radiotherapy platform (hu11B6), labeled with alpha (a)-particle emitting Actinium-225, to specifically treat AR-expressing BCa xenografts under hormone stimulation. Results: D-Norgestrel and DHT activated the AR-pathway, while 17β-Estradiol did not. Competitive binding for AR protein showed similar affinity between DHT and D-Norgestrel; indicating direct AR-ligand interaction. In vivo production of hK2 was sufficient to achieve site-specific delivery of therapeutic radionuclide to tumor tissue at >20-fold over background muscle uptake; effecting long-term local tumor control. Conclusions:[225Ac]hu11B6 targeted radiotherapy was potentiated by DHT and by D-Norgestrel in murine xenograft models of BCa. AR activity in BCa correlates with kallikrein related peptidase-2 and can be activated by D-Norgestrel, a common contraceptive, and AR-induction can be harnessed for hK2-targeted BCa a-emitter radiotherapy.

https://ift.tt/2Du89Kf

The Use of Fetal Bronchoscopy in the Diagnosis and Management of a Suspected Obstructive Lung Mass

AJP Rep 2018; 08: e195-e200
DOI: 10.1055/s-0038-1673378

Etiologies of fetal lung anomalies include congenital pulmonary airway malformation (CPAM), intra- or extralobar pulmonary sequestration, congenital high airway obstruction syndrome (CHAOS), bronchogenic cyst, and bronchial atresia. Fetal tracheobronchoscopy has been reported both as a diagnostic and therapeutic procedure in the setting of severe congenital lung lesions. In this case report, prenatal imaging of a fetus with a large chest mass was suspicious for an obstructive bronchial lesion. The absence of visible normal lung tissue on the right side and mass effect on the left side raised the concern for pulmonary hypoplasia. After antenatal betamethasone and a period observation, hydropic changes developed. Fetal tracheobronchoscopy was then performed in an effort to identify and decompress the suspected obstructive bronchial lesion. Other than release of bronchial debris, no anatomical abnormalities were visualized. However, the right lung lesion and mediastinal shift both decreased after the fetal bronchoscopy. The newborn underwent postnatal resection of a CPAM Type II and is doing well. We hypothesize that fetal tracheobronchoscopy provided the following potential diagnostic and therapeutic benefits: (1) exclusion of an obstructive bronchial lesion; (2) disimpaction of bronchial debris from the saline lavage that we posit may have contributed to the rapid reduction in CPAM size.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Abstract  |  open access Full text

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FDA Approval: Blinatumomab for patients with B-cell precursor acute lymphoblastic leukemia in morphologic remission with minimal residual disease

On March 29, 2018, the FDA granted accelerated approval for blinatumomab (Blincyto; Amgen, Inc.) for the treatment of adults and children with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) in first or second complete remission with minimal residual disease (MRD) greater than or equal to 0.1%. Blinatumomab is a CD3xCD19 bispecific antibody approved previously for the treatment of relapsed or refractory BCP-ALL. The basis for this accelerated approval was a single-arm trial. For the 86 patients in first and second complete remission with MRD greater than or equal to 0.1%, conversion to MRD < 0.01% was achieved after one cycle of blinatumomab by 85.2% (95% CI: 73.8%, 93.0%) and 72.0% (95% CI: 50.6%, 87.9%), respectively, and the estimated median hematological relapse-free survivals (RFS) were 35.2 months (95% CI: 0.4, 53.5) and 12.3 months (95% CI: 0.7, 42.3), respectively. Hematological RFS was considered substantial independent of whether patients underwent subsequent allogeneic stem cell transplantation. The safety profile for blinatumomab was established in prior studies, and no new safety signals were observed in the new population. Cytokine release syndrome and neurotoxicity remain significant risks. FDA is requiring confirmation of clinical benefit in a randomized trial.

https://ift.tt/2QXudzx

Identification of nine cryptic species of Candida albicans, C. glabrata, and C. parapsilosis complexes using one-step multiplex PCR

Candida albicans, Candida glabrata, and Candida parapsilosis are three prevalent causes of candidiasis, worldwide. These species are considered as nine medically important complex species. Limited knowledge about...

https://ift.tt/2xHfRex

Resistant Streptococcus pneumoniae strains in children with acute otitis media– high risk of persistent colonization after treatment

Despite advances in the development of pneumococcal conjugate vaccines, acute otitis media (AOM) is a common childhood infection, caused mainly by Streptococcus pneumoniae. It has been suggested that persistence ...

https://ift.tt/2N3yBJU

Syphilis reinfection is associated with an attenuated immune profile in the same individual: a prospective observational cohort study

Ascertaining if the clinical and immunological response to repeat syphilis differs from that in initial syphilis may assist in designing optimal syphilis screening strategies and vaccine design.

https://ift.tt/2xLz9Qb

An international survey-based study on colorectal cancer pathology reporting—guidelines versus local practice

Abstract

Different guidelines for colorectal cancer (CRC) pathology reporting have been published. We aimed to identify differences between publicly available CRC reporting guidelines and to survey pathologists from different countries to establish the degree of guideline implementation in local routine practice. We compared all core and non-core items of CRC reporting guidelines to identify discrepancies. We then created a survey, which was sent out to 782 pathologists practicing in 30 different countries. It included questions on the demographics of the reporting pathologist as well as resection specimen handling and microscopic evaluation, grading, staging, and additional techniques, such as immunohistochemistry or molecular pathology. First, core and non-core items of five national CRC reporting guidelines were compared and 12 items were found to differ. Different items are considered core or non-core by different guidelines and more than one TNM staging edition was applied across guidelines. The survey was completed by 143 pathologists from 30 countries. We identified differences between local practice and guidelines with potential clinical impact, e.g., tumor budding was never reported by 28.7% of responders, although it has prognostic value for survival in stage II CRC. This is the first international study comparing CRC pathology reporting guidelines with real-world local practices. There are differences in CRC pathology reporting guidelines and in guideline implementation into local practice, both with potential impact on patient care. Harmonization of datasets, use of templates, and audits of local pathology practice are needed to ensure best possible quality of CRC pathology reporting.

https://ift.tt/2N3yxtE

Cyclin F-dependent degradation of RBPJ inhibits IDH1R132H-mediated tumorigenesis

Cyclin F is a substrate recognition subunit of Skp1-Cul1-F-box protein (SCF) E3 ubiquitin ligase complex. Although there have been reports describing the role of cyclin F in the genotoxic stress response, its function under conditions of altered metabolic homeostasis remain unexplored. Here we report that cyclin F is induced upon metabolic stress in a FOXO1-dependent manner. Under metabolic stress conditions, cyclin F mediated polyubiquitylation of RBPJ at Lys315, leading to its proteasomal degradation. RBPJ regulated the expression of IDH1, which is often mutated to an oncogenic form IDH1R132H in cancers. Thus metabolic stress-induced cyclin F attenuated the oncogenic functions of IDH1R132H in an RBPJ-dependent manner. Studies in mouse tumor models indicated that abrogation of cyclin F expression facilitates IDH1R132H-mediated tumorigenesis and metastasis. Additionally, increased IDH1R132H levels correlated with reduced cyclin F levels in increasing grades of glioma. These findings highlight a novel aspect of cyclin F functions in inhibiting tumorigenesis and provide mechanistic insights into regulation of IDH1R132H.

https://ift.tt/2Q7XOEZ

Semaphorin 7A promotes macrophage-mediated lymphatic remodeling during postpartum mammary gland involution and in breast cancer

Postpartum mammary gland involution is a tissue remodeling event that occurs in all mammals in the absence of nursing or after weaning to return the gland to the pre-pregnant state. The tissue microenvironment created by involution has proven to be tumor promotional. Here we report that the GPI-linked protein semaphorin 7a (SEMA7A) is expressed on mammary epithelial cells during involution and use preclinical models to demonstrate that tumors induced during involution express high levels of SEMA7A. Overexpression of SEMA7A promoted the presence of myeloid-derived podoplanin (PDPN)-expressing cells in the tumor microenvironment and during involution. SEMA7A drove the expression of PDPN in macrophages, which led to integrin- and PDPN-dependent motility and adherence to lymphatic endothelial cells to promote lymphangiogenesis. In support of this mechanism, mammary tissue from SEMA7A-knockout mice exhibited decreased myeloid-derived PDPN-expressing cells, PDPN-expressing endothelial cells, and lymphatic vessel density. Furthermore, co-expression of SEMA7A, PDPN, and macrophage marker CD68 predicted for decreased distant metastasis-free survival in a cohort of over 600 cases of breast cancer as well as in ovarian, lung, and gastric cancers. Together our results indicate that SEMA7A may orchestrate macrophage-mediated lymphatic vessel remodeling, which in turn drives metastasis in breast cancer.

https://ift.tt/2NIUiEn

An ATM/TRIM37/NEMO axis counteracts genotoxicity by activating nuclear-to-cytoplasmic NF-{kappa}B signaling

Blocking genotoxic stress-induced NF-κB activation would substantially enhance the anti-cancer efficiency of genotoxic chemotherapy. Unlike the well-established classical NF-κB pathway, the genotoxic agents-induced 'nuclear-to-cytoplasmic' NF-κB pathway is initiated from the nucleus and transferred to the cytoplasm. However, the mechanism linking nuclear DNA damage signalling to cytoplasmic IKK activation remains unclear. Here we report that TRIM37, a novel E3 ligase, plays a vital role in genotoxic activation of NF-κB via monoubiquitination of NEMO at K309 in the nucleus, consequently resulting in nuclear export of NEMO and IKK/NF-κB activation. Clinicallly, TRIM37 levels correlated positively with levels of activated NF-κB and expression of Bcl-xl and XIAP in esophageal cancer specimens, which also associated positively with clinical stage and tumor-node-metastasis classification and associated inversely with overall and relapse-free survival in patients with esophageal cancer. Overexpression of TRIM37 conferred resistance to the DNA-damaging anticancer drug cisplatin in vitro and in vivo through activation of the NF-κB pathway. Genotoxic stress-activated ATM kinase directly interacted with and phosphorylated TRIM37 in the cytoplasm, which induced translocation of TRIM37 into the nucleus where it formed a complex with NEMO and TRAF6 via a TRAF6-binding motif (TBM). Importantly, blocking the ATM/TRIM37/NEMO axis via cell-penetrating TAT-TBM peptide abrogated genotoxic agent-induced NEMO monoubiquitination and NF-κB activity, resulting in hypersensitivity of cancer cells to genotoxic drugs. Collectively, our results unveil a pivotal role for TRIM37 in genotoxic stress and shed light on mechanisms of inducible chemotherapy resistance in cancer.

https://ift.tt/2Q8HNPf

Pharmacological ascorbate reduces radiation-induced normal tissue toxicity and enhances tumor radiosensitization in pancreatic cancer

Chemoradiation therapy is the mainstay for treatment of locally advanced, borderline resectable pancreatic cancer. Pharmacological ascorbate (P-AscH-, i.e., intravenous infusions of ascorbic acid, vitamin C), but not oral ascorbate, produces high plasma concentrations capable of selective cytotoxicity to tumor cells. In doses achievable in humans, P-AscH- decreases the viability and proliferative capacity of pancreatic cancer via a hydrogen peroxide (H2O2)-mediated mechanism. In this study, we demonstrate that P-AscH- radiosensitizes pancreatic cancer cells but inhibits radiation-induced damage to normal cells. Specifically, radiation-induced decreases in clonogenic survival and double-stranded DNA breaks in tumor cells, but not in normal cells, were enhanced by P-AscH-, while radiation-induced intestinal damage, collagen deposition, and oxidative stress were also reduced with P-AscH- in normal tissue. We also report on our first-in-human phase 1 trial that infused P-AscH- during the radiation therapy 'beam on.' Specifically, treatment with P-AscH- increased median overall survival compared to our institutional average (21.7 vs. 12.7 mo, p = 0.08) and the E4201 trial (21.7 vs. 11.1 mo). Progression-free survival in P-AscH--treated subjects was also greater than our institutional average (13.7 vs. 4.6 mo, p < 0.05) and the E4201 trial (6.0 months). Results indicated that P-AscH- in combination with gemcitabine and radiation therapy for locally advanced pancreatic adenocarcinoma is safe and well tolerated with suggestions of efficacy. Because of the potential effect size and minimal toxicity, our findings suggest that investigation of P-AscH- efficacy is warranted in a phase 2 clinical trial.

https://ift.tt/2NGEnGQ

Precise spatio-temporal interruption of regulatory T cell-mediated CD8+ T cell suppression leads to tumor immunity

Tumors can develop despite the presence of competent host immunity via a complex system of immune evasion. One of the most studied factors originating from the host is immune suppression by regulatory T cells (Tregs). Ample laboratory and clinical evidence suggests that Treg ablation leads to robust antitumor immune activation. However, how Tregs specifically achieve their suppression in the context of tumor progression is not entirely clear, particularly with regard to the timing and location where Treg inhibition takes place. In this work, we report that Tregs migrate to tumor draining lymph nodes (TDLN) and block expression of sphingosine-1-phosphate receptor 1 (S1P1) on CD8+ T cells. This event trapped the CD8+ T cells in the TDLN and served as a facilitating factor for tumor growth. Intriguingly, minimalistic depletion of Tregs in TDLN in a short window following tumor inoculation was sufficient to restore CD8+ T cell activities, which resulted in significant tumor reduction. Similar treatments outside this time frame had no such effect. Our work therefore reveals a subtle feature in tumor biology whereby Tregs appear to be driven by newly established tumors for a programmed encounter with newly activated CD8+ T cells in TDLN. Our results suggest the possibility that clinical interception of this step can be tested as a new strategy of cancer therapy with expected high efficacy and low systemic side effects.

https://ift.tt/2Q8HNyJ

A convolutional neural network uses microscopic images to differentiate between mouse and human cell lines and their radioresistant clones

Artificial intelligence (AI) trained with a convolutional neural network (CNN) is a recent technological advancement. Previously, several attempts have been made to train AI using medical images for clinical applications. However, whether AI can distinguish microscopic images of mammalian cells has remained debatable. This study assesses the accuracy of image recognition techniques using the CNN to identify microscopic images. We also attempted to distinguish between mouse and human cells and their radioresistant clones. We used phase-contrast microscopic images of radioresistant clones from two cell lines, mouse squamous cell carcinoma NR-S1 and human cervical carcinoma ME-180. We obtained 10,000 images of each of the parental NR-S1 and ME-180 controls as well as radioresistant clones. We trained the CNN called VGG16 using these images and obtained an accuracy of 96%. Features extracted by the trained CNN were plotted using t-distributed stochastic neighbor embedding, and images of each cell line were well clustered. Overall, these findings suggest the utility of image recognition using AI for predicting minute differences among phase-contrast microscopic images of cancer cells and their radioresistant clones.

https://ift.tt/2NGCBFH

Genomic characterization of six virus-associated cancers identifies changes in the tumor immune microenvironment and altered genetic programs

Viruses affect approximately 20% of all human cancers and induce expression of immunogenic viral oncoproteins that make these tumors potent targets for immune checkpoint inhibitors. In this study, we apply computational tools to The Cancer Genome Atlas and other genomic datasets to define how virus infection shapes the tumor immune microenvironment and genetic architecture of 6 virus-associated tumor types. Across cancers, the cellular composition of the microenvironment varied by viral status, with virus-positive tumors often exhibiting increased infiltration of cytolytic cell types compared to their virus-negative counterparts. Analyses of the infiltrating T cell receptor repertoire in these patients revealed that Epstein-Barr virus infection was associated with decreased receptor diversity in multiple cancers, suggesting an antigen-driven clonal T cell response. Tissue-specific gene expression signatures capturing virus-associated transcriptomic changes successfully predicted virus status in independent datasets and were associated with both immune- and proliferation-related features that were predictive of patient prognosis. Together, the analyses presented suggest viruses have distinct effects in different tumors, with implications for immunotherapy.

https://ift.tt/2Q7Xt5b

AMG 176, a Selective MCL1 Inhibitor, is Effective in Hematological Cancer Models Alone and in Combination with Established Therapies [Research Articles]

The prosurvival BCL-2 family member MCL1 is frequently dysregulated in cancer. To overcome the significant challenges associated with inhibition of MCL1 protein-protein interactions, we rigorously applied small-molecule conformational restriction, which culminated in the discovery of AMG 176, the first selective MCL1 inhibitor to be studied in humans. We demonstrate that MCL1 inhibition induces a rapid and committed step towards apoptosis in subsets of hematological cancer cell lines, tumor xenograft models, and primary patient samples. With the use of a human MCL1 knock-in mouse, we demonstrate that MCL1 inhibition at active doses of AMG 176 is tolerated and correlates with clear pharmacodynamic effects, demonstrated by reductions in B-cells, monocytes and neutrophils. Furthermore, the combination of AMG 176 and venetoclax is synergistic in AML tumor models and in primary patient samples at tolerated doses. These results highlight the therapeutic promise of AMG 176 and the potential for combinations with other BH3 mimetics.

https://ift.tt/2NKcOMU

Exploiting MCL-1 dependency with combination MEK + MCL-1 inhibitors leads to induction of apoptosis and tumor regression in KRAS mutant non-small cell lung cancer [Research Articles]

BH3 mimetic drugs, which inhibit pro-survival BCL-2 family proteins, have limited single-agent activity in solid tumor models. The potential of BH3 mimetics for these cancers may depend on their ability to potentiate the apoptotic response to chemotherapy and targeted therapies. Using a novel class of potent and selective MCL-1 inhibitors, we demonstrate that concurrent MEK + MCL-1 inhibition induces apoptosis and tumor regression in KRAS mutant non-small cell lung cancer (NSCLC) models, which respond poorly to MEK inhibition alone. Susceptibility to BH3 mimetics that target either MCL-1 or BCL-XL was determined by the differential binding of pro-apoptotic BCL-2 proteins to MCL-1 or BCL-XL, respectively. The efficacy of dual MEK + MCL-1 blockade was augmented by prior transient exposure to BCL-XL inhibitors, which promotes the binding of pro-apoptotic BCL-2 proteins to MCL-1. This suggests a novel strategy for integrating BH3 mimetics that target different BCL-2 family proteins for KRAS mutant NSCLC.

https://ift.tt/2Q9zx1z

Education Can Up Emotional Intelligence in Residents

TUESDAY, Sept. 25, 2018 -- Following an educational intervention, residents from pediatrics and med-ped residency programs have an increase in total emotional intelligence (EI), according to a study published online Sept. 20 in Advances in Medical...

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Lack of CHD4 Leads to Abnormal Myofibrils, Heart Defects

TUESDAY, Sept. 25, 2018 -- The absence of CHD4 in heart cells results in inappropriate production of non-cardiac muscle proteins, which subsequently leads to heart defects, according to an animal study published recently in the Proceedings of the...

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Initial Abx Feasible Alternative for Uncomplicated Appendicitis

TUESDAY, Sept. 25, 2018 -- The cumulative incidence of appendicitis recurrence within five years is 39.1 percent among patients with uncomplicated acute appendicitis initially treated with antibiotics, according to research published in the Sept. 25...

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Cancer-Related Gene Variations Frequently Reclassified

TUESDAY, Sept. 25, 2018 -- Among individuals undergoing hereditary cancer testing, some variants of uncertain significance are reclassified, with almost one-quarter of those variants reclassified at a single commercial laboratory, according to a...

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Critics Demand Stop to 'Guinea Pig' Sepsis Clinical Trial

TUESDAY, Sept. 25, 2018 -- A major non-profit advocacy group is asking that a large government trial comparing treatments for sepsis be shut down. The trial, called Clovers, "places seriously ill patients at risk without the possibility of gaining...

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Melanocortin-4 receptor in subthalamic nucleus is involved in the modulation of nociception.

Related Articles

Melanocortin-4 receptor in subthalamic nucleus is involved in the modulation of nociception.

Am J Clin Exp Immunol. 2018;7(4):76-80

Authors: Han DJ, He ZG, Yang H

Abstract
Deep brain stimulation of the subthalamic nucleus (STN-DBS) stimulation produces significant improvement of overall pain related to Parkinson disease; however, the mechanisms underlying analgesic effects of STN-DBS are still unknown. This report describes direct neuroanatomical evidence for the central melanocortinergic-opioidergic circuits in the STN. We investigated melanocortin-4 receptor (MC4R) and mu-opioid receptor (MOR)-positive expression of the STN in MC4R-GFP transgenic mice using fluorescence immunohistochemical detection. Immunohistochemistry showed a large number of MC4R-GFP- and MOR-positive neurons within the STN region, and approximately 50% of MC4R-GFP-positive neurons coexpressed MOR. The results of this study showed direct neuroanatomical evidence for the central melanocortinergic-opioidergic signaling in the STN region. These findings contribute to the view of melanocortinergic-opioidergic circuits in the subthalamic nucleus as a reliable source of modulating of nociception with therapeutic potential for alleviating pain.

PMID: 30245921 [PubMed]

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Induction therapy downregulates the expression of Th17/Tfh cytokines in patients with active lupus nephritis.

Related Articles

Induction therapy downregulates the expression of Th17/Tfh cytokines in patients with active lupus nephritis.

Am J Clin Exp Immunol. 2018;7(4):67-75

Authors: Wang N, Gao C, Cui S, Qin Y, Zhang C, Yi P, Di X, Liu S, Li T, Gao G, Zheng Z

Abstract
To determine the potential changes of IL-6, IL-17A and IL-21 levels during induction therapy, and to assess their relationship with disease activity and immunologic features on patients with active lupus nephritis, twenty-eight patients treated with corticosteroid and immunosuppressants were included in this study. Demographic, clinical, serological data and disease activity were assessed. Blood samples were collected at week 0, 12 and 24, and serum concentrations of IL-17A, IL-6 and IL-21 were measured by cytometric bead array. The serum concentrations of IL-6, IL-17A and IL-21 (P<0.001, P<0.01, P=0.001, respectively) decreased progressively during induction therapy. Concentration of IL-6, IL-17A and IL-21 was higher in non-remission group than that in remission group. A positive correlation was established between the concentration of these cytokines and the severity of proteinuria (P<0.001, P=0.020, P=0.045, respectively), ESR (P<0.001), SLEDAI scores (P<0.05), and ANA titers (P=0.018, P=0.048, P<0.05, respectively). Additionally, ROC curve analysis for IL-6, IL-17A and IL-21 was performed to predict the disease activity. The optimal cutoff level was 5.78 pg/ml, 1.98 pg/ml and 8.59 pg/ml, with AUC=0.809, 0.735 and 0.786. The concentration of IL-6 and IL-21 may be regarded as an indicator for the remission of active lupus nephritis, with cutoff value of 9.12 pg/ml and 11.30 pg/ml, while AUC=0.930 and 0.896. The production of serum IL-6, IL-17A and IL-21 in active LN was dramatically declined during induction therapy, which may improve disease activity while delay disease progression of LN.

PMID: 30245920 [PubMed]

https://ift.tt/2xNfIFv

Effects of allergic stimulation and glucocorticoids on miR-155 in CD4+ T-cells.

Related Articles

Effects of allergic stimulation and glucocorticoids on miR-155 in CD4+ T-cells.

Am J Clin Exp Immunol. 2018;7(4):57-66

Authors: Daniel E, Roff A, Hsu MH, Panganiban R, Lambert K, Ishmael F

Abstract
RATIONALE: MicroRNAs (miRNAs) are emerging as important regulators of allergic inflammation and potential therapeutic targets. We sought to identify which miRNAs are expressed in CD4+ T-cells and determine whether allergic stimuli or glucocorticoids alter their expression.
METHODS: After IRB approval, blood was collected from dust mite (DM) allergic rhinitis subjects (n=20), non-allergic controls (n=8), and asthmatics (n=16). Peripheral blood mononuclear cells were incubated with dust mite extract (DME), diluent control, or DME + dexamethasone (0.1 µM). CD4+ T-cells were collected by magnetic bead column, and RNA was isolated by guanidinium/phenol-chloroform extraction. MicroRNA expression was measured using Nanostring microarray and quantitative real time PCR (qPCR).
RESULTS: We identified 196 miRNAs that were stably expressed in circulating CD4+ T-cells. Allergen stimulation of CD4+ T-cells with DME differentially induced miR-155 expression in cells of DM-allergic subjects as compared to non-allergic subjects. Induction of miR-155 expression was also observed with anti-CD3/anti-CD28 simulation and phorbol-12-Myristate-13-Acetate (PMA) treatment, and further augmented by calcium inophore and bromocyclic AMP in the latter treatment. The level of miR-155 expression was positively associated with expression of the TH2 cytokines IL-5 and IL-13. Inhibition of miR-155 in Jurkat T-cells inhibited the production of these cytokines. Glucocorticoids attenuated the effects of dust mite allergen, raising the possibility that inhibition of this miRNA could be a mechanism through which glucocorticoids exhibit their anti-inflammatory effects. The CD4+ T-cells had a higher level of miR-155 expression in asthma compared to in allergic rhinitis and non-asthmatics. The inhibitory effects of glucocorticoids on CD4+ T-cell miR-155 expression were lost in severe asthmatics.
CONCLUSION: Mir-155 is differentially expressed in allergic T-cells exposed to DM extract compared to in non-allergic cells and it is inhibited by glucocorticoids. MiR-155 may play a role in mediating allergic inflammation in T-cells and could be an anti-inflammatory target of steroids. This pathway may be de-regulated in severe asthma.

PMID: 30245919 [PubMed]

https://ift.tt/2IhY0Ps

Ovarian Cancer

The rapid pace of improvement in the clinical and genomic understanding of ovarian cancer has led to a deeper and more informed comprehension of histologically based risk factors as well as advancements in prevention and treatment strategies. In this issue of Hematology/Oncology Clinics of North America, our esteemed authors cover topics that are germane to the goal of early detection and prevention of ovarian cancer, cover our current understanding of the molecular and genomic underpinnings of ovarian cancer, discuss standard as well as experimental treatment strategies for patients diagnosed with this cancer, review treatment-related toxicities and their management, and update readers on the palliative care of patients with advanced ovarian cancer.

https://ift.tt/2Dt0hIM

Correction to: Multimodal treatment of pediatric patients with Askin’s tumors: our experience

In the original article mentioned above, the name of the sixth author was wrongly mentioned as "Vincenzo Briganti" instead of "Vito Briganti".

https://ift.tt/2QYZ5jd

https://ift.tt/2xQzsIy

https://ift.tt/2ztQgHq

Emergency Department Visits Owing to Intentional and Unintentional Traumatic Brain Injury among Infants in the United States: A Population-Based Assessment

To examine national trends of emergency department (ED) visits owing to traumatic brain injury (TBI) among infants (age <12 months), specifically in the context of intentional and unintentional mechanisms.

https://ift.tt/2Oh5Eii

The Impact of Age on Income-Related Health Status Inequalities from Birth to Adolescence: A Systematic Review with Cross-Country Comparisons

To examine the effect of age on associations between household income and overall health from birth to adolescence, and whether age patterns vary by country. It is uncertain whether income-related health inequalities remain stable, widen, or narrow as children age, which impacts optimal timing of equity-focused interventions.

https://ift.tt/2Oa9CcE

Respiratory Health in Adolescents Born Moderately-Late Preterm in a Community-Based Cohort

To determine the long-term effects of moderately-late preterm (MLP) birth on respiratory and allergic symptoms, lung function, and exercise capacity in adolescence.

https://ift.tt/2Q71C9H

Health Services Use during Transition from Pediatric to Adult Care for Inflammatory Bowel Disease: A Population-Based Study Using Health Administrative Data

To evaluate the impact of the transfer from pediatric to adult care on health services use for adolescents with inflammatory bowel disease (IBD).

https://ift.tt/2Q3lZVd

Hospitalization for Respiratory Syncytial Virus in Children with Down Syndrome Less than 2 Years of Age: A Systematic Review and Meta-Analysis

To compare the respiratory syncytial virus (RSV)-related hospitalization rate, hospital length of stay (LOS), and need for assisted ventilation in children aged <2 years with Down syndrome and those without Down syndrome.

https://ift.tt/2Oh5BTE

Ocular Flutter in Scrub Typhus

A 9-year-old boy presented with a subacute febrile illness with bursts of conjugate horizontal saccadic oscillations on visual fixation (Figure and Video; available at www.jpeds.com) and cerebellar ataxia. Examination revealed hepatosplenomegaly and scrotal eschar. Magnetic resonance imaging of the brain was normal and lumbar cerebrospinal fluid showed lymphocytic pleocytosis (70 cells, protein 105 mg/dL). IgM enzyme-linked immunosorbent assay for scrub typhus was positive. Intravenous doxycycline and dexamethasone for 5 days resulted in complete recovery.

https://ift.tt/2Q4RXR6

https://ift.tt/2Dw2Eux

Variation in Case-Mix Adjusted Unplanned Pediatric Cardiac ICU Readmission Rates

Objectives: To identify modifiable factors leading to unplanned readmission and characterize differences in adjusted unplanned readmission rates across hospitals Design: Retrospective cohort study using prospectively collected clinical registry data Setting: Pediatric Cardiac Critical Care Consortium clinical registry. Patients: Patients admitted to a pediatric cardiac ICU at Pediatric Cardiac Critical Care Consortium hospitals. Interventions: None. Measurements and Main Results: We examined pediatric cardiac ICU encounters in the Pediatric Cardiac Critical Care Consortium registry from October 2013 to March 2016. The primary outcomes were early (

https://ift.tt/2Q6JEEh

Systemic Inflammatory Response Syndrome as Predictor of Poor Outcome in Nontraumatic Subarachnoid Hemorrhage Patients

Objectives: Subarachnoid hemorrhage is a life-threatening disease associated with high mortality and morbidity. A substantial number of patients develop systemic inflammatory response syndrome. We aimed to identify risk factors for systemic inflammatory response syndrome development and to evaluate the role of systemic inflammatory response syndrome on patients'outcome. Design: Retrospective observational cohort study of prospectively collected data. Setting: Neurocritical care unit at a tertiary academic medical center. Patients: Two-hundred and ninety-seven consecutive nontraumatic subarachnoid hemorrhage patients admitted to the neurologic ICU between 2010 and 2017. Interventions: Systemic inflammatory response syndrome was diagnosed based on greater than or equal to two criteria (hypo-/hyperthermia, tachypnea, leukopenia/leukocytosis, tachycardia) and defined as early (≤ 3 d) and delayed (days 6–10) systemic inflammatory response syndrome burden (systemic inflammatory response syndrome positive days within the first 10 d). Using multivariate analysis, risk factors for the development of early and delayed systemic inflammatory response syndrome and the relationship of systemic inflammatory response syndrome with poor 3-month functional outcome (modified Rankin Scale score ≥ 3) were analyzed. Measurements and Main Results: Seventy-eight percent of subarachnoid hemorrhage patients had early systemic inflammatory response syndrome, and 69% developed delayed systemic inflammatory response syndrome. Median systemic inflammatory response syndrome burden was 60% (interquartile range, 10–90%). Risk factors for early systemic inflammatory response syndrome were higher admission Hunt and Hess grade (odds ratio, 1.75; 95% CI, 1.09–2.83; p = 0.02), aneurysm clipping (odds ratio, 4.84; 95% CI, 1.02–23.05; p = 0.048), and higher modified Fisher Scale score (odds ratio, 1.88; 95% CI, 1.25–2.89; p = 0.003). Hunt and Hess grade and pneumonia were independently associated with delayed systemic inflammatory response syndrome development. Systemic inflammatory response syndrome burden (area under the curve, 0.84; 95% CI, 0.79–0.88) had a higher predictive value for 3-month poor outcome compared with early systemic inflammatory response syndrome (area under the curve, 0.76; 95% CI, 0.70–0.81; p

https://ift.tt/2NEPyQf

High-Risk Anticholinergics Prescribed to 6 Percent of Elderly

TUESDAY, Sept. 25, 2018 -- High-risk anticholinergic prescriptions are listed for 6.2 percent of visits of older adults, according to a study published in a recent issue of the Journal of the American Geriatrics Society. Taeho Greg Rhee, Ph.D., from...

https://ift.tt/2Ob8wgR

Total Diabetes at 14 Percent in U.S. Adults for 2013-2016

TUESDAY, Sept. 25, 2018 -- The prevalence of diabetes was 14.0 percent among U.S. adults in 2013 to 2016, with prevalence of undiagnosed diabetes 4.3 percent, according to a September data brief published by the U.S. Centers for Disease Control and...

https://ift.tt/2Q1y510

Facebook Program Doesn't Up Smoking Abstinence at One Year

TUESDAY, Sept. 25, 2018 -- The Tobacco Status Project (TSP) Facebook smoking cessation intervention for young adults does not improve abstinence from smoking over one year, according to a study published in the September issue of Addiction. Danielle...

https://ift.tt/2Ob8uFL

Novel Immunotherapy May Up Survival in Melanoma Brain Mets

TUESDAY, Sept. 25, 2018 -- Checkpoint blockade immunotherapy (CBI) is associated with significant increases in overall survival (OS) in a real-world population of patients undergoing treatment for melanoma brain metastases (MBM), according to...

https://ift.tt/2Q1xZ9E

Inflammatory Back Pain Resolves in Many Patients

TUESDAY, Sept. 25, 2018 -- Inflammatory back pain (IBP) often resolves, while in 30 percent of patients it progresses to spondyloarthritis (SpA) within 10 years, according to a study published in a recent issue of Arthritis &...

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Positive Link Between Air Pollution, Diagnosis of Dementia

TUESDAY, Sept. 25, 2018 -- There is a positive association between residential levels of air pollution and being diagnosed with dementia, according to a study published in the September issue of BMJ Open. Iain M. Carey, Ph.D., from the University of...

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AAP Report Addresses Managing Fetal Alcohol Spectrum Disorder

TUESDAY, Sept. 25, 2018 -- In a clinical report published online Sept. 10 in Pediatrics, recommendations are presented to support pediatric providers in managing patients with a diagnosis of fetal alcohol spectrum disorder (FASD). Noting that FASDs...

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Components of Pharmacist-Led Discharge Counseling Vary

TUESDAY, Sept. 25, 2018 -- Components of pharmacist-led discharge counseling vary widely, and reporting is often poor, according to a review published in a recent issue of the Journal of Evaluation in Clinical Practice. Aline F. Bonetti, Pharm.D.,...

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In 2016, Proportion of Uninsured Americans Down to 10 Percent

TUESDAY, Sept. 25, 2018 -- From 2013 to 2016 there was a reduction in uninsurance among Americans from 17 to 10 percent, according to a report published in September by the Robert Wood Johnson Foundation (RWJF) and the Urban Institute. Laura Skopec,...

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Physician-Group ACOs Generate Medicare Savings

TUESDAY, Sept. 25, 2018 -- Physician-group accountable care organizations (ACOs) participating in the Medicare Shared Savings Program (MSSP) generated significantly more savings for Medicare that grew from 2012 to 2015 compared with...

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Cholera Outbreak in Haiti: Epidemiology, Control, and Prevention

In October 2010, a massive cholera outbreak struck Haiti, and subsequently, thousands of cholera cases have been documented throughout Haiti. After much controversy about its origin, scientific evidence demonstrated its importation from Nepalese United Nations Peacekeepers. Despite national and international efforts to combat this outbreak (such as oral cholera vaccine campaigns), challenges related to funding, water and sanitation infrastructure, and poverty make it difficult to eliminate cholera from Haiti. This article discusses the recent cholera epidemic in Haiti, its origin and spread throughout Haiti, the specific nature and microbiologic characteristics of the pathogen, and ongoing disease management and control efforts. Importantly, this article suggests a future research agenda identifying best strategies for eliminating cholera in Haiti. Correspondence to: Mentor Ali Ber Lucien, MD, Laboratoire National de Santé Publique d'Haïti, No. 52 Route de Delmas 33, commune de Delmas, Port-au-Prince HT6120, Haiti. E-mail: lucienmentor@gmail.com. Author Dr Marcus Zervos reports grants from Merck, Genentech, and Cempra outside the scope of the submitted work; all other authors declare that they have no competing interests. This study was supported by the SP-Haiti Lab project. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Incidence Risk Level and Severity of Orthopedic Surgical Site Infection in Jordan

Background Orthopedic surgical site infections are higher in developing countries compared with developed countries. Purpose This study aimed to determine the following: incidence rate of infection, levels of risk of infection, the severity of orthopedic infection, and the relationship between risk level of and severity level of orthopedic infection. Methods The study used a prospective approach to collect data about orthopedic surgery patients through assessing their health status and reviewing their medical records and monitoring for the occurrence of surgical site infection within 90 days after the operation. A total of 286 patients met the eligibility criteria from 18 hospitals. The severity of wound infection was assessed using the Additional treatment, Serous discharge, Erythema, Purulent exudate, Separation of deep tissues, isolation of bacteria, and duration of inpatient Stay wound scoring scale, and the levels of risk were assessed using the National Nosocomial Infection Surveillance risk index score. Results The incidence rate of orthopedic surgical site infection was (n = 8; 2.8%). Five patients (62.5%) had a moderate-risk level of infection, and 2 patients (25%) had a high-risk level. Most patients (n = 278; 97.2%) had satisfactory healing level. Both risk levels and severity levels of orthopedic surgical site infection were significantly correlated with each other. Conclusion Appropriate risk level and severity level assessment tools should be used to aid in the assessment of orthopedic surgical site infection. Correspondence to: Zeinab M. Hassan, RN, PhD, School of Nursing, The Hashemite University, PO Box 150459, Zarqa 13115, Jordan. E-mail: hassan_zeinab@yahoo.com; drzeinab@hu.edu.jo. The authors have no funding or conflicts of interest to disclose. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Nocardia brasiliensis Preseptal Cellulitis in an Immunocompetent Patient

The Nocardia subspecies are opportunistic pathogens ubiquitous in the environment that most often cause infection in immunocompromised hosts. Here we describe a case of community-acquired preseptal cellulitis in a previously healthy man who we believe acquired the infection from contact with soil while gardening. Correspondence to: Samuel Kareff, MD, MPH, Department of Graduate Medical Education, Medstar Georgetown University Hospital, 3800 Reservoir Rd, Washington, DC 20007. E-mail: sak67@georgetown.edu. The authors have funding or conflicts of interest to disclose. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Mycobacterium avium Complex Cutaneous Infections in Non-HIV Patients: Case Report and Literature Review

We report a rare case of Mycobacterium avium complex cutaneous infection in a non-HIV patient with a report of 13 other cases of M. avium complex cutaneous infection in non-HIV patients found in the literature since 1992. Correspondence to: Louis Donald Saravolatz, MD, MACP, FIDSA, 19251 Mack Ave, Grosse Pointe Woods, MI 48236. E-mail: louis.saravolatz@stjohn.org. The authors have no funding or conflicts of interest to disclose. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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A Swollen Leg: Disseminated Tuberculous Pyomyositis After Treatment of Miliary Tuberculosis in an Immunocompromised Patient

We report a patient with a rheumatic overlap syndrome on hydroxychloroquine and prednisone who developed tuberculous pyomyositis shortly after receiving 9 months of treatment of miliary tuberculosis. Her only presenting symptom was swelling of the left lower extremity without any systemic manifestation, despite extensive radiographic evidence of disseminated abscess formation. Acid-fast bacilli stains and cultures of the purulent material were negative for Mycobacterium tuberculosis (MTB), but polymerase chain reaction confirmed the diagnosis. To our knowledge, this is the first case report of tuberculous pyomyositis that developed shortly after the patient completed a full course of antituberculous therapy. We believe that the concurrent therapy of her rheumatic overlap syndrome with hydroxychloroquine likely led to her treatment failure for MTB and will discuss the possible pathogenesis. Our case also illustrates that MTB can cause significant soft tissue disease without systemic manifestations and that polymerase chain reaction is a valuable diagnostic study. Correspondence to: Lee Bach Lu, MD, Baylor College of Medicine, 1 Baylor Plaza, Houston TX 77004. E-mail: lblu@bcm.edu. The authors have no funding or conflicts of interest to disclose. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Subcutaneous Dirofilariasis in a Returning Traveler From Costa Rica

Dirofilaria genus is the most common cause of zoonotic filariasis. It typically causes cardiopulmonary disease in canines, but in humans, it can cause pulmonary, subcutaneous, and ocular disease. In this report, we present a case of a young woman who traveled to Costa Rica and subsequently developed a subcutaneous nodule. A biopsy performed in our patient showed dirofilariasis, possibly Dirofilaria tenuis. Most human dirofilariases are caused by Dirofilaria immitis and Dirofilaria repens. This is the first case of possible D. tenuis in Central America. The animal reservoir (North American raccoon) has been described in Costa Rica, highlighting the importance of reservoir distribution in human disease. Correspondence to: Jose Antonio Suarez, MD, Instituto Conmemorativo Gorgas de Estudios de la Salud, Calle 35 y Av Justo Arosemena, Panama City, Panama. E-mail: jsuarez@gorgas.gob.pa. The authors have no funding or conflicts of interest to disclose. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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An Underrecognized Adverse Effect of Azithromycin: Agranulocytosis

No abstract available

https://ift.tt/2OaODGt

Using 22C3 Anti-PD-L1 Antibody Concentrate on Biopsy and Cytology Samples from Non-small Cell Lung Cancer Patients

To expand the ability of laboratories worldwide to assess the eligibility of patients with lung cancer for treatment with pembrolizumab, in a reliable and reproducible manner, we developed an assay that uses the 22C3 antibody concentrate on a widely available immunohistochemical autostainer, for both biopsy and cytology specimens.

https://ift.tt/2xNhqHd

Single Droplet Digital Polymerase Chain Reaction for Comprehensive and Simultaneous Detection of Mutations in Hotspot Regions

Here, we present a protocol to accurately quantify multiple genetic alterations of a target region in a single reaction using drop-off ddPCR and a unique pair of hydrolysis probes.

https://ift.tt/2IdueLD

Bronchial Blocker Use in the Difficult Airway Patient Requiring Lung Isolation: Clarification as to What Blockers Are Actually Available

No abstract available

https://ift.tt/2DuByE4

Should We Always Continue β-Blocking Agents Preoperatively?

No abstract available

https://ift.tt/2DGm1RN

Intraoperative Considerations for Transgender Patients

No abstract available

https://ift.tt/2QXTfOL

In Response

No abstract available

https://ift.tt/2Dt9VeD

In Response

No abstract available

https://ift.tt/2QYBE9r

Programmed Intermittent Bolus Regimen for Erector Spinae Plane Blocks in Children: A Retrospective Review of a Single-Institution Experience

With few published reports on erector spinae plane block use in children, limited guidance on perioperative local anesthetic dosing exists. We present a series of 22 patients who received erector spinae plane catheters with programmed intermittent bolus for various surgeries. Median loading dose of 0.4 mL/kg (interquartile range [IQR], 0.1 mL/kg) ropivacaine 0.5%, intraoperative bolus of 0.3 mL/kg/h (IQR, 0.1 mL/kg) ropivacaine 0.2%, and a postoperative programmed intermittent bolus regimen of maximum 0.6 mg/kg/h resulted in highest pain scores on postoperative day 1 with a median score of 1.7 of 10 (IQR, 1.8) and highest morphine equivalents consumed on postoperative day 2 with a median score of 0.16 mg/kg up to 120 hours after surgery. Accepted for publication August 22, 2018. Funding: None. Conflicts of Interest: See Disclosures at the end of the article. Reprints will not be available from the authors. Address correspondence to Ban C. H. Tsui, MD, FRCPC, Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Lucile Packard Children's Hospital Stanford, 300 Pasteur Dr, 3rd Floor, Room H3584, MC 5640, Stanford, CA 94305. Address e-mail to bantsui@stanford.edu. © 2018 International Anesthesia Research Society

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Acute Stroke Management in the First 24 Hours: A Practical Guide for Clinicians

No abstract available

https://ift.tt/2QYBvmp

Obstetric Anesthesiology in the United States: Current and Future Demand for Fellowship-Trained Subspecialists

No abstract available

https://ift.tt/2Dwkcqq

Lack of Bias Evaluation and Inadequate Study Selection May Produce Misleading Results

No abstract available

https://ift.tt/2QYBgrv

Is Tube Thermosoftening Helpful for Videolaryngoscope-Guided Nasotracheal Intubation?: A Randomized Controlled Trial

BACKGROUND: Thermosoftening of the endotracheal tube (ETT) and telescoping the ETT into a rubber catheter have been suggested as a method for reducing epistaxis during nasotracheal intubation (NTI). However, thermosoftening technique is known to make it difficult to navigate the ETT into trachea without the use of Magill forceps during NTI. The cuff inflation technique has been suggested as an effective alternative to the use of Magill forceps to improve the oropharyngeal navigation of the ETT, irrespective of their stiffness, during direct laryngoscope-guided NTI. We evaluated whether thermosoftening of the ETT telescoped into rubber catheters has an additional benefit in reducing nasal injury. Simultaneously, we also evaluated whether thermosoftening of the ETT worsened orotracheal navigability during cuff inflation-supplemented videolaryngoscope-guided NTI. METHODS: One hundred forty patients were randomly assigned to 1 of the 2 groups depending on whether the ETT was softened by warming or not. The primary outcome was the incidence of epistaxis during NTI. The secondary outcome was nasotracheal navigability of the ETT, assessed by navigation grade and time required for insertion of ETT in each phase (from nose to oropharynx, from oropharynx to glottic inlet aided by cuff inflation if needed, and from glottic inlet to trachea). RESULTS: The ETTs were successfully inserted through the selected nostril of all 140 patients. In the thermosoftening group, the incidence and severity of epistaxis was significantly lower (7% vs 51%; difference of 44.2%; 95% confidence interval, 29.9%–56.2%; P .99 and P = .054, respectively) and from the glottic inlet to the trachea (P > .99 and P = .750, respectively) between the 2 groups. In both groups, all ETTs could be navigated into the trachea without the use of Magill forceps. CONCLUSIONS: Supplemented with cuff inflation during videolaryngoscope-guided NTI, thermosoftening of the ETT telescoped into rubber catheters has a substantial benefit because it significantly reduces the incidence of epistaxis without worsening the oropharyngeal navigability of the ETT. Accepted for publication August 17, 2018. Funding: None. The authors declare no conflicts of interest. This study was approved by the Institutional Ethics Committee (institutional review board [IRB] approval number 2017-03-020, IRB contact information: Institutional Review Board, Hallym University Kangnam Sacred Heart Hospital, B1, 12, Siheung-daero 187-gil, Yeongdeungpo-gu, Seoul 07441, Republic of Korea. E-mail: dandelionc@hallym.or.kr. Reprints will not be available from the authors. Address correspondence to Joo Hyun Jun, MD, PhD, Department of Anesthesiology and Pain Medicine, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, 1, Singil-ro, Yeongdeungpo-gu, Seoul 07441, Republic of Korea. Address e-mail to ilpleut@naver.com. © 2018 International Anesthesia Research Society

https://ift.tt/2QRHvxv

Multimodal General Anesthesia: Theory and Practice

Balanced general anesthesia, the most common management strategy used in anesthesia care, entails the administration of different drugs together to create the anesthetic state. Anesthesiologists developed this approach to avoid sole reliance on ether for general anesthesia maintenance. Balanced general anesthesia uses less of each drug than if the drug were administered alone, thereby increasing the likelihood of its desired effects and reducing the likelihood of its side effects. To manage nociception intraoperatively and pain postoperatively, the current practice of balanced general anesthesia relies almost exclusively on opioids. While opioids are the most effective antinociceptive agents, they have undesirable side effects. Moreover, overreliance on opioids has contributed to the opioid epidemic in the United States. Spurred by concern of opioid overuse, balanced general anesthesia strategies are now using more agents to create the anesthetic state. Under these approaches, called "multimodal general anesthesia," the additional drugs may include agents with specific central nervous system targets such as dexmedetomidine and ones with less specific targets, such as magnesium. It is postulated that use of more agents at smaller doses further maximizes desired effects while minimizing side effects. Although this approach appears to maximize the benefit-to-side effect ratio, no rational strategy has been provided for choosing the drug combinations. Nociception induced by surgery is the primary reason for placing a patient in a state of general anesthesia. Hence, any rational strategy should focus on nociception control intraoperatively and pain control postoperatively. In this Special Article, we review the anatomy and physiology of the nociceptive and arousal circuits, and the mechanisms through which commonly used anesthetics and anesthetic adjuncts act in these systems. We propose a rational strategy for multimodal general anesthesia predicated on choosing a combination of agents that act at different targets in the nociceptive system to control nociception intraoperatively and pain postoperatively. Because these agents also decrease arousal, the doses of hypnotics and/or inhaled ethers needed to control unconsciousness are reduced. Effective use of this strategy requires simultaneous monitoring of antinociception and level of unconsciousness. We illustrate the application of this strategy by summarizing anesthetic management for 4 representative surgeries. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Accepted for publication June 11, 2018. Funding: This work was supported by the National Institutes of Health (Bethesda, MD): R01 GM104948 (to E.N.B.) and P01GM118269 (to E.N.B.); and by the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA. Conflicts of Interest: See Disclosures at the end of the article. A glossary of terms is available in the Appendix. Reprints will not be available from the authors. Address correspondence to Emery N. Brown, MD, PhD, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, 55 Fruit St, Grey-Jackson 444, Boston, MA 02114. Address e-mail to enb@neurostat.mit.edu. © 2018 International Anesthesia Research Society

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Performance of Air Seal of Flexible Reinforced Laryngeal Mask Airway in Thyroid Surgery Compared With Endotracheal Tube: A Randomized Controlled Trial

BACKGROUND: Flexible reinforced laryngeal mask airway (FLMA®) has gained popularity in thyroid surgery, but air leak and displacement are still concerns. METHODS: In this randomized, single-blinded, noninferiority, controlled trial, we randomized patients scheduled for elective radical thyroidectomy to an endotracheal tube (ETT) group or a FLMA group. The primary outcomes were ventilation leak volume, peak airway pressure, and partial pressure of end-tidal carbon dioxide (PetCO2). Data for primary outcomes were collected after insertion of ETT/FLMA, at incision, and at 10-minute intervals during surgery. Ten milliliters, 5 cm H2O, and 10 mm Hg were used as the noninferiority deltas for ventilation leak volume, peak airway pressure, and PetCO2, respectively. We assessed noninferiority of FLMA to ETT on the primary outcomes over time using the results of a linear mixed-effects model. The position of FLMA mask was evaluated before and after surgery, and the airway complications were recorded. RESULTS: A total of 132 patients were included: 65 in ETT group and 67 in FLMA group. Differences (FLMA group minus ETT group) of ventilation leak volume, peak airway pressure, and PetCO2 from the mixed-effects models were 2.09 mL (98.3% confidence interval [CI], –6.46 to 10.64), −0.60 cm H2O (98.3% CI, –2.15 to 0.96), and 1.02 mm Hg (98.3% CI, 0.04–1.99), respectively. Score of fiber-optic position of FLMA was significantly higher after surgery than before. There was no severe shift, loss of the mask seal, regurgitation, or aspiration in the FLMA group. One patient in the FLMA group experienced brief and easily controlled laryngospasm. CONCLUSIONS: In thyroid surgery, FLMA is noninferior to ETT in the peak airway pressure and PetCO2 although mild to moderate mask shift could occur during surgical manipulation. There is no evidence for a higher complication rate when FLMA is used. Accepted for publication July 27, 2018. Funding: None. The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/KegmMq). Clinical Trial Number: ChiCTR-IOR-15006602. LMA Flexible and LMA Classic are registered trademarks of Teleflex Incorporated or its affiliates. Reprints will not be available from the authors. Address correspondence to Jie Yi, MD, Department of Anesthesiology, Peking Union Medical College Hospital, Beijing 100730, China. Address e-mail to easyue@163.com. © 2018 International Anesthesia Research Society

https://ift.tt/2R0ndlB

Follow-on RifAximin for the Prevention of recurrence following standard treatment of Infection with Clostridium Difficile (RAPID): a randomised placebo controlled trial

Background

Clostridium difficile infection (CDI) recurs after initial treatment in approximately one in four patients. A single-centre pilot study suggested that this could be reduced using 'follow-on' rifaximin treatment. We aimed to assess the efficacy of rifaximin treatment in preventing recurrence.

Methods

A multisite, parallel group, randomised, placebo controlled trial recruiting patients aged ≥18 years immediately after resolution of CDI through treatment with metronidazole or vancomycin. Participants received either rifaximin 400 mg three times a day for 2 weeks, reduced to 200 mg three times a day for a further 2 weeks or identical placebo. The primary endpoint was recurrence of CDI within 12 weeks of trial entry.

Results

Between December 2012 and March 2016, 151 participants were randomised to either rifaximin or placebo. Primary outcome data were available on 130. Mean age was 71.9 years (SD 15.3). Recurrence within 12 weeks was 29.5% (18/61) among participants allocated to placebo compared with 15.9% (11/69) among those allocated to rifaximin, a difference between groups of 13.7% (95% CI –28.1% to 0.7%, p=0.06). The risk ratio was 0.54 (95% CI 0.28 to 1.05, p=0.07). During 6-month safety follow-up, nine participants died in each group (12%). Adverse event rates were similar between groups.

Conclusion

While 'follow-on' rifaximin after CDI appeared to halve recurrence rate, we failed to reach our recruitment target in this group of frail elderly patients, so the estimated effect of rifaximin lacks precision. A meta-analysis including a previous trial suggests that rifaximin may be effective; however, further, larger confirmatory studies are needed.

https://ift.tt/2IfLqjB

Genetic variations in PRKAA1 predict the risk and progression of gastric Cancer

Abstract

Background

PRKAA1 encodes α-subunit of 5-AMP-activated protein kinase (AMPK), which has been implicated in the pathogenesis of carcinoma of the stomach. Previous works have suggested that polymorphisms in the PRKAA1 may be associated with the risk of non-cardiac gastric cancer (NCGC), but whether PRKAA1 polymorphisms are related to clinical pathologic characteristics of gastric cancer and its clinical outcome is largely unknown.

Methods

We carried out a case-control study including a total of 481 gastric cancer patients and 490 healthy controls. The genotypes of enrolled polymorphisms were identified with Sequenom MassARRAY platform.

Results

This study showed that rs10074991 GG genotype (adjusted OR = 1.44, 95%CI:0.99–2.09, p = 0.056) has a borderline significantly increased risk for gastric cancer, which was consistent with the result of additive model (adjusted OR = 1.21, 95%CI:1.01–1.46, p = 0.042). In similar, an increased risk of gastric cancer was also observed for rs13361707 TC genotype (adjusted OR = 1.47, 95%CI: 1.01–2.14, p = 0.043; additive model: adjusted OR = 1.22, 95%CI: 1.02–1.47, p = 0.033). Furthermore, the rs154268 and rs461404 were also found associated with increased gastric cancer risk, which may be influenced by age, tumor type and differentiation, and tumor stage. Haplotype analysis indicated A-G-C-T-C-G haplotype (rs6882903, rs10074991, rs13361707, rs3805490, rs154268 and rs461404) is associated with increased risk of gastric cancer (OR = 1.29, 95%CI: 1.02–1.62, p = 0.035). The univariate analysis for overall survival (OS) revealed that both of rs10074991 and rs13361707 variants are associated with poor OS in patients with NCGC.

Conclusion

This case-control study provided the evidence thatrs13361707CC, rs10074991GG, rs461404GG, and rs154268CC are associated with increased gastric cancer risk, especially for NCGC, and that patients with rs10074991 G or rs13361707 C allele have a poor OS.

https://ift.tt/2QXBZcs

Single-cell Quantitation of mRNA and Surface Protein Expression in Simian Immunodeficiency Virus-infected CD4+ T Cells Isolated from Rhesus macaques

Described is a methodology to quantitate the expression of 96 genes and 18 surface proteins by single cells ex vivo, allowing for the identification of differentially expressed genes and proteins in virus-infected cells relative to uninfected cells. We apply the approach to study SIV-infected CD4+ T cells isolated from rhesus macaques.

https://ift.tt/2Dw5oI7

Ford creates system to alert drivers to oncoming emergency vehicles

The new system helps drivers give emergency vehicles a route through traffic by forming an "emergency corridor"

https://ift.tt/2N0BbjZ

Stereotactic body radiotherapy based treatment for hepatocellular carcinoma with extensive portal vein tumor thrombosis

Abstract

Background

There is currently no worldwide consensus for the management of hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). We evaluated the efficacy of stereotactic body radiotherapy (SBRT) as the initial treatment for HCC with extensive PVTT based on a relatively large number of patients.

Methods

In our multidisciplinary approach for patients with hepatobiliary tumors, SBRT is recommended for unresectable HCC with PVTT or those with contraindication for transarterial chemoembolization (TACE). The aim is to shrink the tumor thrombus and preserve adequate portal venous flow, thus facilitating subsequent treatments such as TACE and tumor resection. In the present study, 70 continuous cases of HCC patients with extensive PVTT initially treated with SBRT were studied. The median follow-up period was 9.5 months (range, 1.0–21.0 months). The dynamic changes of tumor thrombosis with time after SBRT were also analyzed.

Results

The median survival time for the whole group was 10.0 months (95% CI, 7.7–12.3 months), with a 6- and 12-month overall survival (OS) rate of 67.3%, and 40.0% respectively. Patients who received combined SBRT and TACE showed significantly longer OS than those without indication for TACE after SBRT (12.0 ± 1.6 vs. 3.0 ± 1.0 months). Patients with good response to radiation usually had better survival. SBRT was well tolerated in our patient series.

Conclusions

In conclusion, SBRT used as the initial treatment for HCC patients with extensive PVTT originally unsuitable for resection or TACE can achieve adequate thrombus shrinkage and portal vein flow restoration in the majority of cases. It could thus offer the patients an opportunity to undergo further treatment such as resection or TACE procedure. Such therapeutic strategy may result in survival advantage, especially for those who do receive combined modality with SBRT.

https://ift.tt/2OPOBRI

A Rare Case of Enoxaparin Induced Skin Necrosis Without Thrombocytopenia

No abstract available

https://ift.tt/2N2uXjt

Subcutaneous Interferon-β1a Does Not Increase the Risk of Stroke in Patients with Multiple Sclerosis: Analysis of Pooled Clinical Trials and Post-Marketing Surveillance

Abstract

Introduction

Previous studies suggest that multiple sclerosis (MS) patients have a greater stroke risk than the general population but there is limited evidence of stroke risk in patients receiving disease-modifying treatment. We assessed stroke risk in MS patients treated with subcutaneous interferon-β1a (sc IFN-β1a) using pooled data from clinical trials and post-marketing surveillance.

Methods

Seventeen phase II–IV Merck KGaA-sponsored trials of sc IFN-β1a were assessed to estimate the stroke incidence rate (IR) and IR ratio (IRR) per 100 patient-years (PY), and associated 95% confidence intervals (CI). The association of treatment duration with stroke was assessed through a Cox model. IR, IRR, and hazard ratio (HR) were adjusted by age, sex, presence of any comorbidity, and MS duration. Individual case safety reports were retrieved from the Global Patient Safety Database. The reporting rates of stroke were calculated and classified as medically confirmed or non-medically confirmed according to the source of each report.

Results

In 17 clinical trials, 4412 patients were treated with sc IFN-β1a for a total of 10,622 PY and 1055 patients with placebo for 2005 PY. The IR/100 PY (95% CI) of stroke was 0.025 (0.004, 0.150) in sc IFN-β1a patients and 0.051 (0.008, 0.349) in placebo patients. The IRR for sc IFN-β1a vs placebo was 0.486 (0.238, 0.995) and the HR was 0.496 (0.235, 1.043) for time to stroke-related event for sc IFN-β1a treatment at any dose compared with placebo. Among sc IFN-β1a patients, the IRR in those treated for < 2 years was 0.602 (0.159, 2.277) and for ≥ 2 years 0.469 (0.196, 1.124). Analysis of the safety database showed that the overall reporting rate for stroke was 13.286/10,000 PY.

Conclusion

Safety data from both clinical trial and post-marketing settings indicate that treatment with sc IFN-β1a does not increase stroke risk in patients with MS.

Funding

Merck KGaA, Darmstadt, Germany.

https://ift.tt/2ztRnqv

The Association Between Overactive Bladder and Falls and Fractures: A Systematic Review

Abstract

Introduction

Urinary symptoms are associated with an increased risk of falls, but few studies have focused on patients with overactive bladder (OAB). This study aimed to synthesize estimates of the risk of falls and fractures in patients with OAB.

Methods

Medline, EMBASE, the Cumulative Index to Nursing and Allied Health Literature, and Scopus were systematically searched for observational studies that focused on patients with OAB. When available, data from a non-OAB comparison sample were included. Double independent review and data extraction were performed. Falls and fractures data were summarized by unadjusted and adjusted risks, and percent attributable risk (PAR) of falls and fractures associated with OAB.

Results

Fifteen studies were included in the analyses. The proportion of patients with OAB experiencing at least one fall over a year ranged from 18.9% to 50.0%, and the proportion of patients with OAB experiencing recurrent or serious falls ranged from 10.2% to 56.0%. In studies that included a non-OAB comparison sample, a higher risk of falls was observed in patients with OAB compared to those without. A significantly increased (1.3- to 2.3-fold) adjusted OAB-associated risk of falls was reported, while unadjusted PARs for OAB associated falls ranged from 3.7% to 15.5%. Risk was higher among women and those 65 years of age or older. While analysis of fractures showed elevated point estimates, most studies were underpowered to detect a statistically significant difference between groups.

Conclusions

Evidence from the published literature clearly demonstrates the importance of OAB and its symptoms as risk factors for falls and fractures.

Funding

Astellas.

https://ift.tt/2OR6iAn

Pilot, Randomized, Blinded, Placebo-Controlled Trial Investigating the Correlation Between Acid Control and Heartburn Relief with 14 Days of Esomeprazole Treatment

Abstract

Introduction

Reflux symptoms are frequently associated with esophageal acid exposure. However, other potential causes unrelated to acid secretion are possible, and the relationship between acid control and symptomatic improvement remains unclear. This study investigated the correlation between individual intragastric pH control and heartburn relief among subjects with frequent heartburn who are likely to self-treat with over-the-counter (OTC) medications. We hypothesized that improved acid control would provide greater symptomatic improvement among individuals representative of an OTC population.

Methods

This phase 4, single-center, randomized, double-blind, placebo-controlled study was conducted in subjects without diagnosed gastroesophageal reflux disease or other gastrointestinal conditions who were experiencing frequent heartburn (≥ 3 episodes/week; ≥ 2 nighttime episodes/week over past 30 days) that was responsive to treatment. Subjects entered a 7-day run-in phase, received placebo BID (before breakfast and dinner), and completed symptom diaries. During the treatment phase, subjects received esomeprazole 20 mg BID, esomeprazole 20 mg then placebo, or placebo BID. Subjects underwent 24-h intragastric pH monitoring at baseline and day 14 and completed daily symptom diaries.

Results

In the per-protocol population (n = 39), mean (SD) change from baseline in percentage of time with intragastric pH > 4 was 58.7% (± 26.4%) versus 41.0% (± 30.4%) for those who did and did not achieve 24-h heartburn relief. Significant correlations were observed between change in percentage of time with intragastric pH > 4 and 24-h heartburn relief (OR 1.028; 95% CI 1.001, 1.055; P = 0.0442) and complete resolution (OR 1.034; 95% CI 1.003, 1.065; P = 0.0301).

Conclusions

Individuals with greater improvements in duration of intragastric acid suppression had an increased likelihood of achieving heartburn relief and resolution. These results indicate that individuals not adequately controlling their intragastric pH may require an escalation in dose of their acid-suppressive therapy, assessment with 24-h pH monitoring, or a change in treatment regimen to address non-reflux-related etiologies of their heartburn.

Trial Registration

ClinicalTrials.gov identifier: NCT02708355.

Funding

Pfizer Consumer Healthcare, Madison, NJ, USA.

Plain Language Summary

Plain language summary available for this article.

https://ift.tt/2zsH1qU

Fermented Astragalus in diet altered the composition of fecal microbiota in broiler chickens

The composition and function of the intestinal microbiota play important roles in digestion and degradation of herbal medicines (HMs). However, few studies have examined the relationship between the fecal micr...

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Early decrease in postoperative serum albumin predicts severe complications in patients with colorectal cancer after curative laparoscopic surgery

Abstract

Background

Postoperative severe complications are always associated with prolonged hospital stays, increased economic burdens, and poor prognoses in patients with colorectal cancer (CRC). This present study aimed to investigate potential risk factors including serum albumin (Alb) for severe complications in CRC patients.

Methods

Eligible patients with primary CRC undergoing elective laparoscopic colectomy from July 2015 to July 2017 were included. Postoperative severe complications were defined as grade III and IV according to the Clavien–Dindo classification. ∆Alb was defined as (preoperative Alb − nadir Alb within POD2)/preoperative Alb × 100%. The baseline characteristics, intraoperative data, and laboratory data were obtained from the database for the analysis. Univariate and multivariate logistic regression analyses were utilized for the assessment of the association between risk factors and postoperative severe complications. The predictive value of ∆Alb for postoperative severe complications was evaluated by receiver operating characteristic (ROC) curve analysis.

Results

A total of 193 patients were finally included in the analysis data set, of which 38 (19.7%) patients had postoperative severe complications. In the final multivariate logistic regression analysis, ∆Alb was the only independent factor associated with postoperative severe complications (OR 1.66, 95%CI 1.18–2.33, p = 0.003). The area under the curve (AUC) of ∆Alb was 0.916, with the sensitivity and specificity of 0.842 and 0.858 (p < 0.001).

Conclusions

The ∆Alb was an independent risk factor for severe complications in CRC patients after curative laparoscopic surgery.

https://ift.tt/2QW2uPJ

MiR-452 promotes an aggressive colorectal cancer phenotype by regulating a Wnt/β-catenin positive feedback loop

Abstract

Background

Aberrant activation of Wnt/β-catenin signaling pathway is considered to be an important issue in progression and metastasis of various human cancers, especially in colorectal cancer (CRC). MiR-452 could activate of Wnt/β-catenin signaling. But the mechanism remains unclear.

Methods

The expression of miR-452 in CRC and normal tissues was detected by real-time quantitative PCR. The effect of miR-452 on CRC growth and invasion was conducted by functional experiments in vitro and in vivo. Bioinformatics and cell luciferase function studies verified the direct regulation of miR-452 on the 3'-UTR of the GSK3β, which leads to the activation of Wnt/β-catenin signaling.

Results

MiR-452 was upregulated in CRC compared with normal tissues and was correlated with clinical significance. The luciferase reporter system studies affirmed the direct regulation of miR-452 on the 3'-UTR of the GSK3β, which activate the Wnt/β-catenin signaling. The ectopic upregulation of miR-452 significantly inhibited the expression of GSK3β and enhanced CRC proliferation and invasion in vitro and in vivo. Meanwhile, knockdown of miR-452 significantly recovered the expression of GSK3β and attenuated Wnt/β-catenin-mediated cell metastasis and proliferation. More important, T-cell factor/lymphoid enhancer factor (TCF/LEF) family of transcription factors, which are crucial downstream molecules of the Wnt/β-catenin signaling pathway was verified as a valid transcription factor of miR-452's promoter.

Conclusions

Our findings first demonstrate that miR-452-GSK3β-LEF1/TCF4 positive feedback loop induce CRC proliferation and migration.

https://ift.tt/2OczgO2

Feasibility of whole body vibration during intensive chemotherapy in patients with hematological malignancies – a randomized controlled pilot study

Abstract

Background

Hospitalized cancer patients undergoing intensive or high-dose chemotherapy often experience a considerable decline in functional performance associated with the increased risk of adverse health events. Exercises, particularly resistance-based exercises that may counteract this decline are restricted by therapy-related side effects. Since whole body vibration (WBV) is known to efficiently stimulate the neuromuscular system without significantly raising blood pressure, we hypothesize that especially WBV is particularly feasible even during intensive or high-dose chemotherapy (primary endpoint) and thus induces beneficial functional adaptations.

Methods

Twenty hospitalized patients with hematological malignancies scheduled for intensive or high-dose chemotherapy were randomly allocated to an intervention group (IG) undergoing WBV, or an active control group (CG) cycling. Feasibility was determined by comparing the IG's and CG's training compliance. Furthermore, to assess feasibility, WBV-induced changes in chemotherapy-related side effects, blood pressure, and heart rate immediately after exercising were documented. To assess patients' functional performance, we measured jump height (cm), the duration (sec) of performing the chair rising- (CRT) and timed-up-and-go test (TUG), maximum power output during jumping and CRT (watt/kg) as well as sway path (mm) during balance tasks.

Results

Training compliance was similar between groups (IG: median 62%, range 39–77; CG: 67%, 58–100; p = 0.315). Moreover, we observed neither the IG's reported side effects worsening, nor any increase in blood pressure after WBV. IG's jump height (+ 2.3 cm, 95%CI 0.1–4.4, p = 0.028) and TUG performance (− 1.3 s, 95%CI -2.53 – -0.65, p = 0.027) improved significantly, while sway paths in semi-tandem stance were augmented after the intervention (eyes open: + 60 mm, 95%CI 2–236, p = 0.046; eyes closed: + 88 mm, 95%CI 49–214, p = 0.028). The CG's performances did not change over time. Maximum power output during CMJ and CRT and time during CRT did not change.

Conclusion

Our study is the first proving the feasibility of WBV during intensive/high-dose chemotherapy of hospitalized cancer patients. Additionally, WBV-induced neuromuscular adaptations resulted in functional benefits relevant to patients' autonomy. We believe that WBV can be implemented as an alternative training method during intensive chemotherapy, although the relative benefit compared to conventional resistance training requires more evaluation in future studies.

Trial registration

German Register of Clinical Trials No.: DRKS00004338, prospectively registered on 11/30/2012.

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