NSC 2017: The Importance of Student Engagement

Megan Roos, PT, DPT, discusses what she learned about student engagement while serving as President of the Student Assembly Board of Directors.

https://www.youtube.com/watch?v=iomoW_j_1Cc

NSC 2017: President Has High Hopes For Next Generation of PTs/PTAs

Sharon L. Dunn, PT, PhD, Board-Certified Orthopaedic Clinical Specialist, reflects on her interactions with students at NSC 2017.

https://www.youtube.com/watch?v=67WsOcDKZas

NSC 2017: Finding Your 'Hell, Yes!'

Keaton Ray, PT, DPT, ATC, Board-Certified Orthopaedic Clinical Specialist, describes her struggle to find her career direction as a student and recent graduate.

https://www.youtube.com/watch?v=HMjwGj0HugA

NSC 2017: Mercer-Marquette Challenge

Students can get involved in the annual fundraising campaign to benefit the Foundation of Physical Therapy.

https://www.youtube.com/watch?v=y-TpWoi9hdE

Advances in Microbiology Vol.7,No.9 (September 2017)

Seroprevalence of Helicobacter pylori Infection and Risk Factors among Asymptomatic Subjects in Delta State, Nigeria
Helicobacter pylori, Infection, Risk Factors, Delta State, Nigeria
Paper Information Full Paper: PDF (Size:384KB)
DOI: 10.4236/aim.2017.79050

Antimicrobial Resistance Encountered in Garbage Collection Areas and Dumpsites in Nairobi, Kenya Using Escherichia coli and Klebsiella as Indicator Species
Dumpsite, Garbage Collection Area, Indicator Organisms, Antimicrobial Resistance
Paper Information Full Paper: PDF (Size:768KB)
DOI: 10.4236/aim.2017.79051

Evaluation of Contamination of Hands of the Medical Students in a Medical Teaching Tertiary Care Hospital
Medical Students, Hand Samples, Bacterial Culture, MRSA, ICR
Paper Information Full Paper: PDF (Size:710KB)
DOI: 10.4236/aim.2017.79052

http://ift.tt/1lkzXmf

Identification of hereditary cancer in the general population: development and validation of a screening questionnaire for obtaining the family history of cancer

Abstract

One of the challenges for Latin American countries is to include in their healthcare systems technologies that can be applied to hereditary cancer detection and management. The aim of the study is to create and validate a questionnaire to identify individuals with possible risk for hereditary cancer predisposition syndromes (HCPS), using different strategies in a Cancer Prevention Service in Brazil. The primary screening questionnaire (PSQ) was developed to identify families at-risk for HCPS. The PSQ was validated using discrimination measures, and the reproducibility was estimated through kappa coefficient. Patients with at least one affirmative answer had the pedigree drawn using three alternative interview approaches: in-person, by telephone, or letter. Validation of these approaches was done. Kappa and intraclass correlation coefficients were used to analyze data's reproducibility considering the presence of clinical criteria for HCPS. The PSQ was applied to a convenience sample of 20,000 women of which 3121 (15.6%) answered at least one affirmative question and 1938 had their pedigrees drawn. The PSQ showed sensitivity and specificity scores of 94.4% and 75%, respectively, and a kappa of 0.64. The strategies for pedigree drawing had reproducibility coefficients of 0.976 and 0.850 for the telephone and letter approaches, respectively. Pedigree analysis allowed us to identify 465 individuals (24.0%) fulfilling at least one clinical criterion for HCPS. The PSQ fulfills its function, allowing the identification of HCPS at-risk families. The use of alternative screening methods may reduce the number of excluded at-risk individuals/families who live in locations where oncogenetic services are not established.

This manuscript describes the creation and validation of a questionnaire to identify individuals with possible risk for hereditary cancer predisposition syndromes (HCPS), using different strategies in a Cancer Prevention Service in Brazil. The questionnaire was applied to a convenience sample of 20,000 women of which 3121 (15.6%) reported the presence of cancer cases in the family and 1938 had their pedigrees drawn. The use of alternative screening methods may reduce the number of excluded at-risk individuals/families who live in locations where oncogenetic services are not established.

http://ift.tt/2zt1JnN

Internal preference mapping of milk–fruit beverages: Influence of color and appearance on its acceptability

Abstract

The individual preferences of 100 consumers between 20 and 30 years old for the color of 16 milk–fruit juice beverages (MFJB) were investigated by preference mapping technique. Consumers were asked to evaluate, just by looking at the samples, how much they liked them (from "Extremely dislike" to "Extremely like"). The color of the samples was analyzed by two different instrumental techniques. Results obtained from the instrumental color measurement showed the wide diversity in hues of the beverages available in the market, and correlations between techniques proved that both of them were appropriate to analyze color.

Results showed that participants preferred samples with orangish appearance instead of those with a whiter look. Anyway, punctuations given by the consumers suggest that generally, color of these products is not highly evaluated by consumers, as the best mean punctuation was 6.6.

The appearance of food products has a demonstrated influence in food acceptance. This research provides information on how color influences the acceptability of milk–fruit beverages.

http://ift.tt/2yzBUWe

Procaspase-activating compound-1 induces apoptosis in Trypanosoma cruzi

Abstract

Some therapeutics for parasitic, cardiac and neurological diseases activate apoptosis. Therefore, the study of apoptotic proteins in pathogenic organisms is relevant. However, the molecular mechanism of apoptosis in unicellular organisms remain elusive, despite morphological evidence of its occurrence. In Trypanosoma cruzi, the causative agent of Chagas disease, metacaspase 3 (TcMCA3), seems to have a key role in parasite apoptosis. Accordingly, this work provides data concerning TcMCA3 regulation through its interaction with procaspase-activating compound 1 (PAC-1), a procaspase 3 activator. Indeed, PAC-1 reduced T. cruzi epimastigote viability with an IC₅₀ of 14.12 µM and induced loss of mitochondrial potential and exposure of phosphatidylserine, features of the apoptotic process. Notwithstanding, those PAC-1-inducible effects were not conserved in metacyclic trypomastigotes. Moreover, PAC-1 reduced the viability of mammalian cells with a greater IC₅₀ (25.70 µM) compared to T. cruzi epimastigotes, indicating distinct modes of binding between caspases and metacaspases. To shed light on the selectivity of metacaspases and caspases, we determined the structural features related to the PAC-1 binding sites in both types of proteins. These data are important for improving the understanding of the apoptosis pathway in T. cruzi so that TcMCA3 could be better targeted with future pharmaceuticals.

http://ift.tt/2xWJ8Ef

The Impact of Sentinel Node-Mapping in Staging High-Risk Endometrial Cancer

Abstract

Background

This study aimed to determine the impact of sentinel lymph node (SLN)-mapping on the staging of high-risk endometrial cancer (endometrioid grade 3, serous, clear cell, carcinosarcoma, deep myometrial invasion, or angiolymphatic invasion).

Methods

The study analyzed a series of 236 patients treated at AC Camargo Cancer Center from June 2007 to February 2017. The compared 75 patients who underwent SLN-mapping (SLN group) with 161 patients who received pelvic ± para-aortic lymphadenectomy (N-SLN group). Patients with adnexal, peritoneal, or suspicious node metastases were excluded from the study.

Results

The groups did not differ in terms of age, histologic type, or presence of deep myometrial invasion. The overall detection rate for SLNs was 85.3%, and bilateral SLNs were observed in 60% of the patients. Of 20 positive SLNs, 8 (40%) were detected only after immunohistochemistry (IHC). The findings showed an overall sensitivity of 90%, a negative predictive value of 95.7%, and a false-negative predictive value of 4.3%. The SLN group had more pelvic node metastases detected than the N-SLN group (26.7 vs 14.3%; p = 0.02). However, the rate of para-aortic node metastases did not differ between the two groups (13.5 vs 5.6%; p = 0.12). Five patients (3.5%) in the N-SLN group had isolated para-aortic node metastases versus none in the patients with SLN mapped. Additionally, the SLN group received more adjuvant chemotherapy (48 vs 33.5%; p = 0.03).

Conclusions

The data suggest that SLN-mapping identifies more pelvic node metastases than lymph node dissection alone and increases the node detection rate by 12.5% after IHC. Furthermore, no isolated para-aortic node metastases are observed when SLN is detected.

http://ift.tt/2xeHF7T

Vitamin Status and the Development of Postoperative Cognitive Decline in Elderly Surgical Oncologic Patients

Abstract

Background

This study aimed to evaluate the influence that serum levels of vitamin B12, folate, and homocysteine have on the development of short-term postoperative cognitive decline in the elderly surgical oncology patient.

Methods

This study was part of a prospective cohort study focused on postoperative cognitive outcomes for patients 65 years of age or older undergoing surgery for a solid malignancy. Postoperative cognitive decline was defined as the change in the combined results of the Ruff Figural Fluency Test and the Trail-Making Test Parts A and B. Patients with the highest change in scores 2 weeks postoperatively compared with baseline were considered to be patients with cognitive decline. Patients with the lowest change were considered to be patients without cognitive decline. To analyze the effect of vitamin levels on the changes in postoperative cognitive scores, uni- and multivariate logistic regression analysis were performed.

Results

The study enrolled 61 patients with and 59 patients without postoperative cognitive decline. Hyperhomocysteinemia was present in 14.2% of the patients. Patients with postoperative cognitive decline more often had hyperhomocysteinemia (27.9 vs 10.2%). Hyperhomocysteinemia was associated with a higher chance for the development of postoperative cognitive decline (odds ratio_adjusted, 11.9; 95% confidence interval, 2.4–59.4). Preoperative vitamin B12 or folate deficiency were not associated with the development of postoperative cognitive decline.

Conclusion

Preoperative hyperhomocysteinemia is associated with the development of postoperative cognitive decline. The presence of preoperative hyperhomocysteinemia could be an indicator for an increased risk of postoperative cognitive decline developing in the elderly.

http://ift.tt/2zFJWKY

Performance Analysis of the American Joint Committee on Cancer 8th Edition Staging System for Retroperitoneal Sarcoma and Development of a New Staging Algorithm for Sarcoma-Specific Survival

Abstract

Background

The American Joint Committee on Cancer (AJCC) recently published the 8th edition of the AJCC Cancer Staging Manual. Major changes were made to the staging algorithm for retroperitoneal sarcoma; however, whether these changes improve staging system performance is questionable.

Methods

This retrospective cohort analysis of 3703 adult patients with retroperitoneal sarcoma in the Surveillance, Epidemiology, and End Results (SEER) database compares a novel staging system incorporating histologic subtype of sarcoma with current and prior AJCC soft tissue sarcoma staging systems using multiple statistical techniques. The effect of tumor size on sarcoma-specific survival was also assessed by flexible, non-linear Cox proportional hazard regression using restricted cubic splines and fractional polynomials.

Results

The relationship between the covariate-adjusted log hazard for disease-specific survival and tumor size is non-linear. Although the new AJCC T classification approximates this hazard fairly well, the overall prognostic impact of tumor size is limited after accounting for other predictive factors. Predictive accuracy and concordance indices of the AJCC 8th edition staging system for retroperitoneal sarcoma are significantly lower than the prior 7th edition. A proposed staging system incorporating histologic grade, tumor size, and histologic subtype is superior to both the AJCC 7th and 8th editions in predicting sarcoma-specific survival.

Conclusion

AJCC committees should not revise tumor staging algorithms unless the changes actually improve the staging system. A proposed staging scheme incorporating data regarding histologic subtype of sarcoma performs significantly better than both the 7th and 8th AJCC staging systems.

http://ift.tt/2xdczgX

Rectal Gastrointestinal Stromal Tumor (GIST) in the Era of Imatinib: Organ Preservation and Improved Oncologic Outcome

Abstract

Background

Approximately 5% of gastrointestinal stromal tumors (GISTs) originate in the rectum, and historically, radical resection was commonly performed. Little is known about the outcome for rectal GIST in the era of imatinib.

Methods

Using a prospectively maintained database, this study retrospectively analyzed 47 localized primary rectal GISTs treated at our center from 1982 to 2016, stratified by when imatinib became available in 2000. Overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) were analyzed by the Kaplan–Meier method.

Results

Rectal GISTs represented 7.1% of 663 primary GISTs. The findings showed 17 patients in the pre-imatinib era and 30 patients in the imatinib era. The two groups had similar follow-up evaluation, age, gender, Miettinen risk, and distance to the anal verge. In the imatinib era, tumors were smaller at diagnosis (median 4 vs. 5 cm; p = 0.029), and 24 of the 30 patients received perioperative imatinib. In the high-risk patients, organ preservation and negative margins were more common among the 13 patients treated with neoadjuvant imatinib than among the 21 patients treated directly with surgery. High-risk patients who received perioperative imatinib (n = 15) had greater (or nearly significantly greater) 5-year OS, DSS, local RFS, and distant RFS than those who did not (n = 19) (91, 100, 100, and 71% vs. 47, 65, 74, and 41%; p = 0.049, 0.052, 0.077, 0.051, respectively). In the imatinib era, no patient has had a local recurrence or death due to GIST.

Conclusions

The use of imatinib is associated with organ preservation and improved oncologic outcome for patients with rectal GIST.

http://ift.tt/2zHSUHA

Similar Significance of Lymphovascular Invasion with Different Treatment Modalities Among Esophageal Squamous Cell Carcinoma

http://ift.tt/2xe9OvE

Multiple system atrophy: experimental models and reality

Abstract

Multiple system atrophy (MSA) is a rapidly progressing fatal synucleinopathy of the aging population characterized by parkinsonism, dysautonomia, and in some cases ataxia. Unlike other synucleinopathies, in this disorder the synaptic protein, α-synuclein (α-syn), predominantly accumulates in oligodendroglial cells (and to some extent in neurons), leading to maturation defects of oligodendrocytes, demyelination, and neurodegeneration. The mechanisms through which α-syn deposits occur in oligodendrocytes and neurons in MSA are not completely clear. While some studies suggest that α-syn might transfer from neurons to glial cells, others propose that α-syn might be aberrantly overexpressed by oligodendroglial cells. A number of in vivo models have been developed, including transgenic mice overexpressing α-syn under oligodendroglial promoters (e.g.: MBP, PLP, and CNP). Other models have been recently developed either by injecting synthetic α-syn fibrils or brain homogenates from patients with MSA into wild-type mice or by using viral vectors expressing α-syn under the MBP promoter in rats and non-human primates. Each of these models reproduces some of the neuropathological and functional aspects of MSA; however, none of them fully replicate the spectrum of MSA. Understanding better the mechanisms of how α-syn accumulates in oligodendrocytes and neurons will help in developing better models that recapitulate various pathogenic aspects of MSA in combination with translatable biomarkers of early stages of the disease that are necessary to devise disease-modifying therapeutics for MSA.

http://ift.tt/2iq4a7k

trans-Cinnamaldehyde Inhibits Microglial Activation and Improves Neuronal Survival against Neuroinflammation in BV2 Microglial Cells with Lipopolysaccharide Stimulation

Background. Microglial activation contributes to neuroinflammation and neuronal damage in neurodegenerative disorders including Alzheimer's and Parkinson's diseases. It has been suggested that neurodegenerative disorders may be improved if neuroinflammation can be controlled. trans-cinnamaldehyde (TCA) isolated from the stem bark of Cinnamomum cassia possesses potent anti-inflammatory capability; we thus tested whether TCA presents neuroprotective effects on improving neuronal survival by inhibiting neuroinflammatory responses in BV2 microglial cells. Results. To determine the molecular mechanism behind TCA-mediated neuroprotective effects, we assessed the effects of TCA on lipopolysaccharide- (LPS-) induced proinflammatory responses in BV2 microglial cells. While LPS potently induced the production and expression upregulation of proinflammatory mediators, including NO, iNOS, COX-2, IL-1β, and TNF-α, TCA pretreatment significantly inhibited LPS-induced production of NO and expression of iNOS, COX-2, and IL-1β and recovered the morphological changes in BV2 cells. TCA markedly attenuated microglial activation and neuroinflammation by blocking nuclear factor kappa B (NF-κB) signaling pathway. With the aid of microglia and neuron coculture system, we showed that TCA greatly reduced LPS-elicited neuronal death and exerted neuroprotective effects. Conclusions. Our results suggest that TCA, a natural product, has the potential of being used as a therapeutic agent against neuroinflammation for ameliorating neurodegenerative disorders.

http://ift.tt/2zqZ5yV

Relationship between Activities of Daily Living and Readmission within 90 Days in Hospitalized Elderly Patients with Heart Failure

Aims. To examine the relationship between activities of daily living (ADL) and readmission within 90 days and assess the cutoff value of ADL to predict readmission in hospitalized elderly patients with heart failure (HF). Methods. This cohort study comprised 589 consecutive patients with HF aged ≥65 years, who underwent cardiac rehabilitation from May 2012 to May 2016 and were discharged home. We investigated patients' characteristics, basic attributes, and ADL (motor and cognitive Functional Independence Measure [FIM]). We analyzed the data using the unpaired t-test, χ2 test, Cox proportional hazard model, receiver operating characteristic (ROC) curve, and Kaplan-Meier method. Results. Of 589 patients, 113 met the criteria, and they were divided into the nonreadmission () and readmission groups (). Age, body mass index, New York Heart Association class, hemoglobin level, and motor FIM score were significantly different between the two groups (). The body mass index (hazard ratio [HR]: 0.87; ) and motor FIM score (HR: 0.94; ) remained statistically significant. The cutoff value for the motor FIM score determined by ROC curve analysis was 74.5 points (area under the curve = 0.78; ). Conclusion. The motor FIM score in elderly patients with HF was an independent predictor of rehospitalization within 90 days.

http://ift.tt/2xbXDzr

Exploring the Concept of Degrees of Maternal Morbidity as a Tool for Surveillance of Maternal Health in Latin American and Caribbean Settings

Objectives. To assess a birth registry to explore maternal mortality and morbidity and their association with other factors. Study Design. Exploratory multicentre cross-sectional analysis with over 700 thousand childbirths from twelve Latin American and Caribbean countries between 2009 and 2012. The WHO criteria for maternal morbidity were employed to split women, following a gradient of severity of conditions, into (1) maternal death (MD); (2) maternal near miss (MNM); (3) potentially life-threatening conditions (PLTC); (4) less severe maternal morbidity (LSMM); (5) any maternal morbidity; and (6) women with no maternal morbidity. Their prevalence and estimated risks of adverse maternal outcomes were assessed. Results. 712,081 childbirths had a prevalence of MD and MNM of 0.14% and 3.1%, respectively, while 38% of women had experienced morbidity. Previous maternal morbidity was associated with higher risk of adverse maternal outcomes and also the extremes of reproductive ages, nonwhite ethnicity, no stable partner, no prenatal care, smoking, drug and alcohol use, elective C-section, or induction of labour. Poorer perinatal outcomes were proportional to the severity of maternal outcomes. Conclusions. The findings corroborate WHO concept regarding continuum of maternal morbidity, reinforcing its importance in preventing adverse maternal outcomes and improving maternal healthcare in different settings.

http://ift.tt/2zFIUyC

Biofilm-based photobioreactors: Their design and improving productivity through efficient supply of dissolved inorganic carbon

Abstract

The potential of biofilm-based photobioreactors (PBRs) for various applications has long been recognized and various types of biofilm-based PBRs have been developed for different applications. Compared to suspension-based PBR reactors, biofilm-based systems offer several advantages, including a significantly higher biomass concentration. However, due to the immobilization of the cells, in contrast to suspension-based systems, dissolved inorganic carbon (DIC) has to be transferred into the biofilm for consumption. Thus, to ensure efficient operation of these systems under a given lighting scheme (e.g. depending on geographical location), availability of DIC should be optimized. To achieve this, the dynamics of DIC inside the various biofilm-based PBRs, as well as the operational principles of these PBRs, need to be understood. The mini-review summarizes the designs of existing biofilm-based PBRs and reviews previous studies on DIC dynamics in various biofilms. Strategies to enhance DIC availability for the immobilized cells in biofilm-based PBRs are also discussed.

http://ift.tt/2yFV38k

A Method for the Topographical Identification and Quantification of High Frequency Oscillations in Intracranial Electroencephalography Recordings

Up to one third of patients with focal seizures are medically refractory, and resective epilepsy surgery or responsive nerve stimulation (RNS) placement is required to reduce seizure burden or render the patient seizure free (Wiebe et al., 2001; Engel et al., 2012). High Frequency Oscillations (HFOs) consist of brief (<200 μsec) bursts of energy with a spectral content ranging between 80-600 Hz and have shown promise as a electrophysiological biomarker of epileptogenic brain tissue (Engel et al., 2009; Gotman, 2010; Jacobs et al., 2012).

http://ift.tt/2gYGDqB

Cerebellum and dystonia: The story continues. Will the patients benefit from new discoveries?

When reading the recent paper of Avanzino and colleagues with cogent evidence supporting a possible role of the cerebellum in the expression of the clinical phenotype in dystonia (Avanzino et al., 2017, this issue of Clinical Neurophysiology), I could not resist to feel reminded of an invited review paper published in 2013 in the Clinical Neurophysiology, where we provided a state-of-the-art overview of cerebellar involvement in dystonia, even with possible therapeutic targets for dystonic patients in the future (Bares and Filip, 2013).

http://ift.tt/2zr5EBj

Triple-element compound-specific stable isotope analysis of 1,2-dichloroethane for characterization of the underlying dehalogenation reaction in two Dehalococcoides mccartyi strains

Abstract

Chlorinated ethanes belong to the most common groundwater and soil contaminants. Of these, 1,2-dichloroethane (1,2-DCA) is an man-made, persistent and toxic contaminant, released due to improper waste treatment at versatile production sites. This study investigated the anaerobic transformation of 1,2-DCA by Dehalococcoides mccartyi strain 195 and strain BTF08 using triple-element compound-specific stable isotope analysis (CSIA) of carbon, chlorine and hydrogen for the first time. Isotope fractionation patterns for carbon (ε^C_BTF08 = -28.4 ± 3.7 ‰; ε^C₁₉₅ = -30.9 ± 3.6 ‰) and chlorine (ε^Cl_BTF08 = -4.6 ± 0.7 ‰; ε^Cl₁₉₅ = -4.2 ± 0.5 ‰) within both investigated D. mccartyi strains, as well as the dual-element analysis (Λ_BTF08 = 6.9 ± 1.2; Λ₁₉₅ = 7.1 ± 0.2), supported identical reaction mechanisms for dehalogenation of 1,2-DCA. Hydrogen isotope fractionation analysis revealed dihaloelimination as prevalent reaction mechanism. Vinyl chloride as major intermediate could be excluded by performing the experiment in deuterated aqueous media. Furthermore, evaluation of the derived apparent kinetic isotope effects (AKIE^C_BTF08 = 1.029/AKIE^C₁₉₅ = 1.031; AKIE^Cl_BTF08 = 1.005/AKIE^Cl₁₉₅ = 1.004) pointed towards simultaneous abstraction of both involved chlorine-substituents in a concerted matter. It was shown that D. mccartyi strain BTF08 and strain 195 are capable of complete, direct dihaloelimination of 1,2-DCA to ethene.

http://ift.tt/2zr5auZ

Factors Associated with Prevalence and Treatment of Primary Biliary Cholangitis in United States Health Systems

Reported prevalence of primary biliary cholangitis (PBC) varies widely. Demographic features and treatment patterns are not well characterized in the United States (US). We analyzed data from the Fibrotic Liver Disease (FOLD) consortium, from 11 geographically diverse health systems, to investigate epidemiologic factors and treatment of PBC in the US.

http://ift.tt/2gX7PpG

Harmful and Beneficial Effects of Anti-coagulants in Patients With Cirrhosis and Portal Vein Thrombosis

Vitamin K antagonists (VKAs) promote recanalization of portal vein thrombosis (PVT) in patients with cirrhosis. However, the benefit of PVT recanalization might be offset by major and minor bleeding associated with use of anti-coagulants. We evaluated harmful and beneficial effects of VKA in patients with PVT and cirrhosis.

http://ift.tt/2zqX1Xr

The Murine Choline-Deficient, Ethionine-Supplemented (CDE) Diet Model of Chronic Liver Injury

Here we describe a common method to induce chronic liver injury in mice by feeding of a choline-deficient and ethionine-supplemented (CDE) diet. We demonstrate health monitoring, liver perfusion, isolation, and preservation. A time course of six weeks can inform about liver injury, pathohistology, fibrosis, inflammatory, and liver progenitor cell responses.

http://ift.tt/2xVDWvB

Monitoring Astrocyte Reactivity and Proliferation in Vitro Under Ischemic-Like Conditions

Ischemic stroke is a complex event in which the specific contribution of astrocytes to the affected brain region exposed to oxygen glucose deprivation (OGD) is difficult to study. This article introduces a methodology to obtain isolated astrocytes and study their reactivity and proliferation under OGD conditions.

http://ift.tt/2yFfhPk

Injectable Products by SCA Pharmaceuticals: Recall - Potential Contamination

[Posted 10/21/2017] AUDIENCE: Pharmacy, Health Professional ISSUE: SCA Pharmaceuticals LLC ("SCA Pharmaceuticals") is voluntarily recalling various lots of injectable products to the hospital level. The is a potential for the products to...

http://ift.tt/2yEQHhr

Guiding longitudinal sampling in IBD cohorts

We read with interest the work by Pascal et al published recently in Gut.1 Here, they report the volatile microbial signatures of patients with Crohn's disease (CD), a quality that greatly hinders our ability to classify healthy from affected subjects using 16S rRNA profiles from stool. Nonetheless, their work overcame these and other complications,2 producing a decision tree that classifies subjects with CD, UC, irritable bowel syndrome and anorexia. Although the authors note that both subtypes of IBD, particularly CD, have increased microbial community instability, this information is not used as a feature to improve classifier accuracy. Could microbiome instability become actionable by creating a new classifier that benefits from repeated measurements? If so, how many samples per individual are needed to assess instability?

We collected daily stool samples for up to 6 weeks from 19 CD subjects and 12 controls (see the analysis notebook for cohort description,...

http://ift.tt/2l58eut

Stage distribution of screen-detected colorectal cancers in the Netherlands

We read with interest the results of the pilot study in England, which was performed to establish the acceptability and diagnostic performance of screening with the faecal immunochemical test (FIT) over the guaiac faecal occult blood test (gFOBT).1 When comparing gFOBT to FIT, the uptake increased from 59.4% to 66.4%, positivity rate increased from 1.7% to 7.8% (at a cut-off level of 20 µg Hb/g faeces) and colorectal cancer (CRC) detection doubled. Moreover, this report showed that also with FIT cut-off levels above 20 µg Hb/g faeces, improved clinical outcomes can be achieved over gFOBT. However, for a screening programme to be effective, it is a prerequisite to detect cancers in an early stage. Thus far, information on stage distribution of screen-detected CRCs in a population-based FIT screening programme is lacking.

In our study, we collected data on all CRCs detected in patients aged 60–75 years in the Netherlands in 2015...

http://ift.tt/2zsPuau

ROC-king onwards: intraepithelial lymphocyte counts, distribution and role in coeliac disease mucosal interpretation

We read with interest the paper of Rostami et al, which was recently published in Gut. Counting intraepithelial lymphocytes (IEL) is considered highly useful in the histological evaluation of small intestinal biopsy specimens. When combined with the assessment of mucosal architecture and of inflammatory cells in the lamina propria, a precise histological diagnosis is possible in the majority of cases. Currently, there is an ongoing debate on the number of IEL that can safely be considered diagnostic for coeliac disease (CD). In our opinion, the recently published attempt by Rostami et al1 turns out to be insignificant due to the following shortcomings: the controls used were neither sex-matched nor age-matched. Controls showing any abnormality which might result in an increase in IEL counts were excluded. It was not stated whether biopsies were obtained from the duodenal bulb (D1) or the descending part (D2) of the duodenum. Finally, the...

http://ift.tt/2l7kLNZ

High risk of hepatocellular carcinoma and death in patients with immune-tolerant-phase chronic hepatitis B

Objective

High serum HBV DNA levels are associated with high risks of hepatocellular carcinoma (HCC) and cirrhosis in patients with chronic hepatitis B (CHB). Although the immune-tolerant (IT) phase is characterised by high circulating HBV DNA levels, it remains unknown whether antiviral treatment reduces risks of HCC and mortality.

Design

This historical cohort study included HBeAg-positive patients with CHB with high HBV DNA levels (≥20 000 IU/mL) and no evidence of cirrhosis at a tertiary referral hospital in Korea from 2000 to 2013. The clinical outcomes of 413 untreated IT-phase patients with normal alanine aminotransferase (ALT) levels (females, <19 IU/mL; males, <30 IU/mL) were compared with those of 1497 immune-active (IA)-phase patients (ALT ≥80 IU/mL) treated with nucleos(t)ide analogues.

Results

The IT group was significantly younger than the IA group (mean age, 38 vs 40 years at baseline, p=0.04). The 10-year estimated cumulative incidences of HCC (12.7% vs 6.1%; p=0.001) and death/transplantation (9.7% vs 3.4%; p<0.001) were significantly higher in the IT group than the IA group. In multivariable analyses, the IT group showed a significantly higher risk of HCC (HR 2.54; 95% CI 1.54 to 4.18) and death/transplantation (HR 3.38; 95% CI 1.85 to 6.16) than the IA group, which was consistently identified through inverse probability treatment weighting, propensity score-matched and competing risks analyses.

Conclusions

Untreated IT-phase patients with CHB had higher risks of HCC and death/transplantation than treated IA-phase patients. Unnecessary deaths could be prevented through earlier antiviral intervention in select IT-phase patients.

http://ift.tt/2zqV90T

Serrated polyposis syndrome may go undiagnosed even in structured colorectal cancer screening programmes performed by endoscopists with otherwise good quality indices

We have read the article by Ijspeert et al with great interest as it comprises the largest series of colonoscopies concerning the serrated polyposis syndrome (SPS) published so far.1 SPS is characterised by multiple serrated polyps (SP) throughout the colon and it is associated with an increased risk of colorectal cancer (CRC).2 A 5-year cumulative incidence of CRC during surveillance after clearing of all relevant polyps of 1.5% has been reported.2 Recently published guidelines recommend resection of all clinically relevant lesions and starting annual colonoscopy surveillance thereafter.3 Therefore, early recognition and treatment of SPS is important to achieve low long-term risk of CRC.4

We retrospectively analysed 4161 primary screening colonoscopies of average-risk individuals aged ≥50 years performed by 15 different experienced gastroenterologists (≥300 colonoscopies of all indications per year during the study period) from one academic centre and six private practices...

http://ift.tt/2l6k33I

Injectable Products by SCA Pharmaceuticals: Recall - Potential Contamination

[Posted 10/21/2017] AUDIENCE: Pharmacy, Health Professional ISSUE: SCA Pharmaceuticals LLC ("SCA Pharmaceuticals") is voluntarily recalling various lots of injectable products to the hospital level. The is a potential for the products to...

http://ift.tt/2yEQHhr

Prevention and management of spouting bleeding during endoscopic submucosal dissection for large subpedunculated type colonic tumor

Abstract

Endoscopic submucosal dissection (ESD) is a reliable method for treating superficial colorectal tumors, however it is technically more difficult and requires more experience than gastric ESD, because of difficulties associated with endoscope operability and the anatomical features of the colorectal region, including the presence of folds/flexures, bending of the intestinal tract, and the thinness of the intestinal wall.¹ Main accidental complications during colorectal ESD are perforation and bleeding.^{2, 3} With continued bleeding, the visibility of the operative field would deteriorate. In addition, with the recent rise in the number of elderly individuals, the rate of comorbidities, including cardiovascular and cerebral vascular diseases has been increasing in Japan.

This article is protected by copyright. All rights reserved.

http://ift.tt/2yznOnS

Sedation After Cardiac Surgery With Propofol or Dexmedetomidine: Between Scylla and Charybdis?

No abstract available

http://ift.tt/2yGrpjC

Descriptive Statistics: Reporting the Answers to the 5 Basic Questions of Who, What, Why, When, Where, and a Sixth, So What?

Descriptive statistics are specific methods basically used to calculate, describe, and summarize collected research data in a logical, meaningful, and efficient way. Descriptive statistics are reported numerically in the manuscript text and/or in its tables, or graphically in its figures. This basic statistical tutorial discusses a series of fundamental concepts about descriptive statistics and their reporting. The mean, median, and mode are 3 measures of the center or central tendency of a set of data. In addition to a measure of its central tendency (mean, median, or mode), another important characteristic of a research data set is its variability or dispersion (ie, spread). In simplest terms, variability is how much the individual recorded scores or observed values differ from one another. The range, standard deviation, and interquartile range are 3 measures of variability or dispersion. The standard deviation is typically reported for a mean, and the interquartile range for a median. Testing for statistical significance, along with calculating the observed treatment effect (or the strength of the association between an exposure and an outcome), and generating a corresponding confidence interval are 3 tools commonly used by researchers (and their collaborating biostatistician or epidemiologist) to validly make inferences and more generalized conclusions from their collected data and descriptive statistics. A number of journals, including Anesthesia & Analgesia, strongly encourage or require the reporting of pertinent confidence intervals. A confidence interval can be calculated for virtually any variable or outcome measure in an experimental, quasi-experimental, or observational research study design. Generally speaking, in a clinical trial, the confidence interval is the range of values within which the true treatment effect in the population likely resides. In an observational study, the confidence interval is the range of values within which the true strength of the association between the exposure and the outcome (eg, the risk ratio or odds ratio) in the population likely resides. There are many possible ways to graphically display or illustrate different types of data. While there is often latitude as to the choice of format, ultimately, the simplest and most comprehensible format is preferred. Common examples include a histogram, bar chart, line chart or line graph, pie chart, scatterplot, and box-and-whisker plot. Valid and reliable descriptive statistics can answer basic yet important questions about a research data set, namely: "Who, What, Why, When, Where, How, How Much?"

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“Houston, We Have a Problem!”: The Role of the Anesthesiologist in the Current Opioid Epidemic

No abstract available

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Chronic Opioid Use After Surgery: Implications for Perioperative Management in the Face of the Opioid Epidemic

Physicians, policymakers, and researchers are increasingly focused on finding ways to decrease opioid use and overdose in the United States both of which have sharply increased over the past decade. While many efforts are focused on the management of chronic pain, the use of opioids in surgical patients presents a particularly challenging problem requiring clinicians to balance 2 competing interests: managing acute pain in the immediate postoperative period and minimizing the risks of persistent opioid use after the surgery. Finding ways to minimize this risk is particularly salient in light of a growing literature suggesting that postsurgical patients are at increased risk for chronic opioid use. The perioperative care team, including surgeons and anesthesiologists, is poised to develop clinical- and systems-based interventions aimed at providing pain relief in the immediate postoperative period while also reducing the risks of opioid use longer term. In this paper, we discuss the consequences of chronic opioid use after surgery and present an analysis of the extent to which surgery has been associated with chronic opioid use. We follow with a discussion of the risk factors that are associated with chronic opioid use after surgery and proceed with an analysis of the extent to which opioid-sparing perioperative interventions (eg, nerve blockade) have been shown to reduce the risk of chronic opioid use after surgery. We then conclude with a discussion of future research directions.

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The Opioid Crisis in the United States: Chronic Pain Physicians Are the Answer, Not the Cause

No abstract available

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Neurosurgical Intensive Care

No abstract available

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Do Not Resuscitate and the Surgical Patient: Not a Contradiction in Terms

No abstract available

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Opioids for the Treatment of Chronic Pain: Mistakes Made, Lessons Learned, and Future Directions

An overreliance on opioids has impacted all types of pain management, making it undoubtedly a root cause of the "epidemic" of prescription opioid abuse in the United States. Yet, an examination of the statistics that led the US Centers for Disease Control and Prevention to declare that prescription opioid abuse had reached epidemic levels shows that the abuse occurrences and deaths are arising outside the hospital or hospice setting, which strongly implicates the outpatient use of opioids to treat chronic pain. Such abuse and related deaths are occurring in chronic pain patients themselves and also through diversion. Overprescribing to outpatients has afforded distressed and vulnerable individuals access to these highly addictive drugs. The focus of this article is on what we have learned since opioid treatment of chronic pain was first popularized at the end of the 20th century and how this new information can guide chronic pain management in the future.

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Venovenous Bypass Associated With Acute Kidney Injury Prevention in Liver Transplantation: An Ode to the Retrospective Data Researcher

No abstract available

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Reducing Mortality in Acute Kidney Injury

No abstract available

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The Perioperative Surgical Home Is Not Just a Name

No abstract available

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A Limitation of Intensive Care Unit Sedation Using Volatile Anesthetics

No abstract available

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Tracking Speckles: Overcoming Conventions to Evaluate Right Ventricular Function

No abstract available

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Women and Leadership in Anesthesiology: Can We “Lean In” Further?

No abstract available

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Surveying the Literature: Synopsis of Recent Key Publications

No abstract available

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An Evidence-Based Approach to the Prescription Opioid Epidemic in Orthopedic Surgery

Orthopedic surgery is associated with significant perioperative pain. Providing adequate analgesia is a critical component of patient care and opioids play a vital role in the acute postoperative setting. However, opioid prescribing for patients undergoing orthopedic procedures has recently been identified as a major contributor to the current opioid epidemic. As opioid usage and related morbidity and mortality continue to rise nationwide, opioid-prescribing practices are under increased scrutiny. Here, we update the evidence base and recommendations behind a set of interventions developed at the Hospital for Special Surgery to address the national epidemic at the local level. The main components of our program include (1) guidelines for managing patients who are opioid tolerant and/or have a substance abuse disorder; (2) education programs for patients, emphasizing the role of opioids in recovery after elective orthopedic surgery; (3) education programs for prescribers of controlled substances, including clinical and regulatory aspects; (4) the development of surgery-specific prescribing recommendations for opioid-naive patients; and (5) mechanisms to modify prescribing habits to limit unnecessary prescribing of controlled substances.

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High-Sensitivity Cardiac Troponin T Improves the Diagnosis of Perioperative MI

BACKGROUND: BACKGROUND:The diagnosis of myocardial infarction (MI) after noncardiac surgery has traditionally relied on using relatively insensitive contemporary cardiac troponin (cTn) assays. We hypothesized that using a recently introduced novel high-sensitivity cTnT (hscTnT) assay would increase the detection rate of perioperative MI. METHODS: METHODS:In this ancillary study of the Vitamins in Nitrous Oxide trial, readjudicated incidence rates of myocardial injury (new isolated cTn elevation) and MI were compared when diagnosed by contemporary cTnI versus hscTnT. We probed various relative (eg, >50%) or absolute (eg, +5 ng/L) hscTnT change metrics. Inclusion criteria for this ancillary study were the presence of a baseline and at least 1 postoperative hscTnT value. RESULTS: RESULTS:Among 605 patients, 70 patients (12%) had electrocardiogram changes consistent with myocardial ischemia; 82 patients (14%) had myocardial injury diagnosed by contemporary cTnI, 31 (5.1%) of which had an adjudicated MI. After readjudication, 67 patients (11%) were diagnosed with MI when using hscTnT, a 2-fold increase. Incidence rates of postoperative myocardial injury ranged from 12% (n = 73) to 65% (n = 393) depending on the hscTnT metric used. Incidence rates of MI using various hscTnT change metrics and the presence of ischemic electrocardiogram changes, but without event adjudication, ranged from 3.6% (n = 22) to 12% (n = 74), a >3-fold difference. New postoperative hscTnT elevation, either by absolute or relative hscTnT change metric, was associated with an up to 5-fold increase in 6-month mortality. CONCLUSIONS: CONCLUSIONS:The use of hscTnT compared to contemporary cTnI increases the detection rate of perioperative MI by a factor of 2. Using different absolute or relative hscTnT change metrics may lead to under- or overdiagnosis of perioperative MI.

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No Easy Way Out: A Case of Physician-Assisted Dying in the Emergency Department

Currently, 1 out of 6 Americans lives within a jurisdiction in which physician-assisted dying is legally authorized. In most cases, patients ingest lethal physician-assisted dying medications at home without involvement of emergency medical services (EMS) or the emergency department (ED). However, occasionally the dying process is interrupted as a result of incomplete ingestion or vomiting of medications, confusion about timing of dying trajectory, familial emotional distress, and other variables.

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Gender Differences in the Authorship of Original Research in Pediatric Journals, 2001-2016

To examine the gender of authors of original research in 3 high-impact pediatric journals between 2001 and 2016, given the importance of publishing on academic promotion, and to compare authorship gender with the percentage of women on editorial boards and with academic faculty composition.

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Weight Trajectories from Birth and Bone Mineralization at 7 Years of Age

To assess whether different trajectories of weight gain since birth influence bone mineral content (BMC) and areal bone mineral density (aBMD) at 7 years of age.

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Epilepsy by Any Other Name Would (Not!) Smell as Sweet

Shakespeare, in Romeo and Juliet (Act II, Scene II), implies that what something is called does not detract from its fundamental meaning or worth: "A rose by any other name would smell as sweet." Juliet was expressing her love for Romeo, irrespective of his name (alas, he was a Montague!). But in medicine, the importance of linguistic precision cannot be underestimated.1 Although names (for diseases, conditions, symptoms, signs, etc) differ in various contexts, optimal medical care requires accurate communication between health care providers, patients, and families, and this accuracy begins with consistency in the use of words to communicate medical information.

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Novel mutations in the LRP5 gene in patients with Osteoporosis-pseudoglioma syndrome

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Exploiting poly(I:C) to induce cancer cell apoptosis

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Pipkin Type-III fractures of the femoral head: Fix it or replace it?

Publication date: November 2017
Source:Injury, Volume 48, Issue 11
Author(s): Theodoros Tosounidis, Joseph Aderinto, Peter V. Giannoudis




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Editorial Board/Publication Information

Publication date: November 2017
Source:Injury, Volume 48, Issue 11





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Quality of fracture reduction assessed by radiological parameters and its influence on functional results in patients with pilon fractures—A prospective multicentre study

Publication date: Available online 20 October 2017
Source:Injury
Author(s): Christoph Sommer, Sean E. Nork, Matthew Graves, Michael Blauth, Mark Rudin, Karl Stoffel
IntroductionThe management of pilon fractures remains a challenging issue. Due to the complexity of factors that influence the outcome, it has been questioned if anatomical reductions of articular fracture are relevant. The lack of a commonly accepted assessment of quality of fracture reduction compounded the uncertainty of the importance of anatomical reduction in pilon fracture. The current study aimed to define parameters that can better assess the reduction quality and to investigate the influence of reduction quality on functional outcomes.MethodsPatients with unilateral pilon fracture of the AO type 43-B or 43-C were consecutively recruited to the study and followed up for 2 years after surgery. Postoperative radiographs of the injured and the contralateral joints were evaluated and 13 radiological parameters measured by 2 independent surgeons. The reliability of the measurements for each parameter was assessed by the Intraclass Correlation Coefficient (ICC), and 4 parameters with the highest ICC scores were deemed most reliable and were selected for further analyses. Functional outcome was assessed by the Foot and Ankle Ability Measure (FAAM) for daily living and sports activities. The 4 most reliable radiologic parameters, together with 3 possible baseline confounders (age, AO fracture type, and open versus closed injury), were analysed using both univariable and multivariable analysis for their association with the FAAM scores. Secondary outcome measures including pain, ankle range of motion (ROM), quality of life (QoL), and adverse events were also reported.ResultsThe length of lateral malleolus (LLM), anterior distal tibia angle, anterior talar shift, and length of medial malleolus scored highest on reliability in ICC assessment (ICC=0.76, 0.72, 0.58, and 0.45, respectively). Only LLM exhibited statistical significant association with the 2-year FAAM results. At the 2-year follow-up, the injured joints on average achieved a ROM of 70.7% (95% CI=63.9–77.6) when compared to the contralateral joints, and patients did not regain the pre-injury QoL overall.ConclusionThe multivariable analysis showed that LLM (independent of age, AO fracture type, and open/closed injury) was a reliable indicator of reduction quality and a prognostic factor for patient outcome in pilon fracture surgery.



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Sliding hip screw versus intramedullary nail for trochanteric hip fractures; a randomised trial of 1000 patients with presentation of results related to fracture stability

Publication date: Available online 20 October 2017
Source:Injury
Author(s): Martyn J. Parker
AimsTo determine the optimum choice of implant for a patient with a the different types of trochanteric hip fracturePatients and methods1000 patients with a trochanteric hip fracture were randomised to internal fixation of the fracture with either a Sliding Hip Screw or an intramedullary nail. Fractures were subdivided into two part fractures, comminuted fractures and fractures at the level of the lesser trochanter (reversed/oblique and transverse). Functional assessment for up to one year from injury was undertaken by a research nurse blinded to the treatment allocation.ResultsThe mean age of patients was 82years and 77% were female. There was a significantly improved regain of mobility for those treated with the intramedullary nail. No statistically significant differences between the two types of fixation methods was observed for mortality, fracture healing complications, re-operations, hospital stay, length of surgery, blood transfusion requirements, medical complications, degree of residual pain or regain of independence. These finding were valid for all fracture types.ConclusionThis study is the first adequately powered randomised trial on this topic and demonstrates that there are no notable differences in either process or functional outcomes between these two treatment methods, other than a tendency to better regain of mobility for those fractures fixed with an intramedullary nail.



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Cancers, Vol. 9, Pages 139: CD47-CAR-T Cells Effectively Kill Target Cancer Cells and Block Pancreatic Tumor Growth

Cancers, Vol. 9, Pages 139: CD47-CAR-T Cells Effectively Kill Target Cancer Cells and Block Pancreatic Tumor Growth

Cancers doi: 10.3390/cancers9100139

Authors: Vita Golubovskaya Robert Berahovich Hua Zhou Shirley Xu Hizkia Harto Le Li Cheng-Chi Chao Mike Ming Mao Lijun Wu

CD47 is a glycoprotein of the immunoglobulin superfamily that is often overexpressed in different types of hematological and solid cancer tumors and plays important role in blocking phagocytosis, increased tumor survival, metastasis and angiogenesis. In the present report, we designed CAR (chimeric antigen receptor)-T cells that bind CD47 antigen. We used ScFv (single chain variable fragment) from mouse CD47 antibody to generate CD47-CAR-T cells for targeting different cancer cell lines. CD47-CAR-T cells effectively killed ovarian, pancreatic and other cancer cells and produced high level of cytokines that correlated with expression of CD47 antigen. In addition, CD47-CAR-T cells significantly blocked BxPC3 pancreatic xenograft tumor growth after intratumoral injection into NSG mice. Moreover, we humanized mouse CD47 ScFv and showed that it effectively bound CD47 antigen. The humanized CD47-CAR-T cells also specifically killed ovarian, pancreatic, and cervical cancer cell lines and produced IL-2 that correlated with expression of CD47. Thus, CD47-CAR-T cells can be used as a novel cellular therapeutic agent for treating different types of cancer.

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Adolescent obesity and adult male breast cancer in a cohort of 1,382,093 men

Abstract

Male breast cancer (MBC) accounts for 1% of all breast cancer. Adult obesity and tallness are risk factors for MBC, but the role of adolescent fatness is largely unknown. We aimed to assess the association between body mass index (BMI) in adolescence and the incidence of MBC in a large cohort of 16-19 year-old Israeli males.

1,382,093 Jewish Israeli males aged 16-19 who underwent anthropometric measurements, a General Intelligence Test (GIT) and other examinations during 1967-2011, were followed up to 31.12.2012 for MBC incidence. Cox proportional hazards models assessed the association between adolescent BMI (as WHO BMI categories and as age-specific CDC percentiles) and time to MBC diagnosis, adjusting for sociodemographic covariates.

Of 100 MBC cases diagnosed during 29,386,233 person-years of follow-up, 97 were included in multivariable analyses. Compared to 'healthy' BMI (18.5-24.9kg/m²) and adjusted for year of birth, country of origin and GIT score, higher adolescent BMI was associated with higher MBC risk: hazard ratio (HR)=2.01 (95% confidence interval [CI]1.14-3.55, p=0.015) in overweight (25.0≤BMI<30.0kg/m²) adolescents; and HR=4.97 (95%CI 2.14-11.53, p=0.0002) in obese (BMI≥30.0kg/m²) adolescents. When CDC age-specific BMI percentiles were assessed results were similar and statistically significant for obesity. Additionally, low (vs. high) GIT score (HR=4.76, 95%CI 1.96-12.50, p=0.001) and European (vs. west-Asian) origin (HR=1.99, 95%CI 1.19-3.34, p=0.009) were independent predictors of MBC.

Measured adolescent overweight and obesity are associated with increased risk of MBC, suggesting a modifiable risk factor potentially allowing for early intervention. The novel association with cognitive function should be further explored. This article is protected by copyright. All rights reserved.

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Comparative Efficacy and Tolerability of Antiemetic Prophylaxis for Adult Highly Emetogenic Chemotherapy: A Network Meta-analysis of 143 Randomized Controlled Trials

Abstract

Chemotherapy-induced nausea and vomiting (CINV) is one of the commonest side-effects among cancer patients. However, there is lacking of hierarchical evidences comparing different antiemetics against highly emetogenic chemotherapy. Therefore, we conducted a network meta-analysis to investigate their comparative efficacy and tolerability. Randomized controlled trials that compared different antiemetic categories for adult highly emetogenic chemotherapy were included after searching PubMed, Web of Science, Embase and Cochrane Central. Acute-phase no emesis and no nausea were identified as primary endpoints. We made pairwise and hierarchical calculations by random-effects model. Effect sizes were presented by odds ratio and 95% confidential interval. Subgroup analysis was additionally performed. 143 randomized trials were included into pooled analysis, containing 22776 patients and 18 antiemetic categories. 5-HT₃ RA plus corticosteroid plus NK-1 RA plus other (5CNO) displayed best protection against both acute emesis (SUCRA: 99.7%) and nausea (95.6%). 5CNO (99.7%) and 5-HT₃ RA plus corticosteroid plus other (5CO, 85.3%) topped subgroup hierarchies for no-naivety and anthracycline plus cyclophosphamide (AC)-based studies. On the other hand, 5-HT₃ RA plus dopamine RA plus other (5DO) may be best fit for delayed emesis (92.0%) and nausea (92.7%). Subgroups featuring no-naivety and AC-based trials preferred 5DO (91.9%) and 5CN (88.6%) respectively. In addition, dopamine RA plus other (DO) had the lowest incidence of TRAE in most circumstances, except for AC-based subgroup where corticosteroid plus dopamine RA plus other (CDO) preponderated (69.2%). 5CNO and 5DO should be considered as first-line regimens against highly emetogenic chemotherapy induced acute and delayed CINV respectively. This article is protected by copyright. All rights reserved.

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Malaria, Epstein-Barr virus, vitamin A, and Burkitt's lymphoma: Response to Joob and Wiwanitkit

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Anti-glypican-1 antibody-drug conjugate exhibits potent preclinical antitumor activity against glypican-1 positive uterine cervical cancer

Abstract

Glypican-1 (GPC1) is highly expressed in solid tumors, especially squamous cell carcinomas (SCCs), and is thought to be associated with disease progression. We explored the use of a GPC1-targeted antibody-drug conjugate (ADC) as a novel treatment for uterine cervical cancer. On immunohistochemical staining, high expression levels of GPC1 were detected in about 50% of uterine cervical cancer tissues and also in a tumor that had relapsed after chemoradiotherapy. Novel anti-GPC1 monoclonal antibodies were developed, and clone 01a033 was selected as the best antibody for targeted delivery of the cytotoxic agent monomethyl auristatin F (MMAF) into GPC1-positive cells. The anti-GPC1 antibody was conjugated with MMAF. On flow cytometry, HeLa and ME180 cervical cancer cells highly expressed GPC1, however, RMG-I ovarian clear cell cancer cell line showed weak expression. The GPC1-ADC was rapidly internalized into GPC1-expressing cells in vitro and was potently cytotoxic to cancer cells highly expressing GPC1. There were no inhibitory effects on cancer cells with low expression of GPC1. In a murine xenograft model, GPC1-ADC also had significant and potent tumor growth inhibition. GPC1-ADC–mediated G2/M phase cell cycle arrest was detected, indicating that the dominant antitumor effect in vivo was MMAF-mediated. The toxicity of GPC-ADC was tolerable within the therapeutic dose range in mice. Our data showed that GPC1-ADC has potential as a promising therapy for uterine cervical cancer. This article is protected by copyright. All rights reserved.

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Cancer incidence in adults living in the vicinity of nuclear power plants in France, based on data from the French Network of Cancer Registries

Abstract

Nuclear power plants (NPPs) release toxic emissions into the environment that may affect neighboring populations. This ecologic study was designed to investigate the possibility of an excess incidence of cancer in the vicinity of French NPPs by examining the incidence by municipality of 12 types of cancer in the population aged 15 years and older during the 1995-2011 period. Population exposure to pollution was estimated on the basis of distance from towns of residence to the NPP. Using regression models, we assessed the risk of cancer in a 20-kilometer zone around NPPs and observed an excess incidence of bladder cancer (Relative Risk (RR), 95% Credibility Interval (95% CI)) in men and women (RR_men = 1.08; 95% CI: 1.00, 1.17 and RR_women = 1.19; 95% CI: 1.02, 1.39). Women living within the 20-km proximity areas had a significantly reduced risk of thyroid cancer (RR_women = 0.86; 95% CI: 0.77, 0.96). No excess risk of hematologic malignancies in either sex was seen. The higher than expected incidence of bladder cancer may be due to an excess incidence localized around the Flamanville NPP and the nearby La Hague nuclear waste treatment center, which is a source of chemical contaminants, many (including arsenic) of them known risk factors for bladder cancer. Differences in medical practices could explain the reduced risk of thyroid cancer. In this first study of adults living near NPPs in France, cancer incidence is significantly higher than in the references populations for one of the cancer types studied: bladder cancer. This article is protected by copyright. All rights reserved.

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Malaria, Epstein-Barr virus, vitamin A and Burkitt's lymphoma

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Targeting Class I Histone Deacetylases by the Novel Small Molecule Inhibitor 4SC-202 Blocks Oncogenic Hedgehog-GLI Signaling and Overcomes Smoothened Inhibitor Resistance

Abstract

Aberrant activation of Hedgehog (HH)/GLI signaling is causally involved in numerous human malignancies, including basal cell carcinoma (BCC) and medulloblastoma. HH pathway antagonists targeting Smoothened (SMO), an essential effector of canonical HH/GLI signaling, show significant clinical success in BCC patients and have recently been approved for the treatment of advanced and metastatic BCC. However, rapid and frequent development of drug resistance to SMO inhibitors (SMOi) together with severe side effects caused by prolonged SMOi treatment call for alternative treatment strategies targeting HH/GLI signaling downstream of SMO. In the present study, we report that 4SC-202, a novel clinically validated inhibitor of class I histone deacetylases (HDACs), efficiently blocks HH/GLI signaling. Notably, 4SC-202 treatment abrogates GLI activation and HH target gene expression in both SMOi-sensitive and resistant cells. Mechanistically, we propose that the inhibition of HDACs 1/2/3 is crucial for targeting oncogenic HH/GLI signaling, and that class I HDAC inhibitors either in combination with SMOi or as second line therapy may improve the treatment options for HH-associated malignancies with SMOi resistance. This article is protected by copyright. All rights reserved.

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Lifetime alcohol intake and risk of non-Hodgkin lymphoma: Findings from the Melbourne Collaborative Cohort Study

Abstract

Cohort studies have reported inconsistent evidence regarding alcohol intake and risk of non-Hodgkin lymphoma (NHL), mostly based on alcohol intake assessed close to study enrolment. We examined this association using alcohol intake measured from age 20 onwards. We calculated usual alcohol intake for 10-year periods from age 20 using recalled frequency and quantity of beverage-specific consumption for 37,990 participants aged 40-69 years from the Melbourne Collaborative Cohort Study. Cox regression was performed to derive hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between alcohol intake (g/day) and NHL risk. After a mean follow-up of 19.3 years, 538 NHL cases were diagnosed. Approximately 80% of participants were either lifetime abstainers or consumed below 20 g of ethanol/day. All categories of lifetime alcohol intake were associated with about 20% lower incidence of NHL compared with lifetime abstention, but there was no evidence of a trend by amount consumed (HR = 0.97 per 10 g/day increment in intake, 95% CI: 0.92-1.03; p value=0.3). HRs for beer, wine and spirits were 0.91 (95% CI: 0.83-1.00; p value=0.05), 1.03 (95% CI: 0.94-1.12; p value=0.6) and 1.06 (95% CI: 0.83-1.37; p value=0.6), respectively, per 10 g/day increment in lifetime intake. There were no significant differences in associations between NHL subtypes. In this low-drinking cohort, we did not detect a dose-dependent association between lifetime alcohol intake and NHL risk. This article is protected by copyright. All rights reserved.

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The joint effects of major lifestyle factors on colorectal cancer risk among Chinese men: A prospective cohort study

Abstract

Previous studies have suggested individual healthy lifestyle factors are related to lower risk of colorectal cancer. Their joint effects, however, have rarely been investigated. We aimed to assess the combined lifestyle impact on colorectal cancer risk and to estimate the population attributable risks of these lifestyle factors. Using data from the Shanghai Men's Health Study (2002-2013), we constructed healthy lifestyle index composing the following lifestyle factors: smoking, alcohol consumption, diet, waist-hip ratio and exercise participation. Cox proportional hazards models were used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs). Over a median of 9.28 years' follow-up, 671 colorectal cancer cases occurred (400 colon cancer and 274 rectal cancer) among 59503 men. Each increment of healthy lifestyle index was associated with a 17% lower risk of colorectal cancer (HR=0.83, 95%CI: 0.78, 0.89), 10% of colon cancer (HR=0.90, 95%CI: 0.83, 0.99) and 27% of rectal cancer (HR=0.73, 95%CI: 0.66, 0.82). If all men in the cohort followed a lifestyle as defined by these five factors, 21% colorectal cancer cases would have been prevented (PAR=21%, 95%CI: 4%, 36%). In conclusion, combined lifestyle factors are significantly related to lower risk of colorectal cancer and the effects are more pronounced on rectal cancer than on colon cancer. This article is protected by copyright. All rights reserved.

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Impact of gender-neutral or girls-only vaccination against human papillomavirus – Results of a community-randomized clinical trial (I)

Abstract

Human papillomavirus (HPV) vaccine is efficacious but the real-life effectiveness of gender-neutral and girls-only vaccination strategies is unknown. We report a community-randomized trial on the protective effectiveness [(PE) = vaccine efficacy (VE) + herd effect (HE)] of the two strategies among females in virtually HPV vaccination naïve population. We randomized 33 Finnish communities into Arm A) gender-neutral vaccination with AS04-adjuvanted HPV16/18 vaccine (11 communities), Arm B) HPV vaccination of girls and hepatitis B-virus (HBV) vaccination of boys (11 communities) or Arm C) gender-neutral HBV vaccination (11 communities). All resident 39,420 females and 40,852 males born 1992-95 were invited in 2007-09. Virtually all (99%) 12- to 15-year-old participating males (11,662) and females (20,513) received three doses resulting in uniform 20-30% male and 50% female vaccination coverage by birth cohort. Four years later (2010-14) 11,396 cervicovaginal samples obtained from 18.5 year-old women were tested for HPV DNA, and prevalence of cervical HPV infections by trial arm and birth cohort was the main outcome measure. VEs against HPV16/18 varied between 89.2% and 95.2% across birth cohorts in arms A and B. The VEs against non-vaccine types consistent with cross-protection were highest in those born 1994-95 for HPV45 (VE_A 82.8%; VE_B 86.1%) and for HPV31 (VE_A 77.6%, VE_B 84.6%). The HEs in the non HPV-vaccinated were statistically significant in those born 1994-95 for HPV18 (HE_A 51.0%; 95%CI 8.3-73.8, HE_B 47.2%; 6.5-70.2) and for HPV31/33 in arm A (HE_A 53.7%; 22.1-72.5). For HPV16 and 45 no significant herd effects were detected. PE estimates against HPV16/18 were similar by both strategies (PE_A 58.1%; 45.1-69.4; PE_B 55.7%; 42.9-66.6). PE estimates against HPV31/33 were higher by the gender-neutral vaccination (PE_A 60.5%; 43.6-73.4; PE_B 44.5%; 24.9-60.6). In conclusion, while gender-neutral strategy enhanced the effectiveness of HPV vaccination for cross-protected HPV types with low to moderate coverage, high coverage in males appears to be key to providing a substantial public health benefit also to unvaccinated females. Trial registration http://ift.tt/2gyZfQI NCT000534638 This article is protected by copyright. All rights reserved.

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Species-specific role of gene-adjacent retroelements in human and mouse gastric carcinogenesis

Abstract

Helicobacter pylori (HP) infection promotes the recruitment of bone marrow stem cells into chronic gastritis lesions. Some of these marrow stem cells can differentiate into gastric epithelial cells and neoplastic cells. We propose that HP-associated methylation could stabilize trans-differentiation of marrow-derived stem cells and that an unstable methylation status is associated with a risk of gastric cancer. Pathobiologic behavior of experimental mouse gastric cancer is mild compared to invasive and metastatic human gastric cancer. Differences in epigenetic stabilization of adult cell phenotypes between humans and mice could provide a foundation to explore the development of invasive and metastatic gastric cancer. Retroelements are highly repetitive sequences that play an essential role in the generation of species diversity. In this review, we analyzed retroelements adjacent to human and mouse housekeeping genes and proposed a possible epigenetic mechanism for HP-associated carcinogenesis. This article is protected by copyright. All rights reserved.

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The concomitant apoptosis and EMT underlie the fundamental functions of TGF-β

Abstract

TGF-β's multipotent cellular effects and their relations are critical for TGF-β's pathophysiological functions. However, these effects may appear to be paradoxical in understanding TGF-β's functions. Apoptosis and epithelial–mesenchymal transition (EMT) are two fundamental events that are deeply linked to various physiological and disease-related processes. These two major cellular fates are subtly regulated and can be potently stimulated by TGF-β, which profoundly contribute to the biological roles of TGF-β. Moreover, these two events are also indirectly and directly correlated with TGF-β-mediated growth inhibition and are relevant to the current understanding of the roles of TGF-β in tumorigenesis and cancer progression. Although TGF-β-induced apoptosis and EMT can be singly independent cellular events, they can also be mutually exclusive but interrelated concomitant events in various cases. Thus, the modulation of apoptosis and EMT is essential for the seemingly paradoxical functions of TGF-β. However, the concomitant effect of TGF-β on apoptosis and EMT, the balance and regulated alterations of them are still been ignored or underestimated. This review focuses on the TGF-β-induced concomitant apoptosis and EMT. We aim to provide an insight in understanding their significance, balance, and modulation in TGF-β-mediated biological functions.

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Molecular Targets for Pain Management: More Than Just Mu

No abstract available

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Basic/Translational Development of Forthcoming Opioid- and Nonopioid-Targeted Pain Therapeutics

Opioids represent an efficacious therapeutic modality for some, but not all pain states. Singular reliance on opioid therapy for pain management has limitations, and abuse potential has deleterious consequences for patient and society. Our understanding of pain biology has yielded insights and opportunities for alternatives to conventional opioid agonists. The aim is to have efficacious therapies, with acceptable side effect profiles and minimal abuse potential, which is to say an absence of reinforcing activity in the absence of a pain state. The present work provides a nonexclusive overview of current drug targets and potential future directions of research and development. We discuss channel activators and blockers, including sodium channel blockers, potassium channel activators, and calcium channel blockers; glutamate receptor–targeted agents, including N-methyl-D-aspartate, α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid, and metabotropic receptors. Furthermore, we discuss therapeutics targeted at γ-aminobutyric acid, α2-adrenergic, and opioid receptors. We also considered antagonists of angiotensin 2 and Toll receptors and agonists/antagonists of adenosine, purine receptors, and cannabinoids. Novel targets considered are those focusing on lipid mediators and anti-inflammatory cytokines. Of interest is development of novel targeting strategies, which produce long-term alterations in pain signaling, including viral transfection and toxins. We consider issues in the development of druggable molecules, including preclinical screening. While there are examples of successful translation, mechanistically promising preclinical candidates may unexpectedly fail during clinical trials because the preclinical models may not recapitulate the particular human pain condition being addressed. Molecular target characterization can diminish the disconnect between preclinical and humans' targets, which should assist in developing nonaddictive analgesics.

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Unraveling the Mystery of THC: Cannabinoids and Neuropathic Pain

No abstract available

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Selective Cannabinoids for Chronic Neuropathic Pain: A Systematic Review and Meta-analysis

BACKGROUND: BACKGROUND:There is a lack of consensus on the role of selective cannabinoids for the treatment of neuropathic pain (NP). Guidelines from national and international pain societies have provided contradictory recommendations. The primary objective of this systematic review and meta-analysis (SR-MA) was to determine the analgesic efficacy and safety of selective cannabinoids compared to conventional management or placebo for chronic NP. METHODS: METHODS:We reviewed randomized controlled trials that compared selective cannabinoids (dronabinol, nabilone, nabiximols) with conventional treatments (eg, pharmacotherapy, physical therapy, or a combination of these) or placebo in patients with chronic NP because patients with NP may be on any of these therapies or none if all standard treatments have failed to provide analgesia and or if these treatments have been associated with adverse effects. MEDLINE, EMBASE, and other major databases up to March 11, 2016, were searched. Data on scores of numerical rating scale for NP and its subtypes, central and peripheral, were meta-analyzed. The certainty of evidence was classified using the Grade of Recommendations Assessment, Development, and Evaluation approach. RESULTS: RESULTS:Eleven randomized controlled trials including 1219 patients (614 in selective cannabinoid and 605 in comparator groups) were included in this SR-MA. There was variability in the studies in quality of reporting, etiology of NP, type and dose of selective cannabinoids. Patients who received selective cannabinoids reported a significant, but clinically small, reduction in mean numerical rating scale pain scores (0–10 scale) compared with comparator groups (−0.65 points; 95% confidence interval, −1.06 to −0.23 points; P = .002, I2 = 60%; Grade of Recommendations Assessment, Development, and Evaluation: weak recommendation and moderate-quality evidence). Use of selective cannabinoids was also associated with improvements in quality of life and sleep with no major adverse effects. CONCLUSIONS: CONCLUSIONS:Selective cannabinoids provide a small analgesic benefit in patients with chronic NP. There was a high degree of heterogeneity among publications included in this SR-MA. Well-designed, large, randomized studies are required to better evaluate specific dosage, duration of intervention, and the effect of this intervention on physical and psychologic function.

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Themed Issue on the Opioid Epidemic: What Have We Learned? Where Do We Go From Here?

No abstract available

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