Surgical resection for clinical stage I high-grade neuroendocrine carcinoma of the lung

Abstract

Background

There are few reports about the factor influencing the prognosis of high-grade neuroendocrine carcinoma. In this study, we evaluated surgical outcome of clinical stage I high-grade neuroendocrine carcinoma.

Methods

Patients who underwent curative surgery for high-grade neuroendocrine tumors of the lung in clinical stage I were included in this study. We retrospectively analyzed 27 consecutive patients. The aim of this study was to clarify the clinical course of the disease after surgery and what factors influence the prognosis.

Results

Twenty-two patients have small cell carcinoma, and 5 patients have large cell neuroendocrine carcinoma. Patients who could undergo surgery within 60 days after the first visit (p < 0.01) and undergo lobectomy (p < 0.01) and whose pro-gastrin-releasing peptide ≦ 72 pg/ml (p = 0.04) performed good prognosis after surgery. In multivariate analysis, surgery within 60 days and operative procedure were independent factors associated with OS.

Conclusion

Surgical resection for clinical stage I high-grade neuroendocrine carcinoma of the lung should be performed as early as possible, and better outcome can be obtained with lobectomy than partial resection.

http://ift.tt/2sBRcYF

Progressive Supranuclear Palsy: an Update

Abstract

Purpose of review

Progressive supranuclear palsy (PSP) is a 4R tau neuropathologic entity. While historically defined by the presence of a vertical supranuclear gaze palsy and falls in the first symptomatic year, clinicopathologic studies identify alternate presenting phenotypes. This article reviews the new PSP diagnostic criteria, diagnostic approaches, and treatment strategies.

Recent findings

The 2017 International Parkinson and Movement Disorder Society PSP criteria outline 14 core clinical features and 4 clinical clues that combine to diagnose one of eight PSP phenotypes with probable, possible, or suggestive certainty. Evidence supports the use of select imaging approaches in the classic PSP-Richardson syndrome phenotype. Recent trials of putative disease-modifying agents showed no benefit.

Summary

The new PSP diagnostic criteria incorporating the range of presenting phenotypes have important implications for diagnosis and research. More work is needed to understand how diagnostic evaluations inform phenotype assessment and identify expected progression. Current treatment is symptomatic, but tau-based therapeutics are in active clinical trials.

http://ift.tt/2F8I4NO

Ketamine induces apoptosis in lung adenocarcinoma cells by regulating the expression of CD69

Abstract

Ketamine, an anesthetic, analgesic, or sedative, is widely used for the treatment of cancer pain. Recently, ketamine has been also reported to be tumor repressor for inhibiting proliferation, invasion, and migration, and inducing apoptosis in many cancers. However, whether ketamine can induce the apoptosis of lung adenocarcinoma (LUAD) and which downstream molecular mediates its function remain largely unknown. A LUAD cell line A549 was incubated with ketamine at 0, 1, 10, and 100 μmol/L for 24 h. Trypan blue staining was used to detect the cell viability. Flow cytometry (FACS) was applied to evaluate cell apoptosis proportion. The expression of CD69 was quantitated by western blotting. Ketamine induced the A549 cell apoptosis in a concentration-dependent manner. CD69 was downregulated in LUAD patients' cancer tissue compared with the normal tissue. CD69 can be upregulated in ketamine treating A549 cells and induce the A549 cell apoptosis. Rescue experiment showed that downregulation of CD69 significantly blocked the function of ketamine on inducing apoptosis. Taken together, our results demonstrated that ketamine induced LUAD cells apoptosis by upregulating the CD69 expression. This study suggests that the ketamine can be potential drug for LUAD treatment, and the ketamine/CD69 signaling may be the new potential therapeutic target LUAD therapy.

Whether ketamine can induce the apoptosis of lung adenocarcinoma (LUAD) and which downstream molecular mediates its function remain largely unknown. Our study in A549 demonstrated that ketamine induced LUAD cells apoptosis by upregulating the CD69 expression. This study suggests that the ketamine can be potential drug for LUAD treatment, and the ketamine/CD69 signaling may be the new potential therapeutic target LUAD therapy.

http://ift.tt/2EMKK5T

The brigatinib experience: a new generation of therapy for ALK-positive non-small-cell lung cancer

Future Oncology, Ahead of Print.


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Targeted Temperature Management After Cardiac Arrest: Systematic Review and Meta-analyses

BACKGROUND: Targeted temperature management (TTM) with therapeutic hypothermia is an integral component of postarrest care for survivors. However, recent randomized controlled trials (RCTs) have failed to demonstrate the benefit of TTM on clinical outcomes. We sought to determine if the pooled data from available RCTs support the use of prehospital and/or in-hospital TTM after cardiac arrest. METHODS: A comprehensive search of SCOPUS, Elsevier's abstract and citation database of peer-reviewed literature, from 1966 to November 2016 was performed using predefined criteria. Therapeutic hypothermia was defined as any strategy that aimed to cool post–cardiac arrest survivors to a temperature ≤34°C. Normothermia was temperature of ≥36°C. We compared mortality and neurologic outcomes in patients by categorizing the studies into 2 groups: (1) hypothermia versus normothermia and (2) prehospital hypothermia versus in-hospital hypothermia using standard meta-analytic methods. A random effects modeling was utilized to estimate comparative risk ratios (RR) and 95% confidence intervals (CIs). RESULTS: The hypothermia and normothermia strategies were compared in 5 RCTs with 1389 patients, whereas prehospital hypothermia and in-hospital hypothermia were compared in 6 RCTs with 3393 patients. We observed no difference in mortality (RR, 0.88; 95% CI, 0.73–1.05) or neurologic outcomes (RR, 1.26; 95% CI, 0.92–1.72) between the hypothermia and normothermia strategies. Similarly, no difference was observed in mortality (RR, 1.00; 95% CI, 0.97–1.03) or neurologic outcome (RR, 0.96; 95% CI, 0.85–1.08) between the prehospital hypothermia versus in-hospital hypothermia strategies. CONCLUSIONS: Our results suggest that TTM with therapeutic hypothermia may not improve mortality or neurologic outcomes in postarrest survivors. Using therapeutic hypothermia as a standard of care strategy of postarrest care in survivors may need to be reevaluated.

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Cardiac Arrest in the Operating Room: Part 2—Special Situations in the Perioperative Period

As noted in part 1 of this series, periprocedural cardiac arrest (PPCA) can differ greatly in etiology and treatment from what is described by the American Heart Association advanced cardiac life support algorithms, which were largely developed for use in out-of-hospital cardiac arrest and in-hospital cardiac arrest outside of the perioperative space. Specifically, there are several life-threatening causes of PPCA of which the management should be within the skill set of all anesthesiologists. However, previous research has demonstrated that continued review and training in the management of these scenarios is greatly needed and is also associated with improved delivery of care and outcomes during PPCA. There is a growing body of literature describing the incidence, causes, treatment, and outcomes of common causes of PPCA (eg, malignant hyperthermia, massive trauma, and local anesthetic systemic toxicity) and the need for a better awareness of these topics within the anesthesiology community at large. As noted in part 1 of this series, these events are always witnessed by a member of the perioperative team, frequently anticipated, and involve rescuer–providers with knowledge of the patient and the procedure they are undergoing or have had. Formulation of an appropriate differential diagnosis and rapid application of targeted interventions are critical for good patient outcome. Resuscitation algorithms that include the evaluation and management of common causes leading to cardiac in the perioperative setting are presented. Practicing anesthesiologists need a working knowledge of these algorithms to maximize good outcomes.

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Cardiac Arrest in the Operating Room: Resuscitation and Management for the Anesthesiologist Part 1

Cardiac arrest in the operating room and procedural areas has a different spectrum of causes (ie, hypovolemia, gas embolism, and hyperkalemia), and rapid and appropriate evaluation and management of these causes require modification of traditional cardiac arrest algorithms. There is a small but growing body of literature describing the incidence, causes, treatments, and outcomes of circulatory crisis and perioperative cardiac arrest. These events are almost always witnessed, frequently known, and involve rescuer providers with knowledge of the patient and their procedure. In this setting, there can be formulation of a differential diagnosis and a directed intervention that treats the likely underlying cause(s) of the crisis while concurrently managing the crisis itself. Management of cardiac arrest of the perioperative patient is predicated on expert opinion, physiologic rationale, and an understanding of the context in which these events occur. Resuscitation algorithms should consider the evaluation and management of these causes of crisis in the perioperative setting.

http://ift.tt/2ocrCEj

Cancers, Vol. 10, Pages 53: A Phase I/II Study Targeting Angiogenesis Using Bevacizumab Combined with Chemotherapy and a Histone Deacetylase Inhibitor (Valproic Acid) in Advanced Sarcomas

Cancers, Vol. 10, Pages 53: A Phase I/II Study Targeting Angiogenesis Using Bevacizumab Combined with Chemotherapy and a Histone Deacetylase Inhibitor (Valproic Acid) in Advanced Sarcomas

Cancers doi: 10.3390/cancers10020053

Authors: Varun Monga Umang Swami Munir Tanas Aaron Bossler Sarah L. Mott Brian J. Smith Mohammed Milhem

Epigenetic events and genetic alterations under the control of the tumor microenvironment potentially mediate tumor induced angiogenesis involved in soft tissue sarcoma (STS) metastasis. Addition of antiangiogenic agent, such as bevacizumab, to standard chemotherapy in treatment of sarcoma has been studied in clinical trials, but most of the findings have not supported its use. We hypothesized the existence of an epigenetically mediated "angiogenic switch", and the tumor microenvironment, prevents bevacizumab from truly blocking angiogenesis. The addition of valproic acid (VPA), a weak histone deacetylase inhibitor, and bevacizumab, a monoclonal antibody against vascular endothelial growth factor, together with the cytotoxic effects of gemcitabine and docetaxel, may enhance responses and alter chemoresistance. This was designed as a phase I/II trial with primary endpoints including safety of the treatment combination and tumor response. Unresectable or metastatic sarcoma patients &gt;18 years of age, irrespective of number of prior treatments, received VPA 40 mg/kg orally for 5 days prior to day 1, bevacizumab at 15 mg/kg IV on day 1, gemcitabine 900 mg/m2 (day 1, day 8), and docetaxel 75 mg/m2 (day 8). Cycles were of 28 day duration. Bevacizumab and VPA were continued as maintenance after 6 cycles, until disease progression. A standard 3 + 3 phase I dose de-escalation design was utilized to evaluate safety. Gain of function p53 gene mutation testing was performed on available archival tissue specimens. A total of 46 patients (30 female, 16 male) with median age of 60 (range 24–81) years were enrolled; 34 (73.9%) patients received prior chemotherapy, 14 (30%) of which received prior gemcitabine and docetaxel. Patients received a median of 5.5 cycles (range 0–24 of treatment (min 0, one patient died prior to completing the first cycle; max: 24, one patient received 6 cycles and 18 maintenance cycles before progressing). Seventeen patients underwent dose reduction, of which VPA was reduced in 6 patients. Forty-one patients were evaluable for response. There was a confirmed complete response in 1 (epithelioid sarcoma), and a partial response (PR) in 6 (1 carcinosarcoma, 2 extrauterine leiomyosarcoma (LMS), 2 undifferentiated pleomorphic sarcoma, and 1 uterine LMS) patients. Stable disease (SD) was seen in 21 patients for at least 2 months. One subject with prior gemcitabine and docetaxel had PR, and 7 had SD. Median progression-free survival (PFS) was 5.7 months (95% CI: 2.1–8.0), and overall survival (OS) was 12.9 months (95% CI: 8.3–14.5). Three patients died due to tumor progression while on the study. The combination of VPA, bevacizumab, gemcitabine, and docetaxel appears to be moderately safe and well tolerated. Given that there are very limited options for patients with relapsed refractory STS, this drug combination may be an important therapy to consider. This combination treatment deserves further investigation in epithelioid and carcinosarcoma subtypes.

http://ift.tt/2Hpmqpt

Hard and soft tissue changes around implants activated using plasma of argon: A histomorphometric study in dog

Abstract

Objective

To histologically assess the hard and soft tissue changes after insertion of cleaned and activated titanium implants using plasma of argon.

Materials and methods

Eight dogs were included in this study. The mandibular premolars and first molars were extracted. For each hemi-mandible, four implants, 7 mm long and 3.3 mm of diameter, with a ZirTi surface were used. The surface of two implants was randomly treated with argon plasma (test), while the other two implants were left untreated (control). After 1 month, the same procedure was performed in the contralateral hemi-mandible. The amount of old bone, new bone, overall value of old bone plus new bone, and soft tissue was histologically evaluated.

Results

After 1 month of healing, high percentages of new bone in close contact with the implant surface were found at both the treated (60.1% ± 15.6%; 95% CI 56.5%–78.0%) and untreated (57.2% ± 13.1%; 95% CI 49.3%–67.5%) implants. Low percentages of old bone were found at this stage of healing, at both the treated (4.4% ± 3.0%; 95% CI 1.2%–5.4%) and untreated (3.4% ± 3.1%; 95% CI 0.6%–4.9%) implants. Not statistically significant differences were found between groups (p > .05). After 2 months of healing, treated implants presented a significantly higher (p = .012) new bone formation (72.5% ± 12.4%; 95% CI 69.6%–86.8%) compared to untreated sites (64.7% ± 17.3%; 95% CI 59.4%–83.3%). Controversially, no difference (p = .270) in terms of old bone was present between treated (3.1% ± 1.7%, 95% CI 1.8%–4.2%) and untreated implants (3.8% ± 1.9%, 95% CI 3.2%–5.8%). Significant differences (p = .018) in terms of total mineralized bone were found between treated (75.6% ± 13.0%, 95% CI 73.3%–91.3%) and untreated implants (68.4% ± 16.8%; 95% CI 64.2%–87.6%).

Conclusions

Implants treated using plasma of argon was demonstrated to reach a higher bone-to-implant contact when compared to untreated implants.

http://ift.tt/2GlfQib

Effect of incision design on interproximal bone loss of teeth adjacent to single implants. A randomized controlled clinical trial comparing intrasulcular vs paramarginal incision

Abstract

Purpose

To evaluate the effect of incision design in implant surgery on interproximal bone loss of posterior teeth adjacent to interdental single implants, comparing intrasulcular and paramarginal incision. A further aim was to assess the influence of the incision technique on peri-implant bone remodeling.

Materials and methods

A controlled randomized clinical trial was carried out in a University Clinic. All the patients received an interdental posterior single implant. The incision type was randomly divided into two groups: (a) intrasulcular or (b) paramarginal. Standardized periapical digital radiographs were made with the parallel technique and a silicone index individualized in each patient. Radiographs were made immediately after implant placement, at abutment connection, 6 and 12 months post-loading. Two radiographic reference points were detected at the interproximal aspect of the adjacent teeth: (A) the cementoenamel junction and (B) the most coronal aspect of the bone crest. The interproximal bone loss of the adjacent teeth was calculated as the difference from A to B between the different follow-up periods and baseline. Two different examiners evaluated the radiographic measurements twice.

Results

Sixty patients, each with one implant, were included, 30 in each group. A mean interproximal bone loss in teeth of 0.09 mm in the intrasulcular and 0.10 mm in the paramarginal group was found at 12 months post-loading. Mean peri-implant bone remodeling was 0.17 mm in the intrasulcular group and 0.15 mm in the paramarginal group. Differences between incision types were not statistically significant (p > .05).

Conclusions

Both incision designs used to place interdental single implants resulted in minimum bone loss at the interproximal aspect of adjacent teeth. The incision design did not significantly influence the radiographically assessed interproximal bone loss nor peri-implant bone remodeling.

http://ift.tt/2Hn7Yyb

Clinical and aesthetic outcomes of immediately placed single-tooth implants with immediate vs. delayed restoration in the anterior maxilla: A retrospective cohort study

Abstract

Objective

To evaluate the impact of the timing of restoration on clinical and aesthetic outcomes following immediate implant placement in the maxillary aesthetic zone.

Material and Methods

Forty patients (16 males, 24 females) with a mean age of 50.55 ± 12.79 years (range 19–74) who had a single maxillary anterior tooth replaced by an immediate implant were included in this study. Twenty patients had their implant restored immediately with a provisional restoration (Group A), while the other 20 patients had a delayed restoration placed after 3–4 months of non-submerged healing (Group B). Clinical parameters and hard-tissue changes were evaluated after a mean follow-up period of 3 years. Aesthetic evaluation was carried out using the Pink Esthetic Score (PES) and the White Esthetic Score (WES).

Results

No significant differences were observed in the bone level changes between the two groups: 0.05 ± 0.65 mm mesially and 0.06 ± 0.52 mm distally for the immediate group and 0.30 ± 0.54 mm mesially and 0.21 ± 0.60 mm distally for the delayed group, respectively. The median PES scores were 11.5 for Group A and 10 for Group B. Mean PES and WES scores did not differ significantly between Groups A and B: PES (11.1 vs. 10.3; p = .16) and WES (8.4 vs. 7.8; p = .16). In terms of individual PES variables, the distal papillae were significantly better in Group A as compared to Group B (p = .006).

Conclusions

Within the limits of this study, timing of restoration seemed to positively affect the aesthetic outcomes of immediately placed implants as evidenced by higher median PES values for the immediate restoration group when compared to the delayed restoration group. Restoration timing had no impact on the individual PES variables, except for the distal papillary height which was superior in the immediate restoration group.

http://ift.tt/2GlwFK6

Bone-conditioned medium modulates the osteoconductive properties of collagen membranes in a rat calvaria defect model

Abstract

Objectives

Collagen membranes are not limited to be occlusive barriers as they actively support bone regeneration. However, the impact of bone-derived growth factors on their osteoconductive competence has not been examined.

Methods

Twenty adult Sprague Dawley rats were included in the study. Calvaria defects with a diameter of five millimeter were created. The defect was covered with one layer of a collagen membrane previously soaked in conditioned medium of porcine bone chips or in culture medium alone. After 4 weeks, microcomputed tomography was performed. Undecalcified thin-ground sections were subjected to light and scanning electron microscopy. Primary outcome parameter was the bone volume in the defect. Unit of analysis was the bone-conditioned medium (BCM).

Results

In the central defect area of the control and the BCM group, median new bone connected to the host bone was 0.54 and 0.32 mm³, respectively (p = .10). In the ectocranial defect area, the control group showed significantly more bone than the BCM group (0.90 and 0.26 mm³; p = .02). Based on an exploratory interpretation, the control group had smaller bony islands than the BCM group. Scanning electron microscopy and histology indicate the formation of bone but also the collagen membrane to be mineralized in the defect site.

Conclusions

These results demonstrate that the commercial collagen membrane holds an osteoconductive competence in a rat calvaria defect model. Soaking collagen membranes with BCM shifts bone formation toward the formation of bony islands rather than new bone connected to the host bone.

http://ift.tt/2F9lOn9

Lower pole approach in retroperitoneal laparoscopic radical nephrectomy: a new approach for the management of renal vascular pedicle

Abstract

Background

The objective of this study was to examine the effectiveness and safety of lower pole (LP) approach in retroperitoneal laparoscopic radical nephrectomy (LRN).

Methods

One hundred thirty-two renal cancer patients were scheduled for selective retroperitoneal LRN. The surgery parameters and outcomes were compared. Out of 132 patients, 78 (59.1%) patients underwent LRN via LP approach, while 54 (40.9%) patients underwent LRN via lateroposterior space (LPS) approach.

Results

Compared to LPS group, the LP group had a higher body mass index (27.0 ± 1.7 kg/m² vs. 24.5 ± 1.8 kg/m², P <  0.0001) and a larger tumor size (6.9 ± 3.5 cm vs. 4.1 ± 3.3 cm, P <  0.0001). The LP approach reduced the volumes of blood loss and transfusion significantly (135.3 ± 17.2 mL vs. 219.6 ± 30.9 mL, P <  0.0001; 55.6 ± 28.3 vs. 141.1 ± 50.4 mL, P <  0.0001) as compared to the LPS approach. The LP approach also decreased the risk of conversion to open procedure (1.3 vs. 7.4%, P <  0.05).

Conclusions

The LP approach is an effective and safe alternative to the LPS approach for retroperitoneal LRN and might be more suitable for patients with obesity, large tumors, tumors located at the medial part of the kidney, or renal pedicular adhesion.

http://ift.tt/2o5bUeW

SGEF is a potential prognostic and therapeutic target for lung adenocarcinoma

Abstract

Background

SH3-containing guanine nucleotide exchange factor (SGEF), a RhoG-specific guanine nucleotide exchange factor (GEF), was consider as a key signal that determines cancer cell invasion. Although SGEF has been considered to highly express in glioma and prostate cancer. However, it is not well illustrated in LAC.

Methods

In this experiment, expression of SGEF was detected in 92 LAC and corresponding normal tissue samples by immunohistochemistry. In addition, we evaluated the invasion and migration of lung adenocarcinoma cells by the gain and loss of SGEF expression. Furthermore, RhoG activity was measured by GST pull-down assay.

Results

SGEF is highly expressed in LAC tissues than in normal lung tissues and was associated with the TNM stage. Lung adenocarcinoma patients with low SGEF subgroup had longer overall survival compared to those with high expression. Furthermore, univariate analysis showed that SGEF expression was an independent prognostic factor for overall survival in lung adenocarcinoma. Silencing of SGEF effectively suppressed the invasion and migration of human lung adenocarcinoma cells in vitro by inhibiting RhoG activity, and over-expression of SGEF could reverse this phenomena.

Conclusion

SGEF is a novel prognostic target in human lung adenocarcinoma.

http://ift.tt/2obY8q1

The Role of Quantum Decoherence in FRET

Resonance energy transfer has become an indispensable experimental tool for single-molecule and single-cell biophysics. Its physical underpinnings, however, are subtle: it involves a discrete jump of excitation from one molecule to another, and so we regard it as a strongly quantum-mechanical process. And yet its kinetics differ from what many of us were taught about two-state quantum systems, quantum superpositions of the states do not seem to arise, and so on. Although J. R. Oppenheimer and T.

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Better Stories

The ability to elicit an individual's personal narrative is a vital component of what we do as physicians. Without understanding what drives our patients, we have no context with which to make shared decisions that are consistent with and respectful of their overall goals. In the realm of nephrology, patient narratives can provide a valuable framework for such nuanced treatment decisions as initiating dialysis, determining transplant candidacy, and discussing conservative care. Though culturally-sensitive methods of using patient narratives have been successful in certain marginalized populations, building the trust required to obtain these narratives can be a challenging, intricate process.

http://ift.tt/2EzMn3S

Asparagine Bioavailability Drives Breast Cancer Metastasis [Research Watch]

Asparagine depletion reduces breast cancer invasion and metastasis without affecting primary tumor growth.

http://ift.tt/2Eyg9Kn

The PI3K{alpha} Inhibitor Alpelisib Has Activity in PIK3CA-altered Tumors [Research Watch]

The PI3Kα inhibitor alpelisib achieved a 58.2% disease control rate in PIK3CA-altered solid tumors.

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A Next-Generation Chimeric Antigen Receptor Induces JAK-STAT Signaling [Research Watch]

CAR-T cells designed to activate JAK–STAT signaling show enhanced persistence and antitumor activity.

http://ift.tt/2Ev47kG

DNMT3A DNA-Binding Residues Provide Specificity for CpG DNA Methylation [Research Watch]

DNMT3A-DNMT3L-DNA crystal structures provide a mechanism for DNMT3A methyltransferase activity.

http://ift.tt/2BAEzAf

Natural Killer Cells Recruit Dendritic Cells to Promote Antitumor Immunity [Research Watch]

Natural killer (NK) cells recruit conventional type 1 dendritic cells (cDC1) to the tumor microenvironment.

http://ift.tt/2C26ZDZ

Arvinas, Pfizer Team Up on PROTACs [News in Brief]

Proteolysis-targeting chimeras combat cancer by degrading disease-causing proteins.

http://ift.tt/2BC6Aae

PROMises Made, PROMises To Be Kept: Patient-Reported Outcome Measures in Inflammatory Bowel Diseases

With the Food and Drug Administration's (FDA) mandate to move from clinical disease activity indices to co-primary end points of patient-reported outcomes (PROs) and objective measures of disease for regulatory approval of inflammatory bowel disease (IBD) pharmacotherapy, and with the increasing emphasis on population health management and value-based care, PROs are the buzzword in IBD and other chronic gastrointestinal conditions.1–6 In contrast to conventional clinical disease activity indices such as the Crohn's disease activity index or the Mayo Clinic Score for ulcerative colitis, which includes a combination of patient-reported symptoms, physician interpretation of disease activity, and objective measures of disease activity, PROs are self-administered reports that comes directly from a patient about a health condition or its treatment, without interpretation of the patient's response by a clinician or anyone else.

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The importance of involving midwives before and during the implementation of an antenatal pertussis vaccination program in New South Wales, Australia

Publication date: Available online 15 February 2018
Source:Women and Birth
Author(s): Sonya Nicholl, Holly Seale, Nathan Saul, Sue Campbell-Lloyd
ProblemTypically there is limited opportunity for stakeholder engagement to determine service delivery gaps when implementing an outbreak or supplementary vaccination program.BackgroundIn response to increasing pertussis notifications in NSW, Australia, an antenatal pertussis vaccination program was introduced offering pertussis containing vaccine to all pregnant women in the third trimester.AimTo explore the effectiveness of consulting with midwives prior to and during a new state-wide vaccination program.MethodsA pre-program needs analysis was conducted through an online audit of the NSW Clinical Midwifery Consultants followed by a post-implementation audit at 18 months.FindingsInformation received from the midwives was utilised during program planning which facilitated program implementation without any major issues in all Local Health Districts. The post-implementation audit provided feedback to program planners that that implementation was continuing consistently and Midwives were found to be very supportive and engaged.DiscussionEducation and support of clinicians is vital for high vaccine uptake in new vaccination programs which can be enabled through appropriate educational packages and program resources.ConclusionConsulting with the midwives in advance of a new vaccination program was a new initiative and highly recommended as it was time well spent gaining essential information on program resourcing and operational needs. Conducting a post-implementation audit is also strongly recommended as a check-point for issues and recommendations, to empower frontline staff and support consistent program implementation. Frontline staff engagement before and during implementation of a new vaccination program is a powerful mechanism for effective, efficient and consistent program delivery.



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In Response

No abstract available

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Perioperative Inflammation and Its Modulation by Anesthetics

Surgery and other invasive procedures, which are routinely performed during general anesthesia, may induce an inflammatory response in the patient. This inflammatory response is an inherent answer of the body to the intervention and can be both beneficial and potentially harmful. The immune system represents a unique evolutionary achievement equipping higher organisms with an effective defense mechanism against exogenous pathogens. However, not only bacteria might evoke an immune response but also other noninfectious stimuli like the surgical trauma or mechanical ventilation may induce an inflammatory response of varying degree. In these cases, the immune system activation is not always beneficial for the patients and might carry the risk of concomitant, harmful effects on host cells, tissues, or even whole organ systems. Research over the past decades has contributed substantial information in which ways surgical patients may be affected by inflammatory reactions. Modulations of the patient's immune system may be evoked by the use of anesthetic agents, the nature of surgical trauma and the use of any supportive therapy during the perioperative period. The effects on the patient may be manifold, including various proinflammatory effects. This review focuses on the causes and effects of inflammation in the perioperative period. In addition, we also highlight possible approaches by which inflammation in the perioperative may be modulated in the future.

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Macintosh Blade Videolaryngoscopy Combined With Rigid Bonfils Intubation Endoscope Offers a Suitable Alternative for Patients With Difficult Airways

BACKGROUND: In the armamentarium of an anesthesiologist, videolaryngoscopy is a valuable addition to secure the airway. However, when the videolaryngoscope (VLS) offers no solution, few options remain. Earlier, we presented an intubation technique combining Macintosh blade VLS and Bonfils intubation endoscope (BIE) for a patient with a history of very difficult intubation. In the present study, we evaluated this technique to establish whether it is a valuable alternative. METHODS: In this single-blinded nonrandomized study, 38 patients with a history of difficult intubation or 1 or more predictors of difficult intubation, scoring a Cormack & Lehane (C&L) grade III or IV using Macintosh blade VLS, were included. Patients were intubated combining the VLS with the BIE. The C&L grade was scored 3 times during (1) direct laryngoscopy; (2) indirect videolaryngoscopy; and (3) using the combined technique (VLS + BIE). Afterward, 2 blinded anesthesiologists assessed the C&L grade using the pictures taken during the procedure. RESULTS: Data of 38 patients were analyzed. An improvement of the C&L grade with the combined technique occurred in 33 of 38 patients (86.8%; 95% confidence interval, 71.9%–95.6%). Reviewer 1 reported an improvement of the C&L grade with the combined technique in 37 of 38 patients. Reviewer 2 reported improvement in 33 and deterioration in 2 of the patients. No complications occurred. CONCLUSIONS: The combined use of a VLS with Macintosh blade and BIE gives the anesthesiologist a valuable alternative intubation option in patients with extremely difficult airways.

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Perioperative Cardiac Arrest: Focus on Malignant Hyperthermia (MH)

No abstract available

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In Response

No abstract available

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Efficacy Outcome Measures for Pediatric Procedural Sedation Clinical Trials: An ACTTION Systematic Review

Objective evaluations comparing different techniques and approaches to pediatric procedural sedation studies have been limited by a lack of consistency among the outcome measures used in assessment. This study reviewed those existing measures, which have undergone psychometric analysis in a pediatric procedural sedation setting, to determine to what extent and in what circumstances their use is justified across the spectrum of procedures, age groups, and techniques. The results of our study suggest that a wide range of measures has been used to assess the efficacy and effectiveness of pediatric procedural sedation. Most lack the evidence of validity and reliability that is necessary to facilitate rigorous clinical trial design, as well as the evaluation of new drugs and devices. A set of core pediatric sedation outcome domains and outcome measures can be developed on the basis of our findings. We believe that consensus among all stakeholders regarding appropriate domains and measures to evaluate pediatric procedural sedation is possible and that widespread implementation of such recommendations should be pursued.

http://ift.tt/2ExLXPl

The Effect of Adductor Canal Block on Knee Extensor Muscle Strength 6 Weeks After Total Knee Arthroplasty: A Randomized, Controlled Trial

BACKGROUND: Total knee arthroplasty (TKA) reduces knee extensor muscle strength (KES) in the operated limb for several months after the surgery. Immediately after TKA, compared to either inguinal femoral nerve block or placebo, adductor canal block (ACB) better preserves KES. Whether this short-term increase in KES is maintained several weeks after surgery remains unknown. We hypothesized that 48 hours of continuous ACB immediately after TKA would improve KES 6 weeks after TKA, compared to placebo. METHODS: Patients scheduled for primary unilateral TKA were randomized to receive either a continuous ACB (group ACB) or a sham block (group SHAM) for 48 hours after surgery. Primary outcome was the difference in maximal KES 6 weeks postoperatively, measured with a dynamometer during maximum voluntary isometric contraction. Secondary outcomes included postoperative day 1 (POD1) and day 2 (POD2) KES, pain scores at rest and peak effort, and opioid consumption; variation at 6 weeks of Knee Osteoarthritis Outcome Score, patient satisfaction, and length of hospital stay. RESULTS: Sixty-three subjects were randomized and 58 completed the study. Patients in group ACB had less pain at rest during POD1 and during peak effort on POD1 and POD2, consumed less opioids on POD1 and POD2, and had higher median KES on POD1. There was no significant difference between groups for median KES on POD2, variation of Knee Osteoarthritis Outcome Score, patient satisfaction, and length of stay. There was no difference between groups in median KES 6 weeks after surgery (52 Nm [31–89 Nm] for group ACB vs 47 Nm [30–78 Nm] for group SHAM, P= .147). CONCLUSIONS: Continuous ACB provides better analgesia and KES for 24–48 hours after surgery, but does not affect KES 6 weeks after TKA. Further research could evaluate whether standardized and optimized rehabilitation over the long term would allow early KES improvements with ACB to be maintained over a period of weeks or months.

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Motor Evoked Potential Monitoring During Thoracoabdominal Aortic Surgery: Useful or Not?

No abstract available

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You’re Wrong, I’m Right: Dueling Authors Reexamine Classic Teachings in Anesthesia

No abstract available

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In Response

No abstract available

http://ift.tt/2BvxYqF

Anesthesia Advanced Cardiac Life Support: A Guideline Validated?

No abstract available

http://ift.tt/2o2ngAs

Perioperative Cardiac Arrest: Focus on Anaphylaxis

No abstract available

http://ift.tt/2obsSaP

Hyperglycemia and Elevated Lactate in Trauma: Where Do We Go From Here?

No abstract available

http://ift.tt/2ocsY1E

A Retrospective Analysis of Clinical Research Misconduct Using FDA-Issued Warning Letters and Clinical Investigator Inspection List From 2010 to 2014

BACKGROUND: The US Food and Drug Administration (FDA) conducts inspections of clinical investigation sites as a component of clinical trial regulation. The FDA describes the results of these inspections in the Clinical Investigator Inspection List (CLIIL). More serious violations are followed up in FDA warning letters issued to investigators. The primary objective of the current study is to qualitatively and quantitatively describe the CLIIL data and contents of FDA-issued warning letters from 2010 to 2014. METHODS: We retrospectively analyzed the CLIIL and FDA warning letters. For the CLIIL, we quantified the frequency of each violation among other data points. We compared recent data (2010–2014) to the previous 5 years (2005–2009). To analyze FDA warning letters, we developed a coding system to quantify the frequency of violations found. RESULTS: We analyzed 3637 inspections in the CLIIL database and 60 warning letters. Overall, there was a decrease or no change in all violations in the CLIIL database. The largest violation code reported was "failure to follow investigational plan" in both the 2005–2009 and 2010–2014 timeframes. Coding of FDA warning letters shows that the most common violations reported were failing to maintain accurate case histories (10.82%), enrolling ineligible subjects (8.85%), and failing to perform required tests (8.52%). CONCLUSIONS: The overall decrease in violations is encouraging. But, the high proportion of violations related to failure to follow the investigational plan is concerning as the complexity of trials increases. We conclude that more detailed information is necessary to accurately evaluate these violations. The current study provides a model for creating more granular data of violations to better inform clinical investigators and improve clinical trials.

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Between a ROCK and an IR Place

No abstract available

http://ift.tt/2o2neZm

Chinese Anesthesiologists Have High Burnout and Low Job Satisfaction: A Cross-Sectional Survey

BACKGROUND: The Chinese health care system must meet the needs of 19% of the world's population. Despite recent economic growth, health care resources are unevenly distributed. This creates the potential for job stress and burnout. We therefore conducted a survey among anesthesiologists in the Beijing–Tianjin–Hebei region focusing on job satisfaction and burnout to determine the incidence and associated factors. METHODS: A large cross-sectional study was performed in the Beijing–Tianjin–Hebei region of China. The anonymous questionnaire was designed to collect and analyze the following information: (1) demographic characteristics and employer information; (2) job satisfaction assessed by Minnesota Satisfaction Questionnaire; (3) burnout assessed by Maslach Burnout Inventory-Human Service Survey; and (4) sleep pattern and physician–patient communication. RESULTS: Surveys were completed and returned from 211 hospitals (response rate 74%) and 2873 anesthesiologists (response rate 70%) during the period of June to August 2015. The overall job satisfaction score of Minnesota Satisfaction Questionnaire was 65.3 ± 11.5. Among the participants, 69% (95% confidence interval [CI], 67%–71%) met the criteria for burnout. The prevalence of high emotional exhaustion, high depersonalization, and low personal accomplishment was 57% (95% CI, 55%–59%), 49% (95% CI, 47%–51%), and 57% (95% CI, 55%–58%), respectively. Using multivariable logistic regression analysis, we found that age, hospital category, working hours per week, caseload per day, frequency of perceived challenging cases, income, and sleep quality were independent variables associated with burnout. Anesthesiologists with a high level of depersonalization tended to engage in shorter preoperative conversations with patients, provide less information about pain or the procedure, and to have less empathy with them. CONCLUSIONS: The anesthesiologists in the Beijing–Tianjin–Hebei region of China expressed a below-average level of job satisfaction, and suffered a significant degree of burnout. Improvement in job satisfaction and burnout might create a positive work climate that could benefit both the quality of patient care and the profession of anesthesiology in China.

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Properties of bacterial communities attached to artificial substrates in a hypereutrophic urban river

Bacterial communities of biofilms growing on artificial substrates were examined at two time periods (7 and 14 days) and two locations (lentic and lotic areas) in a hypereutrophic urban river of eastern China....

http://ift.tt/2obmdxl

Rapid optimization of spore production from Bacillus amyloliquefaciens in submerged cultures based on dipicolinic acid fluorimetry assay

Some optimization techniques have been widely applied for spore fermentation based on the plate counting. This study optimized the culture medium for the spore production of Bacillus amyloliquefaciens BS-20 and i...

http://ift.tt/2EL2UVL

Effects of feedstock and co-culture of Lactobacillus fermentum and wild Saccharomyces cerevisiae strain during fuel ethanol fermentation by the industrial yeast strain PE-2

Even though contamination by bacteria and wild yeasts are frequently observed during fuel ethanol fermentation, our knowledge regarding the effects of both contaminants together is very limited, especially con...

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Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging

Endovascular thrombectomy has been shown to be effective for the treatment of acute ischemic stroke in patients with occlusion of the first segment of the middle cerebral artery or occlusion of the internal carotid artery if treatment is initiated within 6 hours. The results of the recently…

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Incorporating Pericytes into an Endothelial Cell Bead Sprouting Assay

This protocol presents a novel in vitro bead assay that more appropriately models the process of in vivo sprouting angiogenesis by incorporating pericytes. This modification enables the bead assay to more faithfully recapitulate the heterotypic cellular interactions between endothelial cells and mural cells that are critical for angiogenesis.

http://ift.tt/2o4wCeH

Correction to: The antiangiogenic activities of ethanolic crude extracts of four Salvia species

After the publication [1] it came to the attention of the authors that one of the co-authors was incorrectly included as Hamza Somrain. The correct spelling is as follows: Hamzeh Sumrein.

http://ift.tt/2Hk74T0

Ultrasensitive Detection of Biomarkers by Using a Molecular Imprinting Based Capacitive Biosensor

Here, we present a protocol for the detection and quantification of low abundant molecules in complex solutions using molecular imprinting in combination with a capacitance biosensor.

http://ift.tt/2oc5VUI

Characterization and Isolation of Mouse Primary Microglia by Density Gradient Centrifugation

A protocol for the isolation of primary microglia from murine brains is presented. This technique aids in furthering the current understanding of neurological conditions. Density gradient centrifugation and magnetic separation are combined to produce sufficient yield of a highly pure sample. Furthermore, we outline the steps for characterization of microglia.

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A Time-lapse, Label-free, Quantitative Phase Imaging Study of Dormant and Active Human Cancer Cells

Dormant and active cancer cell phenotypes were characterized using quantitative phase imaging. Cell proliferation, migration, and morphology assays were integrated and analyzed in one simple method.

http://ift.tt/2FbrL2Y

Enzymatic Cascade Reactions for the Synthesis of Chiral Amino Alcohols from L-lysine

Chiral amino alcohols are versatile molecules for use as scaffolds in organic synthesis. Starting from L-lysine, we synthesize amino alcohols by an enzymatic cascade reaction combining diastereoselective C-H oxidation catalyzed by dioxygenase followed by cleavage of the carboxylic acid moiety of the corresponding hydroxyl amino acid by a decarboxylase.

http://ift.tt/2EzapM0

Public preferences for interventions to prevent emerging infectious disease threats: a discrete choice experiment

Objective

When faced with an emergent epidemic with high mortality and morbidity potential, policy makers must decide what public health interventions to deploy at different stages of the outbreak. However, almost nothing is known about how the public view these interventions or how they trade off risks (of disease) with inconvenience (of interventions). In this paper, we aim to understand public perceptions on pandemic interventions, as well as to identify if there are any distinct respondent preference classes.

Design

A discrete choice experiment.

Setting

This study was fielded in Singapore between November 2012 and February 2013.

Participants

A random sample of 500 Singapore residents aged 21 and over, including 271 women and 229 men, was analysed.

Outcome measures

Demographic information was collected from each participant. Participants were also shown a series of pairs of alternatives, each combining interventions and morbidity, mortality and cost outcomes and declared a preference for one combination. A random utility model was developed to determine the individual's preference for interventions and a hierarchical cluster analysis was performed to identify distinct respondent preference classes.

Results

On average, participants preferred more intense interventions, and preferred scenarios with fewer deaths and lower tax. The number of infections did not significantly influence respondents' responses. We identified two broad classes of respondents: those who were mortality averse and those who were expenditure averse. Education was found to be a predictor of group membership.

Conclusion

Overall, there was considerable support for government interventions to prevent or mitigate outbreaks of emerging infectious diseases, including those that greatly restricted individual liberties, as long as the restrictions showed a reasonable chance of reducing the adverse health effects of the outbreak.

http://ift.tt/2oarNQp

Recurrent epistaxis leading to diagnosis of primary sinonasal melanoma

A 48-year-old man presented to urgent care with recurrent epistaxis over 6 months. Initially, nosebleeds were controlled with packing or cautery. Ultimately, he was referred to ear, nose and throat department and underwent nasal endoscopy which revealed polypoid tissue. A biopsy of the polyp showed non-specific inflammation with no evidence of malignancy. Follow-up maxillofacial CT revealed a large mass lesion in the right maxillary sinus, right nasal fossa, much of the ethmoids and right sphenoid, with destruction of adjacent bony structures. MRI revealed a mass in the right nasal cavity with extension into the ethmoid and anterior sphenoid sinus, anterior cranial fossa and medial orbits. Staging CT discovered metastatic disease in the adrenal glands and lymphadenopathy in the neck. The patient underwent endoscopic sinus surgery with debulking and tissue diagnosis of malignant melanoma. He completed radiation therapy to sinus and was subsequently enrolled in a clinical trial. Most recent imaging revealed complete metabolic response on positron emission tomography.

http://ift.tt/2HmIe4Y

Polymicrobial bacterial pericarditis and cardiac tamponade caused by pericardial penetration of an adjustable gastric band

We describe a case of polymicrobial bacterial pericarditis with Klebsiella pneumoniae and Proteus mirabilis, caused by pericardial penetration of the tip of the catheter of a laparoscopic adjustable gastric band (LAGB). The patient developed a cardiac tamponade, and subsequently emergency pericardiocentesis was performed. Analysis of earlier CT scans showed that the tip of the catheter had migrated through the liver and through the diaphragm into the pericardium, and was in contact with the myocardium. After stabilisation he was operated to remove the LAGB. In this case report, we describe the chain of events that led to the polymicrobial pericarditis—a complication of LAGB placement that to our knowledge has thus far never been reported. We furthermore present a detailed literature review of all published cases of polymicrobial pericarditis and its causes.

http://ift.tt/2Gl9a3U

Renal nutcracker syndrome in a young lady: unusual findings and endovascular management

Nutcracker syndrome (NCS) is caused by compression of left renal vein (LRV), usually between the aorta and the superior mesenteric artery (SMA). This can lead to obstruction of flow into the inferior vena cava and secondary left renal venous hypertension. Despite potential serious consequences, diagnosing NCS is often challenging, circuitous and commonly delayed. We report an extremely unique case of NCS. A 34-year-old woman presented with left flank pain and discomfort. On investigation, it was found that high pressure in the LRV, due to compression by the SMA, had led to a large venous aneurysm that had caused pelviureteric junction obstruction and hydronephrosis. Management was with stenting of the LRV and coil embolisation of the venous aneurysm with excellent clinical outcome.

http://ift.tt/2HnvoUc

Fistulation between a colonic J-Pouch and the upper vagina in an irradiated pelvis: a rare complication following low anterior resection with colonic J-pouch anal anastomosis for rectal cancer

Formation of a colonic J-pouch with anastomosis to the rectal stump is an accepted form of reconstruction after low anterior resection (LAR) for rectal carcinoma. It is thought this can help prevent the onset of LAR syndrome as well as improve the quality of life in the first two years following surgery. Rectovaginal fistulation is a recognised complication of this form of surgery usually occurring because of technical failure leading to inclusion of the vaginal wall into the stapled anastomosis. We present an as of yet unreported case of fistulation between the upper horizontal staple line of a colonic J-pouch—the tip of the 'J'—which was formed extracorporeally with the posterior vaginal fornix. We postulate that pelvic irradiation was partly a causative factor alongside subsequent mechanical irritation. Ultimately, surgical intervention was required, following which the patient made a full recovery. Interposition of omentum may prevent this problem.

http://ift.tt/2GjtAKs

The cat did it: erythema nodosum and additional atypical presentations of Bartonella henselae infection in immunocompetent hosts

A healthy patient presented with painful skin lesions on the anterior surface of her legs. Erythema nodosum was diagnosed but all the usual causes were ruled out. The finding of bilateral enlarged axillary lymph nodes with necrosis and granulomas led to the diagnosis of Bartonella infection, an unusual cause of erythema nodosum. Imaging also revealed splenomegaly and small para-aortic lymph nodes. Up to one quarter of the patients with cat-scratch disease present atypically, a considerably higher prevalence than previously reported. A comprehensive review of the literature (PubMed, since inception, all languages) revealed a remarkable array of unusual presentations which are summarised and briefly discussed.

http://ift.tt/2HjDltk

Implant of a left atrial appendage occluder device (Watchman) and leadless pacing system (Micra) through the same venous access in a single sitting

A left atrial appendage occluder device (Watchman) and leadless pacemaker (Micra) was implanted from a single right femoral vein access in a 73-year-old female patient with persistent atrial fibrillation and symptomatic tachy-brady syndrome and unable to take oral anticoagulants. Standard methods of implantation were followed for both procedures. The Watchman device was implanted first followed by dilatation of the same venous access site in order to implant Micra transcatheter pacing system. The patient tolerated the procedures well and there were no complications. At the end of 1 month, both the devices were found to be working well.

http://ift.tt/2Giyffx

Syncope and cardiogenic shock in an 80-year-old woman

Description

An 80-year-old woman presented with a 2-day history of breathlessness and syncope. Her medical history included Parkinson's disease and a recent diagnosis of myelodysplasia for which she had undergone a (painful) bone marrow aspiration 2 days earlier.

Presentation blood pressure (BP) was 69/38 mm Hg (and fell further to 59/40 mm Hg with impaired conscious level), heart rate 78, respiratory rate 17 and oxygen saturation 100% on air. Her presentation of ECG revealed anteroseptal Q waves with 1 mm ST segment elevation (figure 1).

Figure 1

A 12-lead ECG at presentation.

Emergency primary percutaneous coronary intervention was declined due to the probability of established myocardial infarction with consequent cardiogenic shock. Medical treatment and inotropic therapy with intra-aortic balloon pump (IABP) were directed. She underwent emergency portable echocardiography to understand the aetiology for cardiogenic shock.

The panel of images (figure 2A–C)...

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Making a difference in the developing world

By Marcus Chong

In 2016, while conducting medical research in a rural village of Northern Samar, the Philippines, Professor Allen Ross and his global health research team met a patient with severe electrical burns. He was a construction worker who had suffered an electrical burn at work from an overhanging high voltage electrical wire carrying 20,000 Volts. He had sustained burns to 25% of his body with significant scarring on the skin under the armpits and the amputation of all four limbs.

After the accident, he was transported to a local hospital by a family member; he remained there without medical treatment for eight hours. Public hospitals in Metro Manila are typically overwhelmed – with a lack of physicians available to treat emergency patients. Approximately eight hours later an ambulance was found to transport the patient to a local burns centre. By then his untreated injuries had resulted in thromboses requiring amputations of all four limbs. His relative in Manila sold their company truck in order to pay for his surgical procedures and hospital care. He remained in hospital for a few weeks after the operation. At this point his family had used up all their savings. He was discharged in a wheelchair as physiotherapy, prostheses and rehabilitation were prohibitively expensive. He returned to his home village in Simora Palapag, Northern Samar (Image, left).

The published BMJ case report that resulted can be found here.

In 2017, with the patient and family's consent, Thao Ross (Allen's wife) organised crowd funding on a Go-fund-me website. Funds came from people of all walks of life. It took several months to raise the required funds for four prosthetic limbs.

We were able to buy prostheses made of aluminium and coated with an alloy that made them durable and water-proof in Manila, from the prosthetic limb company Ottobock. There were also sufficient funds to provide the patient with rehabilitation and prosthetic fitting services. The prostheses provided by the company for the lower limbs can be seen in the above image (right) and the patient is currently (2018) having his upper limbs custom made and fitted. The patient was able to walk again after a few weeks of physiotherapy and rehabilitation. The patient waited almost seven years to walk again and we are very happy to have made this possible!

Competing Interests

None Declared

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Barriers to accessing palliative care for pediatric patients with cancer: A review of the literature

Although many of the 16,000 children in the United States diagnosed who are with cancer each year could benefit from pediatric palliative care, these services remain underused. Evidence regarding the barriers impeding access to comprehensive palliative care is dispersed in the literature, and evidence specific to pediatric oncology remains particularly sparse. The purpose of the current review was to synthesize the existing literature regarding these barriers and the strategies offered to address them. The authors completed a literature search using the PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Web of Science databases. In total, 71 articles were reviewed. Barriers to accessing pediatric palliative care were categorized according to the 4 levels of a modified socioecological model (ie, barriers related to policy/payment, health systems, organizations, and individuals). Major themes identified at each level included: 1) the lack of consistent and adequate funding mechanisms at the policy/payment level, 2) the lack of pediatric palliative care programs and workforce at the health systems level, 3) difficulties integrating palliative care into existing pediatric oncology care models at the organizational level, and 4) the lack of knowledge about pediatric palliative care, discomfort with talking about death, and cultural differences between providers and patients and their families at the individual level. Recommendations to address each of the barriers identified in the literature are included. Cancer 2018. © 2018 American Cancer Society.

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Decreased early mortality associated with the treatment of acute myeloid leukemia at National Cancer Institute-designated cancer centers in California

BACKGROUND

To the authors' knowledge, few population-based studies to date have evaluated the association between location of care, complications with induction therapy, and early mortality in patients with acute myeloid leukemia (AML).

METHODS

Using linked data from the California Cancer Registry and Patient Discharge Dataset (1999-2014), the authors identified adult (aged ≥18 years) patients with AML who received inpatient treatment within 30 days of diagnosis. A propensity score was created for treatment at a National Cancer Institute-designated cancer center (NCI-CC). Inverse probability-weighted, multivariable logistic regression models were used to determine associations between location of care, complications, and early mortality (death ≤60 days from diagnosis).

RESULTS

Of the 7007 patients with AML, 1762 (25%) were treated at an NCI-CC. Patients with AML who were treated at NCI-CCs were more likely to be aged ≤65 years, live in higher socioeconomic status neighborhoods, have fewer comorbidities, and have public health insurance. Patients treated at NCI-CCs had higher rates of renal failure (23% vs 20%; P = .010) and lower rates of respiratory failure (11% vs 14%; P = .003) and cardiac arrest (1% vs 2%; P = .014). After adjustment for baseline characteristics, treatment at an NCI-CC was associated with lower early mortality (odds ratio, 0.46; 95% confidence interval, 0.38-0.57). The impact of complications on early mortality did not differ by location of care except for higher early mortality noted among patients with respiratory failure treated at non-NCI-CCs.

CONCLUSIONS

The initial treatment of adult patients with AML at NCI-CCs is associated with a 53% reduction in the odds of early mortality compared with treatment at non-NCI-CCs. Lower early mortality may result from differences in hospital or provider experience and supportive care. Cancer 2018. © 2018 American Cancer Society.

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Randomized phase 2 trial of pemetrexed, pemetrexed/bevacizumab, and pemetrexed/carboplatin/bevacizumab in patients with stage IIIB/IV non–small cell lung cancer and an Eastern Cooperative Oncology Group performance status of 2

BACKGROUND

The best treatment for patients with advanced non–small cell lung cancer (NSCLC) and a poor performance status is not well defined. In this phase 2 trial, patients were randomized to receive treatment with either single-agent pemetrexed or 1 of 2 combination regimens.

METHODS

Patients with newly diagnosed, histologically confirmed nonsquamous NSCLC and an Eastern Cooperative Oncology Group (ECOG) performance status of 2 were stratified by age and serum albumin level and were randomized (1:1:1) to 1 of 3 regimens: pemetrexed (arm 1), pemetrexed and bevacizumab (arm 2), or pemetrexed, carboplatin, and bevacizumab (arm 3). The response to treatment was assessed every 2 cycles; responding and stable patients continued treatment until progression or unacceptable toxicity.

RESULTS

One hundred seventy-two patients were randomized, 162 patients began the study treatment, and 146 patients completed 2 cycles and were evaluated for their response. The median progression-free survival (PFS) was 2.8 months in arm 1, 4.0 months in arm 2, and 4.8 months in arm 3. The overall response rates were 15% in arm 1, 31% in arm 2, and 44% in arm 3. The overall survival was similar in the 3 treatment arms. All 3 regimens were relatively well tolerated. Patients receiving bevacizumab had an increased incidence of hypertension, proteinuria, and bleeding episodes, but most events were mild or moderate.

CONCLUSIONS

All 3 regimens were feasible for patients with advanced NSCLC and an ECOG performance status of 2. The addition of bevacizumab to pemetrexed increased the overall response rate. The efficacy of pemetrexed/carboplatin/bevacizumab (median PFS, 4.8 months) approached the prespecified study PFS goal of 5 months. Larger studies will be necessary to define the role of bevacizumab in addition to standard pemetrexed and carboplatin in this population. Cancer 2018. © 2018 American Cancer Society.

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Phase 1b study of pasireotide, everolimus, and selective internal radioembolization therapy for unresectable neuroendocrine tumors with hepatic metastases

BACKGROUND

Neuroendocrine tumors (NETs) metastasize to the liver. Everolimus and selective internal radioembolization (SIRT) are approved treatments. Pasireotide is a somatostatin analogue with an affinity for somatostatin receptors 1, 2, 3, and 5. Everolimus and pasireotide may potentiate SIRT radiosensitization and inhibit rebound angiogenesis. This study evaluated the safety of pasireotide, everolimus, and SIRT.

METHODS

This 3 + 3 phase 1 trial evaluated 3 dose levels of everolimus (2.5, 5, and 10 mg/day), pasireotide (600 μg twice daily), and SIRT (SIR-Spheres dose on days 9 and 37). Eligibility criteria included well or moderately differentiated NETs, bilobar liver metastases, and progression on long-acting octreotide. Toxicities and responses were evaluated with the Common Terminology Criteria for Adverse Events and the Response Evaluation Criteria in Solid Tumors (version 1.1). Dose-limiting toxicities (DLTs) were defined in the first 28 days. Correlative markers—angiopoietin 1, angiopoietin 2, basic fibroblast growth factor, collagen V, insulin-like growth factor binding protein 1, insulin-like growth factor binding protein 1, interleukin 8, M30, M65, placenta growth factor, and vascular endothelial growth factor receptor 2—were assessed. The Norfolk Quality of Life–Neuroendocrine Tumor Questionnaire was used to assess the quality of life (QOL).

RESULTS

Thirteen patients were enrolled; 1 was not evaluable for the primary endpoint. Eleven patients had well-differentiated tumors. The primary sites included small bowel (4), pancreas (3), lung (2), colon (1), gastric (1), and unknown primary (2) were unknown. Four had liver-only disease; 12 completed the planned treatment. No DLTs were observed. There was no treatment-related mortality. The most common toxicity was hyperglycemia. Clinically significant liver toxicity was not observed. One patient had liver progression. QOL improved on treatment. The median progression-free survival and overall survival were 18.6 and 46.3 months, respectively.

CONCLUSIONS

The recommended phase 2 dose of everolimus is 10 mg daily in combination with pasireotide and SIRT. The regimen is well tolerated. Preliminary activity appears promising. Cancer 2018. © 2018 American Cancer Society.

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Bracing for disaster

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Our 2017 Cancer Cytopathology Young Investigator

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Issue Information

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Detection of ROS1-positive non-small cell lung cancer on cytological specimens using immunocytochemistry

BACKGROUND

Rearrangements of the ROS1 oncogene are found in 1% to 2% of non-small cell lung cancers (NSCLC) and are regarded as mutually exclusive oncogenic driver mutations. Since the approval of targeted therapy for ROS1-positive NSCLC, ROS1 testing has become a part of the diagnostic routine. Fluorescence in situ hybridization (FISH), optionally selected for by immunohistochemistry on histological material, is a common practice for the detection of ROS1 rearrangements. However, NSCLC often is diagnosed by cytology alone, requiring predictive marker testing on cytological specimens. In the current study, the authors explored the accuracy of ROS1 immunocytochemistry (ICC) on non-cell block cytological specimens for the detection of ROS1 rearrangements.

METHODS

ICC using the D4D6 antibody on an automated immunostainer was performed prospectively in the routine diagnostic setting on cytological specimens from 295 patients with NSCLC, including adenocarcinoma (241 patients), NSCLC not otherwise specified (50 patients), and other malignancies (4 patients). Any immunostaining was considered positive.

RESULTS

ICC was positive in all 13 ROS1-rearranged NSCLC cases confirmed by FISH (12 cases) or next-generation sequencing (1 case). Confirmation of 282 ICC-negative cases was available for 208 patients. The sensitivity, specificity, and positive and negative predictive values for ROS1 ICC compared with the final ROS1 status all were 100%.

CONCLUSIONS

ROS1 ICC is an accurate method for the detection of ROS1 rearrangements in NSCLC. Given the high costs and technical challenges of FISH and the rarity of ROS1 rearrangements, ICC is rapid and therefore well suited as a screening method. Cases with equivocal or positive findings on ICC can be confirmed by FISH or molecular tests. Cancer Cytopathol 2018. © 2018 American Cancer Society.

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Well differentiated grade 3 pancreatic neuroendocrine tumors compared with related neoplasms: A morphologic study

BACKGROUND

Pancreatic neuroendocrine neoplasms with a Ki-67 labeling index greater than 20% were reclassified in 2017 by the World Health Organization into well differentiated (WD) and poorly differentiated grade 3 neuroendocrine carcinoma (NEC). The authors describe the cytologic features of grade 3 WD pancreatic neuroendocrine neoplasms compared with grade 2 neoplasms and NEC.

METHODS

Fine-needle aspirates from 65 pancreatic neuroendocrine neoplasms were reviewed, and their cytomorphologic features were compared across grade 2, WD grade 3, and PD small cell type (PD-S), large cell type (PD-L), and type not otherwise specified (PD-NOS) neoplasms.

RESULTS

The 65 aspirates consisted of 19 grade 2 neoplasms, 32 WD grade 3 neoplasms, and 14 NECs (6 PD-S, 5 PD-L, and 3 PD-NOS). The medians Ki-67 proliferation index was 11% (range, 3.2%-17%) in grade 2 neoplasms, 40% (range, 21%-89%) in WD grade 3 neoplasms, 80% (range, 63%-95%) in PD-S neoplasms, 39% (range, 25%-61%) in PD-L neoplasms, and 70% (range, 30%-80%) in PD-NOS neoplasms. Both grade 2 and WD grade 3 neoplasms were associated with plasmacytoid morphology and smooth nuclear contours, but WD grade 3 neoplasms had significant increases in abundant cytoplasm (72% vs 17%; P = .007), nuclear tangles (75% vs 42%; P = .006), and apoptosis (86% vs 58%; P = .005). Compared with NECs, WD grade 3 neoplasms had increased plasmacytoid morphology (75% vs 7%; P < .001), smooth nuclear contours (94% vs 64%; P = .02), round nuclei (59% vs 21%; P = .01), and less pleomorphism (13% vs 50%; P = .004), molding (9% vs 79%; P < .001), and necrosis (13% vs 43%; P = .003). WD grade 3 neoplasms had less pleomorphism (13% vs 50%; P = .04), less necrosis (13% vs 60%; P = .04), and more plasmacytoid morphology (75% vs 20%; P = .03) than PD-L.

CONCLUSIONS

The prevalence of cytologic features differs in WD grade 3 pancreatic neuroendocrine neoplasms compared with grade 2 neoplasms and NECs, and these differences assist in the recognition of this newly classified entity. Cancer Cytopathol 2018. © 2018 American Cancer Society.

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KIAA0247 inhibits growth, migration, invasion of non-small-cell lung cancer through regulating the Notch pathway

Summary

Lung cancer remains the leading cause of cancer-related death worldwide. Previous studies have shown that the novel KIAA0247 gene potentially targeted by the tumor suppressor p53 may inhibit the development of several cancers. However, the exact function of KIAA0247 in non-small-cell lung cancer (NSCLC) is unknown. The purpose of this study was to clarify the role of KIAA0247 in NSCLC. KIAA0247 expression was evaluated in tumors and adjacent normal tissues of 197 NSCLC patients by immunohistochemistry and real-time PCR and analyzed for association with clinicopathological parameters. The results indicated that KIAA0247 levels positively correlated with cell differentiation (P < 0.001) and patient survival (P < 0.0001) and negatively correlated with lymph node metastasis (P < 0.001) and advanced p-TNM stage (P < 0.001). In cultured NSCLC cell lines, KIAA0247 overexpression inhibited cell migration, invasion, and proliferation and downregulated the expression of Jagged1, Notch1 intracellular domain (NICD), Snail, cyclin D1, RhoA, RhoC, and matrix metalloproteinase 9 (MMP9), while upregulating that of E-cadherin and p21. The Notch inhibitor DAPT reduced the biological effects of KIAA0247 knockdown, suggesting that KIAA0247 decreased the carcinogenic activity of NSCLC cells through downregulation of Notch signaling. Our results indicate that KIAA0247 inhibits NSCLC progression by reducing the metastatic potential of cancer cells through downregulation of the Notch pathway, which may underlie the association of KIAA0247 expression with favorable clinicopathological characteristics of NSCLC patients. These findings suggest that KIAA0247 is a candidate prognostic biomarker and potential therapeutic target in NSCLC.

This article is protected by copyright. All rights reserved.

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Does hearing aid use affect audiovisual integration in mild hearing impairment?

Abstract

There is converging evidence for altered audiovisual integration abilities in hearing-impaired individuals and those with profound hearing loss who are provided with cochlear implants, compared to normal-hearing adults. Still, little is known on the effects of hearing aid use on audiovisual integration in mild hearing loss, although this constitutes one of the most prevalent conditions in the elderly and, yet, often remains untreated in its early stages. This study investigated differences in the strength of audiovisual integration between elderly hearing aid users and those with the same degree of mild hearing loss who were not using hearing aids, the non-users, by measuring their susceptibility to the sound-induced flash illusion. We also explored the corresponding window of integration by varying the stimulus onset asynchronies. To examine general group differences that are not attributable to specific hearing aid settings but rather reflect overall changes associated with habitual hearing aid use, the group of hearing aid users was tested unaided while individually controlling for audibility. We found greater audiovisual integration together with a wider window of integration in hearing aid users compared to their age-matched untreated peers. Signal detection analyses indicate that a change in perceptual sensitivity as well as in bias may underlie the observed effects. Our results and comparisons with other studies in normal-hearing older adults suggest that both mild hearing impairment and hearing aid use seem to affect audiovisual integration, possibly in the sense that hearing aid use may reverse the effects of hearing loss on audiovisual integration. We suggest that these findings may be particularly important for auditory rehabilitation and call for a longitudinal study.

http://ift.tt/2EumfXS

H3K9 demethylase KDM4E is an epigenetic regulator for bovine embryonic development and a defective factor for nuclear reprogramming [STEM CELLS AND REGENERATION]

Xin Liu, Yizhi Wang, Yuanpeng Gao, Jianmin Su, Jingcheng Zhang, Xupeng Xing, Chuan Zhou, Kezhen Yao, Quanli An, and Yong Zhang

Aberrant epigenetic reprogramming often results in developmental defects in somatic cell nuclear transfer (SCNT) embryos during embryonic genome activation (EGA). Bovine eight-cell SCNT embryos exhibit global hypermethylation of histone H3 lysine 9 tri- and di-methylation (H3K9me3/2), but the intrinsic reason for this remains elusive. Here, we provide evidence that two H3K9 demethylase genes, lysine-specific demethylase 4D (KDM4D) and 4E (KDM4E), are related to active H3K9me3/2 demethylation in in vitro fertilized (IVF) embryos and are deficiently expressed in cloned embryos at the time of EGA. Moreover, KDM4E plays a more crucial role in IVF and SCNT embryonic development, and overexpression of KDM4E can restore the global transcriptome, improve blastocyst formation and increase the cloning efficiency of SCNT embryos. Our results thereby indicate that KDM4E can function as a crucial epigenetic regulator of EGA and as an internal defective factor responsible for persistent H3K9me3/2 barriers to SCNT-mediated reprogramming. Furthermore, we show that interactions between RNA and KDM4E are essential for H3K9 demethylation during EGA. These observations advance the understanding of incomplete nuclear reprogramming and are of great importance for transgenic cattle procreation.

http://ift.tt/2C4xcC5

{beta}-Catenin signaling is essential for mammalian larynx recanalization and the establishment of vocal fold progenitor cells [RESEARCH ARTICLE]

Vlasta Lungova, Jamie M. Verheyden, Xin Sun, and Susan L. Thibeault

Congenital laryngeal webs result from failure of vocal fold separation during development in utero. Infants present with life-threatening respiratory problems at birth, and extensive lifelong difficulties in breathing and voicing. The molecular mechanisms that instruct vocal fold formation are rarely studied. Here, we show, for the first time, that conditional inactivation of the gene encoding β-catenin in the primitive laryngopharyngeal epithelium leads to failure in separation of the vocal folds, which approximates the gross phenotype of laryngeal webbing. These defects can be traced to a series of morphogenesis defects, including delayed fusion of the epithelial lamina and formation of the laryngeal cecum, failed separation of the larynx and esophagus with reduced and disorganized cartilages and muscles. Parallel to these morphogenesis defects, inactivation of β-catenin disrupts stratification of epithelial cells and establishment of p63⁺ basal progenitors. These findings provide the first line of evidence that links β-catenin function to the cell proliferation and progenitor establishment during larynx and vocal fold development.

http://ift.tt/2sAvrbH

Predictors of persistent prescription opioid analgesic use among people without cancer in Australia

Abstract

Aims

To identify patterns of opioid analgesic use and determine predictors of persistent opioid use among people without cancer.

Methods

A population-based cohort study of Australians initiating prescription opioids from July 2013 to December 2015 was conducted using data from a random 10% sample of people who accessed medicines through Australia's Pharmaceutical Benefits Scheme. A 12-month look-back period was used to define opioid initiation, exclude people with cancer, and determine comorbidities. Persistent use over 12-months since initiation was identified through group-based trajectory modelling. Odds ratios (OR) and 95% confidence intervals (CIs) for predictors of opioid persistence were estimated using logistic regression.

Results

The cohort consisted of 431,963 people without cancer who initiated opioids. A total of 11,323 (2.6%) persistent opioid users were identified. Predictors of persistence included initiation with transdermal formulations (OR 4.2, 95% CI 3.9-4.5), or initiation with total oral morphine equivalents (OME) ≥ 750 mg (3.7, 3.3-4.1), having depression (1.6, 1.5-1.7), or psychotic illness (2.0, 1.9-2.2). Previous dispensing of paracetamol (2.0, 1.9-2.1), pregabalin (2.0, 1.8-2.1) and benzodiazepines (1.53, 1.4-1.6) predicted persistence. Compared to people aged 18-44 years, those ≥75 years were 2.5 (2.3-2.6) times more likely to be persistent users.

Conclusions

Patient-specific characteristics (older age, prior history of mental health comorbidities and use of non-opioid analgesics) and prescriber choice of initial opioid (transdermal formulation and higher total OMEs) were found to strongly predict persistent use. This information may help prescribers target monitoring and early intervention efforts in order to prevent harms associated with the long-term use of opioids.

http://ift.tt/2syAXf5

Intracellular pharmacokinetics of gemcitabine, its deaminated metabolite 2',2'-difluorodeoxyuridine and their nucleotides

Abstract

Aims

Gemcitabine (2',2'-difluoro-2'-deoxycytidine, dFdC) is a prodrug that has to be phosphorylated within the tumour cell to become active. Intracellularly formed gemcitabine diphosphate (dFdCDP) and triphosphate (dFdCTP) are held responsible for the antineoplastic effects. However, a major part of gemcitabine is converted into 2',2'-difluoro-2'-deoxyuridine (dFdU) by deamination. In the cell, dFdU can also be phosphorylated to its monophosphate (dFdUMP), diphosphate (dFdUDP) and triphosphate (dFdUTP). In vitro data suggest that these dFdU nucleotides might also contribute to the antitumor effects. However, little is known about their intracellular pharmacokinetics (PK). Therefore, objective of this study was to gain insight into the intracellular PK of all dFdC and dFdU nucleotides formed during gemcitabine treatment.

Methods

Peripheral blood mononuclear cell (PBMC) samples were collected from 38 patients receiving gemcitabine, at multiple time-points after infusion. Gemcitabine, dFdU and their nucleotides were quantified in PBMCs. In addition, gemcitabine and dFdU plasma concentrations were monitored. The individual PK parameters in plasma and in PBMCs were determined.

Results

Both in plasma and in PBMCs, dFdU was present in higher concentrations than gemcitabine (mean intracellular AUC_0-24h 1650 vs. 95 μM*h). However, the dFdUMP, dFdUDP and dFdUTP concentrations in PBMCs were much lower than the dFdCDP and dFdCTP concentrations. The mean AUC_0-24h for dFdUTP was 312 μM*h vs. 2640 μM*h for dFdCTP.

Conclusions

This study provides the first complete picture of all nucleotides that are intracellularly formed during gemcitabine treatment. Low intracellular dFdU nucleotide concentrations were found, which questions the relevance of these nucleotides for the cytotoxic effects of gemcitabine.

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The Accuracy of Perioperative Noninvasive Blood Pressure Monitoring in Obese Patients

No abstract available

http://ift.tt/2EAoTzi

In Response

No abstract available

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Bivalirudin for Pediatric Procedural Anticoagulation: A Narrative Review

Bivalirudin (Angiomax; The Medicines Company, Parsippany, NJ), a direct thrombin inhibitor, has found increasing utilization as a heparin alternative in the pediatric population, most commonly for the treatment of thrombosis secondary to heparin-induced thrombocytopenia. Due to the relative rarity of heparin-induced thrombocytopenia as well as the lack of Food and Drug Administration–approved indications in this age group, much of what is known regarding the pharmacokinetics and pharmacodynamics of bivalirudin in this population has been extrapolated from adult data. This narrative review will present recommendations regarding the use of bivalirudin for procedural anticoagulation in the pediatric population based on the published literature. Accepted for publication December 19, 2017. Funding: None. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Katherine L. Zaleski, MD, Department of Anesthesiology, Perioperative, and Pain Medicine, Boston Children's Hospital, 300 Longwood Ave, Boston, MA 02115. Address e-mail to Katherine.Zaleski@childrens.harvard.edu. © 2018 International Anesthesia Research Society

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Combined Colloid Preload and Crystalloid Coload Versus Crystalloid Coload During Spinal Anesthesia for Cesarean Delivery: A Randomized Controlled Trial

BACKGROUND: The optimal strategy of fluid administration during spinal anesthesia for cesarean delivery is still unclear. Ultrasonography of the inferior vena cava (IVC) has been recently used to assess the volume status and predict fluid responsiveness. In this double-blind, randomized controlled study, we compared maternal hemodynamics using a combination of 500-mL colloid preload and 500-mL crystalloid coload versus 1000-mL crystalloid coload. We assessed the IVC at baseline and at subsequent time points after spinal anesthesia. METHODS: Two hundred American Society of Anesthesiologists physical status II parturients with full-term singleton pregnancies scheduled for elective cesarean delivery under spinal anesthesia were randomly allocated to receive either 500-mL colloid preload followed by 500-mL crystalloid coload (combination group) or 1000-mL crystalloid coload (crystalloid coload group) administered using a pressurizer. Ephedrine 3, 5, and 10 mg boluses were administered when the systolic blood pressure decreased below 90%, 80% (hypotension), and 70% (severe hypotension) of the baseline value, respectively. The IVC was assessed using the subcostal long-axis view at baseline, at 1 and 5 minutes after intrathecal injection, and immediately after delivery; the maximum and minimum IVC diameters were measured, and the IVC collapsibility index (CI) was calculated using the formula: IVC-CI = (maximum IVC diameter – minimum IVC diameter)/maximum IVC diameter. The primary outcome was the total ephedrine dose. RESULTS: Data from 198 patients (99 patients in each group) were analyzed. The median (range) of the total ephedrine dose was 11 (0–60) mg in the combination group and 13 (0–61) mg in the crystalloid coload group; the median of the difference (95% nonparametric confidence interval) was −2 (−5 to 0.00005) mg, P = .22. There were no significant differences between the 2 groups in the number of patients requiring ephedrine, the incidence of hypotension and severe hypotension, the time to the first ephedrine dose, and neonatal Apgar scores at 1 and 5 minutes. The maximum and minimum IVC diameters in each group increased after spinal anesthesia and after delivery, and they were larger in the combination group. The IVC-CI after delivery was higher in the crystalloid coload group. CONCLUSIONS: The combination of 500-mL colloid preload and 500-mL crystalloid coload did not reduce the total ephedrine dose or improve other maternal outcomes compared with 1000-mL crystalloid coload. The IVC was reliably viewed before and during cesarean delivery, and its diameters significantly changed over time and differed between the 2 groups. Accepted for publication December 29, 2017. Funding: This work was supported by the Department of Anesthesia and Surgical Intensive Care at the Mansoura University Hospital, Mansoura, Egypt. 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 (http://ift.tt/KegmMq). Clinical trial registration: NCT02961842 (ClinicalTrials.gov). The institutional review board approved the study protocol before starting the study; Mansoura Faculty of Medicine Institutional Review Board, http://ift.tt/2Eu0StM, Ahmed Shokeir, MD (Chairman), Professor of Urology, Faculty of Medicine, Mansoura University, Mansoura, Egypt. E-mail: irb.mfm@hotmail.com. Reprints will not be available from the authors. Address correspondence to Mohamed Mohamed Tawfik, MD, Department of Anesthesia and Surgical Intensive Care, Mansoura University Hospital, 26 Elgomhoria St, Mansoura, Dakahlia, Egypt. Address e-mail to m2tawfik@mans.edu.eg. © 2018 International Anesthesia Research Society

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Neuraxial Anesthesia in Children With Ventriculoperitoneal Shunts

Neuraxial anesthesia has been demonstrated to be safe and effective for children undergoing subumbilical surgery. There is limited evidence regarding the safety of neuraxial anesthesia in pediatric patients with a ventriculoperitoneal shunt. We evaluated a series of 25 patients with indwelling ventriculoperitoneal shunts for complications within 30 days of any procedure performed with a neuraxial technique. One patient required a ventriculoperitoneal shunt revision 5 days after a lumbar catheter placement. The neurosurgeon determined the revision to be likely unrelated to the patient's lumbar catheter. Concerns about the use of neuraxial anesthesia in patients with an indwelling ventriculoperitoneal shunt may be overstated. Accepted for publication December 19, 2018. Funding: None. The authors declare no conflicts of interest. A.B.L. and E.C.C. contributed equally to this work. Reprints will not be available from the authors. Address correspondence to Anthony B. Longhini, MD, Department of Anesthesiology, Ann & Robert H. Lurie Children's Hospital of Chicago, 225 E Chicago Ave, Chicago, IL 60611. Address e-mail to alonghini@luriechildrens.org. © 2018 International Anesthesia Research Society

http://ift.tt/2EAooW3

Painless Evidence-Based Medicine, 2nd ed

No abstract available

http://ift.tt/2CobrsD

Approaches to Patient Counseling Regarding Effectiveness of Oral Contraceptives

No abstract available

http://ift.tt/2Ewjych

Retooling NCI MERIT Awards to Support Budding Cancer Researchers

NCI Director Dr. Ned Sharpless discusses how NCI is retooling a grant mechanism, called the MERIT R37 Award, to help early-stage investigators by extending the length of time they can receive funding under their first independent NIH grant.

http://ift.tt/2C2c4fQ

H3K9 demethylase KDM4E is an epigenetic regulator for bovine embryonic development and a defective factor for nuclear reprogramming [STEM CELLS AND REGENERATION]

Xin Liu, Yizhi Wang, Yuanpeng Gao, Jianmin Su, Jingcheng Zhang, Xupeng Xing, Chuan Zhou, Kezhen Yao, Quanli An, and Yong Zhang

Aberrant epigenetic reprogramming often results in developmental defects in somatic cell nuclear transfer (SCNT) embryos during embryonic genome activation (EGA). Bovine eight-cell SCNT embryos exhibit global hypermethylation of histone H3 lysine 9 tri- and di-methylation (H3K9me3/2), but the intrinsic reason for this remains elusive. Here, we provide evidence that two H3K9 demethylase genes, lysine-specific demethylase 4D (KDM4D) and 4E (KDM4E), are related to active H3K9me3/2 demethylation in in vitro fertilized (IVF) embryos and are deficiently expressed in cloned embryos at the time of EGA. Moreover, KDM4E plays a more crucial role in IVF and SCNT embryonic development, and overexpression of KDM4E can restore the global transcriptome, improve blastocyst formation and increase the cloning efficiency of SCNT embryos. Our results thereby indicate that KDM4E can function as a crucial epigenetic regulator of EGA and as an internal defective factor responsible for persistent H3K9me3/2 barriers to SCNT-mediated reprogramming. Furthermore, we show that interactions between RNA and KDM4E are essential for H3K9 demethylation during EGA. These observations advance the understanding of incomplete nuclear reprogramming and are of great importance for transgenic cattle procreation.

http://ift.tt/2C4xcC5

{beta}-Catenin signaling is essential for mammalian larynx recanalization and the establishment of vocal fold progenitor cells [RESEARCH ARTICLE]

Vlasta Lungova, Jamie M. Verheyden, Xin Sun, and Susan L. Thibeault

Congenital laryngeal webs result from failure of vocal fold separation during development in utero. Infants present with life-threatening respiratory problems at birth, and extensive lifelong difficulties in breathing and voicing. The molecular mechanisms that instruct vocal fold formation are rarely studied. Here, we show, for the first time, that conditional inactivation of the gene encoding β-catenin in the primitive laryngopharyngeal epithelium leads to failure in separation of the vocal folds, which approximates the gross phenotype of laryngeal webbing. These defects can be traced to a series of morphogenesis defects, including delayed fusion of the epithelial lamina and formation of the laryngeal cecum, failed separation of the larynx and esophagus with reduced and disorganized cartilages and muscles. Parallel to these morphogenesis defects, inactivation of β-catenin disrupts stratification of epithelial cells and establishment of p63⁺ basal progenitors. These findings provide the first line of evidence that links β-catenin function to the cell proliferation and progenitor establishment during larynx and vocal fold development.

http://ift.tt/2sAvrbH

Primary sebocytes and sebaceous gland cell lines for studying sebaceous lipogenesis and sebaceous gland diseases

Abstract

Sebocytes, the major cell type in sebaceous glands (SGs), are differentiated epithelial cells that gradually accumulate lipids and eventually disrupt, releasing their content (sebum) in a secretory process known as holocrine secretion. Via the hair canal, sebum reaches the skin surface, where it has several known or postulated functions, including pheromonal, thermoregulatory, antimicrobial and antioxidant activities. Altered sebum secretion and/or structural SG changes have also been involved in the pathogenesis of skin diseases, such as acne vulgaris and some forms of alopecia. Here we assess how recent work employing primary sebocytes and SG cell lines contributed for our understanding of sebaceous lipogenesis and its role in skin health and disease.

This article is protected by copyright. All rights reserved.

http://ift.tt/2oapoFf

Advancing a field by building consortia: The example of the European LeukemiaNet

The European LeukemiaNet provides an example of advancing a field in urgent need of progress through cooperation. It has structured leukemia research internationally through the creation of standards, definitions, and high-level management recommendations and has contributed toward improved outcomes. The article summarizes the principles of successful cooperation.

http://ift.tt/2C1QmbG

Isolation of marine xylene-utilizing bacteria and characterization of Halioxenophilus aromaticivorans gen. nov., sp. nov. and its xylene degradation gene cluster

Abstract

Seven xylene-utilizing bacterial strains were isolated from seawater collected off the coast of Japan. Analysis of 16S rRNA gene sequences indicated that six isolates were most closely related to the marine bacterial genera Alteromonas, Marinobacter or Aestuariibacter. The sequence of the remaining strain, KU68F^T, showed low similarity to the 16S rRNA gene sequences of known bacteria with validly published names, the most similar species being Maricurvus nonylphenolicus strain KU41E^T (92.6% identity). On the basis of physiological, chemotaxonomic and phylogenetic data, strain KU68F^T is suggested to represent a novel species of a new genus in the family Cellvibrionaceae of the order Cellvibrionales within the Gammaproteobacteria, for which the name Halioxenophilus aromaticivorans gen. nov., sp. nov. is proposed. The type strain of Halioxenophilus aromaticivorans is KU68F^T ( = JCM 19134^T = KCTC 32387^T). PCR and sequence analysis revealed that strain KU68F^T possesses an entire set of genes encoding the enzymes for the upper xylene methyl-monooxygenase pathway, xylCMABN, resembling the gene set of the terrestrial Pseudomonas putida strain mt-2.

http://ift.tt/2BA7HHQ

Fixation of CO2 and CO on a diverse range of carbohydrates using anaerobic, non-photosynthetic mixotrophy

Abstract

Biological CO₂ fixation is an important technology that can assist in combating climate change. Here, we show an approach called anaerobic, non-photosynthetic mixotrophy can result in net CO₂ fixation when using a reduced feedstock. This approach uses microbes called acetogens that are capable of concurrent utilization of both organic and inorganic substrates. In this study, we investigated the substrate utilization of seventeen different acetogens, both mesophilic and thermophilic, on a variety of different carbohydrates and gases. Compared to most model acetogen strains, several non-model mesophilic strains displayed greater substrate flexibility, including the ability to utilize disaccharides, glycerol, and an oligosaccharide, and growth rates. Three of these non-model strains (Blautia producta, Clostridium scatologenes, and Thermoanaerobacter kivui) were chosen for further characterization, under a variety of conditions including H₂- or syngas-fed sugar fermentations and a CO₂-fed glycerol fermentation. In all cases, CO₂ was fixed and carbon yields approached 100%. Finally, the model acetogen C. ljungdahlii was engineered to utilize glucose, a non-preferred sugar, while maintaining mixotrophic behavior. This work demonstrates the flexibility and robustness of anaerobic, non-photosynthetic mixotrophy as a technology to help reduce CO₂ emissions.

http://ift.tt/2C2vq4h

Secreted bacterial RNA: an unexplored avenue

Abstract

Gradually, it is becoming clear that our well-being depends significantly on the contribution and composition of microorganisms that are associated with us. The majority of human-associated microorganisms are bacteria, which maintain their niche through interactions with the human host and neighboring microorganisms. Secretory products contribute largely to maintaining their position in a complex ecosystem. The role of bacterial-released secreted RNA (seRNA) is mostly unexplored, and the study on seRNA will open a new branch in science. There are observations that have demonstrated the functional potential of seRNA, but more investigations are required to cover the entire path from their origin to function.

http://ift.tt/2BzgBoZ

Over-expression of the periplasmic nitrate reductase supports anaerobic growth by Ensifer meliloti

Abstract

The alfalfa endosymbiont Ensifer meliloti strain1021 is known to be an incomplete denitrifier due to its inability to grow anoxically using nitrate as respiratory substrate to produce ATP and grow under anoxic conditions. Although this bacterium contains and expresses the complete set of denitrification genes napEFDABC, nirK, norECBQD and nosRZDFYLX encoding the periplasmic nitrate reductase (Nap), Cu-containing nitrite reductase (NirK), c-type nitric oxide (cNor) and nitrous oxide reductase (Nos), respectively, the reasons of its inability to grow under anoxic conditions are still very poorly understood. In the present study, we have constructed an E. meliloti strain over-expressing napEFDABC genes (Nap⁺) and demonstrated that this strain is able to grow through anaerobic nitrate respiration. Furthermore, Nap⁺ showed increased NapC levels as well as Nap, Nir, and cNor activities and higher capacity to produce NO and N₂O compared to wild-type cells. These results suggest that the inability of E. meliloti to grow under anaerobic conditions using nitrate as electron acceptor is attributable to a limitation in the expression of the periplasmic nitrate reductase.

http://ift.tt/2C6yooq