bluuebunny/crossref_metadata_2025 huggingface dataset:
Improved endoscopic resection of large flat lesions and early cancers using an external additional working channel (AWC): a case series
Authors: Walter Benjamin , Schmidbaur Simone , Krieger Yannick , Meining Alexander
Published: February 2019

Background En-bloc resection of large, flat lesions or early stages of cancer is challenging. No bimanual tasks are possible using standard endoscopes. Dual-channel endoscopes are not available everywhere and have a small distance between the channels.

Patients and methods A new external additional working channel (AWC) (Ovesco, Tuebingen, Germany) was designed and developed potentially enabling bimanual tasks. Fixed to the tip of a standard gastroscope or pediatric colonoscope, a second endoscopic tool can be inserted through the AWC and used for tissue retraction during endoscopic resection.

Results In the upper and lower gastrointestinal tract, endoscopic mucosal resection (EMR) with a modified grasp-and-snare technique and endoscopic submucosal dissection (ESD) were performed successfully using the AWC in eight patients. Complications were acute arterial bleeding post-EMR in two cases treated by endoscopic clipping.

Conclusions We conclude that a newly developed external additional working channel (AWC) enables endoscopic resection of large lesions in the upper and lower gastrointestinal tract. Potential benefits are its suitability for EMR and ESD, no need for a dual-channel endoscope and an adjustable distance of working channels.
Short-Term Clinical and Radiographical Outcome after Application of Anchored Intervertebral Spacers in Dogs with Disc-Associated Cervical Spondylomyelopathy
Authors: Rohner Deborah , Kowaleski Michael , Schwarz Günter , Forterre Franck
Published: February 2019

Objectives The purpose of this study was to assess the short-term outcome of a new intervertebral anchored fusion device (C-LOX) for the treatment of disc associated cervical spondylomyelopathy (DA-CSM) in dogs, based on clinical and radiographical follow-up data.

Materials and Methods To be included in the study, dogs had to be clinically affected by DA-CSM treated with surgical distraction/stabilization using the anchored intervertebral spacer (C-LOX). Neurological signs, as well as diagnostic imaging performed pre-, immediately postoperatively, and after 6 weeks and 3 months were assessed. If available, clinical follow-up after 3 months was documented.

Results Thirty-seven cases were enrolled in the study. Outcome at 3 months was available in 25 dogs; improvement of neurological status was documented in 25/25 cases.

The most common postoperative complication was screw loosening and/or breakage (n = 22), followed by subsidence (n = 15). Four dogs required revision surgery.

Clinical Significance Distraction/stabilization of DA-CSM in dogs with the C-LOX device resulted in short-term clinical improvement in 33/37 treated cases. The high incidence of screw loosening was taken into consideration and modification of the implant with a new locking system and new screw dimensions was required. The C-LOX device seems to be a valuable alternative to more complicated distraction–fusion techniques.
Evaluation of the Superior Labial Musculomucosal Flap in Dogs: An Angiographic Study and Case Report
Authors: Degner Daniel , Doyle Cody
Published: February 2019

Objective The aim of this study was to evaluate the angiosome of the superior and inferior labial arteries within the superior and inferior labia and to describe superior and inferior labial musculomucosal axial pattern flaps that can be used for intra-oral wound reconstruction. This study also presents the clinical use of a superior labial musculomucosal flap in a dog.

Materials and Methods The common carotid arteries of six canine cadavers were injected with barium sulphate. The skin of the face and labial mucosa was removed and radiographed to study the vascular supply of the superior and inferior labia.

Results The angiograms in all dogs demonstrated that the superior and inferior labial arteries were located within the musculomucosal layer of the labia. At the junction of the rostral and caudal half of the upper lip, extensive choke anastomoses joined the angiosome of the infra-orbital artery. The inferior labial artery perfused the caudal half of the lower labium and had extensive choke anastomoses with the middle and rostral mental arteries.

Clinical Significance The musculomucosal flaps of the superior and inferior labia contain a rich arterial blood supply, which suggests that these flaps may survive in live dogs. The superior labial musculomucosal flap was successfully used to reconstruct a large cleft palate in a single clinical case.
Effect of Hydraulic Expansion on Arteriovenous Fistula of Hemodialysis Patients
Authors: Ren Wanjun , Du Yuejuan , Jiang Huili , Xu Dongmei
Published: February 2019

Background Chronic kidney disease has become a serious public health problem in China. Our study is to explore effect of hydraulic expansion on arteriovenous fistula (AVF) of hemodialysis patients.

Methods A total of 190 patients with end-stage renal disease (ESRD) were randomly divided into hydraulic expansion group (n = 117) and conventional surgery group (n = 73). Age, sex, the cause of ESRD, height, weight, body mass index (BMI), blood pressure, and diameter of artery and vein from ultrasonography before surgery from patients were recorded. Doppler ultrasonography of vessel was performed with a 12-MHz scanning probe for vascular measurements. The time of first cannulation was recorded. Primary and secondary patency rates were compared between the two groups.

Results The mean arterial pressure for this cohort of patients was around 98.12 mm Hg. The mean diameters of artery and vein ready for anastomoses measured by ultrasonography before surgery were 1.96 and 2.04 mm, respectively. Age, weight, BMI, sex ratio, the cause of renal failure, history of catheter insertion, mean arterial pressure, frequency of hemodialysis, blood flow of hemodialysis, and the mode of anastomoses of AVF in conventional surgery group were similar to hydraulic expansion group. There were no differences in stroke volume of radius arterial and venous pressure before dilation between the two groups. The stroke volume of radius artery increased significantly after hydraulic expansion than before dilation and control group. The primary patency rates of AVF in patients with hydraulic expansion were higher significantly than conventional surgery group. The secondary patency rates in conventional surgery group were not different from hydraulic expansion group.

Conclusion Hydraulic expansion showed no difference from conventional surgery in complication after operation, and could decrease the time reliance on catheters and the risk of catheter-related infection, thrombosis, and decrease the related medical care costs.
Three-Dimensional Printing for Chest Wall Reconstruction in Thoracic Surgery: Building on Experience
Authors: Smelt Jeremy , Pontiki Antonia , Jahangiri Marjan , Rhode Kawal , Nair Arjun , Bille Andrea
Published: February 2019

Objectives Patients undergoing surgery for locally advanced lung cancer involving the chest wall require anatomical lung with extensive en-bloc chest wall resection and appropriate reconstruction.

In this proof-of-concept study, we aimed to produce personalized three-dimensional (3D)-printed chest wall prosthesis for a patient undergoing chest wall resection and reconstruction using clinically obtained computed tomography (CT) data.

Methods Preoperative CT scans of three patients undergoing chest wall resection were analyzed and the areas of resection segmented. This was then used to produce a 3D print of the chest wall and a silicone mold was created from the model. This mold was sterilized and used to produce methyl methacrylate prostheses which were then implanted into the patients.

Results Three patients had their chest wall reconstructed using this technique to produce a patient specific prosthesis. There were no early complications or deaths.

Conclusions It is possible to use 3D printing to produce a patient specific chest wall reconstruction for patients undergoing chest wall resection for malignancy that is cost-effective. This chest wall is thought to provide stability in the form of prosthetic ribs as well compliance in the form of an expanded polytetrafluoroethylene patch. Further research is required to measure chest wall compliance during the respiratory cycle and long-term follow-up from this method.
Cryo-EM structure and in vitro DNA packaging of a thermophilic virus with supersized T=7 capsids
Authors: Bayfield Oliver W. , Klimuk Evgeny , Winkler Dennis C. , Hesketh Emma L. , Chechik Maria , Cheng Naiqian , Dykeman Eric C. , Minakhin Leonid , Ranson Neil A. , Severinov Konstantin , Steven Alasdair C. , Antson Alfred A.
Published: February 2019

Double-stranded DNA viruses, including bacteriophages and herpesviruses, package their genomes into preformed capsids, using ATP-driven motors. Seeking to advance structural and mechanistic understanding, we established in vitro packaging for a thermostable bacteriophage, P23-45 of
Thermus thermophilus
. Both the unexpanded procapsid and the expanded mature capsid can package DNA in the presence of packaging ATPase over the 20 °C to 70 °C temperature range, with optimum activity at 50 °C to 65 °C. Cryo-EM reconstructions for the mature and immature capsids at 3.7-Å and 4.4-Å resolution, respectively, reveal conformational changes during capsid expansion. Capsomer interactions in the expanded capsid are reinforced by formation of intersubunit β-sheets with N-terminal segments of auxiliary protein trimers. Unexpectedly, the capsid has T=7 quasi-symmetry, despite the P23-45 genome being twice as large as those of known T=7 phages, in which the DNA is compacted to near-crystalline density. Our data explain this anomaly, showing how the canonical HK97 fold has adapted to double the volume of the capsid, while maintaining its structural integrity. Reconstructions of the procapsid and the expanded capsid defined the structure of the single vertex containing the portal protein. Together with a 1.95-Å resolution crystal structure of the portal protein and DNA packaging assays, these reconstructions indicate that capsid expansion affects the conformation of the portal protein, while still allowing DNA to be packaged. These observations suggest a mechanism by which structural events inside the capsid can be communicated to the outside.
Transition from stochastic events to deterministic ensemble average in electron transfer reactions revealed by single-molecule conductance measurement
Authors: Li Yueqi , Wang Hui , Wang Zixiao , Qiao Yanjun , Ulstrup Jens , Chen Hong-Yuan , Zhou Gang , Tao Nongjian
Published: February 2019

Significance

Electron transfer (ET) is an elementary step in many chemical reactions and biological processes. Measuring ET at the single-molecule level opens new prospects for studying individual reaction steps and heterogeneity in ET. Despite recent advances, the connection between the single-molecule behavior and the ensemble averages remains unclear. By performing direct electrical measurements on ferrocene with variable lengths of molecular linkers, we found that the ET process is stochastic and follows first-order kinetics at the single-molecule level, but ensemble averaging of the single-molecule measurements recovers the thermodynamic behavior. This study provides a framework to connect stochastic single-molecule behavior and deterministic ensemble thermodynamics.
Linkage between retinal ganglion cell density and the nonuniform spatial integration across the visual field
Authors: Kwon MiYoung , Liu Rong
Published: February 2019

Significance

The integration of visual information over space is critical to human pattern vision. For either luminance detection or object recognition, the position of the target in the visual field governs the size of a window within which visual information is integrated. Here we analyze the relationship between the topographic distribution of ganglion cell density and the nonuniform spatial integration across the visual field. We find that the variation in the retinal ganglion cell (RGC) density across the human retina is closely matched to the variation in the extent of spatial integration. Our study suggests that a fixed number of RGCs subserves spatial integration of visual input, independent of the visual-field location.
Ellagic acid affects mRNA expression levels of genes that regulate cholesterol metabolism in HepG2 cells
Authors: Kubota Shizuka , Tanaka Yuma , Nagaoka Satoshi
Published: February 2019

Ellagic acid has been shown to improve cholesterol metabolism in animal studies, but the molecular mechanisms underlying this function have not been fully understood. We performed DNA microarray analysis to elucidate the effects of ellagic acid on cholesterol metabolism in HepG2 hepatocytes. This revealed that the expression levels of several genes related to cholesterol metabolism, including the low-density lipoprotein receptor (LDLR), were changed by ellagic acid treatment. Using a real-time PCR and immunoblot we confirmed that ellagic acid treatment up-regulated mRNA and protein expression level of the LDLR. Moreover, In the presence of 25 μM ellagic acid, extracellular apoB protein and MTP mRNA levels were significantly decreased. These findings indicate that ellagic acid improves cholesterol metabolism through the up-regulation of LDLR, down-regulation of MTP mRNA and reduces extracellular apoB levels. The ellagic acid-induced up-regulation of LDLR occurred via the extracellular signal-regulated kinase (ERK) signaling pathway in HepG2 hepatocytes.

Abbreviations: LDLR: low-density lipoprotein receptor; apoB: apolipoprotein B; PKC: diacylglycerol-protein kinase C; MAPK: mitogen-activated protein kinase; ERK: p42/44 extracellular signal-regulated kinase; JNK: c-Jun N-terminal kinase; VLDLR: very low density lipoprotein receptor; PPARδ: peroxisome proliferator-activated receptor δ; SREBPs: sterol regulatory element-binding proteins; MTP: microsomal triacylglycerol transfer protein; LPDS: lipoprotein-deficient serum
A Regression Tree for Identifying Risk Factors for Fear of Falling: The International Mobility in Aging Study (IMIAS)
Authors: Curcio Carmen-Lucia , Wu Yan Yan , Vafaei Afshin , Barbosa Juliana Fernandez de Souza , Guerra Ricardo , Guralnik Jack , Gomez Fernando
Published: February 2019

Background

We determine the best combination of factors for predicting the risk of developing fear of falling (FOF) in older people via Classification Regression Tree (CaRT) analysis.

Methods

Community-dwelling older adults living in Canada, Albania, Brazil, and Colombia were from International Mobility in Aging Study (IMIAS). In 2014, 1,725 participants (aged 65–74) were assessed. With a retention rate of 81%, in 2016, 1,409 individuals were reassessed. Risk factors for FOF were entered into the CaRT: age, sex, education, self-rated health, comorbidity, medication, visual impairment, frailty, cognitive deficit, depression, fall history, Short Physical Performance Battery (SPPB), walking aid use, and mobility disability measured by the Nagi questionnaire.

Results

The classification tree included 12 end groups representing differential risks of FOF with a minimum of two and a maximum of five predictors. The first split in the tree involved impaired physical function (SPPB scores). Respondents with less than 8 in SPPB score and mobility disability had 82% risk of developing FOF at the end of 2-year follow-up. Between 23.2% and 82.3% of the risk of developing FOF in 2 years of follow-up were explained by only five variables: age, sex, self-rated health, functional impairment measured by SPPB, and mobility disability. In those with no functional impairment or mobility disability, levels of education, sex, and self-rated health were important predictors of FOF in the future.

Conclusion

This classification tree included different groups based on specific combinations of a maximum of five easily measurable predictors with emphasis on impaired physical functioning risk factors for developing FOF.
Rehabilitation After Hip Fracture for Nursing Home Residents: A Controlled Feasibility Trial
Authors: Beaupre Lauren A , Magaziner Jay S , Jones C Allyson , Jhangri Gian S , Johnston D William C , Wilson Donna M , Majumdar Sumit R
Published: February 2019

Background

This study compared functional outcomes at 3 months after hip fracture surgery between nursing home residents participating in a 10-week outreach rehabilitation program and those receiving usual care. Function, health-related quality of life, and mortality were also compared over 12 months, and outreach program feasibility was assessed.

Methods

A feasibility trial was undertaken in Canadian nursing homes; of 77 participants, 46 were allocated to Outreach and 31 to Control prior to assessing function or cognition. Outreach participants received 10 weeks of rehabilitation (30 sessions), and Control participants received usual posthospital fracture care in their nursing homes. The primary outcome was the Functional Independence Measure Physical Domain (FIMphysical) score 3 months post-fracture; we also explored FIM Locomotion and Mobility. Secondary outcomes were FIM scores, EQ-5D-3L scores, and mortality over 12 months. Program feasibility was also evaluated.

Results

The mean age was 88.7 ± 7.0 years, 55 (71%) were female, and 58 (75%) had severe cognitive impairment with no significant group differences (p > .14). Outreach participants had significantly higher FIM Locomotion than usual care (p = .02), but no significant group differences were seen in FIMphysical or FIM Mobility score 3 months post-fracture. In adjusted analyses, Outreach participants reported significant improvements in all FIM and EQ-5D-3L scores compared with Control participants over 12 months (p < .05). Mortality did not differ by group (p = .80). Thirty (65%) Outreach participants completed the program.

Conclusions

Our feasibility trial demonstrated that Outreach participants achieved better locomotion by 3 months post-fracture compared with participants receiving usual postfracture care; benefits were sustained to 12 months post-fracture. In adjusted analyses, Outreach participants also showed sustained benefits in physical function and health-related quality of life.
A User-Friendly Prediction Tool to Identify Colectomy Risk in Patients With Ulcerative Colitis
Authors: Dalal Rahul S , Osterman Mark T , Buchner Anna M , Praestgaard Amy , Lewis James D , Lichtenstein Gary R
Published: February 2019

Background

Many patients with ulcerative colitis (UC) fear the potential side effects of immunosuppressive therapies. However, those with medically refractory disease often require total proctocolectomy (TPC) with a permanent ostomy or pouch, which may reduce quality of life. Prior studies have identified TPC predictors; however, no clinically useful prognostic tools exist to guide shared therapeutic decision-making. We therefore sought to develop a prediction tool of future TPC risk in UC patients.

Methods

In this retrospective study, clinic charts of UC patients were reviewed from January 1, 2017, to December 31, 2017. Cases had TPC performed for refractory UC after January 1, 2008. Controls had no prior UC surgery. Clinical data were assessed 1–12 months preceding TPC or clinic visit for cases and controls, respectively. We randomly selected two-thirds of patients to develop a TPC prediction model using multivariable logistic regression. One-third was reserved for model validation.

Results

We identified 115 cases and 325 controls. TPC predictors included albumin, 9-point Mayo score >5, Mayo endoscopic subscore >1, and corticosteroid use within 6 months. The areas under the receiver operating characteristic curve for the multivariable model were 0.94 (95% confidence interval [CI], 0.92–0.95) and 0.92 (95% CI, 0.89–0.95) for the test and validation cohorts, respectively. The validation cohort demonstrated a significant difference in calculated probability distributions between patients who did and did not have TPC (P < 0.01). We incorporated our model into a web-based application to allow convenient calculation of a patient’s TPC risk.

Conclusions

We created a user-friendly tool to assess TPC risk in UC. Prospective assessment will determine its utility for shared therapeutic decision-making.
Understanding the Family Planning Needs of Female Participants in a Syringe Exchange Program: A Needs Assessment and Pilot Project
Authors: Tschann Mary , Wright Tricia , Lusk Heather , Giorgio Willa , Colon Anaeliz , Kaneshiro Bliss
Published: February 2019

Objectives:

To describe the reproductive health needs of women who inject drugs (WWID) and are participants in a syringe exchange program (SEP) in Hawaii. Our secondary objective was to develop and pilot services in response to those needs.

Methods:

We conducted a reproductive health needs-assessment of women participating in the SEP. We also documented the perspectives and recommendations of key informants who work closely with women in this program. This needs-assessment informed a pilot contraceptive project at the SEP.

Results:

We received surveys from 50 syringe exchange participants and hosted 1 focus group with 6 participants. We completed 8 key informant interviews. The majority of survey respondents indicated that they did not want to become pregnant in the next year, but most were not using a reliable method of contraception. Additionally, for most respondents, prevention of pregnancy was a lower priority than other health and wellness needs. Focus group participants and key informants emphasized the importance of developing a network of accessible providers to address reproductive health needs, and also the importance of using the principles of trauma-informed care when developing a service. We developed a pilot program to offer contraceptive injections at the syringe exchange program. In the first 6 months of offering the service, 1 participant elected to use the injection.

Conclusions:

WWID participating in this SEP may not prioritize their family planning needs when other health and safety needs are unmet. A pilot program to offer contraceptive injections at SEP had almost zero uptake.
Bundled Care for Hip Fractures: A Machine-Learning Approach to an Untenable Patient-Specific Payment Model
Authors: Karnuta Jaret M. , Navarro Sergio M. , Haeberle Heather S. , Billow Damien G. , Krebs Viktor E. , Ramkumar Prem N.
Published: February 2019

Objectives:

With the transition to a value-based model of care delivery, bundled payment models have been implemented with demonstrated success in elective lower extremity joint arthroplasty. Yet, hip fracture outcomes are dependent on patient-level factors that may not be optimized preoperatively due to acuity of care. The objectives of this study are to (1) develop a supervised naive Bayes machine-learning algorithm using preoperative patient data to predict length of stay and cost after hip fracture and (2) propose a patient-specific payment model to project reimbursements based on patient comorbidities.

Methods:

Using the New York Statewide Planning and Research Cooperative System database, we studied 98,562 Medicare patients who underwent operative management for hip fracture from 2009 to 2016. A naive Bayes machine-learning model was built using age, sex, ethnicity, race, type of admission, risk of mortality, and severity of illness as predictive inputs.

Results:

Accuracy was demonstrated at 76.5% and 79.0% for length of stay and cost, respectively. Performance was 88% for length of stay and 89% for cost. Model error analysis showed increasing model error with increasing risk of mortality, which thus increased the risk-adjusted payment for each risk of mortality.

Conclusions:

Our naive Bayes machine-learning algorithm provided excellent accuracy and responsiveness in the prediction of length of stay and cost of an episode of care for hip fracture using preoperative variables. This model demonstrates that the cost of delivery of hip fracture care is dependent on largely nonmodifiable patient-specific factors, likely making bundled care an implausible payment model for hip fractures.
New Five-Factor Modified Frailty Index Predicts Morbidity and Mortality in Geriatric Hip Fractures
Authors: Traven Sophia A. , Reeves Russell A. , Althoff Alyssa D. , Slone Harris S. , Walton Zeke J.
Published: February 2019

Introduction:

Although the 11-factor modified frailty index (mFI-11) has been shown to predict adverse outcomes in elderly patients undergoing surgery for hip fractures, the newer 5-factor index has not been evaluated in this population. The goal of this study is to evaluate the mFI-5 as a predictor of morbidity and mortality in elderly patients undergoing surgical management for hip fractures.

Methods:

The NSQIP database was queried for patients 60 years of age and older who underwent surgical management for hip fractures between 2005 and 2016. The 5-factor score, which comprised diabetic status, history of COPD or current pneumonia, congestive heart failure, hypertension requiring medication, and nonindependent functional status, was calculated for each patient. Multivariate logistic regression models were used to assess the relationship between the mFI-5 and 30-day postoperative complications.

Results:

A total of 58,603 patients were identified. After adjusting for comorbidities, the mFI-5 was a strong predictor for total complications, serious medical complications (cardiac arrest, myocardial infarction, septic shock, pulmonary embolism, postoperative dialysis, reintubation, and prolonged ventilator requirement), surgical site infections, readmission, extended hospital length of stay, and mortality (P ≤ 0.008). For each point increase, the risk for any complication increased by 29.8%, serious medical complications 35.4%, surgical site infections 14.7%, readmission 24.6%, and mortality 33.7%.

Conclusions:

The mFI-5 is an independent predictor of postoperative morbidity and mortality in elderly patients undergoing surgery for hip fractures. This clinical tool can be used by hospitals and surgeons to identify high-risk patients, accurately council patients and families with transparency, and guide perioperative care to optimize patient outcomes.

Level of Evidence:

Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Targeting CD39 Toward Activated Platelets Reduces Systemic Inflammation and Improves Survival in Sepsis: A Preclinical Pilot Study*
Authors: Granja Tiago , Körner Andreas , Glück Christian , Hohmann Jan David , Wang Xiaowei , Köhler David , Streißenberger Ariane , Nandurkar Harshal H. , Mirakaj Valbona , Rosenberger Peter , Peter Karlheinz , Straub Andreas
Published: February 2019

Objectives:

Sepsis is associated with a systemic inflammatory reaction, which can result in a life-endangering organ dysfunction. Pro-inflammatory responses during sepsis are characterized by increased activation of leukocytes and platelets, formation of platelet-neutrophil aggregates, and cytokine production. Sequestration of platelet-neutrophil aggregates in the microvasculature contributes to tissue damage during sepsis. At present no effective therapeutic strategy to ameliorate these events is available. In this preclinical pilot study, a novel anti-inflammatory approach was evaluated, which targets nucleoside triphosphate hydrolase activity toward activated platelets via a recombinant fusion protein combining a single-chain antibody against activated glycoprotein IIb/IIIa and the extracellular domain of CD39 (targ-CD39).

Design:

Experimental animal study and cell culture study.

Setting:

University-based experimental laboratory.

Subjects:

Human dermal microvascular endothelial cells 1, human platelets and neutrophils, and C57BL/6NCrl mice.

Interventions:

Platelet-leukocyte-endothelium interactions were evaluated under inflammatory conditions in vitro and in a murine lipopolysaccharide-induced sepsis model in vivo. The outcome of polymicrobial sepsis was evaluated in a murine cecal ligation and puncture model. To evaluate the anti-inflammatory potential of activated platelet targeted nucleoside triphosphate hydrolase activity, we employed a potato apyrase in vitro and in vivo, as well as targ-CD39 and as a control, nontarg-CD39 in vivo.

Measurements and Main Results:

Under conditions of sepsis, agents with nucleoside triphosphate hydrolase activity decreased platelet-leukocyte-endothelium interaction, transcription of pro-inflammatory cytokines, microvascular platelet-neutrophil aggregate sequestration, activation marker expression on platelets and neutrophils contained in these aggregates, leukocyte extravasation, and organ damage. Targ-CD39 had the strongest effect on these variables and retained hemostasis in contrast to nontarg-CD39 and potato apyrase. Most importantly, targ-CD39 improved survival in the cecal ligation and puncture model to a stronger extent then nontarg-CD39 and potato apyrase.

Conclusions:

Targeting nucleoside triphosphate hydrolase activity (CD39) toward activated platelets is a promising new treatment concept to decrease systemic inflammation and mortality of sepsis. This innovative therapeutic approach warrants further development toward clinical application.
Central Venous Access Capability and Critical Care Telemedicine Decreases Inter-Hospital Transfer Among Severe Sepsis Patients: A Mixed Methods Design
Authors: Ilko Steven A. , Vakkalanka J. Priyanka , Ahmed Azeemuddin , Harland Karisa K. , Mohr Nicholas M.
Published: February 2019

Objectives:

Severe sepsis is a complex, resource intensive, and potentially lethal condition and rural patients have worse outcomes than urban patients. Early identification and treatment are important to improving outcomes. The objective of this study was to identify hospital-specific factors associated with inter-hospital transfer.

Design:

Mixed method study integrating data from a telephone survey and retrospective cohort study of state administrative claims.

Setting and Subjects:

Survey of Iowa emergency department administrators between May 2017 and June 2017 and cohort of adults seen in Iowa emergency departments for severe sepsis and septic shock between January 2005 and December 2013.

Interventions:

None.

Measurements and Main Results:

Multivariable logistic regression was used to identify independent predictors of inter-hospital transfer. We included 114 institutions that provided data (response rate = 99%), and responses were linked to a total of 150,845 visits for severe sepsis/septic shock. In our adjusted model, having the capability to place central venous catheters or having a subscription to a tele-ICU service was independently associated with lower odds of inter-hospital transfer (adjusted odds ratio, 0.69; 95% CI, 0.54–0.86 and adjusted odds ratio, 0.69; 95% CI, 0.54–0.88, respectively). A facility’s participation in a sepsis-specific quality improvement initiative was associated with 62% higher odds of transfer (adjusted odds ratio, 1.62; 95% CI, 1.10–2.39).

Conclusions:

The insertion of central venous catheters and access to a critical care physician during sepsis treatment are important capabilities in hospitals that transfer fewer sepsis patients. In the future, hospital-specific capabilities may be used to identify institutions as regional sepsis centers.
Reflective Practice for Patient Benefit: An Analysis of Doctors' Appraisal Portfolios in Scotland
Authors: Wakeling Judy , Holmes Sarah , Boyd Alan , Tredinnick-Rowe John , Cameron Niall , Marshall Martin , Bryce Marie , Archer Julian
Published: February 2019

Introduction:

Reflective practice has become the cornerstone of continuing professional development for doctors, with the expectation that it helps to develop and sustain the workforce for patient benefit. Annual appraisal is mandatory for all practicing doctors in the United Kingdom as part of medical revalidation. Doctors submit a portfolio of supporting information forming the basis of their appraisal discussion where reflection on the information is mandated and evaluated by a colleague, acting as an appraiser.

Methods:

Using an in-depth case study approach, 18 online portfolios in Scotland were examined with a template developed to record the types of supporting information submitted and how far these showed reflection and/or changes to practice. Data from semistructured interviews with the doctors (n = 17) and their appraisers (n = 9) were used to contextualize and broaden our understanding of the portfolios.

Results:

Portfolios generally showed little written reflection, and most doctors were unenthusiastic about documenting reflective practice. Appraisals provided a forum for verbal reflection, which was often detailed in the appraisal summary. Portfolio examples showed that reflecting on continued professional development, audits, significant events, and colleague multisource feedback were sometimes considered to be useful. Reflecting on patient feedback was seen as less valuable because feedback tended to be uncritical.

Discussion:

The written reflection element of educational portfolios needs to be carefully considered because it is clear that many doctors do not find it a helpful exercise. Instead, using the portfolio to record topics covered by a reflective discussion with a facilitator would not only prove more amenable to many doctors but would also allay fears of documentary evidence being used in litigation.
Pregnancy with successful foetal and maternal outcome in a melanoma patient treated with nivolumab in the first trimester: case report and review of the literature
Authors: Xu Wen , Moor Rebecca J. , Walpole Euan T. , Atkinson Victoria G.
Published: February 2019

Although T-cell checkpoint blockade has revolutionized melanoma therapy, metastatic melanoma in pregnancy remains a challenging area of unmet need. Treatment with anti-PD1 therapy decreases foetal–maternal tolerance and increases the risk of pregnancy loss in animal studies and is considered category D by the Food and Drug Administration. We describe a unique case of conception and pregnancy, with successful maternal and foetal outcomes, in a patient with metastatic melanoma who had received combination anti-CTLA-4 and anti-PD1 therapy. A 32-year-old G0P0 lady, with a 10-year history of infertility of unclear cause, was found to be 7 weeks pregnant after 14 months of nivolumab maintenance therapy, having previously received combination ipilimumab and nivolumab. Nivolumab was ceased upon discovery of pregnancy in the first trimester. The patient had an uneventful pregnancy, followed by spontaneously premature labour, and delivered by caesarean section at 33 weeks’ gestation. The foetus had moderate intrauterine growth restriction, as well as congenital hypothyroidism, which possibly constitutes the first documented case of foetal immune-related adverse event from maternal anti-PD1 exposure. No adverse events were noted in the mother. At 6 months of follow-up postpartum, the mother had a sustained complete response to treatment, and the baby had appropriate weight gain with normal developmental milestones. We summarize and discuss the available literature of immune checkpoint inhibitor exposure in pregnancy, which consists of a total of three case reports.
Parent-Child Interaction Therapy for Children with Developmental Delay: The Role of Sleep Problems
Authors: Acosta Juliana , Garcia Dainelys , Bagner Daniel M.
Published: February 2019

Objective:

Sleep problems are common and associated with externalizing behavior problems in young children, particularly among young children with developmental delay (DD). The aims of the current study, which was a secondary data analysis of 2 previously conducted randomized controlled trials, were to assess whether parent-child interaction therapy (PCIT) led to decreases in child sleep problems and whether initial sleep problems moderated the effect of PCIT on child behavior.

Methods:

The study participants were 44 children (M = 49.19 months, SD = 13.1) with DD or borderline DD and with co-occurring clinically significant levels of externalizing behavior problems and their mothers (M = 35.9 years, SD = 7.3). These participants were randomly assigned to either an immediate treatment group or a waitlist control group.

Results:

Findings revealed a significant direct effect of PCIT on decreases in sleep problems. Additionally, moderation analyses revealed that lower levels of child sleep problems at pretreatment were associated with greater improvements in observed child compliance compared with higher levels of child sleep problems at pretreatment.

Conclusion:

This study extends previous findings by providing support for the preliminary efficacy of PCIT in reducing sleep problems in children with DD and borderline DD and highlighting the role of sleep problems as a factor associated with differential treatment effects in behavioral parenting intervention research.
Is the Pathologic Response of T3 Rectal Cancer to High-Dose-Rate Endorectal Brachytherapy Comparable to External Beam Radiotherapy?
Authors: Garfinkle Richard , Lachance Sebastian , Vuong Te , Mikhail Alexandre , Pelsser Vincent , Gologan Adrian , Morin Nancy A. , Vasilevsky Carol-Ann , Boutros Marylise
Published: February 2019

BACKGROUND:

Endorectal brachytherapy is an attractive option in the neoadjuvant setting for locally advanced rectal cancer, but it is not considered standard of care.

OBJECTIVE:

This study aimed to compare pathologic outcomes of patients with clinical T3 rectal cancer who underwent high-dose-rate endorectal brachytherapy with those who underwent conventional external beam radiotherapy.

DESIGN:

This study is a retrospective chart review.

SETTINGS:

This study was conducted in a single large tertiary academic colorectal surgery practice in Canada.

PATIENTS:

Adult patients with MRI-staged T3 rectal adenocarcinoma treated with neoadjuvant radiotherapy followed by total mesorectal excision from 2007 to 2016 were included.

INTERVENTIONS:

Neoadjuvant radiotherapy was delivered by high-dose-rate endorectal brachytherapy or conventional external beam radiotherapy.

MAIN OUTCOME MEASURES:

Primary outcome was pathologic complete response, defined as ypT0N0. Secondary outcomes included tumor (T stage) and lymph node (N stage) downstaging and tumor regression grade.

RESULTS:

Ninety-nine patients were identified as having clinical T3 rectal cancer based on blinded pretreatment MRI review. Mean age was 66.2 years (± 6.2) and 59 patients (59.6%) were male. Thirty-three patients were clinically node negative (33.3%), 45 had c-N1 disease (45.5%), and 21 had c-N2 disease (21.2%). Sixty-four patients (64.6%) underwent high-dose-rate endorectal brachytherapy and 35 (35.4%) underwent external beam radiotherapy. The high-dose-rate endorectal brachytherapy group had a lower median mesorectal depth of invasion (4 mm vs 5 mm, p = 0.010); all other preoperative tumor characteristics were similar in both groups. Eighteen patients (18.2%) achieved pathologic complete response: 12 in the high-dose-rate endorectal brachytherapy group and 6 in the conventional external beam radiotherapy group (18.8% vs 17.1%, p = 0.84). High-dose-rate endorectal brachytherapy was superior to conventional radiotherapy for tumor (T stage) downstaging (59.4% vs 28.6%, p = 0.0030) but not for lymph node (N stage) downstaging (35.9% vs 51.4%, p = 0.14).

LIMITATIONS:

This study was limited by its retrospective nature and modest sample size.

CONCLUSIONS:

Neoadjuvant treatment of T3 rectal cancer with high-dose-rate endorectal brachytherapy appears to achieve equivalent rates of pathologic complete response and superior T-stage downstaging compared with conventional external beam radiotherapy. See Video Abstract at http://links.lww.com/DCR/A905.
Laparoscopic Mesorectal Excision in Obesity: Novel Insights and Technical Strategies
Authors: Ng Jia Lin , Kajohnwongsatit Krittin , Sahakitrungruang Chucheep
Published: February 2019

INTRODUCTION:

Obesity is a burgeoning problem worldwide. Although beneficial in obese patients, conventional laparoscopic mesorectal excision for rectal cancer is technically challenging, with a higher conversion rate to open compared with nonobese patients. We describe novel strategies to circumvent these difficulties.

TECHNIQUE:

The key steps are 1) lateral-to-medial colonic mobilization and left-sided mesorectal excision with the surgeon on the patient’s right; 2) switching to the patient’s left for right-sided mesorectal excision; 3) further rectal retraction with cotton tape and preperitoneal fat sling; and 4) caudal-to-cephalad mobilization of colon after distal transection, which facilitates extrapelvic mesenteric dissection and vessel ligation.

RESULTS:

These techniques optimize gravity to negate the lack of exposure due to visceral obesity. Triangulation is improved by changing the surgeon’s position during mesorectal dissection. This allows accurate identification of anatomical planes and avoids excessive pneumoperitoneum pressures and Trendelenburg tilt.

CONCLUSIONS:

Adopting these strategies can facilitate laparoscopic mesorectal excision in the obese patient and may reduce conversion to open.
A Diagnostic Challenge: Changes in Histopathologic Tumor Diagnosis of Atypical Squamous Proliferations After Surgical Removal
Authors: Rubin Ashley G. , Brian Jiang Shang I.
Published: February 2019

BACKGROUND

Biopsy-proven “atypical squamous proliferations” (ASPs) may prove difficult to diagnose histologically because of partial sampling, lack of complete criteria for definitive diagnosis, or overlap of histopathological features with other neoplasms. There are no guidelines concerning the management of ASPs.

OBJECTIVE

To retrospectively clarify the diagnosis of biopsy-proven ASPs after surgical removal, specifically, to ascertain what fraction represent malignant tumors.

METHODS

Medical records of patients who underwent surgical removal of biopsy-proven ASPs in an academic dermatologic surgical unit from June 2008 to July 2013 were examined. The resultant histopathologic diagnosis of these lesions after surgical removal, along with other demographic data, was obtained.

RESULTS

Of the 71 biopsy-proven ASPs that were treated by surgical removal in the study period, 54.9% exhibited resultant pathologic diagnosis of nonmelanoma skin cancer (NMSC).

CONCLUSION

Biopsy-proven ASPs present a therapeutic challenge. The authors' data illustrate the importance of subsequent tissue sampling, as these lesions often represent NMSCs.
Assessment of Skin Physiology Change and Safety After Intradermal Injections With Botulinum Toxin: A Randomized, Double-Blind, Placebo-Controlled, Split-Face Pilot Study in Rosacea Patients With Facial Erythema
Authors: Kim Min Jung , Kim Jin Hee , Cheon Hye In , Hur Min Seok , Han Song Hee , Lee Yang Won , Choe Yong Beom , Ahn Kyu Joong
Published: February 2019

BACKGROUND

Botulinum toxin (BTX) has been used cosmetically with good clinical efficacy and tolerable safety.

OBJECTIVE

This randomized, double-blind, split-face clinical study aimed to investigate the efficacy and safety of intradermal BTX in patients with rosacea.

MATERIALS AND METHODS

Twenty-four participants were enrolled and randomly given intradermal injections of BTX and normal saline in both cheeks. Clinician Erythema Assessment (CEA) score, Global Aesthetic Improvement Scale (GAIS) score, skin hydration, transepidermal water loss (TEWL), melanin content, erythema index, elasticity, and sebum secretions were evaluated at baseline and 2, 4, 8, and 12 weeks.

RESULTS

On the BTX-treated side, the CEA score significantly decreased and the GAIS score significantly increased. The erythema index decreased at Weeks 4 and 8. Skin elasticity was improved at Weeks 2 and 4 and skin hydration, at Weeks 2, 4, and 8. However, TEWL and sebum secretion did not show significant differences.

CONCLUSION

Intradermal BTX injections reduced erythema and rejuvenated the skin effectively and safely in patients with rosacea.
TOXIC POSTERIOR SEGMENT SYNDROME AFTER DROPLESS CATARACT SURGERY WITH COMPOUNDED TRIAMCINOLONE-MOXIFLOXACIN
Authors: Patel Sagar B. , Reddy Nikitha K. , He Yu-Guang
Published: February 2019

Purpose:

To report toxic posterior segment syndrome after dropless cataract surgery using locally compounded triamcinolone-moxifloxacin.

Methods:

A retrospective case review of 7 patients presenting with a decrease in visual acuity after dropless cataract surgery.

Results:

All patients experienced significant reductions in best-corrected visual acuity of the postoperative eye ranging from 20/40 to count finger at 4 feet (average best-corrected visual acuity 20/220) immediately after surgery. The presenting symptoms included flashes, floaters, photophobia, glare, halos, visual distortions, and problems assessing colors. In three cases, foveal retinal pigment epithelium changes were noted on dilated fundus exam (DFE). Ellipsoid zone loss was noted on ocular coherence tomography in five of the seven affected eyes. Electrophysiology testing in five of the seven affected eyes demonstrated large decreases in full-field electroretinogram amplitude, oscillatory potentials, multifocal electroretinogram, and visual evoked potential, along with a negative electroretinogram. One patient was treated with a dexamethasone implant, but no improvement in visual acuity was noted.

Conclusion:

This is the first case series of toxic posterior segment syndrome occurring secondary to intracameral compounded triamcinolone-moxifloxacin in dropless cataract surgery. The FDA has attributed the toxicity to abnormally high levels of the binding agent poloxamer 407 in the compounded medication. Clinicians should be aware of this phenomenon and exhibit caution when using compounded medications.
OCULAR ADVERSE EVENTS ASSOCIATED WITH MEK INHIBITORS
Authors: Méndez-Martínez Silvia , Calvo Pilar , Ruiz-Moreno Oscar , Pardiñas Barón Nieves , Leciñena Bueno Jesús , Gil Ruiz María del Rocío , Pablo Luis
Published: February 2019

Purpose:

Mitogen-activates protein kinase (MAPK) inhibitors, particularly MEK inhibitors, have shifted the treatment paradigm for metastatic BRAF-mutant cutaneous melanoma; however, oncologists, ophthalmologists, and patients have noticed different toxicities of variable importance. This review aims to provide an update of the ocular adverse events (OAEs), especially retinal toxicity, associated with the use of MEK inhibitors.

Methods:

We conducted a scientific literature search using the PubMed database up to July 2018 with the terms “MEK inhibitors” with a “review” filter and “MEK inhibitors” with a “clinical trials” filter. Phase I–III experimental studies and reviews were selected. Current principles and techniques for diagnosing and managing MEK inhibitor retinopathy and other OAEs are discussed.

Results:

In patients treated with MEK inhibitors, including asymptomatic patients, OAEs occur with an incidence of up to 90%. Mild to severe ophthalmic toxicities are described, including visual disturbances, a 2-line decrease in Snellen visual acuity, dry eye symptoms, ocular adnexal abnormalities, visual field defects, panuveitis, and retinal toxicities, such as different degrees of MEK-associated retinopathy, vascular injury, and retinal vein occlusion.

Conclusion:

MEK inhibitors can lead to different degrees of retinal, uveal, and adnexal OAE, causing visual disturbances or discomfort. One of the most relevant OAE of MEK therapy is MEK inhibitor–associated retinopathy (MEKAR), which is usually mild, self-limited, and may subside after continuous use of the drug for weeks or months, or discontinuation, thereby restoring the normal visual function of the retina, with some exceptions. Ocular adverse events are often associated with other systemic adverse effects that can modify the dosage of treatment, so the communication with the oncologist is fundamental.