Citations

Sepsis in patients with cirrhosis is associated with high mortality. An impaired immune response accounts for the increased infection risk observed in these patients. Hemodynamic and systemic changes suggestive of sepsis may be observed in patients with cirrhosis in the absence of infection; therefore, diagnosis and treatment of sepsis may be delayed. The optimal management of the critically ill patient with sepsis and cirrhosis has not been well established and is generally extrapolated from consensus guidelines and expert recommendations made for management of patients without cirrhosis with sepsis. Despite the lack of strong evidence, we propose a contemporary pragmatic approach to sepsis management in patients with cirrhosis, including the choice of fluids, vasopressors, and antibiotics.

Background: The association between quadriceps strength and functional outcomes after anterior cruciate ligament reconstruction (ACLR) is a focus of current research, while evaluations of hamstring strength are limited, despite the frequent use of hamstring autografts. Purpose/Hypothesis: The purpose of this study was to determine the relationship between changes in quadriceps and hamstring strength symmetry and self-reported outcomes before ACLR and at 12 and 24 weeks after surgery. We hypothesized that improvements in quadriceps and hamstring strength symmetry would be correlated with improvements in self-reported outcome measures within the first 6 months after ACLR. Study Design: Cohort study; Level of evidence, 2. Methods: Thirty patients who underwent ACLR with a hamstring autograft were enrolled. Quadriceps and hamstring strength and Knee injury and Osteoarthritis Outcome Score (KOOS) values were assessed before and at 12 and 24 weeks after ACLR; limb symmetry indexes for strength were calculated at each time point. The Friedman and Wilcoxon signed-rank tests were used to analyze changes in KOOS values over time. Spearman rank-order correlations were used to test the relationship between changes in strength and KOOS values between each time point. Results: Hamstring and quadriceps limb symmetry significantly increased with time ( P ≤ .03). Fair correlations were observed between changes in the hamstring index and changes in the KOOS Symptoms subscore from before surgery to 12 weeks postoperatively ( r = 0.48; P ≤ .05). Changes in the quadriceps index (QI) were moderately correlated with changes in the KOOS Sport/Recreation subscore ( r = 0.60; P = .001), and fair correlations were seen between the QI and the KOOS Quality of Life subscore ( r = 0.39; P ≤ .04) from preoperatively to 12 weeks after surgery. Moderate correlations were seen between the QI and the KOOS Sport/Recreation subscore ( r = 0.57; P = .005) from 12 to 24 weeks after surgery. Conclusion: Improvements in quadriceps and hamstring strength symmetry were modestly associated with improvements in athletes’ perceived function in the first 6 months after ACLR. Specifically, improvements in hamstring symmetry were associated with improvements in knee symptoms within the first 12 weeks postoperatively, while improvements in quadriceps symmetry were associated with improvements in self-reported sport function throughout the first 6 months after ACLR. The restoration of strength symmetry within the first 6 months may be a critical component of rehabilitation aimed at maximizing function after ACLR. Further investigation is warranted to comprehensively evaluate whether the timing of strength gains predicts future function, including those who successfully return to their preinjury activity level after ACLR.

ABSTRACT The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell‐released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV‐associated functional activities. Finally, a checklist is provided with summaries of key points.

Behavioral and psychological symptoms of dementia (BPSD) have varied presentations and frequently occur throughout the trajectory of dementia. Hypersexuality and general disinhibition of societal and cultural norms are commonly documented in all types of dementia. However, sparse literature exists on polyembolokoilamania (insertion of foreign objects in bodily orifices) without a sexual component as a dementia-related symptom. We review an unusual case of a 94-year-old man who presented with urethral polyembolokoilamania without hypersexuality or other behavioral disinhibition. We highlight clinical considerations of managing urethral polyembolokoilamania in an elderly patient without a previous neurocognitive disorder diagnosis. A multidisciplinary team approach with input from Internal Medicine, Urology, Psychiatry, and Neurology lead to a comprehensive assessment of a patient that could have been managed solely as a surgical case. This spearheaded a formal diagnosis of neurocognitive disorder—guiding successful management, follow-up, caregiver education, and reduction of further harm.

Purpose: To analyze and provide an overview of the incidence, management, and prevention of conjunctival erosion in Argus II clinical trial subjects and postapproval patients. Methods: This retrospective analysis followed the results of 274 patients treated with the Argus II Retinal Prosthesis System between June 2007 and November 2017, including 30 subjects from the US and European clinical trials, and 244 patients in the postapproval phase. Results were gathered for incidence of a serious adverse event, incidence of conjunctival erosion, occurrence sites, rates of erosion, and erosion timing. Results: Overall, 60% of subjects in the clinical trial subjects versus 83% of patients in the postapproval phase did not experience device- or surgery-related serious adverse events. In the postapproval phase, conjunctival erosion had an incidence rate of 6.2% over 5 years and 11 months. In 55% of conjunctival erosion cases, erosion occurred in the inferotemporal quadrant, 25% in the superotemporal quadrant, and 20% in both. Sixty percent of the erosion events occurred in the first 15 months after implantation, and 85% within the first 2.5 years. Conclusion: Reducing occurrence of conjunctival erosion in patients with the Argus II Retinal Prosthesis requires identification and minimization of risk factors before and during implantation. Implementing inverted sutures at the implant tabs, use of graft material at these locations as well as Mersilene rather than nylon sutures, and accurate Tenon's and conjunctiva closure are recommended for consideration in all patients.

Objectives: Preclinical studies demonstrated antitumor activity of dovitinib in pancreatic cancer models. This phase Ib study aimed to determine the maximum tolerated dose (MTD) of dovitinib in combination with gemcitabine and capecitabine and to characterize the safety and pharmacokinetic profile in patients with advanced pancreatic and biliary tract cancers and solid malignancies. Materials and Methods: Patients received gemcitabine 1000 mg/m² intravenously on days 1 and 8, capecitabine 1300 mg/m² oral daily from day 1 to 14, and dovitinib oral daily 5 days on and 2 days off, every 21-day cycle. The standard 3+3 dose escalation design was utilized and the study expanded to treat an additional 20 advanced pancreatic and biliary tract cancers patients at MTD. Results: A total of 29 patients were enrolled. One patient experienced dose-limiting grade 3 colitis. Two patients developed clinically significant neuropathy after the first cycle requiring dose reduction. The MTD was not reached and dovitinib 300 mg was declared the recommended dose for expansion. The most frequent grade 2 or worse adverse events were fatigue (45%), neutropenia (41%), thrombocytopenia (34%), anemia (24%), nausea (24%), and palmer-plantar erythrodysaesthesia syndrome (21%). Partial responses were observed in 5 patients. Pharmacokinetic studies showed no drug-drug interaction between dovitinib, capecitabine and gemcitabine. Fibroblast growth factor 23 plasma level increased in 4 of 5 patients during the first cycle of treatment. Conclusions: Dovitinib 300 mg daily is the recommended dose when combined with gemcitabine and capecitabine, achieving clinically relevant plasma concentrations. The study combination demonstrated encouraging efficacy signals in advanced pancreatic cancer.

Abstract Nonalcoholic steatohepatitis (NASH) is a growing indication for liver transplant whether the primary or secondary cause of liver disease, and it is expected to be the leading indication in the years to come. Nonalcoholic steatohepatitis recurs after transplant but the impact of the recurrence on allograft and patient outcomes is unclear. A group of multidisciplinary transplant practice providers convened at the International Liver Transplantation Society NASH consensus conference with the purpose of determining the current knowledge and future directions for understanding the recurrence rates, risk and management of NASH in the transplant allograft. Specific questions relating to posttransplant NASH were proposed and reviewed in detail with recommendations on future actions to fill the knowledge gaps.