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Objectives Epithelial ovarian cancer (EOC) is a heterogeneous, essentially peritoneal disease. Standard treatment consists of staging, cytoreductive surgery (CRS), and adjuvant chemotherapy. In this study, we intended to assess the effectiveness of single-dose intraperitoneal (IP) chemotherapy in optimally debulked advanced EOC patients. Materials and Methods A prospective randomized study of 87 patients with advanced EOC was done from January 2017 to May 2021 in a tertiary care center. Patients who underwent primary and interval cytoreduction received a single dose of IP chemotherapy for 24 hours after being divided into four groups: group A, IP cisplatin; group B, IP paclitaxel; group C, IP paclitaxel and cisplatin; and group D, saline. Pre- and postperitoneal IP cytology was assessed along with possible complications. Statistical Analysis Logistic regression analysis was used to assess for intergroup significance in cytology and complications. Kaplan–Meir analysis was done to assess disease-free survival (DFS). Results Of 87 patients, 17.2% of patients had FIGO stage IIIA, 47.2% had IIIB, and 35.6% had IIIC. Also, 22 (25.3%) patients were in group A (cisplatin), 22 (25.3%) patients in group B (paclitaxel), 23 (26.4%) in group C (cisplatin and paclitaxel), and 20 (23%) in group D (saline). Cytology samples taken during staging laparotomy were positive, and 48 hours post-IP chemotherapy, 2 (9%) of 22 samples in cisplatin group and 14 (70%) of 20 samples in saline group were positive; all of the post-IP samples in groups B and C were negative. No major morbidity was noted. In our study, DFS in saline group was 15 months, while in IP chemotherapy group it was 28 months and was statistically significant based log-rank test. However, there was no significant difference in DFS between different IP chemotherapy groups. Conclusion Complete or optimal CRS in advanced EOC does have a possibility of microscopic peritoneal residue. Adjuvant locoregional strategies should be considered to prolong DFS. Single-dose normothermic IP chemotherapy can be offered to the patients with minimal morbidity, and its prognostic benefits are comparable to hyperthermic IP chemotherapy. Future clinical trials are required to validate these protocols.

Background Burnout is common among physicians and physician leaders, including residency program directors (PDs). The effects of the COVID-19 pandemic and other stressors in 2020 on PDs is unknown. Objective To measure the prevalence of burnout among internal medicine (IM) residency PDs 6 months into the COVID-19 pandemic. Methods A total of 429 IM PDs, representing 83% of accredited residency programs, were surveyed from August to December 2020. Burnout, using a 2-item screening tool, and self-reported consideration of resigning in 2020, were compared to their annual prevalence since 2012 and tested for possible associations with pandemic stressors and program characteristics. Results The survey response rate was 61.5% (264 of 429). One-third (33.6%, 87 of 259) of PD respondents met burnout criteria, and 45.1% (110 of 244) reported considering resigning in the past year, which were within the range of preceding years. PDs who reported feeling highly supported by institutional leadership were less likely to meet burnout criteria and to have considered resigning. There were no associations between burnout or consideration of resigning and the amount of clinical time PDs spent in their roles, duration of maximum stress on programs, budget cuts to programs, or geographic region. Conclusions The prevalence of burnout among PDs in fall 2020 was similar to the prevalence of burnout in pre-pandemic years despite uniquely extreme stressors. PDs' perception of being highly supported by institutional leadership was associated with lower prevalence of burnout and consideration of resigning. Perceived leadership support may be a protective factor against burnout during periods of high stress.

Introduction Research shows autologous chondrocyte implantation (ACI) is a promising treatment for articular cartilage lesions. In this study, we assessed mid-term efficacy and safety of gel-based ACI or autologous adult live cultured chondrocytes (CARTIGROW®) implantation in patients with cartilage defects of the knee joint. Methods In this prospective, open-label study, patients (19–38 years) with focal, international cartilage repair society grade III or IV articular cartilage defects of the knee joint were enroled at four centres across India from April 2015 to September 2015. Punch biopsy was conducted to harvest cartilage, from which chondrocytes were isolated and cultured, and the characterised chondrocytes were implanted into the cartilage defect. Key efficacy outcomes were assessed by quantitative changes in international knee documentation committee (IKDC), visual analogue scale (VAS) scores, and qualitative changes in magnetic resonance imaging at six months and four years from baseline. Results Of the14 patients enroled in the study, all patients completed the six month follow-up and 11 completed the four year follow-up. The IKDC score improved significantly from 32.84 ± 9.25 at baseline to 67.49 ± 13.03 at six months (mean difference [MD] 34.66 ± 13.00, p p = 0.0001). The VAS score reduced from 72.00 ± 14.40 at baseline to 16.64 ± 17.03 at six months (MD 55.36 ± 24.50, p p Conclusion Autologous adult live cultured chondrocytes (CARTIGROW®) implantation showed good mid-term efficacy in patients with cartilage defects of the knee joint with no side-effects.

Background Peripheral arterial disease (PAD) of lower extremities comprises a clinical spectrum that extends from asymptomatic patients to critical limb ischemia (CLI) patients. 10% to 40% of the patients are at the risk of primary amputation. This study was planned in “no-option” patients of CLI due to atherosclerotic PAD to assess the efficacy and safety of pooled, allogeneic, adult human bone marrow-derived mesenchymal stromal cells which is already approved for marketing in India for CLI due to Buerger’s disease. Methods This was a single-arm, multi-centric, phase III study where mesenchymal stromal cells was injected as 2 million cells/kg body weight in the calf muscle and around the ulcer. Twenty-four patients of lower extremity CLI due to PAD with Rutherford III-5 or III-6 and ankle–brachial pressure index ≤ 0.6 and having have at least one ulcer with area between 0.5 and 10 cm2 were included in the study. These patients were evaluated over 12 months from drug administration. Results Over a period of 12 months, statistical significant reduction of rest pain and ulcer size along with improvement in ankle–brachial pressure index and ankle systolic was observed. The quality of life of patients improved together with increase in total walking distance and major amputation-free survival time. Conclusion Mesenchymal stromal cells may be a feasible option to treat “no-option” patients with atherosclerotic PAD. Trial registration This study is registered prospectively in National Institutes of Health and Clinical Trials Registry—India (CTRI) website: CTRI/2018/06/014436. Registered 6th June 2018. http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=24050&EncHid=&userName=stempeutics.

OBJECTIVE As Ambulatory Surgical Centers (ASCs) become more common in academic medical centers, large hospital systems must determine how to shift resident education from inpatient to outpatient surgical centers. This study aims to define stakeholders’ views regarding the integration of surgical residents into ASCs. DESIGN Long-form interviews lasting 30 to 60 minutes were conducted. Interviews were hand-transcribed and analyzed by qualitative analysis to determine benefits of learning in ASCs for residents, challenges that arise from integrating residents, and recommendations to improve resident incorporation. SETTING Interviews were conducted using a video conferencing platform. PARTICIPANTS Residency program directors, attending surgeons, graduate medical learners, and a nursing manager were interviewed. Twenty-one total interviews were conducted, representing ten different departments. RESULTS Stakeholders agreed that residents benefit from being placed in ASCs because the fast, surgical pace allows the residents to engage in more cases. However, different stakeholders highlighted different challenges, all centered around the notion of inter-stakeholder conflict due to conflicting priorities among residents, attending physicians, and administration. Likewise, recommendations differed by stakeholder group–faculty members sought more defined learning objectives and enhanced communication, whereas residents desired that ambulatory surgical time be more structured. CONCLUSIONS Despite the pressures of rapid case turnover, stakeholders agreed that there are many benefits to resident education in ASCs. Findings related to challenges and recommendations support the need to strengthen communication between stakeholder groups and better plan for resident integration into ASCs.

Background Plasmodium falciparum-infected red blood cells (iRBCs) bind and sequester in deep vascular beds, causing malaria-related disease and death. In pregnant women, VAR2CSA binds to chondroitin sulfate A (CSA) and mediates placental sequestration, making it the major placental malaria (PM) vaccine target. Methods In this study, we characterize an invariant protein associated with PM called P falciparum chondroitin sulfate A ligand (PfCSA-L). Results Recombinant PfCSA-L binds both placental CSA and VAR2CSA with nanomolar affinity, and it is coexpressed on the iRBC surface with VAR2CSA. Unlike VAR2CSA, which is anchored by a transmembrane domain, PfCSA-L is peripherally associated with the outer surface of knobs through high-affinity protein-protein interactions with VAR2CSA. This suggests that iRBC sequestration involves complexes of invariant and variant surface proteins, allowing parasites to maintain both diversity and function at the iRBC surface. Conclusions The PfCSA-L is a promising target for intervention because it is well conserved, exposed on infected cells, and expressed and localized with VAR2CSA.

Buerger's disease or thromboangiitis obliterans is a type of obstructive vascular diseases categorized as vasculitis and usually present in 95% of young smoker men. The main pathogenetic mechanism is interplay between immune system and inflammation. Earlier our phase II study has shown that Stempeucel is safe when injected at 2 million cells/kg body weight by virtue of its anti‐inflammatory, immunomodulatory, and angiogenetic properties. The present study was conducted to further assess the safety and efficacy of Stempeucel in critical limb ischemia due to Buerger's disease after obtaining approval from Indian FDA based on the data generated in the phase II study. This is an open label, multicenteric phase IV PMS study conducted across India with experienced vascular surgeons. Fifty patients of critical limb ischemia due to Buerger's disease with Rutherford III‐5 or III‐6 were included in the study and each individual received a dose of 2 million cells/kg body weight of Stempeucel in the calf muscles and around the ulcer. These patients were evaluated over 12 months from drug administration. The present study showed the continued long term efficacy over a period of 12 months follow up in these patients corroborating the result obtained in the previous phase II studies. There was significant improvement in rest pain, ankle systolic pressure, and ankle brachial pressure index with accelerated ulcer healing. In conclusion, the present study shows that the intramuscular administration of Stempeucel continues to be safe, tolerable, and effective alternative treatment in patients with Buerger's disease., Stempeucel showed the continued long term efficacy over a period of 12 months follow up in patients with CLI due to Buerger's disease. Significant improvement in rest pain, ankle systolic pressure and ankle brachial pressure index with accelerated ulcer healing was observed. Stempeucel continues to be safe, tolerable and effective alternative treatment in patients with Buerger's disease.

Patients with advanced carcinoma tongue in the Indian subcontinent have an additional component of submucosal fibrosis (SMF) due to chewing of betel. We intend to evaluate mandibular pull-through approach for total or near-total glossectomy and assessed its functional and survival outcome. Prospective study of 77 patients with carcinoma tongue, who underwent total or near-total glossectomy at our institute, were assessed retrospectively. All the patients who underwent glossecomy through mandibular pull through approach with pedicled or free flap reconstruction were assessed for functional and survival outcomes. Of the 77 patients, 45 (58.44%) patients underwent total glossectomy, while 32 (41.55%) patients near-total glossectomy, 61 (79.22%) cases had operative time ≤ 30 min, 69 (89.61%) patients had margins of > 5 mm, and none of the margins were involved. Flaps were reconstructed with 42 (54.54%) PMMC, 24 (31.16%) FRAFF, and 11 (14.28%) ALT. Five (6.49%) patients had surgical site infections, 6 patients each had to undergo re-explorations and partial flap loss, 7 patients had oro-cutaneous fistula, while 53 (68.83%) patients had no complications/osteoradionecrosis. A total of 94% of patients underwent decannulation, 92% of patients got discharged, and 89% got NG tube removed within 21 POD. Forty patients had reasonably good speech. On the long-term follow-up, 9% of the patients developed local recurrence and 11% of patients had regional/lymph node recurrence. Mandibular pull-through approach had the advantages of good accessibility to the tumour with the least mutilating techniques with shorter operation time, lower rates of postoperative complications, and better aesthetics and based on available data, it is superior to the mandibular lip-spilt surgery for advanced tongue involving BOT and floor of mouth cancers when coupled with SMF surgeries for the Indian scenario.

Background The COVID-19 pandemic forced numerous unprecedented systemic changes within residency programs and hospital systems. Objective We explored how the COVID-19 pandemic, and associated changes in clinical and educational experiences, were related to internal medicine residents' well-being in the early months of the pandemic. Methods Across 4 internal medicine residency programs in the Northeast United States that have previously participated in the iCOMPARE study, all 394 residents were invited to participate in a study with open-ended survey prompts about well-being approximately every 2 weeks in academic year 2019–2020. In March and April 2020, survey prompts were refocused to COVID-19. Content analysis revealed themes in residents' open-ended responses to 4 prompts. Results One hundred and eighty-six residents expressed interest, and 88 were randomly selected (47%). There were 4 main themes: (1) in early days of the pandemic, internal medicine residents reported fear and anxiety about uncertainty and lack of personal protective equipment; (2) residents adapted and soon were able to reflect, rest, and pursue personal wellness; (3) communication from programs and health systems was inconsistent early in the pandemic but improved in clarity and frequency; (4) residents appreciated the changes programs had made, including shorter shifts, removal of pre-rounding, and telemedicine. Conclusions COVID-19 introduced many challenges to internal medicine residency programs and to resident well-being. Programs made structural changes to clinical schedules, educational/conference options, and communication that boosted resident well-being. Many residents hoped these changes would continue regardless of the pandemic's course.

Human and animal malaria parasites increase their host erythrocyte permeability to a broad range of solutes as mediated by parasite-associated ion channels. Molecular and pharmacological studies have implicated an essential role in parasite nutrient acquisition, but inhibitors suitable for development of antimalarial drugs are missing. Here, we generated a potent and specific drug lead using Plasmodium falciparum, a virulent human pathogen, and derivatives of MBX-2366, a nanomolar affinity pyridazinone inhibitor from a high-throughput screen. As this screening hit lacks the bioavailability and stability needed for in vivo efficacy, we synthesized 315 derivatives to optimize drug-like properties, establish target specificity, and retain potent activity against the parasite-induced permeability. Using a robust, iterative pipeline, we generated MBX-4055, a derivative active against divergent human parasite strains. MBX-4055 has improved oral absorption with acceptable in vivo tolerability and pharmacokinetics. It also has no activity against a battery of 35 human channels and receptors and is refractory to acquired resistance during extended in vitro selection. Single-molecule and single-cell patch-clamp indicate direct action on the plasmodial surface anion channel, a channel linked to parasite-encoded RhopH proteins. These studies identify pyridazinones as novel and tractable antimalarial scaffolds with a defined mechanism of action. SIGNIFICANCE STATEMENT: Because antimalarial drugs are prone to evolving resistance in the virulent human P. falciparum pathogen, new therapies are needed. This study has now developed a novel drug-like series of pyridazinones that target an unexploited parasite anion channel on the host cell surface, display excellent in vitro and in vivo ADME properties, are refractory to acquired resistance, and demonstrate a well defined mechanism of action.

Background Molecular and genetic studies of blood-stage Plasmodium falciparum parasites require limiting dilution cloning and prolonged cultivation in microplates. The entire process is laborious and subject to errors due to inaccurate dilutions at the onset and failed detection of parasite growth in individual microplate wells. Methods To precisely control the number of parasites dispensed into each microplate well, parasitaemia and total cell counts were determined by flow cytometry using parasite cultures stained with ethidium bromide or SYBR Green I. Microplates were seeded with 0.2 or 0.3 infected cells/well and cultivated with fresh erythrocytes. The c-SNARF fluorescent pH indicator was then used to reliably detect parasite growth. Results Flow cytometry required less time than the traditional approach of estimating parasitaemia and cell numbers by microscopic examination. The resulting dilutions matched predictions from Poisson distribution calculations and yielded clonal lines. Addition of c-SNARF to media permitted rapid detection of parasite growth in microplate wells with high confidence. Conclusion The combined use of flow cytometry for precise dilution and the c-SNARF method for detection of growth improves limiting dilution cloning of P. falciparum. This simple approach saves time, is scalable, and maximizes identification of desired parasite clones. It will facilitate DNA transfection studies and isolation of parasite clones from ex vivo blood samples.

Protozoan parasites acquire essential ions, nutrients and other solutes from their insect and vertebrate hosts by transmembrane uptake. For intracellular stages, these solutes must cross additional membranous barriers. At each step, ion channels and transporters mediate not only this uptake, but also the removal of waste products. These transport proteins are best isolated and studied with patch-clamp, but these methods remain accessible to only a few parasitologists due to specialized instrumentation and the required training into both theory and practice. Here, we provide an overview of patch-clamp, describing the advantages and limitations of the technology and highlighting issues that may lead to incorrect conclusions. We aim to help non-experts understand and critically assess patch-clamp data in basic research studies.

Purpose To determine whether curettage of the cartilage on the glenoid edge in arthroscopic Bankart repair reduces the postoperative recurrence rate compared with noncuretted glenoid. Methods Between January 2010 and December 2013, 134 patients underwent arthroscopy and stabilization for recurrent anterior dislocation of shoulder; 42 patients were excluded. Alternate glenoid edge was curetted in 92 patients undergoing arthroscopic Bankart repair. Twelve patients were lost to follow-up. The remaining 80 patients were divided into 2 groups of 40 patients each, curettage and noncurettage. In both groups, the Bankart lesion was repaired using ≥3 bioanchors loaded with nonabsorbable braided sutures. Postoperative rehabilitation was the same for the 2 groups. We recorded recurrence of instability, pain, and Constant and Rowe shoulder scores. Statistical analysis of data was performed using unpaired t test (significance level P Results The 2 groups were comparable in terms of age, number of dislocations, and bone loss. The average follow-up was 7 years and 9 months (range 6 to 10 years). Of the total 40 patients in the curettage group, 6 (15%) had recurrence of dislocation and none had subluxations, whereas in the noncurettage group, 13 (32.5%) had recurrence of dislocation and 3 (7.5%) had subluxations. The difference in postoperative recurrence of instability was statistically significant (P = .012). The average (standard deviation) Rowe score was 83.75 (23.28) in the curettage group and 70.13 (31.29) in the noncurettage group (P = .030). Conclusions During arthroscopic Bankart repair, curettage of the cartilage on the anterior glenoid edge reduces the incidence of postoperative recurrence of instability. Level of Evidence II, therapeutic; prospective, randomized, controlled study.

Background The management of displaced 4-part fractures of proximal humerus is a challenge, as it is difficult to produce consistently good results with the current methods of fixation. Varus collapse of the head and eventual failure of plate fixation have been reported in up to 45% of cases. We present an innovative method of intramedullary fixation for displaced 4-part proximal humeral fractures. The aim of this study was to present the results of an intramedullary fixation device used for displaced 4-part proximal humeral fractures in patients younger than 70 years. Materials and methods Fixation was performed with an intramedullary device in 30 patients with an average age of 56 years who had displaced 4-part proximal humeral fractures. The device consists of a circular staple that is impacted in the head and engages into the neck of an intramedullary uncemented stem. The stem has a sleeve that provides the ability to adjust the height and thereby facilitates accurate reduction of the tuberosity with ease. Fracture union was assessed with plain radiographs, and clinical outcomes were assessed using American Shoulder and Elbow Surgeons and Constant scores. Results Union was achieved in 93.33% of patients and the mean American Shoulder and Elbow Surgeons and Constant scores were 75.2 and 73.97, respectively, at an average follow-up of 25.83 months. None of the patients had tuberosity avulsion, tuberosity nonunion, or resorption. However, 2 patients had humeral head nonunion and 2 had avascular necrosis. Revision surgery was performed in 2 patients (6.67%), because of avascular necrosis in 1 and nonunion in 1. Conclusion In patients younger than 70 years with displaced 4-part proximal humeral fractures, the described intramedullary device provides a simple and reproducible method of internal fixation with predictable tuberosity union and shoulder function.

The patient-physician clinical encounter is the cornerstone of medical training, yet residents spend as little as 12% of their time in direct patient contact.To use a real-time locating system (RTLS) to characterize intern work experiences in the hospital, understand factors associated with time spent at patients' bedsides, and inform future interventions to increase time spent with patients.This cross-sectional study was conducted from July 1, 2018, to June 30, 2019 (ie, the academic year 2018-2019). Internal medicine residents from postgraduate year 1 (interns) at an academic medical center wore an infrared badge that recorded location and duration (eg, patient room, ward hall, physician workroom). Data were analyzed from September 1, 2020, to August 30, 2021.Main outcome was time (in minutes) at the bedside; the unit of analysis was a 24-hour intern day or interval of time within the day (eg, rounding period). Descriptive statistics are reported overall, by intern, and for 5 clinical service categories. Multilevel modeling assessed the association of intern, service, and calendar time with time spent at the bedside.Data from 43 of 52 interns (82.7%) encompassing 95 275 hours of observations were included for analyses. Twenty-six interns (60.5%) were women. Interns were detected for a mean (SD) of 722.8 (194.4) minutes per 24-hour period; 13.4% of this time was spent in patient rooms (mean [SD] time, 96.8 [57.2] minutes) and 33.3% in physician workrooms (mean [SD] time, 240.9 [228.8] minutes). Mean percentage of time at the bedside during a 24-hour period varied among interns from 8.8% to 18.3%. Mean (SD) percentage of time at the bedside varied by service for the 24-hour period from 11.7% (6.6%) for nononcology subspecialties to 15.4% (6.0%) for oncology, and during rounds from 8.0% (12.4%) for nononcology subspecialties to 26.5% (12.1%) for oncology. In multilevel modeling, the individual intern accounted for 8.1% of overall variance in time spent at the bedside during a 24-hour period, and service accounted for 18.0% of variance during rounds.The findings of this cross-sectional study support previous evidence suggesting that interns spend only a small proportion of time with hospitalized patients. The differences in time spent in patients' rooms among interns and during rounds constitute an opportunity to design interventions that bring trainees back to the bedside.

BACKGROUND: The learning and working environment for resident physicians shifted dramatically over the past two decades, with increased focus on work hours, resident wellness, and patient safety. Following two multi-center randomized trials comparing 16-h work limits for PGY-1 trainees to more flexible rules, the ACGME implemented new flexible work hours standards in 2017. OBJECTIVE: We sought to determine program directors’ (PDs) support for the work hour changes and programmatic response. DESIGN: In 2017, US Internal Medicine PDs were surveyed about their degree of support for extension of PGY-1 work hour limits, whether they adopted the new maximum continuous work hours permitted, and reasons for their decisions. KEY RESULTS: The response rate was 70% (266/379). Fifty-seven percent of PDs (n = 151) somewhat/strongly support the new work hour rules for PGY-1 residents, while only 25% of programs (N = 66) introduced work periods greater than 16-h on any rotation. Higher rates of adopting change were seen in PDs who strongly/somewhat supported the change (56/151 [37%], P 100, 28/68 [41%], P = 0.005). Areas with the greatest influence for PDs not extending work hours were the 16-h rule working well (56%) and risk to PGY1 well-being (47%). CONCLUSIONS: Although the majority of PDs support the ACGME 2017 work hours rules, only 25% of programs made immediate changes to extend hours. These data reveal that complex, often competing, forces influence PDs’ decisions to change trainee schedules. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11606-020-06109-1) contains supplementary material, which is available to authorized users.

The invention of the incandescent light bulb by Edison in 1879, led to the introduction of the laparo-thoracoscope in 1910. Attempts were made to use this device in the knee joint as well. Development of the arthroscope really took off after the introduction of “cold-light” and rod lens optical system by Hopkins in 1960. Kenji Takagi and later Masaki Watanabe get the credit for developing the modern form of arthroscopy. The spillover of knee arthroscopy into the shoulder was inevitable and began in 1980’s. Shoulder arthroscopy started with instability repair, followed by subacromial decompression. Through the 1980’s and 1990’s, with the development in biotechnology, more sophisticated tools and anchors became available leading to refinement of instability repair procedures. The 2000’s saw improvement in arthroscopic rotator cuff repair techniques including the double- row and trans-osseous equivalent. The last decade has witnessed the development of more complex arthroscopic procedures such as Latarjet and Superior Capsule Reconstruction. However, arthroscopic surgery continues to be equipment intensive and we need to remind ourselves that the arthroscope is no “magic wand” and good clinical evaluation continues to prevail.

The genealogy of graduate medical education in America begins at the bedside. However, today’s graduate medical trainees work in a training environment that is vastly different from medical training a century ago. The goal of the Graduate Medical Education Laboratory (GEL) Study, supported by the American Medical Association’s (AMA) “Reimagining Residency” initiative, is to determine the factors in the training environment that most contribute to resident well-being and developing diagnostic skills. We believe that increasing time at the bedside will improve clinical skill, increase professional fulfillment, and reduce workplace burnout. Our graduate medical education laboratory will test these ideas to understand which interventions can be shared among all training programs. Through the GEL Study, we aim to ensure resident readiness for practice as we understand, then optimize, the learning environment for trainees and staff.

Dr Sanjai Desai, Dr Nicholas Inston, and Dr Alexandros Mallios provide an update on a new method to enhance vascular access outcomes for dialysis patients. While arteriovenous fistulas (AVFs) are the ‘gold standard’ for haemodialysis access, the path to a functional AVF is steep, and far too many fail before they can be used for dialysis. Fist Assist, a lightweight, wearable medical device, provides gentle, intermittent pneumatic compression that can safely and effectively help veins to enlarge before, and after, AVF surgery. This article covers the risks of AVF failure, early research with Fist Assist on dilation, a concise cost analysis, and the potential for such a device to improve outcomes for both percutaneous and standard AVFs. Fist Assist is expected to launch in Europe in March 2020.

Background Medical school academic achievements do not necessarily predict house staff job performance. This study explores a selection mechanism that improves house staff-program fit that enhances the Accreditation Council for Graduate Medical Education Milestones performance ratings. Objective Traditionally, house staff were selected primarily on medical school academic performance. To improve residency performance outcomes, the Program designed a theory-driven selection tool to assess house staff candidates on their personal values and goals fit with Program values and goals. It was hypothesized cohort performance ratings will improve because of the intervention. Methods Prospective quasi-experimental cohort design with data from two house staff cohorts at a university-based categorical Internal Medicine Residency Program. The intervention cohort, comprising 45 house staff from 2016 to 2017, was selected using a Behaviorally Anchored Rating Scales (BARS) tool for program fit. The control cohort, comprising 44 house staff from the prior year, was selected using medical school academic achievement scores. House staff performance was evaluated using ACGME Milestones indicators. The mean scores for each category were compared between the intervention and control cohorts using Student’s t-tests with Bonferroni correction and Cohen’s d for effect size. Results The cohorts were no different in academic performance scores at time of Program entry. The intervention cohort outperformed the control cohort on all 6 dimensions of Milestones by end-PGY1 and 3 of 6 dimensions by mid-PGY3. Conclusion Selecting house staff based on compatibility with Residency Program values and objectives may yield higher job performance because trainees benefit more from a better fit with the training program.

PURPOSE: Most of what is known about resident burnout and wellness comes from cross-sectional snapshot surveys. The purpose of this study was to elicit qualitative perspectives on wellness from a cohort of internal residents over time using ecological momentary assessment. METHOD: Drawing on principles of ecological momentary assessment, 13 different open-ended survey prompts were delivered between October and March during the 2019–2020 academic year. Participants were 88 randomly selected internal medicine residents from 4 internal medicine training programs in the Northeast. RESULTS: The response rate was 95%. Three main themes regarding wellness were self, program/education environment, and medical/structural system. A fourth theme, the desire to provide quality patient care, cut across all other themes. The patient care theme repeatedly stressed residents’ desire to spend more time with patients. The self theme primarily reflected messages about personal emotions and the need for work–life balance and wellness. The program/education environment theme reflected the value of learning, teamwork and community, and program culture. The medical/structural system theme showed that residents’ experiences were shaped by the efficiency of their days, and largely a product of their schedules and administrative support. Closing advice to future trainees was optimistic and reassuring. CONCLUSIONS: While findings support much of what has been learned via single-occasion survey snapshots, an ecological momentary assessment design allowed a deeper dive into contextual associations. The results affirm the primacy of patient care and also highlight the value of teamwork and culture. Peers and program leaders are heavily influential in setting the tone for the learning experience, whether for the day or with a more enduring message of respect and support. There is opportunity to maximize high- or higher-value learning experiences for residents and find solutions to reduce and reframe the perceived “low-value administrative work” that is part of care coordination.

The intracellular human malaria parasite, Plasmodium falciparum, uses the PfATP4 cation pump to maintain Na+ and H+ homeostasis in parasite cytosol. PfATP4 is the target of advanced antimalarial leads, which produce many poorly understood metabolic disturbances within infected erythrocytes. Here, we expressed the mammalian ligand-gated TRPV1 ion channel at the parasite plasma membrane to study ion regulation and examine the effects of cation leak. TRPV1 expression was well-tolerated, consistent with negligible ion flux through the nonactivated channel. TRPV1 ligands produced rapid parasite death in the transfectant line at their activating concentrations, but were harmless to the wild-type parent. Activation triggered cholesterol redistribution at the parasite plasma membrane, reproducing effects of PfATP4 inhibitors and directly implicating cation dysregulation in this process. In contrast to predictions, TRPV1 activation in low Na+ media accentuated parasite killing but a PfATP4 inhibitor had unchanged efficacy. Selection of a ligand-resistant mutant revealed a previously uncharacterized G683V mutation in TRPV1 that occludes the lower channel gate, implicating reduced permeability as a mechanism for parasite resistance to antimalarials targeting ion homeostasis. Our findings provide key insights into malaria parasite ion regulation and will guide mechanism-of-action studies for advanced antimalarial leads that act at the host-pathogen interface.

Rationale: Geographic co-localization of patients and provider teams (geography) may improve care efficiency and quality. Patients requiring intermediate care present a unique challenge to the geographic model. Objective: Identify the best organizational and staffing model for intermediate care at our academic medical center. Methods: A modified nominal group technique was employed to assess the benefits and limitations of an existing model of intermediate care, identify and review potential alternative models, and choose a new model. Results: In addition to the institution's current model, the benefits and limitations of six alternative organizational and staffing models were characterized. The anticipated impact of each model on nurse: provider communication, maintenance of nursing competencies, nurse satisfaction, efficient utilization of technical and human resources, triage of patients to the unit, care continuity, and the impact on trainee education are described. After considering these features, stakeholders ranked a closed provider staffing model on a unit dedicated to intermediate care highest of the six alternative models. Important outcomes to monitor following transition to a closed staffing model included patient outcomes, nursing job satisfaction and retention, provider and trainee experience, unexpected patient transfers to higher or lower levels of care, and administrative costs. Conclusions: After considering six alternative staffing models for intermediate care, stakeholders ranked a closed provider staffing model highest. Further qualitative and quantitative comparisons to determine optimal models of intermediate care are needed.

Background: Arteriovenous fistula (AVF) creation and maturation for hemodialysis is globally a topic of importance given the poor results and high costs associated with renal care. Successful AVF (surgical or endovascular) creation requires appropriate superficial veins and quality arteries. Many procedures fail due to initial small veins with limited blood flow capacity and distensibility. Intermittent pneumatic compression has previously shown success in trials to increase superficial veins in patients with end stage renal disease post AVF. The objective of this study is to investigate the role of an intermittent pneumatic device, the Fist Assist®, to dilate cephalic arm veins in patients with advanced chronic kidney disease (CKD) prior to AVF placement. Methods: Three centers enrolled subjects from June 2019 through July 2021. Baseline Doppler measurements of the cephalic vein in standard locations the forearm and upper arm with and without a blood pressure cuff were recorded. Patients were instructed and used Fist Assist® on their non-dominant arm for up to 4 h daily for 90 days. At approximately 3 months, Doppler measurements were repeated. The primary endpoint was cephalic vein enlargement with secondary endpoints based on percentage of veins approaching 2.5 mm in the forearm and 3.5 mm in the upper arm. Results: Thirty-seven subjects with CKD (mean eGFR 13.8 mL/min) were enrolled and completed the trial. Paired-difference t-tests (one tail) for aggregate data showed significant venous dilation of the cephalic vein in both the forearm and upper arm after use with the Fist Assist® ( p ® application. There were no major complications reported by any subject during the trial. Conclusions: Fist Assist® use in patients with CKD is effective to enhance vein dilation. Forearm and upper arm cephalic veins increased on average 0.6 and 1.1 mm respectively after Fist Assist® application. This is the first trial to evaluate the effect of intermittent, focal pneumatic compression on pre-surgery vein diameter in patients with advanced CKD before AVF creation.

Background Iatrogenic hypoglycemia is a common occurrence among hospitalized patients and is associated with poor clinical outcomes and increased mortality. Clinical decision support systems can be used to reduce the incidence of this potentially avoidable adverse event. Objective This study aims to determine the desired features and functionality of a real-time informatics alert to prevent iatrogenic hypoglycemia in a hospital setting. Methods Using the Agency for Healthcare Research and Quality Five Rights of Effective Clinical Decision Support Framework, we conducted a mixed methods study using an electronic survey and focus group sessions of hospital-based providers. The goal was to elicit stakeholder input to inform the future development of a real-time informatics alert to target iatrogenic hypoglycemia. In addition to perceptions about the importance of the problem and existing barriers, we sought input regarding the content, format, channel, timing, and recipient for the alert (ie, the Five Rights). Thematic analysis of focus group sessions was conducted using deductive and inductive approaches. Results A 21-item electronic survey was completed by 102 inpatient-based providers, followed by 2 focus group sessions (6 providers per session). Respondents universally agreed or strongly agreed that inpatient iatrogenic hypoglycemia is an important problem that can be addressed with an informatics alert. Stakeholders expressed a preference for an alert that is nonintrusive, accurate, communicated in near real time to the ordering provider, and provides actionable treatment recommendations. Several electronic medical record tools, including alert indicators in the patient header, glucose management report, and laboratory results section, were deemed acceptable formats for consideration. Concerns regarding alert fatigue were prevalent among both survey respondents and focus group participants. Conclusions The design preferences identified in this study will provide the framework needed for an informatics team to develop a prototype alert for pilot testing and evaluation. This alert will help meet the needs of hospital-based clinicians caring for patients with diabetes who are at a high risk of treatment-related hypoglycemia.

Background Medical interns are at risk for sleep deprivation from long and often rotating work schedules. However, the effects of specific rotations on sleep are less clear. Objective To examine differences in sleep duration and alertness among internal medicine interns during inpatient intensive care unit (ICU) compared to general medicine (GM) rotations. Methods This secondary analysis compared interns during a GM or ICU rotation from a randomized trial (2015–2016) of 12 internal medicine residency programs assigned to different work hour limit policies (standard 16-hour shifts or no shift-length limits). The primary outcome was sleep duration/24-hour using continuous wrist actigraphy over a 13-day period. Secondary outcomes assessed each morning during the concomitant actigraphy period were sleepiness (Karolinska Sleepiness Scale [KSS]), alertness (number of Brief Psychomotor Vigilance Test [PVT-B] lapses), and self-report of excessive sleepiness over past 24 hours. Linear mixed-effect models with random program intercept determined associations between each outcome by rotation, controlling for age, sex, and work hour policy followed. Results Of 398 interns, 386 were included (n = 261 GM, n = 125 ICU). Average sleep duration was 7.00±0.08h and 6.84±0.10h, and number of PVT lapses were 5.5±0.5 and 5.7±0.7 for GM and ICU, respectively (all P > .05). KSS was 4.8±0.1 for both rotations. Compared to GM, ICU interns reported more days of excessive sleepiness from 12am–6am (2.6 vs 1.7, P < .001) and 6am–12pm (2.6 vs 1.9, P = .013) and had higher percent of days with sleep duration < 6 hours (27.6% vs 23.4%, P < .001). GM interns reported more days with no excessive sleepiness (5.3 vs 3.7, P < .001). Conclusions Despite ICU interns reporting more excessive sleepiness in morning hours and more days of insufficient sleep (

Background To maintain the patency and longevity of arteriovenous fistula, the availability of a venous segment with adequate diameter is important. In Indian population, many chronic kidney disease patients have poor caliber veins. The study aimed to evaluate the efficacy of hydrostatic dilatation versus Primary balloon angioplasty of small caliber cephalic veins of (≤2.5 mm) preoperatively in terms of patency rate and maturation time of arteriovenous fistula. Methods Patients ( n = 80) with an end-stage renal disease requiring arteriovenous access surgery for hemodialysis with small caliber cephalic veins were randomized into two groups, i.e., hydrostatic dilatation and primary balloon angioplasty, each with 40 patients. All patients underwent a thorough clinical examination as well as duplex ultrasound vein mapping of both upper extremities. Patients were followed up for six months and primary patency, maturation time, and complications were noted. Results Immediate technical success with good palpable thrill was achieved in 97.5% of patients in the primary balloon angioplasty group and 87.5% in the hydrostatic dilatation group. The fistula maturation time in the primary balloon angioplasty group was 34.41 days and 46.18 days in the hydrostatic dilatation group. In the primary balloon angioplasty group, the primary patency of the fistula was 97.5% and 87.5% in the hydrostatic dilatation group, at six months. The arteriovenous fistula functioning rate was 77.5% in the hydrostatic dilatation group as compared to 92.5% in the primary balloon angioplasty group at six months. The incidence of surgical site infection was 5% in the primary balloon angioplasty group as compared to 10% in the hydrostatic dilatation group. Conclusion Primary balloon angioplasty of small caliber cephalic veins (≤2.5 mm) performed prior to arteriovenous fistula creation for hemodialysis is a beneficial procedure.

Intracellular malaria parasites export many proteins into their host cell, inserting several into the erythrocyte plasma membrane to enable interactions with their external environment. While static techniques have identified some surface-exposed proteins, other candidates have eluded definitive localization and membrane topology determination. Moreover, both export kinetics and the mechanisms of membrane insertion remain largely unexplored. We introduce Reporter of Insertion and Surface Exposure (RISE), a method for continuous nondestructive tracking of antigen exposure on infected cells. RISE utilizes a small 11 aa NanoLuc fragment inserted into a target protein and detects surface exposure through high-affinity complementation. We tracked insertion of CLAG3, a malaria parasite protein linked to nutrient uptake, throughout the P. falciparum cycle in human erythrocytes. Our approach also revealed key determinants of trafficking and surface exposure. Removal of a C-terminal transmembrane domain aborted export. Unexpectedly, certain increases in the exposed reporter size improved surface exposure by up to 50-fold, revealing that both size and charge of the extracellular epitope influence membrane insertion. Insertion of parasite proteins at the host cell surface and antigen accessibility is regulated by multiple factors, enabling intracellular parasite survival and immune evasion under a broad range of conditions.

Guidance regarding indications for initial or follow-up blood cultures is limited. We conducted a scoping review of articles published between January 2004 and June 2019 that reported the yield of blood cultures and/or their impact in the clinical management of fever and common infectious syndromes in nonneutropenic adult inpatients. A total of 2893 articles were screened; 50 were included. Based on the reported incidence of bacteremia, syndromes were categorized into low, moderate, and high pretest probability of bacteremia. Routine blood cultures are recommended in syndromes with a high likelihood of bacteremia (eg, endovascular infections) and those with moderate likelihood when cultures from the primary source of infection are unavailable or when prompt initiation of antibiotics is needed prior to obtaining primary source cultures. In syndromes where blood cultures are low-yield, blood cultures can be considered for patients at risk of adverse events if a bacteremia is missed (eg, patient with pacemaker and severe purulent cellulitis). If a patient has adequate source control and risk factors or concern for endovascular infection are not present, most streptococci or Enterobacterales bacteremias do not require routine follow-up blood cultures.

Behçet disease is a multisystem disorder presenting with recurrent oral and genital ulcerations as well as with ocular involvement. Vascular involvement can occur in up to 50% of affected patients. Arterial aneurysms are often multiple and are characterized by a saccular configuration with increased risk of unexpected rupture, thrombosis, and aneurysm recurrence. Here we report a case of giant infrarenal abdominal aortic aneurysm in a 34-year-old man with Behçet disease who underwent aneurysmorrhaphy and aortobifemoral bypass.

Objective: Venous thromboembolism (VTE) includes deep vein thrombosis (DVT) and pulmonary embolism (PE). VTE affects all races, age groups, and genders. The objective of this registry was to analyze the patient characteristics, clinical outcomes, management strategies, and temporal trends in VTE at a single center. Materials and Methods: Consecutive medical records of inpatients between January 2007 and March 2018, meeting the inclusion criteria (confirmed diagnosis of DVT by Doppler ultrasound scan and/or PE by chest computed tomography) were identified and collected. A total of 1,024 patients were reviewed. Results: Eight hundred and twelve patients with VTE were enrolled into the study; 37.4% were referrals from outside hospitals, 33.1% of the total patients had no risk factors, hence classified as unprovoked VTE and the rest of the patients had single or multiple risk factors which may have provoked the VTE, 68.8% presented with swelling and pain, and 88.5% had proximal DVT. Conclusion: VTE is no longer a rare phenomenon in the Indian population, as believed earlier. The knowledge of VTE, prophylaxis, and treatment strategies is minimal among small institutes, nursing homes, and among general practitioners who are not affiliated with teaching institutes. Therefore, educating primary care physicians/surgeons on VTE is paramount, as this would reduce the incidence of VTE in India as well as associated morbidity and mortality rates.

BACKGROUND: Concern persists that extended shifts in medical residency programs may adversely affect patient safety. METHODS: We conducted a cluster-randomized noninferiority trial in 63 internal-medicine residency programs during the 2015–2016 academic year. Programs underwent randomization to a group with standard duty hours, as adopted by the Accreditation Council for Graduate Medical Education (ACGME) in July 2011, or to a group with more flexible duty-hour rules that did not specify limits on shift length or mandatory time off between shifts. The primary outcome for each program was the change in unadjusted 30-day mortality from the pretrial year to the trial year, as ascertained from Medicare claims. We hypothesized that the change in 30-day mortality in the flexible programs would not be worse than the change in the standard programs (difference-in-difference analysis) by more than 1 percentage point (noninferiority margin). Secondary outcomes were changes in five other patient safety measures and risk-adjusted outcomes for all measures. RESULTS: The change in 30-day mortality (primary outcome) among the patients in the flexible programs (12.5% in the trial year vs. 12.6% in the pretrial year) was noninferior to that in the standard programs (12.2% in the trial year vs. 12.7% in the pretrial year). The test for noninferiority was significant (P = 0.03), with an estimate of the upper limit of the one-sided 95% confidence interval (0.93%) for a between-group difference in the change in mortality that was less than the prespecified noninferiority margin of 1 percentage point. Differences in changes between the flexible programs and the standard programs in the unadjusted rate of readmission at 7 days, patient safety indicators, and Medicare payments were also below 1 percentage point; the noninferiority criterion was not met for 30-day readmissions or prolonged length of hospital stay. Risk-adjusted measures generally showed similar findings. CONCLUSIONS: Allowing program directors flexibility in adjusting duty-hour schedules for trainees did not adversely affect 30-day mortality or several other measured outcomes of patient safety. (Funded by the National Heart, Lung, and Blood Institute and Accreditation Council for Graduate Medical Education; iCOMPARE ClinicalTrials.gov number, NCT02274818.)

BACKGROUND: A purpose of duty-hour regulations is to reduce sleep deprivation in medical trainees, but their effects on sleep, sleepiness, and alertness are largely unknown. METHODS: We randomly assigned 63 internal-medicine residency programs in the United States to follow either standard 2011 duty-hour policies or flexible policies that maintained an 80-hour workweek without limits on shift length or mandatory time off between shifts. Sleep duration and morning sleepiness and alertness were compared between the two groups by means of a noninferiority design, with outcome measures including sleep duration measured with actigraphy, the Karolinska Sleepiness Scale (with scores ranging from 1 [extremely alert] to 9 [extremely sleepy, fighting sleep]), and a brief computerized Psychomotor Vigilance Test (PVT-B), with long response times (lapses) indicating reduced alertness. RESULTS: Data were obtained over a period of 14 days for 205 interns at six flexible programs and 193 interns at six standard programs. The average sleep time per 24 hours was 6.85 hours (95% confidence interval [CI], 6.61 to 7.10) among those in flexible programs and 7.03 hours (95% CI, 6.78 to 7.27) among those in standard programs. Sleep duration in flexible programs was noninferior to that in standard programs (between-group difference, −0.17 hours per 24 hours; one-sided lower limit of the 95% confidence interval, −0.45 hours; noninferiority margin, −0.5 hours; P = 0.02 for noninferiority), as was the score on the Karolinska Sleepiness Scale (between-group difference, 0.12 points; one-sided upper limit of the 95% confidence interval, 0.31 points; non-inferiority margin, 1 point; P

Two large national studies of resident duty hours incidentally revealed surgical and medical resident dissatisfaction with residency training. Aiming for an inclusive and democratic approach to improve graduate medical education, we conducted a national innovation tournament--reaching out to the program directors of all 474 US internal medicine residency programs to invite them and their residents and associate program directors to participate. Participants could submit multiple ideas as individuals or teams in four domains: [1] resident well-being and personal and professional development; [2] resident education and clinical preparedness; [3] resident sleep and alertness; and [4] patient safety. Residents and program directors were reinvited to rate ideas, whether they had submitted ideas themselves or not. We used a schedule of lottery-based prizes to stimulate the submission and rating of ideas and encourage engagement. 164 residents and program directors from 51 different programs submitted 328 ideas. 153 residents and program directors from 48 different programs submitted 15,345 ratings of ideas. Winning ideas aimed to reduce residents' work burden or improve their mental health, sleep, eating, or relaxation or reflected technical fixes to the operations of residency, such as changing vacation schedules and the timing of pay. The results of this tournament provided actionable suggestions to improve residency training now being tested in our own residency programs. Innovation tournaments drive engagement and generate value by their opportunities for inclusion and by shifting problem solving to the end user.