The impact of disclosure of conflicts of interest in studies comparing robot-assisted and laparoscopic cholecystectomies-a persistent problem.

INTRODUCTION: Accurate disclosure of conflicts of interest (COI) is critical to interpretation of study results, especially when industry interests are involved. We reviewed published manuscripts comparing robot-assisted cholecystectomy (RAC) and laparoscopic cholecystectomy (LC) to evaluate the relationship between COI disclosures and conclusions drawn on the procedure benefits and safety profile. METHODS: Searching Pubmed and Embase using key words "cholecystectomy", laparoscopic" and "robotic"/"robot-assisted" retrieved 345 publications. Manuscripts that compared benefits and safety of RAC over LC, had at least one US author and were published between 2014 and 2020 enabling verification of disclosures with reported industry payments in CMS's Open Payments database (OPD) (up to 1 calendar year prior to publication) were included in the analysis (n = 37). RESULTS: Overall, 26 (70%) manuscripts concluded that RAC was equivalent or better than LC (RAC +) and 11 (30%) concluded that RAC was inferior to LC (RAC-). Six manuscripts (5 RAC + and 1 RAC-) did not have clearly stated COI disclosures. Among those that had disclosure statements, authors' disclosures matched OPD records among 17 (81%) of RAC + and 9 (90%) RAC- papers. All 11 RAC- and 17 RAC + (65%) manuscripts were based on retrospective cohort studies. The remaining RAC + papers were based on case studies/series (n = 4), literature review (n = 4) and clinical trial (n = 1). A higher proportion of RAC + (85% vs 45% RAC-) manuscripts used data from a single institution. Authors on RAC + papers received higher amounts of industry payments on average compared to RAC- papers. CONCLUSIONS: It is imperative for authors to understand and accurately disclose their COI while disseminating scientific output. Journals have the responsibility to use a publicly available resource like the OPD to verify authors' disclosures prior to publication to protect the process of scientific authorship which is the foundation of modern surgical care.

Outcomes following robot-assisted versus laparoscopic sleeve gastrectomy: the New York State experience.

INTRODUCTION: Laparoscopic sleeve gastrectomy (LSG) represents more than half of all bariatric procedures in the USA, and robot-assisted sleeve gastrectomy (RSG) is becoming increasingly common. There is a paucity of evidence regarding postoperative surgical outcomes (> 30 days) in RSG patients, especially as these patients move between multiple hospital systems. METHODS: Using 2012-2018 New York State's inpatient and ambulatory data from the Statewide Planning and Research Cooperative System, bivariate and multivariate analyses were employed to examine patient long-term outcomes, postoperative complications, and charges following RSG versus LSG in unmatched and propensity score-matched (PSM) samples. RESULTS: Among the 72,157 minimally invasive sleeve gastrectomies identified, 2365 (2.6%) were RSGs. In the PSM sample (2365 RSG matched to 23,650 LSG), RSG cases were more likely to be converted to an open procedure (2.3% vs 0.2% LSG patients, p < 0.01) and had a longer mean length of stay (LOS; 2.1 vs. 1.8 days LSG, p < 0.01). Postoperative complications were not different between RSG and LSG patients, but the proportion of emergency room visits resulting in inpatient readmissions was higher among RSG patients (5.5% vs. 4.2% in LSG patients, p < .01). Among the super obese (body mass index ≥ 50) patients, conversions to open procedure and LOS were also significantly higher for RSG versus LSG cases. Average hospital charges for the index admission ($47,623 RSG vs $35,934 LSG) and cumulative changes for 1 year from the date of surgery ($57,484 RSG vs $43,769 LSG) were > 30% higher for RSG patients. CONCLUSIONS: RSG patients were more likely to have conversions to open procedures, longer postoperative stay, readmissions, and higher charges for both the index admission and beyond, compared to LSG patients. No clear advantages emerged for the utilization of the robotic platform for either average risk or extremely obese patients.

Is New York State good at managing hollow viscus injury?

BACKGROUND: There are an estimated 100,000 cases of abdominal injury (ABI) in the USA, annually resulting in over $12 billion in direct medical cost and $18 billion in lost productivity. This study assesses the timeliness, safety, and efficacy of the surgical management of abdominal injuries (ABIs), hollow viscus injuries (HVIs), and colonic injuries (CIs) for patients residing in New York State (NYS). METHODS: Using data from NYS's Statewide Planning and Research Cooperative System (SPARCS), we identified all trauma patients with ABI admitted between 2006 and 2015. We subdivided ABI into HVI and CI using diagnosis and procedure codes and examined processes of care and outcomes adjusting for patient characteristics, injury severity score, structural, and process indicators. RESULTS: We identified 31,043 hospitalized patients with ABI, 71% were incurred from blunt forces. Most patients with ABI (72%) were treated at a Level I/II trauma center (TC) and 7% patients were transferred to Level I/II TC. Failure to be treated at Level I/II TC was associated with 16% increased hazard of death. HVI was diagnosed in 23% of ABI patients (n = 7294); 18% experienced delayed hollow viscus repair (dHVR); dHVR was associated with a 76% increased hazard of death. CI was diagnosed in 9% of ABI patients (n = 2921) and 18% experienced dHVR. Seventy-five percent of CI were repaired primarily (n = 1354). Less than 37% of stomas were reversed by 4 years of index trauma. CONCLUSION: Most abdominal trauma in NYS was caused by motor vehicle accidents, falls, and assault. dHVR and not being treated at Level I/II TC were associated with worse outcomes. More research is needed to reduce under-triage and delays in the operative treatment of blunt abdominal trauma.

Multisite study of Titan SGS stapler in longitudinal gastric resection.

BACKGROUND: Standardization of the laparoscopic sleeve gastrectomy procedure is needed to improve patient outcomes. A single-fire 23 cm stapler was developed to streamline the operation. Comparative testing conducted on excised human tissue has demonstrated the superiority of the novel Titan SGS stapler to two commonly utilized commercial devices in both staple line integrity and burst pressure. We hypothesized that the stapler would be safe and effective in creating longitudinal gastric resections in human patients. METHODS: 61 patients were enrolled to undergo gastric resection with the Titan SGS stapler. Perioperative interventions and post-operative adverse events were recorded. Upper GI study was completed on post-operative day 1, and patients were followed for 6 weeks post-operatively to determine any subacute device-related adverse events. RESULTS: Surgeon feedback for intraoperative device utilization and post-operative gastric pouch shape were positive. Adverse events were found to be mild, limited, and generally well-known effects of bariatric surgery. One episode of post-operative hemorrhage required surgical takeback, with no criminal bleeding vessel identified. CONCLUSION: The Titan SGS stapler is both safe and effective in sleeve gastrectomy pouch creation.

Engaging Physicians in Leadership: Motivations, Challenges, and Identity-Based Considerations.

GOAL: Physician leadership has been associated with improved patient outcomes, increased provider satisfaction, and decreased physician burnout as well as more profitable, higher-quality healthcare delivery. However, physicians frequently struggle when assuming leadership positions, given the dissonance between their administrative and clinical roles. Informed by social identity theory, we aimed to identify why physicians lead, how they experience leadership roles, and the challenges they face during the transition into those roles. METHODS: We conducted 27 semistructured interviews with primary care physician leaders between January and April 2020. Interviews were transcribed and analyzed using the constant comparative method. PRINCIPAL FINDINGS: Four themes were developed from the analysis, including (1) desire for change, (2) desire for growth, (3) challenges experienced during the transition to a leadership role, and (4) changes to professional identity. The results of this study identified aspects of leadership perceived by physicians as attractive and motivating. The study also revealed challenges that occur during the transition into leadership as well as shifts in professional identity experienced by physicians. APPLICATIONS TO PRACTICE: The results can be used by healthcare managers and executives to empower more physicians to take on leadership roles and implement changes that alleviate stresses associated with physicians transitioning into leadership roles.

The Early (2009-2017) Experience With Robot-assisted Cholecystectomy in New York State.

OBJECTIVE: The aim of this study was to examine real-life patterns of care and patient outcomes associated with robot-assisted cholecystectomy (RAC) in New York State (NYS). BACKGROUND: Although robotic assistance may offer some technological advantages, RACs are associated with higher procedural costs and longer operating times compared to traditional laparoscopic cholecystectomies (LCs). Evidence on long-term patient outcomes after RAC from large population-based datasets remains limited and inconsistent. METHODS: Using NYS inpatient and ambulatory surgery data from the Statewide Planning and Research Cooperative System (2009-2017), we conducted bivariate and multivariate analyses to examine patterns of utilization, complications, and secondary procedures following cholecystectomies. RESULTS: Among 299,306 minimally invasive cholecystectomies performed in NYS between 2009 and 2017, one thousand one hundred eighteen (0.4%) were robot-assisted. Compared to those undergoing LC, RAC patients were older, travelled further for surgery, and were more likely to have public insurance and preoperative comorbidities. RAC versus LC patients were more significantly likely to have conversions to open procedure (4.9% vs 2.8%), bile duct injuries (1.3% vs 0.4%), and major reconstructive interventions (0.6% vs 0.1%), longer median length of stay (3 vs 1 day), readmissions (7.3% vs 4.4%), and higher 12-month post-index surgery hospital charges (P < 0.01 for all estimates). Other postoperative complications decreased over time for LC but remained unchanged for RAC patients. CONCLUSIONS: Patients receiving RAC in NYS experienced higher rates of complications compared to LC patients. Addressing patient-, surgeon-, and system-level factors associated with intra/postoperative complications and applying recently promulgated safe cholecystectomy strategies coupled with advanced imaging modalities like fluorescence cholangiography to RAC may improve patient outcomes.

Teaching surgery novices and trainees advanced laparoscopic suturing: a trial and tribulations.

INTRODUCTION: The benefits of minimally invasive surgery are numerous; however, considerable variability exists in its application and there is a lack of standardized training for important advanced skills. Our goal was to determine whether participation in an advanced laparoscopic curriculum (ALC) results in improved laparoscopic suturing skills. METHODS AND PROCEDURES: Study design was a prospective, randomized controlled trial. Surgery novices and trainees underwent baseline FLS training and were pre-tested on bench models. Participants were stratified by pre-test score and randomized to undergo either further FLS training (control group) or ALC training (intervention group). All were post-tested on the same bench model. Tests for differences between post-test scores of cohorts were performed using least squared means. Multivariable regression identified predictors of post-test score, and Wilcoxon rank sum test assessed for differences in confidence improvement in laparoscopic suturing ability between groups. RESULTS: Between November 2018 and May 2019, 25 participants completed the study (16 females; 9 males). After adjustment for relevant variables, participants randomized to the ALC group had significantly higher post-test scores than those undergoing FLS training alone (mean score 90.50 versus 82.99, p = 0.001). The only demographic or other variables found to predict post-test score include level of training (p = 0.049) and reported years of video gaming (p = 0.034). There was no difference in confidence improvement between groups. CONCLUSIONS: Training using the ALC as opposed to basic laparoscopic skills training only is associated with superior advanced laparoscopic suturing performance without affecting improvement in reported confidence levels. Performance on advanced laparoscopic suturing tasks may be predicted by lifetime cumulative video gaming history and year of training but does not appear to be associated with other factors previously studied in relation to basic laparoscopic skills, such as surgical career aspiration or musical ability.

Epigenetic inhibition of the tumor suppressor ARHI by light at night-induced circadian melatonin disruption mediates STAT3-driven paclitaxel resistance in breast cancer.

Disruption of circadian time structure and suppression of circadian nocturnal melatonin (MLT) production by exposure to dim light at night (dLAN), as occurs with night shift work and/or disturbed sleep-wake cycles, is associated with a significantly increased risk of breast cancer and resistance to tamoxifen and doxorubicin. Melatonin inhibition of human breast cancer chemoresistance involves mechanisms including suppression of tumor metabolism and inhibition of kinases and transcription factors which are often activated in drug-resistant breast cancer. Signal transducer and activator of transcription 3 (STAT3), frequently overexpressed and activated in paclitaxel (PTX)-resistant breast cancer, promotes the expression of DNA methyltransferase one (DNMT1) to epigenetically suppress the transcription of tumor suppressor Aplasia Ras homolog one (ARHI) which can sequester STAT3 in the cytoplasm to block PTX resistance. We demonstrate that breast tumor xenografts in rats exposed to dLAN and circadian MLT disrupted express elevated levels of phosphorylated and acetylated STAT3, increased DNMT1, but reduced sirtuin 1 (SIRT1) and ARHI. Furthermore, MLT and/or SIRT1 administration blocked/reversed interleukin 6 (IL-6)-induced acetylation of STAT3 and its methylation of ARH1 to increase ARH1 mRNA expression in MCF-7 breast cancer cells. Finally, analyses of the I-SPY 1 trial demonstrate that elevated MT1 receptor expression is significantly correlated with pathologic complete response following neo-adjuvant therapy in breast cancer patients. This is the first study to demonstrate circadian disruption of MLT by dLAN driving intrinsic resistance to PTX via epigenetic mechanisms increasing STAT3 expression and that MLT administration can reestablish sensitivity of breast tumors to PTX and drive tumor regression.

Phase Ib Safety, Two-Dose Study of MultiGeneAngio in Patients with Chronic Critical Limb Ischemia.

Critical limb ischemia (CLI) is the most severe presentation of peripheral arterial disease. We developed cell-based therapy entailing intra-arterial injection of autologous venous endothelial cells (ECs) modified to express angiopoietin 1, combined with autologous venous smooth muscle cells (SMCs) modified to express vascular endothelial growth factor. This combination promoted arteriogenesis in animal models and was safe in patients with limiting claudication. In an open-label, phase Ib study, we assessed the safety and efficacy of this therapy in CLI patients who failed or were unsuitable for surgery or intravascular intervention. Of 23 patients enrolled, 18 with rest pain or non-healing ulcers (Rutherford categories 4 and 5) were treated according to protocol, and 5 with significant tissue loss (Rutherford 6) were treated under compassionate treatment. Patients were assigned randomly to receive 1 × 107 or 5 × 107 (EC-to-SMC ratio, 1:1) of the cell combination. One-year amputation-free survival rate was 72% (13/18) for Rutherford 4 and 5 patients; all 5 patients with Rutherford 6 underwent amputation. Of the 12 with unhealing ulcers at dosing, 6 had complete healing and 2 others had >66% reduction in ulcer size. Outcomes did not differ between the dose groups. No severe adverse events were observed related to the therapy.

Derivation and Implementation of a Protocol in Israel for Organ Donation after Cardio-Circulatory Death.

BACKGROUND: Strategies aimed at expanding the organ donor pool have been sought, which has resulted in renewed interest in donation after cardio-circulatory death (DCCD), also known as non-heart beating donors (NHBDs). OBJECTIVES: To describe the derivation and implementation of a protocol for DCCD in Israel and report on the results with the first six cases. METHODS: After receiving approval from an extraordinary ethics committee, Ministry of Health, the steering committee of the National Transplant Center defined and reached consensus on the unique challenges presented by a DCCD program. These protocol included medical aspects (construction of a clinical pathway), social and ethical aspects (presentation of the protocol at a public gathering(, legal/ethical aspects (consent for organ preservation procedures being either implied if the donor had signed an organ donor card or received directly from a surrogate decision maker), and logistical aspects (pilot study confined to kidney retrieval and to four medical centers). Data regarding organ donors and recipients were recorded. RESULTS: The protocol was implemented at four medical centers. Consent for organ donation was received from four of the six potential donors meeting criteria for inclusion, in all cases, from a surrogate decision maker. Of the eight kidneys retrieved, only four were suitable for transplantation, which was carried out successfully for four recipients. Graft function remained normal in all cases in 6-12 months follow-up. CONCLUSIONS: The DCCD program was successfully implemented and initial results are encouraging, suggesting that expansion of the program might further aid in decreasing the gap between needs and availability of organs.

PIWI-interacting RNA 021285 is involved in breast tumorigenesis possibly by remodeling the cancer epigenome.

Although PIWI-interacting RNAs (piRNAs) account for the largest class of the small non-coding RNA superfamily, virtually nothing is known of their function in human carcinogenesis. Once thought to be expressed solely in the germ line where they safeguard the genome against transposon-induced insertional mutations, piRNAs are now believed to play an active role in somatic gene regulation through sequence-specific histone modification and DNA methylation. In the current study, we investigate the role of piRNA-021285 (piR-021285) in the regulation of the breast cancer methylome. Genotypic screening of a panel of single-nucleotide polymorphism (SNP)-containing piRNAs revealed a significant association between SNP rs1326306 G>T in piR-021285 and increased likelihood for breast cancer in a Connecticut-based population (441 cases and 479 controls). Given nascent but compelling evidence of piRNA-mediated gene-specific methylation in the soma, a genome-wide methylation screen was then carried out using wild type (WT) and variant piR-021285 mimic-transfected MCF7 cells to explore whether the observed association could be attributed in part to piR-021285-induced methylation at cancer-relevant genes. We found significant methylation differences at a number of experimentally implicated breast cancer-related genes, including attenuated 5' untranslated region (UTR)/first exon methylation at the proinvasive ARHGAP11A gene in variant mimic-transfected cells. Follow-up functional analyses revealed both concurrent increased ARHGAP11A mRNA expression and enhanced invasiveness in variant versus WT piR-021285 mimic-transfected breast cancer cell lines. Taken together, our findings demonstrate the first evidence supporting a role of piRNAs, a novel group of non-coding RNA, in human tumorigenesis via a piRNA-mediated epigenetic mechanism, which warrants further confirmation and investigation.

The circadian gene CRY2 is associated with breast cancer aggressiveness possibly via epigenomic modifications.

Although the role of core circadian gene cryptochrome 2 (CRY2) in breast tumorigenesis has been demonstrated, the correlations of CRY2 with clinical parameters in breast cancer patients and its involvement in epigenetic processes such as DNA methylation remain relatively unexplored. In the current study, we first queried the Oncomine database and the Gene Expression-Based Outcome for Breast Cancer Online (GOBO) database to identify associations between CRY2 expression levels and clinical parameters in breast cancer patients. We then silenced CRY2 in vitro and performed a genome-wide methylation array to determine the epigenetic impact of CRY2 silencing. The Ingenuity Pathway Analysis software was used to further explore the genes exhibiting altered methylation identified using the array. We found that CRY2 was frequently down-regulated in breast cancer tissue compared to adjacent normal tissue or breast tissue from healthy controls. Lower CRY2 expression was associated with estrogen receptor (ER)-negativity (P < 0.0001), higher tumor grade (P < 0.0001), and shorter overall survival time in breast cancer patients (HR = 1.44, 95 % confidence interval (CI) 1.09-1.91). Genome-wide methylation analysis showed that a total of 515 CpG sites were hypermethylated following CRY2 knockdown, while 730 sites were hypomethylated. The pathway analysis revealed several cancer-relevant networks with genes exhibiting significantly altered methylation following CRY2 silencing. These findings suggest that the core circadian gene CRY2 is associated with breast cancer progression and prognosis, and that knockdown of CRY2 causes the epigenetic dysregulation of genes involved in cancer-relevant pathways, which provide further evidence supporting a role of the circadian system in breast tumorigenesis.

Melatonin enhances DNA repair capacity possibly by affecting genes involved in DNA damage responsive pathways.

BACKGROUND: Melatonin, a hormone-like substance involved in the regulation of the circadian rhythm, has been demonstrated to protect cells against oxidative DNA damage and to inhibit tumorigenesis. RESULTS: In the current study, we investigated the effect of melatonin on DNA strand breaks using the alkaline DNA comet assay in breast cancer (MCF-7) and colon cancer (HCT-15) cell lines. Our results demonstrated that cells pretreated with melatonin had significantly shorter Olive tail moments compared to non-melatonin treated cells upon mutagen (methyl methanesulfonate, MMS) exposure, indicating an increased DNA repair capacity after melatonin treatment. We further examined the genome-wide gene expression in melatonin pretreated MCF-7 cells upon carcinogen exposure and detected altered expression of many genes involved in multiple DNA damage responsive pathways. Genes exhibiting altered expression were further analyzed for functional interrelatedness using network- and pathway-based bioinformatics analysis. The top functional network was defined as having relevance for "DNA Replication, Recombination, and Repair, Gene Expression, [and] Cancer". CONCLUSIONS: These findings suggest that melatonin may enhance DNA repair capacity by affecting several key genes involved in DNA damage responsive pathways.

Restoration of renal responsiveness to atrial natriuretic peptide in experimental nephrotic syndrome by albumin infusion.

BACKGROUND: The natriuretic/diuretic response to atrial natriuretic peptide (ANP), an important regulator of water and Na(+) balance, is markedly attenuated in nephrotic syndrome (NS). It has been suggested that the diminished renal responsiveness to ANP may contribute to the pathogenesis of salt retention and edema formation in NS. However, the mechanisms underlying the renal hyporesponsiveness to ANP remain largely unknown. METHODS: The acute effects of exogenous infusion of ANP (5 µg/kg + 10 µg/kg/h) were studied by clearance methodology in control rats, hypoalbuminemic rats with Adriamycin (ADR)-induced NS and in ADR-treated rats infused with hyperoncotic albumin sufficient to restore plasma albumin to normal levels. RESULTS: Administration of ANP to control rats resulted in a significant increase in urinary flow rate, absolute rate of sodium excretion (+456%) and glomerular filtration rate (GFR). Mean arterial blood pressure decreased following infusion of the peptide. In the nephrotic rats, baseline GFR and Na(+) excretion were significantly lower than in the control animals, and the renal effects of ANP were markedly blunt compared to the control animals. In contrast, the hypotensive effect of ANP in the ADR-treated rats was largely preserved. Infusion of hyperoncotic albumin prior to ANP administration reversed the decrease in baseline GFR and Na(+) excretion and completely restored the renal effects of ANP in the nephrotic rats. CONCLUSION: These findings indicate that renal hyporesponsiveness to ANP in rats with ADR-induced NS is a reversible phenomenon that appears to be of functional origin rather than reflecting permanent cellular damage.

Diabetes mellitus and colorectal cancer prognosis: a meta-analysis.

BACKGROUND: Diabetes mellitus is associated with an increased incidence of colorectal cancer, but the impact of diabetes mellitus on colorectal cancer prognosis is not clear. OBJECTIVE: We conducted a meta-analysis of observational studies to examine the association between preexisting diabetes mellitus and colorectal cancer all-cause mortality, cancer-specific mortality, and recurrence. DATA SOURCES: Medline and Embase were searched through August 22, 2012. STUDY SELECTION: We included studies reporting all-cause mortality, cancer-specific mortality, disease-free survival, or recurrence in patients who have colorectal cancer according to diabetic status. INTERVENTION: Meta-analyses were performed by the use of random-effects models. MAIN OUTCOME MEASURES: The primary outcomes measured were all-cause mortality, cancer-specific mortality, and disease-free survival. RESULTS: Twenty-six articles met our inclusion criteria. Patients with colorectal cancer who had diabetes mellitus had a 17% increased risk of all-cause mortality (relative risk, 1.17; 95% CI, 1.09-1.25) and a 12% increased risk of cancer-specific mortality (relative risk, 1.12; 95% CI, 1.01-1.24) in comparison with those who did not have diabetes mellitus. Those with diabetes mellitus also had poorer disease-free survival (relative risk, 1.54; 95% CI, 1.08-2.18) compared with their nondiabetic counterparts. In subgroup analyses, diabetes mellitus was associated with all-cause mortality in both rectal (relative risk, 1.24; 95% CI, 1.07-1.29) and colon cancer patients (relative risk, 1.17; 95% CI, 1.07-1.29). Sensitivity analyses including only patients with nonmetastatic disease identified stronger associations between diabetes mellitus and both all-cause (relative risk, 1.32; 95% CI, 1.21-1.44) and cancer-specific (relative risk, 1.27; 95% CI, 1.06-1.52) mortality. LIMITATIONS: Some studies had short follow-up or did not report mean or median follow-up. The included studies were heterogeneous in study population, diabetes mellitus diagnostic criteria, and outcome ascertainment. CONCLUSION: Patients with colorectal cancer who have diabetes mellitus are at greater risk for all-cause and cancer-specific mortality and have worse disease-free survival than those who do not have diabetes mellitus. Studies are warranted to determine whether the proper treatment could attenuate the excess mortality among patients with colorectal cancer who have diabetes mellitus.

Giant phagocytes (Gφ) and neutrophil-macrophage hybrids in human carotid atherosclerotic plaques - An activated phenotype.

Introduction: A small subpopulation of CD66b+ neutrophils with extended lifespan and immensely large size was identified in vitro. They internalized dead neutrophil remnants and cellular debris, transforming them into giant phagocytes (Gφ) resembling macrophage-foam cells with a massive lipid content and CD68+ scavenger receptor expression. Thus, we sought to investigate if similar CD66b+ neutrophils with altered morphology and functions exist in inflammatory/atherosclerotic conditions in vivo, by using human carotid atherosclerotic plaques. Methods: Thirty-three plaques were obtained from 31 patients undergoing endarterectomy. Carotid plaques were analyzed for CD markers by immunohistochemistry and immunofluorescence and quantitatively analyzed by confocal microscopy. Intra-plaque lipids were stained with Oil Red O. Results: Plaque CD66b+ neutrophils co-expressed myeloperoxidase (MPO)+ and neutrophil elastase (NE)+. Also, co-expression of CD66b+/CD68+, CD66b+/CD36+, CD66b+/vascular-endothelial-growth- factor (VEGF)+ and 3-nitrotyrosine (3-NT)+/NE+ was noted. Similarly, macrophages co-expressed CD163+/CD68+, CD163+/VEGF+ and CD163+/3-NT+. Both cell types were predominantly localized in lipid-rich areas and stained for lipids. CD66b+ and CD163+ expressions were highly positively correlated with each other and each with CD68+, and 3-NT+. Morphologically, CD66+ cells were big, had a rounded nucleus, and resembled macrophage-foam cell morphology as well as that of Gφ in vitro. To clarify whether CD66b+ and CD163+ cells represent two distinct plaque-populations, plaques were double-stained for CD66b/CD163 co-localization. A third of the plaques was negative for CD66b/CD163 co-localization. Other plaques had a low co-localization, but in few plaques, co-localization was high, collectively, indicating that in some of plaques there were two distinct cell populations, those resembling Gφ, and those co-expressing CD66b+/CD163+, demonstrating a hybrid neutrophil-macrophage phenotype. Interestingly, CD66b+/CD163+ co-localization was highly positively correlated with the oxidant 3-NT, hence, supporting trans-differentiation of CD66b+ cells to CD163+ Cells. Conversely, phagocytosis of dead neutrophils by macrophages might have also occurred. Discussion: Thus, we conclude that in some of the plaques CD66b+ cells might represent cells resembling Gφ that developed in prolonged culture conditions. Yet, CD66b+/CD163+ co-expressing cells represent a new neutrophil-macrophage hybrid population of unknown transitioning point, possibly by adopting macrophage markers or contrariwise. Nonetheless, the significance and functions of these cells in plaque biology or other inflammatory/atherosclerotic conditions should be unveiled.

Primary care physician leaders' perspectives on opportunities and challenges in healthcare leadership: a qualitative study.

BACKGROUND: There is an increasing demand for physicians to assume leadership roles in hospitals, health systems, clinics and community settings, given the documented positive outcomes of physician leadership and the systemic shifts towards value-based care. The purpose of this study is to examine how primary care physicians (PCPs) perceive and experience leadership roles. Better understanding how PCPs perceive leadership affords the opportunity to influence changes in primary care training in order to more adequately prepare and support physicians for current and future leadership roles. METHODS: This study used qualitative interviews, conducted from January to May 2020. The participants included 27 PCPs, recruited via the Harvard Medical School Center for Primary Care newsletters and through snowball sampling techniques. Participants worked in 22 different organisations, including major urban health systems, corporate pharmacy, public health departments and academic medical centres. RESULTS: Using content analysis and qualitative comparative analysis methodologies, three major themes and seven subthemes emerged from the interviews. The primary themes included the advantage PCPs have in leadership positions, the lack of leadership training and development, and disincentives to leading. CONCLUSIONS: While PCPs perceive primary care to hold a unique position that would incline them towards leadership, the lack of training and other noted disincentives are barriers to leadership. Therefore, health organisations should seek to invest in, better train and promote PCPs in leadership.

Primary Care Physician Leadership in Top Ranked US Hospitals.

This assessment of the "top hospitals" in the US according to 4 leading rankings reveals only 4 to 7% of represented CEOs are primary care physicians by training. Greater attention to leadership development from primary care residency through health system practice is needed to avoid diminishing primary care's critical role and salutary global benefits.

Simultaneous Renal Transplantation With Bilateral Nephrectomy and Ureterocystoplasty.

Bladder augmentation (BA) may be required before renal transplantation in children with end stage renal disease (ESRD). Herein we report a case of a 7-year-old boy with ESRD, contracted bladder and severe bilateral reflux secondary to posterior urethral valve (PUV), successfully managed by simultaneous bilateral nephrectomy, bilateral ureterocystoplasty and renal transplantation.

Feasibility and Efficacy of Magnetic Sphincter Augmentation for the Management of Gastroesophageal Reflux Disease Post-Sleeve Gastrectomy for Obesity.

BACKGROUND: Patients with medically intractable GERD after laparoscopic sleeve gastrectomy (LSG) have limited surgical options. Fundoplication is difficult post-LSG. Roux-en-Y gastric bypass may be used as a conversion procedure but is more invasive with potential for serious complications. Magnetic sphincter augmentation (MSA) is a less invasive GERD treatment alternative. The objective of this study was to assess safety and efficacy outcomes of MSA after LSG. METHODS: The primary outcome of this observational, multicenter, single-arm prospective study was the rate of serious device and/or procedure-related adverse events (AEs). The efficacy of the LINX device was measured comparing baseline to 12-month post-implant reductions in distal acid exposure, GERD-HRQL score, and average daily PPI usage. RESULTS: Thirty subjects who underwent MSA implantation were followed 12 months post-implant. No unanticipated adverse device effects were observed. There were two adverse events deemed serious (dysphagia, pain, 6.7%) which resolved without sequelae. GERD-HRQL scores showed significant improvement (80.8%, P < 0.001), and reduction in daily PPI usage was seen (95.8%, P < 0.001). Forty-four percent of subjects demonstrated normalization or > = 50% reduction of total distal acid exposure time (baseline 16.2%, 12 months 11%; P = 0.038). CONCLUSIONS: Post-LSG, MSA showed an overall improvement of GERD symptoms, and reduction in PPI use with explants within anticipated range along with improvement in distal esophageal acid exposure time.