Phase I study, and dosing regimen selection for a pivotal COVID-19 trial of GST-HG171.

This study is aimed to evaluate the safety, tolerability, and pharmacokinetics (PK), as well as to select an appropriate dosing regimen for the pivotal clinical trial of GST-HG171, an orally bioavailable, potent, and selective 3CL protease inhibitor by a randomized, double-blind, and placebo-controlled phase I trial in healthy subjects. We conducted a Ph1 study involving 78 healthy subjects to assess the safety, tolerability, and PK of single ascending doses (150-900 mg) as well as multiple ascending doses (MADs) (150 and 300 mg) of GST-HG171. Additionally, we examined the food effect and drug-drug interaction of GST-HG171 in combination with ritonavir through a MAD regimen of GST-HG171/ritonavir (BID or TID) for 5 days. Throughout the course of these studies, no serious AEs or deaths occurred, and no AEs necessitated study discontinuation. We observed that food had no significant impact on the exposure of GST-HG171. However, the presence of ritonavir substantially increased the exposure of GST-HG171, which facilitated the selection of the GST-HG171/ritonavir dose and regimen (150/100 mg BID) for subsequent phase II/III trials. The selected dose regimen was achieved through concentrations continuously at 6.2-9.9-fold above the levels required for protein-binding adjusted 50% inhibition (IC50) of viral replication in vitro. The combination of 150 mg GST-HG171/100 mg ritonavir demonstrated favorable safety and tolerability profiles. The PK data obtained from GST-HG171/ritonavir administration guided the selection of appropriate dose for a pivotal phase II/III trial currently in progress. (This study has been registered at ClinicalTrials.gov under identifier NCT05668897).

Infectivity of pseudotyped SARS-CoV-2 variants of concern in different human cell types and inhibitory effects of recombinant spike protein and entry-related cellular factors.

Since the report of the first COVID-19 case in 2019, SARS-CoV-2 variants of concern (VOCs) have continued to emerge, manifesting diverse infectivity, evasion of host immunity and pathology. While ACE2 is the predominant receptor of SARS-CoV-2, TMPRSS2, Kim-1, NRP-1, CD147, furin, CD209L, and CD26 have also been implicated as viral entry-related cofactors. To understand the variations in infectivity and pathogenesis of VOCs, we conducted infection analysis in human cells from different organ systems using pseudoviruses of VOCs including Alpha, Beta, Gamma, and Delta. Recombinant spike S1, RBD, ACE2, Kim-1, and NRP-1 proteins were tested for their ability to block infection to dissect their roles in SARS-CoV-2 entry into cells. Compared with wild type SARS-CoV-2 (WT), numerous VOCs had significant increases of infectivity across a wide spectrum of cell types. Recombinant ACE2 protein more effectively inhibited the infection of VOCs including Delta and Omicron (BA.1 and BA.2) than that of WT. Interestingly, recombinant S1, RBD, Kim-1, and NRP-1 proteins inhibited the infection of all pseudoviruses in a manner dependent on the levels of ACE2 expression in different cell types. These results provide insights into the diverse infectivity of SARS-CoV-2 VOCs, which might be helpful for managing the emergence of new VOCs.

Improved benefit of continuing luspatercept therapy: sub-analysis of patients with lower-risk MDS in the MEDALIST study.

Red blood cell transfusion independence (RBC-TI) is an important goal in treating lower-risk myelodysplastic syndromes with ring sideroblasts. In the phase 3 MEDALIST study, RBC-TI of ≥ 8 weeks was achieved by significantly more luspatercept- versus placebo-treated patients in the first 24 weeks of treatment. In this post hoc analysis, we evaluated RBC transfusion units and visits based on patients' baseline transfusion burden level and the clinical benefit of luspatercept treatment beyond week 25 in initial luspatercept nonresponders (patients who did not achieve RBC-TI ≥ 8 weeks by week 25) but continued luspatercept up to 144 weeks. RBC transfusion burden, erythroid response, serum ferritin levels, and hemoglobin levels relative to baseline were evaluated. Through week 25, fewer RBC transfusion units and visits were observed in luspatercept-treated patients versus placebo, regardless of baseline transfusion burden. This continued through 144 weeks of luspatercept treatment, particularly in patients with low baseline transfusion burden. Sixty-eight patients were initial nonresponders at week 25 but continued treatment; most (81%) received the maximum dose of luspatercept (1.75 mg/kg). Sixteen percent achieved RBC-TI for ≥ 8 weeks during weeks 25-48, 26% had reduced RBC transfusion burden, 10% achieved an erythroid response, 44% had reduced serum ferritin, and hemoglobin levels increased an average of 1.3 g/dL from baseline. These data have implications for clinical practice, as transfusion units and visits are less in luspatercept-treated patients through week 25 regardless of baseline transfusion burden, and continuing luspatercept beyond week 25 can potentially provide additional clinical benefits for initial nonresponders. Trial registration: NCT02631070.

Ultrarapid and ultrasensitive detection of SARS-CoV-2 antibodies in COVID-19 patients via a 3D-printed nanomaterial-based biosensing platform.

Rapid detection of antibodies during infection and after vaccination is critical for the control of infectious outbreaks, understanding immune response, and evaluating vaccine efficacy. In this manuscript, we evaluate a simple ultrarapid test for SARS-CoV-2 antibodies in COVID-19 patients, which gives quantitative results (i.e., antibody concentration) in 10-12 s using a previously reported nanomaterial-based three-dimensional (3D)-printed biosensing platform. This platform consists of a micropillar array electrode fabricated via 3D printing of aerosolized gold nanoparticles and coated with nanoflakes of graphene and specific SARS-CoV-2 antigens, including spike S1, S1 receptor-binding domain (RBD) and nucleocapsid (N). The sensor works on the principle of electrochemical transduction, where the change of sensor impedance is realized by the interactions between the viral proteins attached to the sensor electrode surface and the antibodies. The three sensors were used to test samples from 17 COVID-19 patients and 3 patients without COVID-19. Unlike other serological tests, the 3D sensors quantitatively detected antibodies at a concentration as low as picomole within 10-12 s in human plasma samples. We found that the studied COVID-19 patients had higher concentrations of antibodies to spike proteins (RBD and S1) than to the N protein. These results demonstrate the enormous potential of the rapid antibody test platform for understanding patients' immunity, disease epidemiology and vaccine efficacy, and facilitating the control and prevention of infectious epidemics.

Neutralizing antibodies to SARS-CoV-2 variants of concern including Delta and Omicron in subjects receiving mRNA-1273, BNT162b2, and Ad26.COV2.S vaccines.

SARS-CoV-2 vaccines have contributed to the control of COVID-19 in some parts of the world. However, the constant emergence of variants of concern (VOCs) challenges the effectiveness of SARS-CoV-2 vaccines over time. In particular, Omicron contains a high number of mutations in the spike (S) protein gene, on which most vaccines were developed. In this study, we quantitated neutralizing antibodies in vaccine recipients at various times postvaccination using S protein-based pseudoviruses derived from wild type (WT) SARS-CoV-2 and five VOCs including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), and Omicron (B.1.1.529). We found that two-dose mRNA-1273 and BNT162b2 vaccines elicited robust neutralizing antibodies against WT, Alpha, Beta, Gamma, and Delta, but wanned after 6 months with a faster decline observed for BNT162b2. Both mRNA-1273 and BNT162b2 elicited weak neutralizing antibodies against Omicron. One dose of Ad26.COV2.S vaccine induced weaker neutralizing antibodies against WT and most VOCs than mRNA-1273 and BNT162b2 did but moderate neutralizing antibodies against Delta and Omicron, which lasted for 6 months. These results support current recommendations of the Centers for Disease Control and Prevention for a booster 5 months after full immunization with an mRNA-based vaccine and the use of an mRNA-based vaccine 2 months after Ad26.COV2.S vaccination.

Association of preoperative vein mapping with hemodialysis access characteristics and outcomes in the Vascular Quality Initiative.

BACKGROUND: Preoperative vein mapping before arteriovenous fistula (AVF) or arteriovenous graft (AVG) placement has been debated as a possible method of improving hemodialysis access outcomes for patients. However, high-quality national studies that have addressed this relationship are lacking. Thus, we assessed the association of preoperative vein mapping with hemodialysis access configuration and outcomes. METHODS: In the present cohort study, we analyzed all patients who had undergone AVF or AVG placement with data captured in the Vascular Quality Initiative hemodialysis access dataset from August 2011 to September 2019. The patients were stratified by whether they had undergone preoperative vein mapping. The primary (configuration) outcomes were access type (AVF vs AVG) and location (upper arm vs forearm). The secondary (longitudinal) outcomes were the successful initiation of hemodialysis, maintenance of secondary patency, and the need for reintervention 1 year after the index operation. RESULTS: Overall, 85.6% of the 46,010 included patients had undergone preoperative vein mapping. Of the 46,010 patients, 76.1% and 23.9% had undergone AVF and AVG creation, respectively. AVF creation (77.6% vs 67.3%) and forearm location (54.6% vs 47.3%) were more frequent for the patients who had undergone preoperative vein mapping than for those who had not (P < .001). After adjusting for baseline differences between the groups, preoperative vein mapping was associated with increased odds of receiving an AVF vs AVG (adjusted odds ratio, 1.64; 95% confidence interval [CI], 1.55-1.75) and forearm vs upper arm access (adjusted odds ratio, 1.22; 95% CI, 1.16-1.30). The incidence of the loss of secondary patency was lower for patients with preoperative vein mapping (P < .001), and persisted after risk adjustment (adjusted hazard ratio, 0.81; 95% CI, 0.75-0.88). CONCLUSIONS: Preoperative vein mapping was associated with favorable hemodialysis access configurations and outcomes in real-world practice. These data suggest that the use of preoperative vein mapping could improve the likelihood of favorable outcomes for patients requiring hemodialysis access.

Transcarotid artery revascularization is associated with similar outcomes to carotid endarterectomy regardless of patient risk status.

BACKGROUND: Carotid artery stenting (CAS), including both transfemoral carotid artery stenting (TFCAS) and transcarotid artery revascularization (TCAR), reimbursement has been limited to high-risk patients by the Centers for Medicare & Medicaid Services (CMS) since 2005. We aimed to assess the association of CMS high-risk status with perioperative outcomes for carotid endarterectomy (CEA), TFCAS, and TCAR. METHODS: We performed a retrospective review of all Vascular Quality Initiative patients who underwent carotid revascularization between 2015 and 2020. Patients were stratified by whether they met CMS CAS criteria, and univariable and multivariable logistic regression analyses were performed to assess the association of procedure type (CEA, TFCAS, TCAR) with perioperative outcomes. RESULTS: Of 124,531 individuals who underwent carotid revascularization procedures, 91,687 (73.6%) underwent CEA, 17,247 (13.9%) underwent TFCAS, and 15,597 (12.5%) underwent TCAR. Among patients who met the CMS CAS criteria (ie, high-risk patients), the incidence of perioperative stroke was 2.7% for CEA, 3.4% for TFCAS, and 2.4% for TCAR (P < .001). Among standard-risk patients, the incidence of perioperative stroke was 1.7% for CEA, 2.7% for TFCAS, and 1.8% for TCAR (P < .001). After adjusting for baseline demographic and clinical characteristics, the odds of perioperative stroke were lower for TCAR versus CEA in high-risk patients (adjusted odds ratio [aOR], 0.82; 95% confidence interval [CI], 0.68-0.99) and similar in standard-risk patients (aOR, 1.05; 95% CI, 0.84, 1.31). In contrast, the adjusted odds of perioperative stroke were higher for TFCAS versus CEA in high-risk patients (aOR, 1.23; 95% CI, 1.03-1.46) and standard-risk patients (aOR, 1.60; 95% CI, 1.37-1.86). In both populations, TFCAS and TCAR patients had significantly lower odds of myocardial infarction than CEA patients (both P < .001). CONCLUSIONS: The perioperative risks associated with CEA, TFCAS, and TCAR in high-risk patients support the current CMS criteria, although the risks associated with each revascularization approach in standard-risk patients suggest that distinguishing TCAR from TFCAS may be warranted.

Discovery and preclinical evaluations of GST-HG131, a novel HBV antigen inhibitor for the treatment of chronic hepatitis B infection.

Chronic hepatitis B (CHB) remains a significant health challenge worldwide. The current treatments for CHB achieve less than 10% cure rates, majority of the patients are on therapy for life. Therefore, cure of CHB is a high unmet medical need. HBV surface antigen (HBsAg) loss and seroconversion are considered as the key for the cure. RG7834 is a novel, orally bioavailable small molecule reported to reduce HBV antigens. Based on RG7834 chemistry, we designed and discovered a series of dihydrobenzopyridooxazepine (DBP) series of HBV antigen inhibitors. Extensive SAR studies led us to GST-HG131 with excellent reduction of HBV antigens (both HBsAg and HBeAg) in vitro and in vivo. GST-HG131 improved safety in rat toxicology studies over RG7834. The promising inhibitory activity, together with animal safety enhancement, merited GST-HG131 progressed into clinical development in 2020 (NCT04499443).

Converting laparoscopic colectomies to open is associated with similar outcomes as a planned open approach among Crohn's disease patients.

PURPOSE: There has been a noted reluctance to offer laparoscopic surgery to Crohn's Disease patients due to the potential risks, and high rate, of converting the procedure to open. The purpose of this study was to compare clinical outcomes between Crohn's Disease patients undergoing a planned open colectomy, to those undergoing a laparoscopic colectomy that was converted to open. METHODS: Crohn's Disease patients undergoing an elective colectomy were identified using the ACS-NSQIP database (2012-2019). Patients were stratified based on operative approach: open, laparoscopic, and laparoscopic converted to open. Multivariable logistic regression was used to assess the impact of conversion to open on overall and serious postoperative morbidity. RESULTS: Among 8039 elective colectomies, 40.5% were performed open, 46.9% were completed laparoscopically, and 12.6% were converted to open. The conversion rate among all laparoscopic cases was 21.3%. On unadjusted analysis, conversion to open demonstrated similar rates of overall morbidity (P = 0.355) and serious morbidity (P = 0.724) compared to a planned open approach. On multivariable analysis, conversion to open was not associated with increased odds of overall morbidity (OR 1.12, 95% CI 0.94-1.30, P = 0.238) or serious morbidity (OR 1.20, 95% CI 0.98-1.46, P = 0.074), when compared to an open approach. CONCLUSION: Among Crohn's Disease patients, cases converted from laparoscopic to open exhibited similar outcomes as a planned open approach. Despite the limitations associated with this retrospective study, our findings suggest that laparoscopic surgery may be safely pursued among Crohn's Disease patients, as the risks of conversion are potentially balanced by the benefits of laparoscopic surgery.

US medical student perspectives on asian american patient inclusion in medical education: a qualitative Study.

BACKGROUND: Asian American (AsAm) representation is lacking in conversations surrounding cultural humility in healthcare. We aimed to investigate US medical student perspectives on AsAm patient inclusion in cultural humility training in medical education. METHODS: This qualitative study analyzed free-text responses to an optional, open-ended question presented at the conclusion of an online survey assessing medical student experiences with and perceptions regarding AsAm patients in their medical education. This survey was distributed to a convenience sample of nine US medical schools. Medical students who completed at least one clinical rotation were eligible to participate in the survey. Qualitative analysis of free-text responses was conducted in an iterative process to generate emergent themes. RESULTS: There was a total of 195 optional free-text responses from 688 participants (28%). Motivation to learn about AsAm population included shared identity and desire to better serve the AsAm population in their local community and future careers. Topics of interest included healthcare-related cultural preferences, healthcare delivery strategies, and health disparities for the AsAm population and other minority patients. Students reported that they drew on personal experiences and some pre-clinical or clinical exposures to learn about AsAm patients. Respondents cited the lack of exposure in the medical school curriculum and clinical experiences as the main challenge to learning about AsAm health and provided suggestions for the delivery of this education in their pre-clinical and clinical education. Respondents emphasized that AsAms are treated as a monolith in medical education and healthcare, despite their heterogeneity. CONCLUSIONS: Medical students identified a need and interest for greater inclusion of AsAm topics in medical education on cultural humility and minority health.

Edoxaban for the Treatment of Cancer-Associated Venous Thromboembolism.

BACKGROUND: Low-molecular-weight heparin is the standard treatment for cancer-associated venous thromboembolism. The role of treatment with direct oral anticoagulant agents is unclear. METHODS: In this open-label, noninferiority trial, we randomly assigned patients with cancer who had acute symptomatic or incidental venous thromboembolism to receive either low-molecular-weight heparin for at least 5 days followed by oral edoxaban at a dose of 60 mg once daily (edoxaban group) or subcutaneous dalteparin at a dose of 200 IU per kilogram of body weight once daily for 1 month followed by dalteparin at a dose of 150 IU per kilogram once daily (dalteparin group). Treatment was given for at least 6 months and up to 12 months. The primary outcome was a composite of recurrent venous thromboembolism or major bleeding during the 12 months after randomization, regardless of treatment duration. RESULTS: Of the 1050 patients who underwent randomization, 1046 were included in the modified intention-to-treat analysis. A primary-outcome event occurred in 67 of the 522 patients (12.8%) in the edoxaban group as compared with 71 of the 524 patients (13.5%) in the dalteparin group (hazard ratio, 0.97; 95% confidence interval [CI], 0.70 to 1.36; P=0.006 for noninferiority; P=0.87 for superiority). Recurrent venous thromboembolism occurred in 41 patients (7.9%) in the edoxaban group and in 59 patients (11.3%) in the dalteparin group (difference in risk, -3.4 percentage points; 95% CI, -7.0 to 0.2). Major bleeding occurred in 36 patients (6.9%) in the edoxaban group and in 21 patients (4.0%) in the dalteparin group (difference in risk, 2.9 percentage points; 95% CI, 0.1 to 5.6). CONCLUSIONS: Oral edoxaban was noninferior to subcutaneous dalteparin with respect to the composite outcome of recurrent venous thromboembolism or major bleeding. The rate of recurrent venous thromboembolism was lower but the rate of major bleeding was higher with edoxaban than with dalteparin. (Funded by Daiichi Sankyo; Hokusai VTE Cancer ClinicalTrials.gov number, NCT02073682 .).

Considerations from the Innovation and Quality Induction Working Group in Response to Drug-Drug Interaction Guidance from Regulatory Agencies: Guidelines on Model Fitting and Recommendations on Time Course for In Vitro Cytochrome P450 Induction Studies Including Impact on Drug Interaction Risk Assessment.

Translational and ADME Sciences Leadership Group Induction Working Group (IWG) presents an analysis on the time course for cytochrome P450 induction in primary human hepatocytes. Induction of CYP1A2, CYP2B6, and CYP3A4 was evaluated by seven IWG laboratories after incubation with prototypical inducers (omeprazole, phenobarbital, rifampicin, or efavirenz) for 6-72 hours. The effect of incubation duration and model-fitting approaches on induction parameters (Emax and EC50) and drug-drug interaction (DDI) risk assessment was determined. Despite variability in induction response across hepatocyte donors, the following recommendations are proposed: 1) 48 hours should be the primary time point for in vitro assessment of induction based on mRNA level or activity, with no further benefit from 72 hours; 2) when using mRNA, 24-hour incubations provide reliable assessment of induction and DDI risk; 3) if validated using prototypical inducers (>10-fold induction), 12-hour incubations may provide an estimate of induction potential, including characterization as negative if <2-fold induction of mRNA and no concentration dependence; 4) atypical dose-response ("bell-shaped") curves can be addressed by removing points outside an established confidence interval and %CV; 5) when maximum fold induction is well defined, the choice of nonlinear regression model has limited impact on estimated induction parameters; 6) when the maximum fold induction is not well defined, conservative DDI risk assessment can be obtained using sigmoidal three-parameter fit or constraining logistic three- or four-parameter fits to the maximum observed fold induction; 7) preliminary data suggest initial slope of the fold induction curve can be used to estimate Emax/EC50 and for induction risk assessment. SIGNIFICANCE STATEMENT: Regulatory agencies provide inconsistent guidance on the optimum length of time to evaluate cytochrome P450 induction in human hepatocytes, with EMA recommending 72 hours and FDA suggesting 48-72 hours. The Induction Working Group analyzed a large data set generated by seven member companies and determined that induction response and drug-drug risk assessment determined after 48-hour incubations were representative of 72-hour incubations. Additional recommendations are provided on model-fitting techniques for induction parameter estimation and addressing atypical concentration-response curves.

Geographical socioeconomic disadvantage is associated with adverse outcomes following major amputation in diabetic patients.

OBJECTIVE: Socioeconomic disadvantage is a known predictor of adverse outcomes and amputation in patients with diabetes. However, its association with outcomes after major amputation has not been described. Here, we aimed to determine the association of geographic socioeconomic disadvantage with 30-day readmission and 1-year reamputation rates among patients with diabetes undergoing major amputation. METHODS: Patients from the Maryland Health Services Cost Review Commission Database who underwent major lower extremity amputation with a concurrent diagnosis of diabetes mellitus between 2015 and 2017 were stratified by socioeconomic disadvantage as determined by the area deprivation index (ADI) (ADI1 [least deprived] to ADI4 [most deprived]). The primary outcomes were rates of 30-day readmission and 1-year reamputation, evaluated using multivariable logistic regression models and Kaplan-Meier survival analyses. RESULTS: A total of 910 patients were evaluated (66.0% male, 49.2% Black), including 30.9% ADI1 (least deprived), 28.6% ADI2, 19.1% ADI3, and 21.2% ADI4 (most deprived). After adjusting for differences in baseline demographic and clinical factors, the odds of 30-day readmission was similar among ADI groups (P > .05 for all). Independent predictors of 30-day readmission included female sex (odds ratio [OR], 1.45), Medicare insurance (vs private insurance; OR, 1.76), and peripheral artery disease (OR, 1.49) (P < .05 for all). The odds of 1-year reamputation was significantly greater among ADI4 (vs ADI1; OR, 1.74), those with a readmission for stump complication or infection/sepsis (OR, 2.65), and those with CHF (OR, 1.53) or PAD (OR, 1.59) (P < .05 for all). CONCLUSIONS: Geographic socioeconomic disadvantage is independently associated with 1-year reamputation, but not 30-day readmission, among Maryland patients undergoing a major amputation for diabetes. A directed approach at improving postoperative management of chronic disease progression in socioeconomically deprived patients may be beneficial to reducing long-term morbidity in this high-risk group.

What Does a Diagnosis of Depression Mean for Patients Undergoing Colorectal Surgery?

BACKGROUND: Depression has been linked to increased morbidity and mortality in patients after surgery. The purpose of this study is to investigate the impact of documented depression diagnosis on in-hospital postoperative outcomes of patients undergoing colorectal surgery. MATERIALS AND METHODS: Patients from the National Inpatient Sample (2002-2017) who underwent proctectomies and colectomies were included. The outcomes measured included total hospital charge, length of stay, delirium, wound infection, urinary tract infection (UTI), pneumonia, deep vein thrombosis, pulmonary embolism, mortality, paralytic ileus, leak, and discharge trends. Multivariable logistic and Poisson regression analyses were performed. RESULTS: Of the 4,212,125 patients, depression diagnosis was present in 6.72% of patients who underwent colectomy and 6.54% of patients who underwent proctectomy. Regardless of procedure type, patients with depression had higher total hospital charges and greater rates of delirium, wound infection, UTI, leak, and nonroutine discharge, with no difference in length of stay. On adjusted analysis, patients with a depression diagnosis who underwent colectomies had increased risk of delirium (odds ratio (OR) 2.11, 95% confidence interval (CI) 1.93-2.32), wound infection (OR 1.08, 95% CI 1.03-1.12), UTI (OR 1.15, 95% CI 1.10-1.20), paralytic ileus (OR 1.06, 95% CI 1.03-1.09), and leak (OR 1.37, 95% CI 1.30-1.43). Patients who underwent proctectomy showed similar results, with the addition of significantly increased total hospital charges among the depression group. Depression diagnosis was independently associated with lower risk of in-hospital mortality (colectomy OR 0.58, 95% CI 0.53-0.62; proctectomy OR 0.72, 95% CI 0.55-0.94). CONCLUSIONS: Patients with a diagnosis of depression suffer worse in-hospital outcomes but experience lower risk of in-hospital mortality after undergoing colorectal surgery. Further studies are needed to validate and fully understand the driving factors behind this.

Impact of Geographic Socioeconomic Disadvantage on Minor Amputation Outcomes in Patients With Diabetes.

BACKGROUND: Socioeconomic disadvantage is a known contributor to adverse events and higher admission rates in the diabetic population. However, its impact on outcomes after lower extremity amputation is unclear. We aimed to assess the association of geographic socioeconomic disadvantage with short- and long-term outcomes after minor amputation in patients with diabetes. MATERIALS AND METHODS: Geographic socioeconomic disadvantage was determined using the area deprivation index (ADI). All patients from the Maryland Health Services Cost Review Commission database (2012-2019) who underwent minor amputation with a concurrent diagnosis of diabetes were included and stratified by the ADI quartile. Associations of the ADI quartile with 30-day readmission and 1-year reamputation were evaluated using Kaplan-Meier survival analyses and multivariable logistic regression models adjusting for baseline differences. RESULTS: A total of 7415 patients with diabetes underwent minor amputation (70.1% male, 38.7% black race), including 28.1% ADI1 (least deprived), 42.8% ADI2, 22.9% ADI3, and 6.2% ADI4 (most deprived). After adjusting for demographic and clinical factors, the odds of 30-day readmission were greater in the intermediate ADI groups than those in the ADI1 group, but not among the most deprived. Adjusted odds of 1-year reamputation were greater among ADI4 than those among ADI1. Kaplan-Meier analysis confirmed a greater likelihood of reamputation with an increasing ADI quartile over a 1-year period (P < 0.001). CONCLUSIONS: Geographic socioeconomic disadvantage is independently associated with both short- and long-term outcomes after minor diabetic amputations in Maryland. A targeted approach addressing the health care needs of deprived regions may be beneficial in optimizing postoperative care in this vulnerable population.

History of depression is associated with worsened postoperative outcomes following colectomy.

AIM: Depression is a prevalent disorder that is associated with adverse health outcomes, but an understanding of its effect in colorectal surgery remains limited. The purpose of this study was to examine the impact of history of depression among patients undergoing colectomy. METHOD: United States patients from Marketscan (2010-2017) who underwent colectomy were included and stratified by whether they had a history of depression within the past year, defined as (1) a diagnosis of depression during the index admission, (2) a diagnosis of depression during any inpatient or (3) outpatient admission within the year, and/or (4) a pharmacy claim for an antidepressant within the year. The primary outcomes were length of stay (LOS) and inpatient hospital charge. Secondary outcomes included in-hospital mortality and postoperative complications. Logistic, negative binomial, and quantile regressions were performed. RESULTS: Among 88 981 patients, 21 878 (24.6%) had a history of depression. Compared to those without, patients with a history of depression had significantly longer LOS (IRR = 1.06, 95% CI [1.05, 1.07]), increased inpatient charge (ß = 467, 95% CI [167, 767]), and increased odds of in-hospital mortality (OR = 1.37, 95% CI [1.08, 1.73]) after adjustment. History of depression was also independently associated with increased odds of respiratory complication, pneumonia, and delirium (all P < 0.05). CONCLUSION: History of depression was prevalent among individuals undergoing colectomy, and associated with greater mortality and inpatient charge, longer LOS, and higher odds of postoperative complication. These findings highlight the impact of depression in colorectal surgery patients and suggest that proper identification and treatment may reduce postoperative morbidity.

Do specific operative approaches and insurance status impact timely access to colorectal cancer care?

INTRODUCTION: The increased use of minimally invasive surgery in the management of colorectal cancer has led to a renewed focus on how certain factors, such as insurance status, impact the equitable distribution of both laparoscopic and robotic surgery. Our goal was to analyze surgical wait times between robotic, laparoscopic, and open approaches, and to determine whether insurance status impacts timely access to treatment. METHODS: After IRB approval, adult patients from the National Cancer Database with a diagnosis of colorectal cancer were identified (2010-2016). Patients who underwent radiation therapy, neoadjuvant chemotherapy, had wait times of 0 days from diagnosis to surgery, or had metastatic disease were excluded. Primary outcomes were days from cancer diagnosis to surgery and days from surgery to adjuvant chemotherapy. Multivariable Poisson regression analysis was performed. RESULTS: Among 324,784 patients, 5.9% underwent robotic, 47.5% laparoscopic, and 46.7% open surgery. Patients undergoing robotic surgery incurred the longest wait times from diagnosis to surgery (29.5 days [robotic] vs. 21.7 [laparoscopic] vs. 17.2 [open], p < 0.001), but the shortest wait times from surgery to adjuvant chemotherapy (48.9 days [robotic] vs. 49.9 [laparoscopic] vs. 54.8 [open], p < 0.001). On adjusted analysis, robotic surgery was associated with a 1.46 × longer wait time to surgery (IRR 1.462, 95% CI 1.458-1.467, p < 0.001), but decreased wait time to adjuvant chemotherapy (IRR 0.909, 95% CI 0.905-0.913, p < 0.001) compared to an open approach. Private insurance was associated with decreased wait times to surgery (IRR 0.966, 95% CI 0.962-0.969, p < 0.001) and adjuvant chemotherapy (IRR 0.862, 95% CI 0.858-0.865, p < 0.001) compared to Medicaid. CONCLUSION: Though patients undergoing robotic surgery experienced delays from diagnosis to surgery, they tended to initiate adjuvant chemotherapy sooner compared to those undergoing open or laparoscopic approaches. Private insurance was independently associated not only with access to robotic surgery, but also shorter wait times during all stages of treatment.

Operative Approach Does Not Impact Radial Margin Positivity in Distal Rectal Cancer.

BACKGROUND: Robotic surgery is attractive for resection of low rectal cancer due to greater dexterity and visualization, but its benefit is poorly understood. We aimed to determine if operative approach impacts radial margin positivity (RMP) and postoperative outcomes among patients undergoing abdominoperineal resection (APR). METHODS: This was a retrospective cohort study of patients from the National Surgical Quality Improvement Program who underwent APR for low rectal cancer from 2016 to 2019. Patients were stratified by operative approach: robotic, laparoscopic, and open APR (R-APR, L-APR, and O-APR). Emergent cases were excluded. The primary outcome was RMP. 30-day postoperative outcomes were also evaluated, using logistic regression analysis. RESULTS: Among 1,807 patients, 452 (25.0%) underwent R-APR, 474 (26.2%) L-APR, and 881 (48.8%) O-APR. No differences regarding RMP (13.5% R-APR vs. 10.8% L-APR vs. 12.3% O-APR, p = 0.44), distal margin positivity, positive nodes, readmission, or operative time were observed between operative approaches. Adjusted analysis confirmed that operative approach did not predict RMP (p > 0.05 for all). Risk factors for RMP included American Society of Anesthesiologists (ASA) classification III (ASA I-II ref; OR 1.46, p = 0.039), pT3-4 stage (T0-2 ref, OR 4.02, p < 0.001), pN2 stage (OR 1.98, p = 0.004), disseminated cancer (OR 1.90, p = 0.002), and lack of preoperative radiation (OR 1.98, p < 0.01). CONCLUSIONS: No difference in RMP was observed among R-APR, L-APR, and O-APR. Postoperatively, R-APR yielded greater benefit when compared to O-APR, but was comparable to that of L-APR. Minimally invasive surgery may be an appropriate option and worthy consideration for patients with distal rectal cancer requiring APR.

The Global Anatomic Staging System Does Not Predict Limb Based Patency of Tibial Endovascular Interventions.

OBJECTIVE: Anatomic grading systems have historically been poor predictors of patency after endovascular tibial interventions. The Global Vascular Guidelines proposed a new Global Anatomic Staging System (GLASS) to estimate one-year limb-based patency (LBP). The purpose of this study was to determine the association of GLASS with LBP following endovascular tibial interventions. METHODS: We included all patients presenting to our multidisciplinary diabetic limb preservation service between 01/2012 and 8/2020 who underwent first-time endovascular tibial revascularization for chronic limb-threatening ischemia. Diagnostic angiograms were reviewed to define the preferred target artery pathway and assign a GLASS stage to each treated limb. One-year LBP was calculated and compared across GLASS stages using Kaplan-Meier curves with log-rank tests and Cox proportional hazards models. RESULTS: We performed tibial revascularization in 96 limbs (5.2% rest pain, 56.3% ulcer, 37.5% gangrene), including isolated tibial interventions in 61.5% and tibial + femoropopliteal interventions in 38.5%. 15.6% of limbs were GLASS stage 1, 28.1% were GLASS stage 2, and 56.3% were GLASS stage 3. Overall, one-year LBP was 43.2 ± 6.3%, and did not differ significantly across GLASS stages (P = 0.42). The hazard ratio for failed LBP was 1.94 (95% CI 0.70-5.41) for GLASS stage 2 and 1.49 (95% CI 0.56-3.94) for GLASS stage 3 limbs (versus GLASS stage 1). When analyzed excluding the calcium modifier, LBP remained similar across GLASS stages (P = 0.72). Major amputation was uncommon, occurring in 9.3 ± 3.4% of limbs at one year, and did not significantly differ by GLASS stage (P = 0.98). CONCLUSION: The Global Anatomic Staging System did not predict limb-based patency following tibial endovascular interventions. Given the low major amputation rates in this cohort, anatomic complexity should not preclude endovascular limb salvage efforts below the knee.

Knowledge and attitudes of U.S. medical students regarding the care of Asian American patients: a cross-sectional survey study.

BACKGROUND: Asian Americans (AsAm) are a rapidly growing population in the U.S. With this growing population, U.S. healthcare providers must be equipped to provide culturally competent care for AsAm patients. This project surveyed U.S. medical students on their knowledge of and attitudes towards AsAm to assess predictors of readiness to care for AsAm patients. METHOD: This cross-sectional study surveyed medical students who had completed at least one clinical rotation. The survey was distributed online to nine medical schools throughout the U.S. The survey measured self-rated knowledge of, comfort with, cultural competency (CC) towards, and explicit biases towards AsAm patients. The first three domains were analyzed in a multivariate regression model including sociodemographic characteristics and past clinical, curricular, and social experiences with AsAm. Explicit bias questions were reported descriptively. RESULTS: There were 688 respondents. Asian race, AsAm-prevalent hometown, AsAm-related extracurricular activities, Asian language knowledge, and having taken a population health course predicted increased AsAm knowledge. Social interactions with AsAm increased comfort with AsAm patients. Increasing year in medical school, more frequent exposure to AsAm patients on rotations, and prior travel to an Asian country were predictors of increased CC toward AsAm. Importantly, having completed a CC course was a significant predictor in all domains. In terms of explicit bias, students felt that AsAm patients were more compliant than Caucasian patients. Students also believed that Caucasian patients were generally more likely to receive self-perceived "preferred" versus "acceptable" care, but that in their own clinical experiences neither group received preferred care. CONCLUSION: Experience with and exposure to AsAm prior to and during medical school and CC courses may increase medical student knowledge, comfort, and CC with AsAm patients. Standardized and longitudinal CC training, increased simulations with AsAm patients, diverse student recruitment, and support for students to engage in AsAm-related activities and interact with AsAm may improve CC of future physicians towards AsAm patients and possibly other minority populations.