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Background: Enrollment of Medicare beneficiaries in medicare advantage (MA) plans has been steadily increasing. Prior research has shown differences in healthcare access and outcomes based on Medicare enrollment status. This study sought to compare utilization of minimally invasive colorectal cancer (CRC) surgery and postoperative outcomes between MA and Fee-for-Service (FFS) beneficiaries. Methods: A retrospective cohort study of beneficiaries  ≥ 65.5 years of age enrolled in FFS and MA plans was performed of patients undergoing a CRC resection from 2016 to 2019. The primary outcome was operative approach, defined as minimally invasive (laparoscopic) or open. Secondary outcomes included robotic assistance, hospital length-of-stay, mortality, discharge disposition, and hospital readmission. Using balancing weights, we performed a tapered analysis to examine outcomes with adjustment for potential confounders. Results: MA beneficiaries were less likely to have lymph node (12.9 vs 14.4%, p< 0.001) or distant metastases (15.5% vs 17.0%, p< 0.001), and less likely to receive chemotherapy (6.2% vs 6.7%, p< 0.001), compared to FFS beneficiaries. MA beneficiaries had a higher risk-adjusted likelihood of undergoing laparoscopic CRC resection (OR 1.12 (1.10–1.15), p< 0.001), and similar rates of robotic assistance (OR 1.00 (0.97–1.03), p= 0.912), compared to FFS beneficiaries. There were no differences in risk-adjusted length-of-stay (βcoefficient 0.03 (− 0.05–0.10), p= 0.461) or mortality at 30-60-and 90-days (OR 0.99 (0.95–1.04), p= 0.787; OR 1.00 (0.96–1.04), p= 0.815; OR 0.98 (0.95–1.02), p= 0.380). MA beneficiaries had a lower likelihood of non-routine disposition (OR 0.77 (0.75–0.78), p< 0.001) and readmission at 30-60-and 90-days (OR 0.76 (0.73–0.80), p< 0.001; OR 0.78 (0.75–0.81), p< 0.001; OR 0.79 (0.76–0.81), p< 0.001). Conclusions: MA beneficiaries had less advanced disease at the time of CRC resection and a greater likelihood of undergoing a laparoscopic procedure. MA enrollment is associated with improved health outcomes for elderly beneficiaries undergoing operative treatment for CRC.

IMPORTANCE: Many early-career surgeons struggle to develop their clinical practices, leading to high rates of burnout and attrition. Furthermore, women in surgery receive fewer, less complex, and less remunerative referrals compared with men. An enhanced understanding of the social and structural barriers to optimal growth and equity in clinical practice development is fundamental to guiding interventions to support academic surgeons. OBJECTIVE: To identify the barriers and facilitators to clinical practice development with attention to differences related to surgeon gender. DESIGN, SETTING, AND PARTICIPANTS: A multi-institutional qualitative descriptive study was performed using semistructured interviews analyzed with a grounded theory approach. Interviews were conducted at 5 academic medical centers in the US between July 12, 2022, and January 31, 2023. Surgeons with at least 1 year of independent practice experience were selected using purposeful sampling to obtain a representative sample by gender, specialty, academic rank, and years of experience. MAIN OUTCOMES AND MEASURES: Surgeon perspectives on external barriers and facilitators of clinical practice development and strategies to support practice development for new academic surgeons. RESULTS: A total of 45 surgeons were interviewed (23 women [51%], 18 with ≤5 years of experience [40%], and 20 with ≥10 years of experience [44%]). Surgeons reported barriers and facilitators related to their colleagues, department, institution, and environment. Dominant themes for both genders were related to competition, case distribution among partners, resource allocation, and geographic market saturation. Women surgeons reported additional challenges related to gender-based discrimination (exclusion, questioning of expertise, role misidentification, salary disparities, and unequal resource allocation) and additional demands (related to appearance, self-advocacy, and nonoperative patient care). Gender concordance with patients and referring physicians was a facilitator of practice development for women. Surgeons suggested several strategies for their colleagues, department, and institution to improve practice development by amplifying facilitators and promoting objectivity and transparency in resource allocation and referrals. CONCLUSIONS AND RELEVANCE: The findings of this qualitative study suggest that a surgeon’s external context has a substantial influence on their practice development. Academic institutions and departments of surgery may consider the influence of their structures and policies on early career surgeons to accelerate practice development and workplace equity.

The sequence of pelvic examinations affects patient-reported pain.

Microsomal triglyceride transfer protein (MTP), a chaperone for the biosynthesis of apolipoprotein B lipoproteins and CD1d, is a therapeutic candidate to decrease plasma lipids and to diminish inflammation. MTP inhibition increases plasma transaminases and tissue lipids, and therefore new approaches are needed to avoid them.

Apolipoprotein B (apoB) and microsomal triglyceride transfer protein (MTP) are known to interact with each other. We evaluated the effect of different lipids on the protein-protein interactions between MTP and apoB100 or its C-terminally truncated forms. Negatively charged lipids decreased protein-protein interactions between apoB and MTP. In contrast, zwitterionic phospholipids enhanced (2-4-fold) the binding of apoB100 to MTP by increasing affinity (1.5-3-fold) between these proteins without affecting the number of binding sites. Similarly, phospholipids augmented (1.5-4-fold) the binding of various C-terminally truncated apoB peptides to MTP. The increased binding was greater for apoB peptides containing lipid-binding domains, such as apoB28 and apoB42. Surprisingly, preincubation of apoB28 with lipid vesicles had no effect on MTP binding. In contrast, incubation of MTP with lipid vesicles resulted in a stable association of MTP with vesicles, and MTP-lipid vesicles bound better (5-fold increase) to LDL than did lipid-free MTP. To determine whether MTP exists stably associated with lipids in cells, microsomal contents from COS cells expressing MTP, HepG2 cells, and mouse liver were ultracentrifuged, and MTP was visualized in different density fractions. MTP was found associated and unassociated with lipids. In contrast, apoB17 and apoB:270-570 were present unassociated with lipids in COS cells. These studies show that the binding of MTP to lipids results in increased affinity for apoB and that stable MTP-lipid complexes exist in the lumen of the endoplasmic reticulum. Protein-protein interactions between apoB and MTP may juxtapose lipids associated with MTP to lipid-binding domains of apoB and facilitate hydrophobic interactions leading to enhance affinity. We speculate that MTP-lipid complexes may serve as nuclei to form "primordial lipoproteins" and may also play a role in the bulk addition of lipids during the "core expansion" of these lipoproteins.

Actinomycesspecies has been described as a rare cause of primary breast, abdominal, and cutaneous infections, and can present as recurrent abscesses, tissue fibrosis, and fistulous draining sinuses, particularly in the setting of immune compromise. We present a case of a 48-year-old woman who underwent bilateral mastectomy with muscle sparing transverse rectus abdominus muscle free flap reconstruction thirteen years prior and developed recurrent abscesses in her reconstructed breast, ultimately attributable to chronic infection with Actinomyces. This is the first reported case of Actinomycesinfection in the autologously reconstructed breast. Definitive treatment included surgical mastotomy and debridement with vacuum assisted wound closure and prolonged course of intravenous (IV) ampicillin-sulbactam followed by oral amoxicillin-clavulanate. Actinomycesinfection of the breast may present as recurrent abscesses and requires a high index of suspicion to preserve the architecture of the autologously reconstructed breast.

The microsomal triglyceride transfer protein (MTP) is essential for the hepatic secretion of apolipoprotein (apo) B-containing lipoproteins. Previous studies have indicated that inhibition of MTP results in decreased apoB plasma levels and decreased hepatic triglyceride secretion. However, the metabolic effects of overexpression of MTP have not been investigated. We constructed a recombinant adenovirus expressing MTP (AdhMTP) and used it to assess the effects of hepatic overexpression of MTP in mice. Injection of AdhMTP into C57BL/6 mice resulted in a 3-fold increase in hepatic microsomal triglyceride transfer activity compared to mice injected with Adnull. On day 4 after virus injection, AdhMTP-injected mice had significantly elevated plasma TG levels as compared to control virus (Adnull)-injected mice. Hepatic TG secretion rates were significantly greater in AdhMTP-injected mice (184 +/- 12 mg/kg/h) compared with Adnull-injected mice (65 +/- 9 mg/kg/h, P < 0.001). In addition, hepatic very low density lipoprotein (VLDL) apoB secretion in the AdhMTP-injected group was 74% higher than in the control virus group. Hepatic secretion of apoB-48 and apoB-100 contributed equally to this increase.These results provide the first data that hepatic overexpression of MTP results in increased secretion of VLDL-triglycerides as well as VLDL-apoB in vivo. These results suggest that MTP is rate-limiting for VLDL apoB secretion in wild-type mice under basal chow-fed conditions.

Several studies have demonstrated protein-protein interactions between microsomal triglyceride transfer protein (MTP) and apolipoprotein B (apoB). However, the binding sites involved in these interactions have not been elucidated. To identify an MTP binding site in apoB, we have expressed several apoB sequences as fusion proteins with the eight-amino acid FLAG peptide. The chimeras were transiently expressed in COS cells, and conditioned media were used to study the binding of these sequences to either immobilized or soluble MTP. A polypeptide containing amino acids 270-570 (B:270-570), but not 1-300, bound to MTP. AGI-S17, an antagonist of apoB-MTP binding, inhibited the binding of B:270-570 to MTP but not to M2, a monoclonal antibody that recognizes the FLAG peptide. These data indicated that B:270-570 contains an MTP binding site. Next, sequences within 270-570 were subjected to C-terminal truncations at natural proline residues. B:270-509 bound less efficiently than B:270-570, whereas, B:270-430 and other shorter chimeras did not bind to MTP. Furthermore, truncations at amino acids 502 and 509 decreased MTP binding by 73 and 42%, respectively. These data indicate that B:430-570 in the alpha1-globular domain of apoB plays a crucial role in MTP binding and presumably in the initiation and maturation of apoB-containing lipoproteins.

Diabetic microangiopathy is characterized by a thickening of capillary basement membranes associated with type IV collagen accumulation. An increase in type IV collagen content of the aortic wall is also observed in macroangiopathy. In order to analyse the importance of the polyol pathway in the development of the collagen metabolism alterations seen in diabetic angiopathy and their prevention by aldose reductase inhibitors, we have studied the effects of sorbinil on the high glucose-induced stimulation of type IV collagen biosynthesis in human umbilical vein endothelial cells. Primary cultures were exposed to high glucose (16.7 mmol/l), with and without 0.11 mmol/l sorbinil, for 3 or 6 days after beginning of confluence. We measured the soluble type IV collagen secreted into the culture medium and the insoluble type IV collagen accumulated in the extracellular matrix and cells, by ELISA. We also studied [14C]proline incorporation into the newly synthesized collagenous and total proteins in the culture supernatant and in the extracellular matrix and cell fraction. High glucose decreased the number of cells and increased the amount of type IV collagen in the culture supernatant and in the extracellular matrix and cell fraction. It also increased proline incorporation into the newly synthesized collagenous and total proteins in the culture supernatant and in the extracellular matrix and cell fraction. Sorbinil corrected all these high glucose-induced alterations. The corrective effects of sorbinil on the proliferation and on type IV collagen metabolism of endothelial cells cultured in high glucose may be attributed to prevention of polyol pathway dysregulation.

Several studies have demonstrated protein-protein interactions between microsomal triglyceride transfer protein (MTP) and apolipoprotein B (apoB). However, the binding sites involved in these interactions have not been elucidated. To identify an MTP binding site in apoB, we have expressed several apoB sequences as fusion proteins with the eight-amino acid FLAG peptide. The chimeras were transiently expressed in COS cells, and conditioned media were used to study the binding of these sequences to either immobilized or soluble MTP. A polypeptide containing amino acids 270–570 (B:270–570), but not 1–300, bound to MTP. AGI-S17, an antagonist of apoB-MTP binding, inhibited the binding of B:270–570 to MTP but not to M2, a monoclonal antibody that recognizes the FLAG peptide. These data indicated that B:270–570 contains an MTP binding site. Next, sequences within 270–570 were subjected to C-terminal truncations at natural proline residues. B:270–509 bound less efficiently than B:270–570, whereas, B:270–430 and other shorter chimeras did not bind to MTP. Furthermore, truncations at amino acids 502 and 509 decreased MTP binding by 73 and 42%, respectively. These data indicate that B:430–570 in the α1-globular domain of apoB plays a crucial role in MTP binding and presumably in the initiation and maturation of apoB-containing lipoproteins.

Background:Endothelial dysfunction in diabetes has been attributed to lack of nitric oxide (NO) bioavailability. Oxidized LDL (OxLDL) and NO play antagonist roles in endothelium dysfunction. OxLDL inhibits NO-mediated arterial vasodilatory function, but it is not clear whether other modified LDLs influence NO availability or not. We investigated the relationship between plasma NO and modified LDLs in African Americans with diabetes.Methods:146 patients with diabetes were recruited from medical clinics over 6-month period. Plasma total NO and modified LDLs levels (Glycated, gLDL; Oxidized, oxLDL; Nitrated, nLDL; and Carbamylated, cLDL) were measured by ELISA. Microvascular function was assessed by vascular reactivity index (VRI), which assess changes in digital temperature before and after release of arterial cuff occlusion. Large artery stiffness was assessed by carotid-femoral pulse wave velocity (PWV) using applanation tonometry. Patient population was categorized into two groups: good glycemic control (HbA1c?7.0; N=85) and poor glycemic control (HbA1c>7.0; N=61).Results:Age 60?8 years, female 64%, hypertension 82%, dyslipidemia 83%, diabetes duration 10.2?7.6 years, HbA1c= 8.1?2.2%. In the total population, NO levels were negatively correlated with oxLDL (r=-0.425, p=0.0001) and gLDL (r=-0.303, p=0.0001), but not nLDL nor cLDL. OxLDL alone correlated with VRI (r=-0.252, p=0.002) and PWV (r=0.187, p=0.027). There was no correlation between NO and vascular outcome. In poorly-controlled group, NO correlated with oxLDL (r=-0.455, p=0.0001), gLDL (r=-0.265, p=0.0001) and nLDL (r=- 0.265, p=0.0140). Univariate analysis showed that oxLDL independently predicted NO availability (?=-0.551, p=0.0001) and VRI (?=-0.853, p=0.007) but not PWV. Multiple linear regression analysis showed that total NO was independently associated with plasma oxLDL levels (?=-0.422, p=0.034, r2=0.462) even after adjusting for other variables.Conclusion:oxLDL is the only predictor for NO bioavailability, suggesting that generation of oxLDL and reduced NO bioavailability could contribute to early microvascular dysfunction in diabetic patients. Larger prospective studies are needed to clarify these findings.