What is MIS fellowship? Community and academic program experience.

INTRODUCTION: Minimally invasive surgery (MIS) fellowship is one of the most popular fellowship programs, but little is known about the individual fellow's clinical experience. Our goal was to determine the differences in case volume and case type in academic and community programs. METHODS: A retrospective review of advanced gastrointestinal, MIS, foregut, or bariatric fellowship cases logged into the Fellowship Council directory of fellowships during the 2020 and 2021 academic years included for analysis. The final cohort included 57,324 cases from all fellowship programs, that list data on the Fellowship Council website, including 58 academic programs and 62 community-based programs. All comparisons between groups were completed using Student's t-test. RESULTS: The mean number of cases logged during a fellowship year was 477.7 ± 149.9 with similar case numbers in academic and community programs, 462.5 ± 115.0 and 491.9 ± 176.2 respectively (p = 0.28). The mean data is illustrated in Fig. 1. The most common performed cases were in the following categories: bariatric surgery (149.8 ± 86.9 cases), endoscopy (111.1 ± 86.4 cases), hernia (68.0 ± 57.7 cases) and foregut (62.8 ± 37.3 cases). In these case-type categories, no significant differences in case volume were found between academic and community-based MIS fellowship programs. However, community-based programs had significantly more case experience compared to academic programs in all of the less commonly performed case-type categories: appendix 7.8 ± 12.8 vs 4.6 ± 5.1 cases (p = 0.08), colon 16.1 ± 20.7 vs 6.8 ± 11.7 cases (p = 0.003), hepato-pancreatic-biliary 46.9 ± 50.8 vs 32.5 ± 18.5 cases (p = 0.04), peritoneum 11.7 ± 16.0 vs 7.0 ± 7.6 cases (p = 0.04), and small bowel 11.9 ± 9.6 vs 8.8 ± 5.9 cases (p = 0.03). CONCLUSION: MIS fellowship has been a well-established fellowship program under the Fellowship Council guideline. In our study, we aimed to identify the categories of fellowship training and the perspective case volumes in academic vs community setting. We conclude that fellowship training experience is similar in case volumes of commonly performed cases when comparing academic and community programs. However, there is substantial variability in the operative experience among MIS fellowship programs. Further study is necessary to identify the quality of fellowship training experience.

Short communication: HIV+ viremic slow progressors maintain low regulatory T cell numbers in rectal mucosa but exhibit high T cell activation.

Viremic slow progressors (VSP) are a rare subset of HIV-infected persons who exhibit slow immunologic progression despite high viremia. The mechanisms associated with this slow progression remain to be defined. Clinical characteristics of VSP are similar to those of natural hosts for simian immunodeficiency virus (SIV), such as sooty mangabeys (SM) and African green monkeys (AGM), who maintain near-normal CD4 counts despite high-level viremia but maintain low immune activation. Immune activation is a powerful predictor of disease progression, and we hypothesized that low immune activation might also explain the VSP phenotype. Using multiparameter flow cytometry, we assessed levels of T cell activation and regulatory T cells (Treg) in blood and rectal mucosa of VSP, typical progressors, virologic controllers, and seronegative controls. We also assessed Treg function and CD4 T cell proliferative capacity in VSP. Contrary to expectations, we found that VSP subjects have high levels of T cell activation in the gastrointestinal mucosa. The ratio of Treg to CD3+ T cells in the mucosa of VSP was relatively low, potentially contributing to increased immune activation. Nonetheless, CD4+CD25- T cells isolated from these individuals displayed a comparatively weak proliferative response to anti-CD3 stimulation. These data reveal that the VSP phenotype is associated with elevated markers of mucosal immune activation and low numbers of mucosal Treg, suggesting that factors other than immune activation account for this phenotype.

Impact of highly active antiretroviral therapy initiation on CD4(+) T-cell repopulation in duodenal and rectal mucosa.

OBJECTIVE: The objective of this study was to assess the effects of HAART initiation on CD4(+) T-cell repopulation and T-cell immune activation in rectal and duodenal mucosa. DESIGN: The effects of HAART on the gastrointestinal tract remain controversial, and studies have reached different conclusions regarding its effectiveness at restoring mucosal CD4(+) T cells depending upon time of initiation, duration of treatment and gastrointestinal tract region studied. METHODS: We obtained blood, rectal biopsies and duodenal biopsies from 14 chronically infected individuals at baseline and at 4-9 months post-HAART initiation. We examined CD4(+) T-cell frequencies in blood, rectum and duodenum at both time points, and performed a detailed assessment of CD4(+) T-cell phenotype, immune activation marker expression and HIV-specific CD8(+) T-cell responses in blood and rectal mucosa. RESULTS: CD4(+) T-cell percentages increased significantly in blood, rectal and duodenal mucosa after 4-9 months of HAART (P = 0.02, 0.0005, 0.0002), but remained lower than in uninfected controls. HIV-specific CD8(+) T-cell responses in blood and rectal mucosa declined following HAART initiation (P = 0.0015, 0.021). CD8(+) T-cell coexpression of CD38 and HLA-DR in blood and mucosa, as well as plasma sCD14, declined significantly. CD28 expression on blood and mucosal CD8(+) T cells increased, whereas programmed death receptor-1 expression on blood HIV-specific CD4(+) and CD8(+) T cells decreased. CONCLUSION: Within the first months of HAART, limited CD4(+) T-cell reconstitution occurs in small and large intestinal mucosa. Nevertheless, decreased immune activation and increased CD28 expression suggest rapid immunological benefits of HAART despite incomplete CD4(+) T-cell reconstitution.

Randomized pilot trial of a synbiotic dietary supplement in chronic HIV-1 infection.

BACKGROUND: Infection with HIV-1 results in marked immunologic insults and structural damage to the intestinal mucosa, including compromised barrier function. While the development of highly active antiretroviral therapy (HAART) has been a major advancement in the treatment of HIV-1 infection, the need for novel complementary interventions to help restore intestinal structural and functional integrity remains unmet. Known properties of pre-, pro-, and synbiotics suggest that they may be useful tools in achieving this goal. METHODS: This was a 4-week parallel, placebo-controlled, randomized pilot trial in HIV-infected women on antiretroviral therapy. A synbiotic formulation (Synbiotic 2000®) containing 4 strains of probiotic bacteria (10(10) each) plus 4 nondigestible, fermentable dietary fibers (2.5 g each) was provided each day, versus a fiber-only placebo formulation. The primary outcome was bacterial translocation. Secondary outcomes included the levels of supplemented bacteria in stool, the activation phenotype of peripheral T-cells and monocytes, and plasma levels of C-reactive protein and soluble CD14. RESULTS: Microbial translocation, as measured by plasma bacterial 16S ribosomal DNA concentration, was not altered by synbiotic treatment. In contrast, the synbiotic formulation resulted in significantly elevated levels of supplemented probiotic bacterial strains in stool, including L. plantarum and P. pentosaceus, with the colonization of these two species being positively correlated with each other. T-cell activation phenotype of peripheral blood lymphocytes showed modest changes in response to synbiotic exposure, with HLA-DR expression slightly elevated on a minor population of CD4+ T-cells which lack expression of HLA-DR or PD-1. In addition, CD38 expression on CD8+ T-cells was slightly lower in the fiber-only group. Plasma levels of soluble CD14 and C-reactive protein were unaffected by synbiotic treatment in this study. CONCLUSIONS: Synbiotic treatment for 4 weeks can successfully augment the levels of probiotic species in the gut during chronic HIV-1 infection. Associated changes in microbial translocation appear to be absent, and markers of systemic immune activation appear largely unchanged. These findings may help inform future studies aimed at testing pre- and probiotic approaches to improve gut function and mucosal immunity in chronic HIV-1 infection. TRIAL REGISTRATION: Clinical Trials.gov: NCT00688311.

Increased frequency of regulatory T cells accompanies increased immune activation in rectal mucosae of HIV-positive noncontrollers.

Gut-associated lymphoid tissue (GALT) is a major site of HIV replication and CD4(+) T cell depletion. Furthermore, microbial translocation facilitated by mucosal damage likely contributes to the generalized immune activation observed in HIV infection. Regulatory T cells (Treg) help maintain homeostasis and suppress harmful immune activation during infection; however, in the case of persistent viral infections such as HIV, their role is less clear. Although a number of studies have examined Treg in blood during chronic infection, few have explored Treg in the gastrointestinal mucosa. For this study, paired blood and rectal biopsy samples were obtained from 12 HIV noncontrollers (viral load of >10,000 copies/ml plasma), 10 HIV controllers (viral load of <500 copies/ml plasma for more than 5 years), and 12 HIV seronegative control subjects. Noncontrollers had significantly higher percentages of Treg in rectal mononuclear cells (RMNC), but not in blood, compared to seronegative subjects (P = 0.001) or HIV controllers (P = 0.002). Mucosal Treg positively correlated with viral load (P = 0.01) and expression of immune activation markers by CD4(+) (P = 0.01) and CD8(+) (P = 0.07) T cells. Suppression assays indicated that mucosal and peripheral Treg of noncontrollers and controllers maintained their capacity to suppress non-Treg proliferation to a similar extent as Treg from seronegative subjects. Together, these findings reveal that rather than experiencing depletion, mucosal Treg frequency is enhanced during chronic HIV infection and is positively correlated with viral load and immune activation. Moreover, mucosal Treg maintain their suppressive ability during chronic HIV infection, potentially contributing to diminished HIV-specific T cell responses and viral persistence.

HIV controllers with HLA-DRB1*13 and HLA-DQB1*06 alleles have strong, polyfunctional mucosal CD4+ T-cell responses.

A small percentage of human immunodeficiency virus (HIV)-infected individuals, termed elite controllers, are able to spontaneously control HIV replication in blood. As the gastrointestinal mucosa is an important site of HIV transmission and replication as well as CD4+ T-cell depletion, it is important to understand the nature of the immune responses occurring in this compartment. Although the role of the HIV-specific CD8+ T-cell responses in mucosal tissues has been described, few studies have investigated the role of mucosal HIV-specific CD4+ T cells. In this study, we assessed HIV-specific CD4+ T-cell responses in the rectal mucosa of 28 "controllers" (viral load [VL] of <2,000 copies/ml), 14 "noncontrollers" (VL of >10,000 copies/ml), and 10 individuals on highly active antiretroviral therapy (HAART) (VL of <75 copies/ml). Controllers had higher-magnitude Gag-specific mucosal CD4+ T-cell responses than individuals on HAART (P<0.05), as measured by their ability to produce gamma interferon (IFN-γ), interleukin-2 (IL-2), tumor necrosis factor alpha (TNF-α), and macrophage inflammatory protein 1ß (MIP-1ß). The frequency of polyfunctional mucosal CD4+ T cells was also higher in controllers than in noncontrollers or individuals on HAART (P<0.05). Controllers with the strongest HIV-specific CD4+ T-cell responses possessed class II HLA alleles, HLA-DRB1*13 and/or HLA-DQB1*06, previously associated with a nonprogression phenotype. Strikingly, individuals with both HLA-DRB1*13 and HLA-DQB1*06 had highly polyfunctional mucosal CD4+ T cells compared to individuals with HLA-DQB1*06 alone or other class II alleles. The frequency of polyfunctional CD4+ T cells in rectal mucosa positively correlated with the magnitude of the mucosal CD8+ T-cell response (Spearman's r=0.43, P=0.005), suggesting that increased CD4+ T-cell "help" may be important in maintaining strong CD8+ T-cell responses in the gut of HIV controllers.