Intraoperative imaging and management of common duct stones during subtotal cholecystectomy.

BACKGROUND: Subtotal cholecystectomy is advocated in patients with severe inflammation and distorted anatomy preventing safe removal of the entire gallbladder. Not well documented in this surgically complex population is the feasibility of intraoperative imaging and management of common bile duct (CBD) stones. We evaluated these operative maneuvers in our subtotal cholecystectomy patients. METHODS: We retrospectively reviewed all cholecystectomy cases from 2014 to 2023 at a single Veterans Affairs (VA) Medical Center using VASQIP (VA Surgical Quality Improvement Program), selecting subtotal cholecystectomy cases for detailed analysis. We reviewed operative reports, imaging and laboratory studies, and clinical notes to understand biliary imaging, stone management, complications, and late outcomes including retained stones (within 6 months), and recurrent stones (beyond 6 months). RESULTS: 419 laparoscopic (n = 406) and open (n = 13) cholecystectomies were performed, including 40 subtotal cholecystectomies (36 laparoscopic, 4 laparoscopic converted to open). Among these 40 patients IOC was attempted in 35 and completed in 26, with successful stone management in 11 (9 common bile duct exploration [CBDE], 2 intraoperative endoscopic retrograde cholangiopancreatography [ERCP]). In follow-up, 3 additional patients had CBD stones managed by ERCP, including 1 with a negative IOC and 2 without IOC. Thus, 14 (35%) of 40 patients had CBD stones. Of note, IOC permitted identification and oversewing or closure of the cystic duct in 32 patients. There were no major bile duct injuries and one cystic duct stump leak (2.5%) that resolved spontaneously. CONCLUSIONS: Subtotal cholecystectomy patients had a high incidence of bile duct stones, with most detected and managed intraoperatively with CBDE, making a strong argument for routine IOC and single-stage care. When intraoperative imaging is not possible, postoperative imaging should be considered. Routine imaging, biliary clearance, and cystic duct closure during subtotal cholecystectomy is feasible in most patients with low rates of retained stones and bile leaks.

Evaluating clinical practice guidelines for the management of rectal cancer: Did they get it RIGHT?

BACKGROUND AND OBJECTIVES: Clinical Practice Guidelines (CPGs) are crucial tools for clinicians seeking to deliver evidence-based patient care. We utilized the Reporting Items for practice Guidelines in HealThcare (RIGHT) checklist to assess the reporting quality of CPGs addressing the management of rectal cancer. METHODS: Four multidisciplinary rectal cancer CPGs published 2017-2022 were evaluated: American Society of Colon and Rectal Surgeons (ASCRS), European Society for Medical Oncology (ESMO), National Comprehensive Cancer Network (NCCN), and National Institute for Health and Care Excellence (NICE). We quantitatively assessed each CPG using the RIGHT checklist and qualitative analysis was performed to generate common themes. RESULTS: RIGHT checklist items fulfilled by each CPG ranged from 12 to 17 (out of 22). Each guideline demonstrated unique categories of weakness: ASCRS in Basic Information (1 of 4 items), ESMO in Evidence (1 of 3), NCCN in Recommendations (1 of 3), and NICE in Review and Quality Assurance (0 of 2). Common themes that emerged included sprase discussion on the financial aspects of rectal cancer management and lack of transparency in formulating recommendations. CONCLUSIONS: Despite their variability, each of the 22 checklist elements are present in contemporary CPGs. Utilizing the RIGHT checklist would allow experts to create guidelines adhering to high-quality reporting standards.

The Laparoscopy in Biliary Exploration Research and Training Initiative (LIBERTI) trial: simulator-based training for laparoscopic management of choledocholithiasis.

BACKGROUND: Laparoscopic cholecystectomy with common bile duct exploration (LCBDE) is equivalent in safety and efficacy to endoscopic retrograde cholangiopancreatography (ERCP) plus laparoscopic cholecystectomy (LC) while decreasing number of procedures and length of stay (LOS). Despite these advantages LCBDE is infrequently utilized. We hypothesized that formal, simulation-based training in LCBDE would result in increased utilization and improve patient outcomes across participating institutions. METHODS: Data was obtained from an on-going multi-center study in which simulator-based transcystic LCBDE training curricula were instituted for attending surgeons and residents. A 2-year retrospective review of LCBDE utilization prior to LCBDE training was compared to utilization up to 2 years after initiation of training. Patient outcomes were analyzed between LCBDE strategy and ERCP strategy groups using χ2, t tests, and Wilcoxon rank tests. RESULTS: A total of 50 attendings and 70 residents trained in LCBDE since November 2020. Initial LCBDE utilization rate ranged from 0.74 to 4.5%, and increased among all institutions after training, ranging from 9.3 to 41.4% of cases. There were 393 choledocholithiasis patients analyzed using LCBDE (N = 129) and ERCP (N = 264) strategies. The LCBDE group had shorter median LOS (3 days vs. 4 days, p < 0.0001). No significant differences in readmission rates between LCBDE and ERCP groups (4.7% vs. 7.2%, p = 0.33), or in post-procedure pancreatitis (0.8% v 0.8%, p > 0.98). In comparison to LCBDE, the ERCP group had higher rates of bile duct injury (0% v 3.8%, p = 0.034) and fluid collections requiring intervention (0.8% v 6.8%, p < 0.009) secondary to cholecystectomy complications. Laparoscopic antegrade balloon sphincteroplasty had the highest technical success rate (87%), followed by choledochoscopic techniques (64%). CONCLUSION: Simulator-based training in LCBDE results in higher utilization rates, shorter LOS, and comparable safety to ERCP plus cholecystectomy. Therefore, implementation of LCBDE training is strongly recommended to optimize healthcare utilization and management of patients with choledocholithiasis.

A Review and Assessment of Open Access Surgery Journals.

INTRODUCTION: Open access publishing has exhibited rapid growth in recent years. However, there is uncertainty surrounding the quality of open access journals and their ability to reach target audiences. This study reviews and characterizes open access surgical journals. MATERIALS AND METHODS: The directory of open access journals was used to search for open access surgical journals. PubMed indexing status, impact factor, article processing charge (APC), initial year of open access publishing, average weeks from manuscript submission to publication, publisher, and peer-review processes were evaluated. RESULTS: Ninety-two open access surgical journals were identified. Most (n = 49, 53.3%) were indexed in PubMed. Journals established >10 y were more likely to be indexed in PubMed compared to journals established <5 y (28 of 41 [68.3%] versus 4 of 20 [20%], P < 0.001). 44 journals (47.8%) used a double-blind review method. 49 (53.2%) journals received an impact factor for 2021, ranging from <0.1 to 10.2 (median 1.4). The median APC was $362 United States dollar [interquartile range $0 - 1802 United States dollar]. 35 journals (38%) did not charge a processing fee. There was a significant positive correlation between the APC and impact factor (r = 0.61, P < 0.001). If accepted, the median time from manuscript submission to publication was 12 wk. CONCLUSIONS: Open access surgical journals are largely indexed on PubMed, have transparent review processes, employ variable APCs (including no publication fees), and proceed efficiently from submission to publication. These results should increase readers' confidence in the quality of surgical literature published in open access journals.

A Call to Assess the Impacts of Course-Based Undergraduate Research Experiences for Career and Technical Education, Allied Health, and Underrepresented Students at Community Colleges.

Course-based undergraduate research experiences (CUREs) have the potential to impact student success and reduce barriers for students to participate in undergraduate research. Literature review has revealed that, while CUREs are being implemented at both community colleges (CCs) and bachelor's degree-granting institutions, there are limited published studies on the differential impacts CUREs may have on CC students in allied health programs, career and technical education, and nursing pathways (termed "workforce" in this essay). This essay summarizes proposed outcomes of CURE instruction and explores possible reasons for limited reporting on outcomes for CC and workforce students. It also provides recommendations to guide action and effect change regarding CURE implementation and assessment at CCs. This essay is a call to action to expand the science, technology, engineering, and mathematics career development pathway to include workforce students, implement CUREs designed for workforce students, and assess the differential impacts CUREs may have on workforce student populations at CCs.

CXCL8 protects human neurons from amyloid-ß-induced neurotoxicity: relevance to Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by amyloid-ß (Aß) deposition in senile plaques colocalized with activated microglia and astrocytes. Recent studies suggest that CXCL8 is involved in the AD pathogenesis. The objective of this study was to determine the cellular sources of CXCL8 in the central nervous system during AD pathogenesis, and investigate the effects of CXCL8 on neuronal survival and/or functions. Our results showed significantly higher CXCL8 levels in AD brain tissue lysates as compared to those of age-matched controls. Upon Aß and/or pro-inflammatory cytokine stimulation, microglia, astrocytes and neurons were all capable of CXCL8 production in vitro. Although CXCL8-alone did not alter neuronal survival, it did inhibit Aß-induced neuronal apoptosis and increased neuronal brain-derived neurotrophic factor (BDNF) production. We conclude that microglia, astrocytes and neurons, all contribute to the enhanced CXCL8 levels in the CNS upon Aß and/or pro-inflammatory cytokine stimulation. Further, CXCL8 protects neurons possibly by paracrine or autocrine loop and regulates neuronal functions, therefore, may play a protective role in the AD pathogenesis.

Inhibition of highly productive HIV-1 infection in T cells, primary human macrophages, microglia, and astrocytes by Sargassum fusiforme.

BACKGROUND: The high rate of HIV-1 mutation and increasing resistance to currently available antiretroviral (ART) therapies highlight the need for new antiviral agents. Products derived from natural sources have been shown to inhibit HIV-1 replication during various stages of the virus life cycle, and therefore represent a potential source of novel therapeutic agents. To expand our arsenal of therapeutics against HIV-1 infection, we investigated aqueous extract from Sargassum fusiforme (S. fusiforme) for ability to inhibit HIV-1 infection in the periphery, in T cells and human macrophages, and for ability to inhibit in the central nervous system (CNS), in microglia and astrocytes. RESULTS: S. fusiforme extract blocked HIV-1 infection and replication by over 90% in T cells, human macrophages and microglia, and it also inhibited pseudotyped HIV-1 (VSV/NL4-3) infection in human astrocytes by over 70%. Inhibition was mediated against both CXCR4 (X4) and CCR5 (R5)-tropic HIV-1, was dose dependant and long lasting, did not inhibit cell growth or viability, was not toxic to cells, and was comparable to inhibition by the nucleoside analogue 2', 3'-didoxycytidine (ddC). S. fusiforme treatment blocked direct cell-to-cell infection spread. To investigate at which point of the virus life cycle this inhibition occurs, we infected T cells and CD4-negative primary human astrocytes with HIV-1 pseudotyped with envelope glycoprotein of vesicular stomatitis virus (VSV), which bypasses the HIV receptor requirements. Infection by pseudotyped HIV-1 (VSV/NL4-3) was also inhibited in a dose dependant manner, although up to 57% less, as compared to inhibition of native NL4-3, indicating post-entry interferences. CONCLUSION: This is the first report demonstrating S. fusiforme to be a potent inhibitor of highly productive HIV-1 infection and replication in T cells, in primary human macrophages, microglia, and astrocytes. Results with VSV/NL4-3 infection, suggest inhibition of both entry and post-entry events of the virus life cycle. Absence of cytotoxicity and high viability of treated cells also suggest that S. fusiforme is a potential source of novel naturally occurring antiretroviral compounds that inhibit HIV-1 infection and replication at more than one site of the virus life cycle.

Development of a rapid autopsy program for studies of brain immunity.

Human glia are essential cellular models used for studies of neurodegenerative diseases. Fetal neuroglia are commonly used, as they can be recovered in large quantities and sustained for long periods in culture. However, fetal neuroglia may have limitations in reflecting adult diseases and additionally can pose ethical issues in translating products of abortion for research use. To address these concerns, we developed a rapid autopsy program to procure age- and disease-specific neuroglia from adult brain tissues within hours of death. The challenges in developing this initiative, reflecting experiences from 69 autopsies over 4 years, are presented.

Neuroinflammatory responses from microglia recovered from HIV-1-infected and seronegative subjects.

Microglial and macrophage infection and immune activation underlie the pathogenesis of HIV-1-associated dementia (HAD). To assess microglial function in HAD, we isolated cells from brain tissues recovered from an HIV-1-infected patient within 4 h of death. Brain tissue from seronegative patients served as controls. Regional neuropathology was correlated to microglial function. HIV-1-patient microglia formed multinucleated giant cells and produced progeny virions. These microglia secreted reduced basal and LPS-stimulated TNF-alpha levels compared to controls. Monocytes from seronegative donors paralleled these diminished immune responses following repeated LPS-activation. These results demonstrate changes in innate microglial function following viral infection or chronic immune activation.

Mitochondrial glutaminase enhances extracellular glutamate production in HIV-1-infected macrophages: linkage to HIV-1 associated dementia.

Dysfunction in mononuclear phagocyte (MP, macrophages and microglia) immunity is thought to play a significant role in the pathogenesis of HIV-1 associated dementia (HAD). In particular, elevated extracellular concentrations of the excitatory neurotransmitter glutamate, produced by MP as a consequence of viral infection and immune activation, can induce neuronal injury. To determine the mechanism by which MP-mediated neuronal injury occurs, the concentration and rates of production of extracellular glutamate were measured in human monocyte-derived macrophage (MDM) supernatants by reverse phase high-performance liquid chromatography (RP-HPLC). Measurements were taken of supernatants from MDM infected with multiple HIV-1 strains including ADA and DJV (macrophage tropic, M-tropic), and 89.6 (dual tropic). High levels of glutamate were produced by MDM infected with M-tropic viruses. AZT, an inhibitor of HIV-1 replication, inhibited glutamate generation, demonstrating a linkage between HIV-1 infection and enhanced glutamate production. In our culture system, glutamate production was dependent upon the presence of glutamine and was inhibited by 6-diazo-5-oxo-L-norleucine, a glutaminase inhibitor. Supernatants collected from HIV-1-infected MP generated more glutamate following glutamine addition than supernatants isolated from uninfected MP. These findings implicate the involvement of a glutamate-generating enzyme, such as phosphate-activated mitochondrial glutaminase (PMG) in MP-mediated glutamate production.

Neuronal injury regulates fractalkine: relevance for HIV-1 associated dementia.

Fractalkine (FKN), a chemokine highly expressed in the central nervous system, participates in inflammatory responses operative in many brain disorders including HIV-1 associated dementia (HAD). In this report, HIV-1 progeny virions and pro-inflammatory products led to FKN production associated with neuronal injury and apoptosis. FKN was produced by neurons and astrocytes; but differentially produced by the two cell types. Laboratory tests paralleled those in infected people where cerebrospinal fluid FKN levels in HIV-1 infected cognitively impaired (n=16) patients were found to be increased when compared to infected patients without cognitive impairment (n=8, P=0.0345). These results demonstrate a possible role of FKN in HAD pathogenesis.

Macrophages, chemokines and neuronal injury in HIV-1-associated dementia.

Human immunodeficiency virus type-one (HIV- 1)-associated dementia (HAD) is manifested as a spectrum of behavioral, motor and cognitive dysfunctions. The disorder commonly occurs during late stage HIV disease and remains an important complication despite highly active antiretroviral therapies. A metabolic encephalopathy, fueled by neurotoxic secretions from brain mononuclear phagocytes (MP) (macrophages and microglia) underlies HIV- I neuropathogenesis. One pivotal question, however, is how brain MP evolve from neurotrophic to neurotoxic cells. The interplay between the virus, the macrophage and the neuron has just recently begun to be unraveled. Along with a multitude of other MP secretory products, chemokines effect neuronal function by engaging neuronal receptors then activating pathways that alter synaptic transmission, cell growth, injury and protection. Both neurons and glia secrete chemokines. Interestingly, HIV-1 and its gene products can mimic chemokine neuronal signaling by binding to neuronal chemokine receptors or by other non-specific mechanisms. The elucidation of mechanisms involved in chemokine-mediated neural compromise will likely provide unique insights into the pathogenesis and treatment, not only of HAD, but of a wide range of neurodegenerative disorders.