Not just a GIST: an unclassifiable neoplasm in the genomics era.

Unclassifiable primary tumors despite adequate tissue for pathologic examination are quite rare. We present a case of a 72-year-old female who was found to have an abdominal mass after she reported to the emergency department with complaints of abdominal pain with spasms, bloating and nausea. Computed tomography scan demonstrated a 12.3 × 15.7 × 15.9 large multilobulated mass, abutting and compressing the stomach, compatible with neoplasm. She underwent esophagogastroduodenoscopy with findings concerning for gastrointestinal stromal tumor. The patient underwent en bloc resection of the mass. The neoplasm was unable to be classified on pathologic examination despite a comprehensive workup and multiple consultations with specialized pathologists from local institutions, as well as national specialists. Final pathology was unclassified malignant neoplasm displaying calretinin expression only. This presents a difficult clinical entity to treat. Even in the genomics era, there are tumors that cannot be even broadly classified on pathologic examination.

Dynamics of the infant gut microbiota in the first 18 months of life: the impact of maternal HIV infection and breastfeeding.

BACKGROUND: Access to antiretroviral therapy (ART) during pregnancy and breastfeeding for mothers with HIV has resulted in fewer children acquiring HIV peri- and postnatally, resulting in an increase in the number of children who are exposed to the virus but are not infected (HEU). HEU infants have an increased likelihood of childhood infections and adverse growth outcomes, as well as increased mortality compared to their HIV-unexposed (HUU) peers. We explored potential differences in the gut microbiota in a cohort of 272 Nigerian infants born to HIV-positive and negative mothers in this study during the first 18 months of life. RESULTS: The taxonomic composition of the maternal vaginal and gut microbiota showed no significant differences based on HIV status, and the composition of the infant gut microbiota at birth was similar between HUU and HEU. Longitudinal taxonomic composition of the infant gut microbiota and weight-for-age z-scores (WAZ) differed depending on access to breast milk. HEU infants displayed overall lower WAZ than HUU infants at all time points. We observed a significantly lower relative abundance of Bifidobacterium in HEU infants at 6 months postpartum. Breast milk composition also differed by time point and HIV infection status. The antiretroviral therapy drugs, lamivudine and nevirapine, as well as kynurenine, were significantly more abundant in the breast milk of mothers with HIV. Levels of tiglyl carnitine (C5) were significantly lower in the breast milk of mothers without HIV. ART drugs in the breast milk of mothers with HIV were associated with a lower relative abundance of Bifidobacterium longum. CONCLUSIONS: Maternal HIV infection was associated with adverse growth outcomes of HEU infants in this study, and these differences persist from birth through at least 18 months, which is a critical window for the development of the immune and central nervous systems. We observed that the relative abundance of Bifidobacterium spp. was significantly lower in the gut microbiota of all HEU infants over the first 6 months postpartum, even if HEU infants were receiving breast milk. Breastfeeding was of benefit in our HEU infant cohort in the first weeks postpartum; however, ART drug metabolites in breast milk were associated with a lower abundance of Bifidobacterium. Video abstract.

Bifidobacterium animalis subsp. lactis BB-12 Protects against Antibiotic-Induced Functional and Compositional Changes in Human Fecal Microbiome.

The administration of broad-spectrum antibiotics is often associated with antibiotic-associated diarrhea (AAD), and impacts gastrointestinal tract homeostasis, as evidenced by the following: (a) an overall reduction in both the numbers and diversity of the gut microbiota, and (b) decreased short-chain fatty acid (SCFA) production. Evidence in humans that probiotics may enhance the recovery of microbiota populations after antibiotic treatment is equivocal, and few studies have addressed if probiotics improve the recovery of microbial metabolic function. Our aim was to determine if Bifidobacterium animalis subsp. lactis BB-12 (BB-12)-containing yogurt could protect against antibiotic-induced fecal SCFA and microbiota composition disruptions. We conducted a randomized, allocation-concealed, controlled trial of amoxicillin/clavulanate administration (days 1-7), in conjunction with either BB-12-containing or control yogurt (days 1-14). We measured the fecal levels of SCFAs and bacterial composition at baseline and days 7, 14, 21, and 30. Forty-two participants were randomly assigned to the BB-12 group, and 20 participants to the control group. Antibiotic treatment suppressed the fecal acetate levels in both the control and probiotic groups. Following the cessation of antibiotics, the fecal acetate levels in the probiotic group increased over the remainder of the study and returned to the baseline levels on day 30 (-1.6% baseline), whereas, in the control group, the acetate levels remained suppressed. Further, antibiotic treatment reduced the Shannon diversity of the gut microbiota, for all the study participants at day 7. The magnitude of this change was larger and more sustained in the control group compared to the probiotic group, which is consistent with the hypothesis that BB-12 enhanced microbiota recovery. There were no significant baseline clinical differences between the two groups. Concurrent administration of amoxicillin/clavulanate and BB-12 yogurt, to healthy subjects, was associated with a significantly smaller decrease in the fecal SCFA levels and a more stable taxonomic profile of the microbiota over time than the control group.

Changes in the Gut Microbiota Following Bariatric Surgery Are Associated with Increased Alcohol Intake in a Female Rat Model.

AIMS: We aimed to investigate if differences in gut microbiota diversity and composition are associated with post-operative alcohol intake following bariatric surgery in a rat model. METHODS: Twenty-four female rats were randomized to three treatment groups: sham surgery, vertical sleeve gastrectomy (VSG) or Roux-en-Y gastric bypass (RYGB). Stool was collected pre- and post-operatively and 16S rRNA gene amplification and sequencing was performed. Analysis focused on correlating microbial diversity, type of surgery and alcohol (EtOH) intake. RESULTS: Pre-operative stools samples on regular diet showed similar taxonomic composition and Shannon diversity among the three treatment groups. There was a significant decrease in Shannon diversity and a change in taxonomic composition of the gut microbiota after rats was fed high fat diet. Post-operatively, the RYGB group showed significantly lower taxonomic diversity than the VSG and sham groups, while the VSG and sham groups diversity were not significantly different. Taxonomic composition and function prediction based on PICRUSt analysis showed the RYGB group to be distinct from the VSG and sham groups. Shannon diversity was found to be negatively associated with EtOH intake. CONCLUSIONS: Changes in the taxonomic profile of the gut microbiota following bariatric surgery, particularly RYGB, are associated with increased EtOH intake and may contribute to increased alcohol use disorder risk through the gut-brain-microbiome axis.

Love at First Click: Surgery Residency Websites in the Virtual Era.

INTRODUCTION: Frequently, a residency program's website is the first interaction students interested in surgery have with the program. In the setting of virtual interviews for residency in 2020, the online availability of program information is of heightened importance. We sought to assess how academic versus community-based general surgery residency programs compared with respect to certain details on their websites. METHODS: A total of n = 268 surgery residency programs were investigated. Our database of website characteristics included: direct link to residency website from the American Council on Graduate Medical Education (ACGME) program page, resident research requirement, listing of residents' publications, availability of residents' demographic information, program alumni information, board pass rates, attrition rate, detail of educational/academic activities, residents' evaluation methods, diversity, and mentorship. Inter-group analyses between academic and community-based programs were performed using Pearson's Chi-squared test. RESULTS: Academic and community-based general surgery residency program websites were compared based on twelve (12) different parameters. Statistically significant differences were observed for eight of these comparisons: direct website access from ACGME (p = 0.007), research highlighted (p < 0.001), resident research requirement (p = 0.002), resident demographic information available (p=0.004), alumni information (p = 0.005), resident evaluation methods (p = 0.016), diversity (p < 0.001), and mentorship (p = 0.012). Across these domains, academic programs had more information available on their websites than the community programs did. The program websites did not differ significantly based on the frequency of mentioning resident publications, board pass rate, attrition rate, or resident education. CONCLUSION: Many general surgery programs are lacking detailed information on their websites. The amount of website information available on general surgery residency programs differs when comparing academic and community-based programs.

Understanding the Well-Being of General Surgery Residents.

BACKGROUND: In 2017, the Accreditation Council for Graduate Medical Education program guidelines changed to include a section that requires programs to optimize resident and faculty member well-being. There is still a poor understanding of general surgery resident wellness, and there are few well-established wellness programs. METHODS: We created a novel 50-question anonymous survey to assess burnout, depression, and wellness that was distributed to the general surgery residents as part of a pilot study. Univariate analysis was performed to assess wellness and wellness changes. Bivariate analysis was performed to determine the association between wellness variables and gender, age, and postgraduate year (PGY) level. RESULTS: Thirty-five of 55 residents participated in the survey. Over half of the residents (54%) reported gaining weight during residency. Nearly 70% reported working while having an ongoing family issue, and 77% worked at least once while ill. Fourteen residents (40%) reported that their wellness worsened over the previous academic year, while 7 (20%) reported that it remained the same, and 11 (31%) reported that it improved. These changes varied significantly by the PGY level (P < .01). Age (younger vs older than 30) and sex were found to be effective measure modifiers of the association between wellness change and PGY level. DISCUSSION: The overall wellness of the general surgery residents at our institution varies greatly. Poor wellness may lead to inferior patient care, burnout and depression, and negative resident morale. Residency programs need to implement programming to address wellness deficiencies.

Analysis of Melanoma Secretome for Factors That Directly Disrupt the Barrier Integrity of Brain Endothelial Cells.

We have recently demonstrated that invasive melanoma cells are capable of disrupting the brain endothelial barrier integrity. This was shown using ECIS biosensor technology, which revealed rapid disruption via the paracellular junctions. In this paper, we demonstrate that melanoma cells secrete factors (e.g., cytokines) that weaken the endothelial barrier integrity. Through proteome profiling, we attempt to identify the barrier-disrupting cytokines. Melanoma conditioned media were collected from three New Zealand melanoma lines. ECIS technology was used to assess if the conditioned media disrupted the endothelial barrier independent of the melanoma cells. The melanoma cell secretome was assessed using cytometric bead array (CBA), Luminex immunoassay and multiplex Proteome Profilers, to detect the expression of secretory proteins, which may facilitate metastasis. Finally, ECIS technology was used to assess the direct effects of secreted proteins identified as candidates from the proteome screens. We show that melanoma-conditioned media significantly disrupted the brain endothelial barrier, however, to a much lesser extent than the cells from which they were collected. Cytokine and proteome profiling of the conditioned media showed evidence of high concentrations of approximately 15 secreted proteins (including osteopontin, IL-8, GDF-15, MIF and VEGF). These 15 secreted proteins were expressed variably across the melanoma lines. Surprisingly, the addition of these individually to the brain endothelial cells did not substantially affect the barrier integrity. ANGPTL-4 and TGFß were also produced by the melanoma cells. Whilst TGFß-1 had a pronounced effect on the barrier integrity, surprisingly ANGPTL-4 did not. However, its C-terminal fragment did and within a very similar period to the conditioned media, albeit not to the same extent. Herein we show that melanoma cells produce a wide-range of soluble factors at high concentrations, which most likely favour support or survival of the cancer cells. Most of these, except for TGFß-1 and the C-terminal fragment of ANGPTL-4, did not have an impact on the integrity of the brain endothelial cells.

Colorectal Cancer Screening in African American HOPE VI Public Housing Residents.

This study explores whether colorectal cancer screening outreach via home visits and follow-up calls is effective among public housing African American residents. It reports on the proportion of returned Fecal Immunochemical Test kits, on the characteristics of study participants, and on their primary reasons for returning the kit. By conducting home visits and follow-up calls, our colorectal cancer-screening outreach resulted in a higher Fecal Immunochemical Test kit return rate than anticipated. Findings suggest that a more personalized outreach approach can yield higher colorectal cancer-screening rates among urban minority populations, which are at higher risk to be diagnosed with late-stage colorectal cancer.

Holistic General Practice: A Student`s Perspective.

This patient was a lady in her 50s who had previously been diagnosed with anxiety, depression and rectal cancer. She had undergone neo-adjuvant chemotherapy designed to shrink the tumour before it was removed surgically. However, the cancer responded better than expected to the chemotherapy, and the oncologists could no longer find evidence of active cancer within the patient. The oncologist had recently been speaking with the patient about whether or not she should continue with the surgery they had originally planned. The oncologist was keen to go ahead with the surgery, as it offered the best chance of long term disease free survival. The patient, however, was extremely nervous about going through major surgery, and was less sure that it was the right option now that she had been told that there was no evidence of active cancer. However, she had been unable to come to a definitive decision despite 3 consultations with her oncologist and the surgeons ready to perform the operation and the oncologist had written to the patients GP to this effect. This patient taught me a variety of things. Firstly, the background given to me about this patients' first consultation opened my eyes to the importance of certain parts of the medical history. For example, the rectal cancer was only picked up due to additional symptoms found during the review of systems. The patient consultation that I witnessed was regarding a decision the patient was struggling to make over whether or not to have surgery following seemingly successful neo-adjuvant chemotherapy. The patient was struggling to make this decision due to a lack of support and the GP had scheduled this appointment to help her come to terms with the decision that she needed to make.

Comparison of the duration and power spectral changes of monopolar and bipolar M waves caused by alterations in muscle fibre conduction velocity.

The muscle compound action potential (M wave) recorded under monopolar configuration reflects both the propagation of the action potentials along the muscle fibres and their extinction at the tendon. M waves recorded under a bipolar configuration contain less cross talk and noise than monopolar M waves, but they do not contain the entire informative content of the propagating potential. The objective of this study was to compare the effect of changes in muscle fibre conduction velocity (MFCV) on monopolar and bipolar M waves and how this effect depends on the distance between the recording electrodes and tendon. The study was based on a simulation approach and on an experimental investigation of the characteristics of surface M waves evoked in the vastus lateralis during 4-s step-wise isometric contractions in knee extension at 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, and 90% MVC. The peak-to-peak duration (Durpp) and median frequency (Fmedian) of the M waves were calculated. For monopolar M waves, changes in Durpp and Fmedian produced by MFCV depended on the distance from the electrode to the tendon, whereas, for bipolar M waves, changes in Durpp and Fmedian were largely independent of the electrode-to-tendon distance. When the distance between the detection point and tendon lay between approximately 15 and 40mm, changes in Durpp of bipolar M waves were more pronounced than those of distal monopolar M waves but less marked than those of proximal monopolar M waves, and the opposite occurred for Fmedian. Since, for bipolar M waves, changes in duration and power spectral features produced by alterations in MFCV are not influenced by the electrode-to-tendon distance, the bipolar electrode configuration is a preferable choice over monopolar arrangements to estimate changes in conduction velocity.

Pathological Findings in Feto-maternal Hemorrhage.

Feto-maternal hemorrhage (FMH) is the cause of late fetal death in 1.6%-11% of cases. In spite of this high frequency, its pathological features have received little attention. The definitive diagnosis of lethal FMH requires confirmation of sufficient fetal blood volume loss. This is determined by tests such as the Kleihauer-Betke test, which may not have been obtained or not have been available before the autopsy. The pathologist may offer a tentative diagnosis of FMH from the autopsy findings. The objective of this study was to better characterize the placental and fetal autopsy findings in lethal FMH. This was a retrospective study of 17 cases of FMH proven by a positive Kleihauer-Betke test. The cases were selected from the autopsy files of the Department of Pathology, Centre Hospitalier Universitaire de Bordeaux. The pathological reports as well as the placental and fetal photographs and the microscopic slides of each case were systematically reviewed. The fetal autopsy findings in FMH are characterized by a eutrophic pale macerated fetus, low liver weight, absent intrathoracic petechiae, increased extramedullary hematopoiesis in the liver and kidney, and increased circulating nucleated red blood cells. The placenta shows an increased frequency of intervillous thrombi. Although nonpathognomonic, some of the pathological features are strongly suggestive of FMH. When the latter is present, a Kleihauer-Betke test should be performed, even some days after the delivery.