Genetic hypogonadal (Gnrh1 hpg ) mouse model uncovers influence of reproductive axis on maturation of the gut microbiome during puberty.

The gut microbiome plays a key role in human health and gut dysbiosis is linked to many sex-specific diseases including autoimmune, metabolic, and neurological disorders. Activation of the hypothalamic-pituitary-gonadal (HPG) axis during puberty leads to sexual maturation and development of sex differences through the action of gonadal sex steroids. While the gut microbiome also undergoes sex differentiation, the mechanisms involved remain poorly understood. Using a genetic hypogonadal (hpg) mouse model, we sampled the fecal microbiome of male and female wild-type and hpg mutant mice before and after puberty to determine how microbial taxonomy and function are influenced by age, sex, and the HPG axis. We showed that HPG axis activation during puberty is required for sexual maturation of the gut microbiota composition, community structure, and metabolic functions. We also demonstrated that some sex differences in taxonomic composition and amine metabolism developed independently of the HPG axis, indicating that sex chromosomes are sufficient for certain sex differences in the gut microbiome. In addition, we showed that age, independent of HPG axis activation, led to some aspects of pubertal maturation of the gut microbiota community composition and putative functions. These results have implications for microbiome-based treatments, indicating that sex, hormonal status, and age should be considered when designing microbiome-based therapeutics.

Trends and Distribution of IPAAs in the United States: Becoming Harder to Find in Colon and Rectal Surgery Residency Training?

BACKGROUND: There has been concern among colon and rectal surgery residency programs in the United States that IPAA procedures have been decreasing, but evidence is limited. OBJECTIVE: The study aimed to evaluate the number of IPAAs performed by colon and rectal surgery residents in the United States and analyze the distribution of these cases on a national level. DESIGN: Retrospective. SETTINGS: The Accreditation Council for Graduate Medical Education Case Log National Data Reports were used to evaluate the number of IPAAs performed by residents from 2005 to 2021. The Nationwide Inpatient Sample database was used to identify all patients undergoing these procedures from 2005 to 2019. PATIENTS: All IPAA procedures regardless of indication. MAIN OUTCOME MEASURES: The primary outcome was the number of IPAAs performed by residents yearly. The secondary outcome was the national distribution of these procedures. RESULTS: Among colon and rectal surgery residents, case log data revealed an increase in mean and total number of IPAAs from 2005 to 2013, followed by a decline in both metrics after 2013. Despite the decrease, the mean number of cases per resident remained fewer than 6 between 2011 and 2021. A weighted national estimate of 48,532 IPAA patients were identified in the Nationwide Inpatient Sample database. A significant decrease was noted in the number of IPAAs after 2015 that persisted through 2019. There was a significant decrease in rural and urban nonteaching hospitals (from 2.1% to 1.6% and 25.6% to 4.3%, respectively; p < 0.001) and an increase in urbanteaching hospitals (from 72.4% to 94.1%; p < 0.001). LIMITATIONS: Nonrandomized retrospective study design. CONCLUSIONS: Despite the recent increase in the percentage of IPAAs performed at urban academic centers, there has been a decrease in cases performed by colon and rectal surgery residents. This can have significant implications for residents who graduate without adequate experience in performing this complex procedure independently, as well as training programs that may face challenges with maintaining accreditation. See Video Abstract. TENDENCIAS Y DISTRIBUCIN DE LA ANASTOMOSIS ANAL CON BOLSA ILEAL EN LOS ESTADOS UNIDOS SE EST VOLVIENDO MS DIFCIL DE ENCONTRAR EN LA CAPACITACIN DE RESIDENCIA EN CIRUGA DE COLON Y RECTO: ANTECEDENTES:Ha habido preocupación entre los programas de capacitación de residencia en cirugía de colon y recto en los Estados Unidos porque los procedimientos de anastomosis anal con bolsa ileal han estado disminuyendo; sin embargo, la evidencia es limitada.OBJETIVO:Evaluar el número de anastomosis anales con bolsa ileal realizadas por residentes de cirugía de colon y recto en los Estados Unidos y examinar la distribución de estos casos a nivel nacional.DISEÑO:Retrospectivo.AJUSTES:Se utilizaron los informes de datos nacionales del registro de casos de educación médica de posgrado del Consejo de Acreditación para examinar el número de anastomosis anales con bolsa ileal realizadas por residentes de 2005 a 2021. Se utilizó la base de datos de muestra nacional de pacientes hospitalizados para identificar a todos los pacientes sometidos a estos procedimientos de 2005 a 2019.PACIENTES:Todos los procedimientos de anastomosis anal con bolsa ileal independientemente de la indicación.MEDIDA DE RESULTADO PRINCIPAL:El resultado primario es el número de anastomosis anales con bolsa ileal realizadas por los residentes anualmente. El resultado secundario es la distribución nacional de estos procedimientos.RESULTADOS:Entre los residentes de cirugía de colon y recto, los datos de los registros de casos revelaron un aumento en el número medio y total de anastomosis anal con bolsa ileal de 2005 a 2013, seguido de una disminución en ambas métricas después de 2013. A pesar de la disminución, el número medio de casos por El residente permaneció >6 entre 2011 y 2021. Se identificó una estimación nacional ponderada de 48 532 pacientes con anastomosis anal con bolsa ileal en la base de datos de la Muestra Nacional de Pacientes Hospitalizados. Se observó una disminución significativa en el número de anastomosis anales con bolsa ileal después de 2015 que persistió hasta 2019. Hubo una disminución significativa en los hospitales no docentes rurales y urbanos (del 2,1% al 1,6% y del 25,6% al 4,3% respectivamente, p < 0,001) y un aumento en los hospitales universitarios urbanos (del 72,4% al 94,1%, p < 0,001).LIMITACIONES:Estudio retrospectivo no aleatorizado.CONCLUSIÓN:A pesar del reciente aumento en el porcentaje de anastomosis anal con bolsa ileal realizadas en centros académicos urbanos, ha habido una disminución en los casos realizados por residentes de cirugía de colon y recto. Esto puede tener implicaciones significativas para los residentes que se gradúan sin la experiencia adecuada en la realización de este complejo procedimiento de forma independiente, así como para los programas de capacitación que pueden enfrentar desafíos para mantener la acreditación. (Traduccion-AI-generated).

Does Operating Volume On-Call Vary by Surgeon? Analysis of On-Call Cases in an Academic Colorectal Practice.

The aim was to determine whether on-call case volumes differ amongst colorectal surgeons, and what cases are performed on-call in an academic colorectal surgery practice. The on-call schedule for the year 2021 of a colorectal surgery practice was analyzed. Details of the case origin and operative details were collected. Average cases performed per call per surgeon were compared. Ten surgeons were included, and average cases per call ranged from .5 to 1.4 with 1.0 the overall average (P = .007). Analyzing individual pairs, differences existed between the 2 busiest and the least busy on-call surgeon (both P < .05). Most patients operated on-call were admitted via the emergency department (59%), and the most common operations were exams under anesthesia (39%) and bowel resections (33%). On average, 1 on-call case was performed per day. Surgeon on-call volume was similar aside from the busiest and least busy on-call surgeons.

Assessing the stops framework for coping with intraoperative errors: Evidence of efficacy, hints of hubris, and a bridge to abridging burnout.

BACKGROUND: Answering calls in the literature, we developed and introduced an evidence-based tool for surgeons facing errors in the operating room: the STOPS framework (stop, talk to you team, obtain help, plan, succeed). The purpose of this research was to assess the impact of presenting this psychological tool on resident coping in the operating room and the related outcome of burnout while examining sex differences. METHODS: In a natural experiment, general surgery residents were invited to attend 2 separate educational conferences regarding coping with errors in the operating room. Three months later, all residents were asked to fill out a survey assessing their coping in the operating room, level of burnout, and demographics. We assessed the impact of the educational intervention by comparing those who attended the coping conferences with those who did not attend. RESULTS: Thirty-five residents responded to the survey (65% response rate, 54% female respondents, 49% junior residents). Our hypothesized moderated mediation model was supported. Sex was found to moderate the impact of the STOPS framework-female residents who attended the coping educational conference reported higher coping self-efficacy, whereas attendance had no statistically significant impact on male levels of coping self-efficacy. In turn, higher coping self-efficacy was associated with lower levels of burnout. CONCLUSION: Our results suggest that there is evidence of efficacy in this instruction-female residents presented this material report higher levels of coping in the operating room compared to those who did not receive the framework. Further, increase in coping ability was associated with reduced levels of burnout for both genders.

Colorectal Sarcomatoid Carcinoma: 30-Year Experience.

Background: Primary colorectal sarcomatoid carcinoma is a rare and aggressive malignant neoplasm that displays mixed epithelial and mesenchymal differentiation, with uncertain histogenesis. First described in 1986, there is a paucity of literature related to this condition and there are no evidence-based treatment guidelines. The aim of our study is to present our 30-year experience with primary colorectal sarcomatoid carcinoma. Methods: Retrospective single-center analysis of all patients treated for primary colorectal sarcomatoid carcinoma from 1992 to 2022. The primary outcome was response to treatment strategy and overall survival. Results: A total of six cases met eligibility criteria. Three were male (50%) with a mean age at diagnosis of 59 years (range, 49-72). Four neoplasms were located in the rectum (66%) and two in the colon. Mean tumor size at diagnosis was 4.8 cm (range, 2.8-7.0). Three patients were treated endoscopically and three underwent oncologic surgical resection. Five experienced recurrence and one expired from other comorbidities. The mean survival among those with colonic and rectal sarcomatoid carcinoma was 7 months (range, 3-11) and 39 months (range, 9-60), respectively. Discussion: Primary colorectal sarcomatoid carcinoma is a rare malignant tumor with poor prognosis. Treatment modalities have not been standardized and despite multimodal therapy, disease recurrence and/or metastasis is likely to occur. Further studies are necessary to determine optimal treatment to improve outcomes.

Common design and data elements on rectal artery embolization for treatment of symptomatic internal hemorrhoidal disease: an interactive systematic review of clinical trials.

BACKGROUND: Internal hemorrhoids (IH) is a common medical condition that can result in morbidity secondary to bleeding and discomfort. Treatment for IH has traditionally consisted of dietary and conservative medical management, focal treatments including banding and sclerotherapy or hemorrhoidectomy. Recently, rectal artery embolization (RAE) has been studied as a potential treatment for bleeding predominant IH. We performed a common design and data element analysis of studies that report on RAE. MATERIALS AND METHODS: We conducted a qualitative systematic literature review for rectal artery embolization (RAE) for symptomatic hemorrhoidal disease. The screening process involved five online databases (PubMed, Embase, Google Scholar, DOAJ, and Scopus). Additionally, ClinicalTrials.gov was examined for active, unpublished completed studies. The initial search yielded 2000 studies, with 15 studies meeting the inclusion criteria after screening and assessment. The included studies comprised one RCT, one case series, one pilot study and 12 cohort studies. RESULTS: The population analysis revealed a male predominance across all studies, with varying cohort sizes. The baseline Goligher hemorrhoid grade was utilized in 80% of studies. The majority (73.3%) employed a transfemoral approach, and coils were the primary embolic material in 60% of studies, 26.6% were combination of coils and particles, and 6.6% were particles only. Patient selection criteria highlighted RAE's applicability for high surgical risk patients and those with anemia, chronic hematochezia, or treatment-refractory cases. Exclusion criteria emphasized factors such as previous surgeries, colorectal cancer, rectal prolapse, acute hemorrhoidal complications, and contrast allergy. Study designs varied, with cohort studies being the most common (12/15; 80%). Procedural details included the use of metallic coils and detachable micro-coils, with a high technical success rate reported in most studies ranging from 72 to 100%. The follow-up ranged from 1 to 18 months. The majority of studies reported no major immediate or post-procedural complications. CONCLUSION: While all studies focused on RAE as a treatment for IH, there was a great degree of heterogeneity among included studies, particularly regarding inclusion criteria, exclusion criteria, outcomes measures and timeframe. Future literature should attempt to standardize these design elements to help facilitate secondary analyses and increase understanding of RAE as a treatment option.

Ischiorectal Fossa Tumors: 30-year Single-Institution Experience.

BACKGROUND: Primary tumors of the ischiorectal fossa are rare and comprise a wide array of pathologies with varying malignant potential. Because of the low prevalence, there is a paucity of data in the literature. This article presents a case series on the management of ischiorectal fossa tumors. OBJECTIVE: To present experience from 30 years of managing ischiorectal fossa tumors. DESIGN: Retrospective single-center analysis. SETTINGS: A quaternary referral academic health care center. PATIENTS: All patients treated for ischiorectal fossa tumors were included in the study. INTERVENTIONS: All patients underwent surgical management of their disease. MAIN OUTCOME MEASURES: Disease recurrence and overall survival. RESULTS: A total of 34 patients (53% women) were identified with a median follow-up of 23 months. Twenty-one patients (62%) were diagnosed with benign and 13 (38%) with malignant tumors. All underwent surgical resection. The median tumor size was 8.4 cm. R0 resection was obtained in 28 patients. Twelve patients (35%) developed recurrence (9 after R0 resection) after a median time of 6.5 months. There were no surgical-related mortalities. LIMITATIONS: Limitations to the study include its retrospective nature, single-center experience, and small patient sample size. CONCLUSIONS: Ischiorectal fossa tumors are primarily benign; however, they are associated with high recurrence rates even in the setting of an R0 resection. Treatment should be approached in a multidisciplinary manner, preferably in centers with experience treating these tumors. Close posttreatment surveillance is imperative. See Video Abstract . TUMORES DE LA FOSA ISQUIORRECTAL EXPERIENCIA DE AOS EN UNA SOLA INSTITUCIN: ANTECEDENTES:Los tumores primarios de la fosa isquiorrectal son raros y comprenden una amplia gama de patologías con potencial maligno variable. Debido a la baja prevalencia, hay escasez de datos en la literatura. Este artículo presenta una serie de casos sobre el tratamiento de los tumores de la fosa isquiorrectal.OBJETIVO:Presentar una experiencia de 30 años en el manejo de tumores de la fosa isquiorrectal.DISEÑO:Análisis retrospectivo de un solo centro.AJUSTES:Un centro de atención médica académico de referencia cuaternaria.PACIENTES:Todos los pacientes tratados por tumores de la fosa isquiorrectal.INTERVENCIONES:Todos los pacientes se sometieron a tratamiento quirúrgico de su enfermedad.PRINCIPALES MEDIDAS DE RESULTADO:Recurrencia de la enfermedad y supervivencia general.RESULTADOS:Se identificaron un total de 34 pacientes (53% mujeres) con una mediana de seguimiento de 23 meses. Veintiún pacientes (62%) fueron diagnosticados con tumores benignos y 13 (38%) con tumores malignos. Todos fueron sometidos a resección quirúrgica. El tamaño medio del tumor fue de 8,4 cm. La resección R0 se obtuvo en 28 pacientes. Doce (35%) desarrollaron recurrencia (nueve después de la resección R0) con una mediana de tiempo de 6,5 meses. No hubo mortalidades relacionadas con la cirugía.LIMITACIONES:Las limitaciones del estudio incluyen su naturaleza retrospectiva, experiencia en un solo centro y tamaño pequeño de la muestra de pacientes.CONCLUSIONES:Los tumores de la fosa isquiorrectal son principalmente benignos, sin embargo, se asocian con altas tasas de recurrencia incluso en el contexto de una resección R0. El tratamiento debe abordarse de forma multidisciplinaria y preferentemente en centros con experiencia en el tratamiento de estos tumores. Vigilancia cercana posterior al tratamiento es imperativa. (Traducción-Dr. Aurian Garcia Gonzalez).

Surgical management of duodenal crohn's disease.

BACKGROUND: Operative options for duodenal Crohn's disease include bypass, stricturoplasty, or resection. What factors are associated with operation selection and whether differences exist in outcomes is unknown. METHODS: Patients with duodenal Crohn's disease requiring operative intervention across a multi-state health system were identified. Patient and operative characteristics, short-term surgical outcomes, and the need for future endoscopic or surgical management of duodenal Crohn's disease were analyzed. RESULTS: 40 patients underwent bypass (n = 26), stricturoplasty (n = 8), or resection (n = 6). Median age of diagnosis of Crohn's disease was 23.5 years, and over half of the patients had undergone prior surgery for CD. Operation type varied by the most proximal extent of duodenal involvement. Patients with proximal duodenal CD underwent bypass operations more commonly than those with mid- or distal duodenal disease (p = 0.03). Patients who underwent duodenal stricturoplasty more often required concomitant operations for other sites of small bowel or colonic CD (63%) compared to those who underwent bypass (39%) or resection (33%). No patients required subsequent surgery for duodenal CD at a median follow-up of 2.8 years, but two patients required endoscopic dilation (n = 1 after stricturoplasty, n = 1 after resection). CONCLUSION: Patients who require surgery for duodenal Crohn's disease appear to have an aggressive Crohn's disease phenotype, represented by a younger age of diagnosis and a high rate of prior resection for Crohn's disease. Choice of operation varied by proximal extent of duodenal Crohn's disease.

Robotic-assisted reoperative ileal pouch-anal anastomosis: robotic pouch excision and pouch revision.

BACKGROUND: Up to 20% of patients with ileal pouch will develop pouch failure, ultimately requiring surgical reintervention. As a result of the complexity of reoperative pouch surgery, minimally invasive approaches were rarely utilized. In this series, we present the outcomes of the patients who underwent robotic-assisted pouch revision or excision to assess its feasibility and short-term results. METHODS: All the patients affected by inflammatory bowel diseases and familial adenomatous polyposis who underwent robotic reoperative surgery of an existing ileal pouch were included. RESULTS: Twenty-two patients were included; 54.6% were female. The average age at reoperation was 51 ± 16 years, with a mean body mass index of 26.1 ± 5.6 kg/m2. Fourteen (63.7%) had a diagnosis of ulcerative colitis at reoperation, and seven (31.8%) had Crohn's disease. The mean time to pouch reoperation was 12.8 ± 11.8 years. Seventeen (77.3%) patients underwent pouch excision, and five (22.7%) had pouch revision surgery. The mean operative time was 372 ± 131 min, and the estimated blood loss was 199 ± 196.7 ml. The conversion rate was 9.1%, the 30-day morbidity rate was 27.3% (with only one complication reaching Clavien-Dindo grade IIIB), and the mean length of stay was 5.8 ± 3.9 days. The readmission rate was 18.2%, the reoperation rate was 4.6%, and mortality was nihil. All patients in the pouch revisional group are stoma-free. CONCLUSION: Robotic reoperative pouch surgery in highly selected patients is technically feasible with acceptable outcomes.

Evolution of laparoscopic ileal pouch-anal anastomosis: impact of enhanced recovery program, medication changes, and staged approaches on outcomes.

BACKGROUND: Although laparoscopic Ileal pouch-anal anastomosis (IPAA) has become the gold standard in restorative proctocolectomy, surgical techniques have experienced minimal changes. In contrast, substantial shifts in perioperative care, marked by the enhanced recovery program (ERP), modifications in steroid use, and a shift to a 3-staged approach, have taken center stage. METHODS: Data extracted from our prospective IPAA database focused on the first 100 laparoscopic IPAA cases (historic group) and the latest 100 cases (modern group), aiming to measure the effect of these evolutions on postoperative outcomes. RESULTS: The historic IPAA group had more 2-staged procedures (92% proctocolectomy), whereas the modern group had a higher number of 3-staged procedures (86% proctectomy) (P < .001). Compared with patients in the modern group, patients in the historic group were more likely to be on steroids (5% vs 67%, respectively; P < .001) or immunomodulators (0% vs 31%, respectively; P < .001) at surgery. Compared with the historic group, the modern group had a shorter operative time (335.5 ± 78.4 vs 233.8 ± 81.6, respectively; P < .001) and length of stay (LOS; 5.4 ± 3.1 vs 4.2 ± 1.6 days, respectively; P < .001). Compared with the modern group, the historic group exhibited a higher 30-day morbidity rate (20% vs 33%, respectively; P = .04) and an elevated 30-day readmission rate (9% vs 21%, respectively; P = .02). Preoperative steroids use increased complications (odds ratio [OR], 3.4; P = .01), whereas 3-staged IPAA reduced complications (OR, 0.3; P = .03). ERP was identified as a factor that predicted shorter stays. CONCLUSION: Although ERP effectively reduced the LOS in IPAA surgery, it failed to reduce complications. Conversely, adopting a 3-staged IPAA approach proved beneficial in reducing morbidity, whereas preoperative steroid use increased complications.

Gastrointestinal histoplasmosis with small intestinal perforation: 20-year experience.

Postmortem studies show gastrointestinal tract involvement in as many as 70% of patients affected by disseminated histoplasmosis. Although gastrointestinal involvement is common in disseminated disease, the presentation of small intestinal perforation is exceedingly rare with few reported cases in the literature. Herein we present our institutional case series. The aim of the study is to describe small intestinal perforation in gastrointestinal histoplasmosis with attention to management and outcomes. This is a retrospective single-institution review of patients ≥ 18 years of age treated for small intestinal perforation due to gastrointestinal histoplasmosis. A prospectively maintained institutional database was searched from 2002 to 2022. Data obtained included demographics, comorbidities, treatment course, and outcomes. Five patients with a mean age of 54 years (range 25-72) were identified. Pertinent underlying comorbid conditions included Crohn's disease, psoriatic arthritis, rheumatoid arthritis, and solid organ transplantation. All patients were on chronic immunosuppressive medication(s) with the most common being tumor necrosis factors alpha inhibitors and corticosteroids. Four had a clinical diagnosis of perforation based on physical examination and imaging. All patients underwent segmental resection(s) of the small intestine and received medical treatment with intravenous amphotericin B and eventual transition to an oral antifungal. No patients experienced complications related to surgery. The limitations of the study include nonrandomized retrospective review, single-institution experience, and small patient sample size. Although rare, histoplasmosis should be considered in the differential of patients on chronic immunosuppressive therapy who present with gastrointestinal symptoms concerning perforation, especially from endemic areas. Small intestinal perforation due to gastrointestinal histoplasmosis can be successfully treated with resection and antifungal therapy.

AutoPhy: Automated phylogenetic identification of novel protein subfamilies.

Phylogenetic analysis of protein sequences provides a powerful means of identifying novel protein functions and subfamilies, and for identifying and resolving annotation errors. However, automation of functional clustering based on phylogenetic trees has been challenging and most of it is done manually. Clustering phylogenetic trees usually requires the delineation of tree-based thresholds (e.g., distances), leading to an ad hoc problem. We propose a new phylogenetic clustering approach that identifies clusters without using ad hoc distances or other pre-defined values. Our workflow combines uniform manifold approximation and projection (UMAP) with Gaussian mixture models as a k-means like procedure to automatically group sequences into clusters. We then apply a "second pass" clade identification algorithm to resolve non-monophyletic groups. We tested our approach with several well-curated protein families (outer membrane porins, acyltransferase, and nuclear receptors) and showed our automated methods recapitulated known subfamilies. We also applied our methods to a broad range of different protein families from multiple databases, including Pfam, PANTHER, and UniProt, and to alignments of RNA viral genomes. Our results showed that AutoPhy rapidly generated monophyletic clusters (subfamilies) within phylogenetic trees evolving at very different rates both within and among phylogenies. The phylogenetic clusters generated by AutoPhy resolved misannotations and identified new protein functional groups and novel viral strains.

Data-driven mathematical and visualization approaches for removing rare features for Compositional Data Analysis (CoDA).

Sparse feature tables, in which many features are present in very few samples, are common in big biological data (e.g. metagenomics). Ignoring issues of zero-laden datasets can result in biased statistical estimates and decreased power in downstream analyses. Zeros are also a particular issue for compositional data analysis using log-ratios since the log of zero is undefined. Researchers typically deal with this issue by removing low frequency features, but the thresholds for removal differ markedly between studies with little or no justification. Here, we present CurvCut, an unsupervised data-driven approach with human confirmation for rare-feature removal. CurvCut implements two distinct approaches for determining natural breaks in the feature distributions: a method based on curvature analysis borrowed from thermodynamics and the Fisher-Jenks statistical method. Our results show that CurvCut rapidly identifies data-specific breaks in these distributions that can be used as cutoff points for low-frequency feature removal that maximizes feature retention. We show that CurvCut works across different biological data types and rapidly generates clear visual results that allow researchers to confirm and apply feature removal cutoffs to individual datasets.

Metagenomic analysis of microbial communities and antibiotic resistant genes in the Tijuana river, and potential sources.

The Tijuana River is a transborder river that flows northwest across the border from Baja California in Mexico into Southern California before discharging into the Pacific Ocean. The river is frequently contaminated with raw sewage due to inadequate sanitary infrastructure in Tijuana. To assess the type and degree of microbial contamination, water samples were collected monthly from a near-border and an estuarine site from August 2020 until May 2021. A portion of each sample was used for epifluorescent microscopy and DNA was extracted directly from the rest for shotgun metagenomic sequencing. After sequence quality checking and processing, we used the rapid taxonomic identifier tool Kaiju to characterize the microbial diversity of the metagenomes and matched the sequences against the Comprehensive Antibiotic Resistance Database (CARD) to examine antimicrobial resistance genes (ARGs). Bacterial and viral-like particle (VLP) abundance was consistently higher in the near-border samples than in the estuarine samples, while alpha diversity (within sample biodiversity) was higher in estuarine samples. Beta-diversity analysis found clear compositional separation between samples from the two sites, and the near-border samples were more dissimilar to one another than were the estuarine sites. Near-border samples were dominated by fecal-associated bacteria and bacteria associated with sewage sludge, while estuarine sites were dominated by marine bacteria. ARGs were more abundant at the near-border site, but were also readily detectable in the estuarine samples, and the most abundant ARGs had multi-resistance to beta-lactam antibiotics. SourceTracker analysis identified human feces and sewage sludge to be the largest contributors to the near-border samples, while marine waters dominated estuarine samples except for two sewage overflow dates with high fecal contamination. Overall, our research determined human sewage microbes to be common in the Tijuana River, and the prevalence of ARGs confirms the importance of planned infrastructure treatment upgrades for environmental health.

Metabolic dysregulation and gut dysbiosis linked to hyperandrogenism in female mice.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is a common endocrine pathology in women. In addition to infertility, women with PCOS have metabolic dysregulation which predisposes them to Type 2 diabetes, cardiovascular disease and non-alcoholic fatty liver disease. Moreover, women with PCOS have changes in their gut microbial community that may be indicative of dysbiosis. While hyperandrogenism is associated with both the development of metabolic dysfunction and gut dysbiosis in females, the mechanisms involved are not well understood. METHODS: We used dihydrotestosterone (DHT) and ovariectomy (OVX) mouse models coupled with metabolic assessments and 16S rRNA gene sequencing to explore the contributions of hyperandrogenism and oestrogen deficiency to the development of insulin resistance and gut microbial dysbiosis in pubertal female mice. RESULTS: We demonstrated that, while DHT treatment or OVX alone were insufficient to induce insulin resistance during the pubertal-to-adult transition, combining OVX with DHT resulted in insulin resistance similar to that observed in letrozole-treated mice with elevated testosterone and decreased oestrogen levels. In addition, our results showed that OVX and DHT in combination resulted in a distinct shift in the gut microbiome compared to DHT or OVX alone, suggesting that the substantial metabolic dysregulation occurring in the OVX + DHT model was accompanied by unique changes in the abundances of gut bacteria including S24-7, Rikenellaceae and Mucispirillum schaedleri. CONCLUSIONS: While hyperandrogenism plays an important role in the development of metabolic dysregulation in female mice, our results indicate that investigation into additional factors influencing insulin resistance and the gut microbiome during the pubertal-to-adult transition could provide additional insight into the pathophysiology of PCOS.

Aggressive Angiomyxoma of the Pelvis: 35-Year Experience.

BACKGROUND: Aggressive angiomyxoma is a very rare mesenchymal tumor most commonly found in the pelvic and perineal regions. Although many are estrogen and progesterone hormone receptor positive, the pathogenesis is unknown. Due to its rarity, there is a paucity of literature relating to this pathology. This article presents a case series on the management of aggressive angiomyxoma of the pelvis. OBJECTIVE: To present a 35-year experience managing aggressive angiomyxoma of the pelvis. DESIGN: This was a retrospective single-system analysis. SETTINGS: This study was conducted at a quaternary referral academic health care system. PATIENTS: All patients treated for aggressive angiomyxoma of the pelvis. INTERVENTIONS: All patients underwent surgical or medical management of their disease. MAIN OUTCOME MEASURES: The primary outcomes were disease recurrence and mortality. Secondary outcomes included risk factors for recurrence. RESULTS: A total of 32 patients (94% women) were identified with a median follow-up of 65 months. Thirty patients (94%) underwent operative resection and 2 patients were treated solely with medical management. Fifteen achieved an R0 resection (negative microscopic margins) at the index operation, of which 4 (27%) experienced tumor recurrence. There were no mortalities. No risk factors for disease recurrence were identified. LIMITATIONS: Limitations to our study include its nonrandomized retrospective nature, single health care system experience, and small patient sample size. CONCLUSIONS: Aggressive angiomyxoma is a rare, slow-growing tumor with locally invasive features and a high potential for recurrence even after resection with negative margins. Imaging modalities such as CT or MRI should be obtained to aid in diagnosis and surgical planning. Workup should be paired with preoperative biopsy and testing for hormone receptor status, which can increase diagnostic accuracy and guide medical treatment. Close posttreatment surveillance is imperative to detect recurrence. See Video Abstract . ANGIOMIXOMA AGRESIVO DE PELVIS EXPERIENCIA DE AOS: ANTECEDENTES:El angiomixoma agresivo es un tumor mesenquimal muy raro que se encuentra más comúnmente en las regiones pélvica y perineal. Aunque muchos son positivos para los receptores hormonales como el estrógeno y la progesterona, la patogénesis es aún desconocida. Debido a su rareza, existe escasa literatura relacionada con esta patología. Este artículo presenta una serie de casos sobre el tratamiento del angiomixoma agresivo de pelvis.OBJETIVO:Presentar una experiencia de 35 años en el manejo del angiomixoma agresivo de pelvis.DISEÑO:Este fue un análisis retrospectivo de sistema único.AJUSTES:Este estudio se llevó a cabo en un sistema de salud académico de referencia de nivel cuaternario.PACIENTES:Todos los pacientes tratados por angiomixoma agresivo de pelvis.INTERVENCIONES:Todos los pacientes se sometieron a tratamiento quirúrgico y/o médico de su enfermedad.PRINCIPALES MEDIDAS DE RESULTADO:Los resultados primarios fueron la recurrencia de la enfermedad y la mortalidad. Los resultados secundarios incluyeron factores de riesgo de recurrencia.RESULTADOS:Se identificaron un total de 32 pacientes (94% mujeres) con una mediana de seguimiento de 65 meses. Treinta (94%) fueron sometidos a resección quirúrgica y dos fueron tratados únicamente con tratamiento médico. Quince lograron una resección R0 (márgenes microscópicos negativos) en la operación inicial, de los cuales cuatro (27%) experimentaron recurrencia tumoral. No hubo mortalidades. No se identificaron factores de riesgo para la recurrencia de la enfermedad.LIMITACIONES:Las limitaciones de nuestro estudio incluyen su naturaleza retrospectiva no aleatoria, la experiencia de un solo sistema de atención médica y el tamaño pequeño de la muestra de pacientes.CONCLUSIONES:El angiomixoma agresivo es un tumor raro, de crecimiento lento, con características localmente invasivas y un alto potencial de recurrencia incluso después de una resección con márgenes negativos. Se deben obtener modalidades de imágenes como CT y/o MRI para la ayuda diagnóstica y la planificación quirúrgica. El estudio debe combinarse con una biopsia preoperatoria y pruebas del estado de los receptores hormonales, que pueden aumentar la precisión del diagnóstico y guiar el tratamiento médico. Es imperativa una estrecha vigilancia posterior al tratamiento para detectar recurrencia. (Traducción-Dr Osvaldo Gauto ).

Improving R0 Resection Rates With a Posterior-First, 2-Stage Approach for En Bloc Resection of Locally Advanced Primary and Recurrent Anorectal Cancers Involving the Deep Pelvic Sidewall.

BACKGROUND: Using standard anterior approaches, consistent R0 resection of locally advanced primary and recurrent rectal and anal cancer involving the deep pelvic sidewall may be unattainable. Therefore, to improve R0 resection rates, we have used a posterior-first, then anterior 2-stage approach to resection of tumors in this location. OBJECTIVE: To assess the R0 resection rate and surgical outcomes of the first 10 patients operated on using this approach. DESIGN: We conducted a retrospective case series review of our prospectively maintained surgical pathology and tumor registries. SETTING: This study was conducted at the Mayo Clinic in Rochester, Minnesota. PATIENTS: Ten patients (6 female individuals, median age 53.5 years) with primary or recurrent anal or rectal cancer treated with a posterior-first, then anterior 2-stage approach were identified. MAIN OUTCOME MEASURES: The primary outcome measures were the R0 resection rate and surgical outcomes. RESULTS: An R0 resection was achieved in all 10 patients. Nine patients developed 1 or more 30-day Clavien-Dindo grade III complications. Nine patients developed gluteal wound complications ranging from superficial wound dehiscence to flap necrosis. During the follow-up period, 4 patients were found to have metastatic disease and 1 patient had local re-recurrence. LIMITATIONS: Small cohort with heterogeneous tumors and a short follow-up duration. CONCLUSION: A posterior-first, then anterior 2-stage approach has allowed us to achieve consistent R0 resection margins in locally advanced primary and recurrent rectal and anal cancers involving the deep pelvic sidewall. Poor wound healing of the posterior gluteal incision is a common complication. See Video Abstract. MEJORANDO LAS TASAS DE RESECCIN R CON UN ABORDAJE DE DOS ETAPAS PRIMERO POSTERIOR PARA LA RESECCIN EN BLOQUE DE CNCERES ANORRECTALES PRIMARIOS Y RECURRENTES LOCALMENTE AVANZADOS QUE AFECTAN LA PARED LATERAL PLVICA PROFUNDA: ANTECEDENTES:Utilizando abordajes anteriores estándares, la resección R0 consistente del cáncer de recto y ano primario y recurrente localmente avanzado involucrando la pared lateral pélvica profunda puede ser inalcanzable. Por lo tanto, para mejorar las tasas de resección R0, hemos empleado un abordaje de 2 etapas primero posterior y luego anterior para la resección de tumores en esta ubicación.OBJETIVO:Este estudio tuvo como objetivo evaluar la tasa de resección R0 y los resultados quirúrgicos de los primeros 10 pacientes operados con este abordaje.DISEÑO:Realizamos una revisión retrospectiva de series de casos de nuestros registros de patología quirúrgica y tumores mantenidos prospectivamente.AJUSTE:Este estudio se realizó en la Clínica Mayo en Rochester, Minnesota, EE. UU.PACIENTES:Se identificaron diez pacientes (6 mujeres, mediana de edad 53.5 años) con cáncer anal o rectal primario o recurrente tratados con un abordaje de dos etapas, primero posterior y luego anterior.PRINCIPALES MEDIDAS DE RESULTADO:Las medidas de resultado primarias fueron la tasa de resección R0 y los resultados quirúrgicos.RESULTADOS:Se logró una resección R0 en los 10 pacientes. Nueve pacientes desarrollaron una o más complicaciones de grado III de Clavien-Dindo a los 30 días. Nueve pacientes desarrollaron complicaciones de la herida del glúteo que variaron desde dehiscencia superficial de la herida hasta necrosis del colgajo. Durante el período de seguimiento, se encontró que 4 pacientes tenían enfermedad metastásica y un paciente tuvo recurrencia local.LIMITACIONES:Cohorte pequeño con tumores heterogéneos y corta duración de seguimiento.CONCLUSIÓN:Un abordaje en 2 etapas, primero posterior y luego anterior, nos ha permitido lograr márgenes de resección R0 consistentes en cánceres de recto y anal primarios y recurrentes localmente avanzados que afectan la pared lateral pélvica profunda. La mala cicatrización de la incisión glútea posterior es una complicación común. (Traducción-Dr. Aurian Garcia Gonzalez).

Genetic hypogonadal mouse model reveals niche-specific influence of reproductive axis and sex on intestinal microbial communities.

BACKGROUND: The gut microbiome has been linked to many diseases with sex bias including autoimmune, metabolic, neurological, and reproductive disorders. While numerous studies report sex differences in fecal microbial communities, the role of the reproductive axis in this differentiation is unclear and it is unknown how sex differentiation affects microbial diversity in specific regions of the small and large intestine. METHODS: We used a genetic hypogonadal mouse model that does not produce sex steroids or go through puberty to investigate how sex and the reproductive axis impact bacterial diversity within the intestine. Using 16S rRNA gene sequencing, we analyzed alpha and beta diversity and taxonomic composition of fecal and intestinal communities from the lumen and mucosa of the duodenum, ileum, and cecum from adult female (n = 20) and male (n = 20) wild-type mice and female (n = 17) and male (n = 20) hypogonadal mice. RESULTS: Both sex and reproductive axis inactivation altered bacterial composition in an intestinal section and niche-specific manner. Hypogonadism was significantly associated with bacteria from the Bacteroidaceae, Eggerthellaceae, Muribaculaceae, and Rikenellaceae families, which have genes for bile acid metabolism and mucin degradation. Microbial balances between males and females and between hypogonadal and wild-type mice were also intestinal section-specific. In addition, we identified 3 bacterial genera (Escherichia Shigella, Lachnoclostridium, and Eggerthellaceae genus) with higher abundance in wild-type female mice throughout the intestinal tract compared to both wild-type male and hypogonadal female mice, indicating that activation of the reproductive axis leads to female-specific differentiation of the gut microbiome. Our results also implicated factors independent of the reproductive axis (i.e., sex chromosomes) in shaping sex differences in intestinal communities. Additionally, our detailed profile of intestinal communities showed that fecal samples do not reflect bacterial diversity in the small intestine. CONCLUSIONS: Our results indicate that sex differences in the gut microbiome are intestinal niche-specific and that sampling feces or the large intestine may miss significant sex effects in the small intestine. These results strongly support the need to consider both sex and reproductive status when studying the gut microbiome and while developing microbial-based therapies.

Microbial communities in the intestinal tract, known as the gut microbiome, regulate many critical aspects of host physiology. Previous studies have shown that the diversity of the gut microbiome differs between the sexes. There are also many diseases with a sex bias linked to the gut microbiome, including autoimmune, metabolic, neurological, and reproductive disorders. The gut microbiome differentiates during puberty, but it is unknown if the reproductive axis, the system responsible for sexual maturation and production of gonadal sex hormones, is critical for this process. Furthermore, since most studies use feces to examine the gut microbiome, it is unknown how sex influences the microbial communities within different segments of the small and large intestine. To address this gap in knowledge, we used DNA-based molecular methods to compare the intestinal-specific microbiomes of a mouse model with a genetically inactivated reproductive axis to that of wild-type mice. We found that both sex and the reproductive axis impacted gut microbial diversity in an intestinal section-specific manner. We also detected significant differences in intestinal microbial diversity between male and female mutant mice, suggesting that sex chromosome factors also affect the gut microbiome. We also showed that fecal samples were dissimilar to small intestine microbial communities, indicating that studies only sampling feces likely miss sex differences specific to the small intestine. Our results strongly support the need to consider both sex and reproductive status when studying the gut microbiome and while developing microbial-based therapies.