Anastomotic leak occurs independently from microbiota shifts associated with surgical bowel preparation.

Following bowel surgery, infectious complications, including anastomotic leak (AL), remain major sources of morbidity and mortality. Bowel preparation is often administered with the assumption that gut decontamination reduces post-surgical complications. In this study, we tested this hypothesis using a murine model of colon surgery. The mice were fed either regular chow or a high-fat, high-sugar Western diet. The day before surgery, the mice received one of four interventions: water (control), mechanical bowel preparation (MBP), oral antibiotics (OA), or both MBP and OA. We found no differences in the rates of AL among the experimental groups, and diet did not appear to affect the outcomes. Exploratory analyses showed changes in the gut microbiome consistent with the different treatments, but investigations of fecal short-chain fatty acids and RNA sequencing of colonic tissue did not reveal specific effects of the treatments or the presence of AL. However, we did identify bacterial genera that may be causally associated with AL and developed a predictive index from stool samples as a marker for the presence of AL. Future research is needed to identify and validate a microbial predictive tool and to uncover the microbial-driven mechanisms that lead to AL.

Splenic flexure adenocarcinoma: A national cohort analysis of extent of surgical resection and outcomes.

AIM: The optimal extent of resection for splenic flexure adenocarcinoma remains debated. These tumours straddle the left- and right-sided vasculature with lymphatic drainage in a watershed area; current guidelines recommend either segmental or extended colectomy. We analysed surgical management of splenic flexure tumours and compared outcomes between approaches. METHOD: The Surveillance, Epidemiology and End Results database was searched for adults with Stage I-III splenic flexure adenocarcinoma, 2004-2019. RESULTS: Of 5238 patients, 55% underwent extended colectomy. Compared to segmental colectomy, these patients were more likely to have advanced stage. On multivariable analysis, age ≤ 65 years remained independently associated with extended colectomy. Although fewer nodes were examined in segmental colectomy (median 14 vs. 16, p < 0.001), the number of positive nodes (both, median 0 [interquartile ratio 0-2], p = 0.20) and the lymph node ratio were similar between cohorts. Surgical approach was not significantly associated with increased positive nodal yield in adjusted analyses. Five-year overall and disease-specific survival were 73% and 84% for segmental and 72% and 83% for extended colectomy (p > 0.4); these remained comparable after adjustment. CONCLUSIONS: Nationally, we observed similar rates of segmental and extended colectomy for splenic flexure adenocarcinoma. Extended colectomy was not more common in Stage III disease, indicating lack of stage migration, and was not associated with better oncological outcomes. These observations support current practice involving either approach, which should be tailored to patient-related factors and preferences, while considering technical aspects and quality of life.

Size-Increased All-Phenylene Molecular Spoked Wheels - A Combined Theoretical and Experimental Approach.

A lateral expansion of molecular spoked wheels (MSWs) based on an all-phenylene backbone is described. The MSWs contain a central hub, six spokes and a rim that is formed by a sixfold Yamamoto coupling of the respective non-cyclized dodecabromo precursor yielding MSWs with up to 30 phenylene rings in the perimeter. Attempts to prepare compounds of such size without flexible side groups at the spokes were unsuccessful, most probably due to an aggregation and accompanying oligomerization of the precursors during the cyclization. To overcome these problems, fluorene units are inserted into the spokes. These contain additional alkyl chains and lead to a curvature of the wheels. Quantum chemical calculations on the mechanism of the Yamamoto coupling leads to geometry and strain-related criteria for the successful rim closure to the respective MSW. Subsequently, MSWs are prepared with four and even six phenylene units at each edge of the hexagonal wheels. The resulting MSWs are characterized by spectroscopic methods, and additionally some of them are visualized via scanning tunneling microscopy (STM).

The Role of Tumor Location on Endoscopic and Surgical Management of Malignant Colon Polyps.

BACKGROUND: Endoscopic polypectomy could be an appropriate, definitive treatment for pathologic T1 (pT1) colon polyps without high-risk features. Prior studies suggested worse prognosis for proximal versus distal advanced-stage colon cancers following curative treatment. However, there is limited evidence on the prognostic impact of tumor location for pT1s. PATIENTS AND METHODS: This was a retrospective cohort study using the Surveillance, Epidemiology, and End Results database to identify adults with T1NxMx or T1N0-3M0/x colon adenocarcinoma from 2000 to 2019. RESULTS: A total of 3398 patients underwent endoscopic polypectomy (17% proximal) and 28,334 had a partial colectomy (49% proximal) for pT1 adenocarcinoma. Following endoscopic polypectomy, 5-year overall and cancer-specific survival rates were 64% and 91% for proximal versus 83% and 96% for distal polyps, compared with 82% and 95% for proximal versus 88% and 97% for distal tumors after colectomy. In multivariable models, there was a greater difference in overall survival between proximal and distal polyps for those who underwent endoscopic versus surgical resection [hazard ratio (HR) 1.73, 95% confidence interval (CI) 1.49-2.02 vs. HR 1.13, 95% CI 1.08-1.18]. Patients with proximal versus distal polyps who underwent polypectomy also exhibited increased cancer-specific mortality (HR 1.94, 95% CI 1.37-2.75). However, cancer-specific survival variations based on tumor location were no longer observed in patients undergoing partial colectomy (HR 1.09, 95% CI 0.98-1.21). CONCLUSIONS: Proximal tumor location was independently associated with worse overall and cancer-specific survival following endoscopic polypectomy. However, after colectomy, the cancer-specific disparity based on tumor laterality was mitigated. These findings suggest that proximal location may be considered a high-risk feature in endoscopic polypectomy.

Management and staging of anal adenocarcinoma in the United States: a population-based analysis.

BACKGROUND: Anal adenocarcinoma is rare with no standardized treatment regimen or staging system. Therefore, different combinations of chemotherapy, radiation, and surgery are used in management. Within the staging system, tumor stage can be based on the depth of invasion, as for rectal adenocarcinoma, or size, as in anal squamous cell carcinoma. This study aimed to analyze patterns of care and clinically available staging systems for anal adenocarcinoma using a national database. METHODS: Adults diagnosed with anal adenocarcinoma were identified in the Surveillance, Epidemiology, and End Results database (2004-2019). In addition, 6 different treatment regimens were identified. Stages were categorized according to the American Joint Committee on Cancer classifications of rectal adenocarcinoma and anal squamous cell carcinoma. RESULTS: Of 1040 patients, 48% were female, the median age was 67 years, and 18% had distant metastases. Chemoradiotherapy + abdominoperineal resection was the most common treatment regimen (22%). Moreover, 5-year overall survival (OS) and disease-specific survival (DSS) were the highest for local excision only (67% and 85%) and the lowest in the alternative group (34% and 48%). After adjustment, the treatment groups that did not include surgery were associated with worse 5-year OS. In multivariable analysis, the T stage based on depth of invasion showed incrementally lower OS for T2 and T3 anal adenocarcinomas. CONCLUSION: Omission of surgical resection in combination with chemoradiotherapy was associated with worse OS and DSS, suggesting the relevance of surgery in anal adenocarcinoma management. Prognostically, rectal staging based on depth of invasion better discriminated between T stages, indicating that providers should consider using this system in practice.

A population-based analysis on the incidence of metachronous colon cancer after endoscopic resection of advanced adenomas with high-grade dysplasia: does location matter?

BACKGROUND: Advanced adenomas (AAs) with high-grade dysplasia (HGD) represent a risk factor for metachronous neoplasia, with guidelines recommending short-interval surveillance. Although the worse prognosis of proximal (vs distal) colon cancers (CCs) is established, there is paucity of evidence on the impact of laterality on the risk of subsequent neoplasia for these AAs. METHODS: Adults with HGD adenomas undergoing polypectomy were identified in the Surveillance, Epidemiology, and End Results database (2000-2019). Cumulative incidence of malignancy was estimated using the Kaplan-Meier method. Fine-Gray models assessed the effect of patient and disease characteristics on CC incidence. RESULTS: Of 3199 patients, 26% had proximal AAs. A total of 65 cases of metachronous adenocarcinoma were identified after polypectomy of 35 proximal and 30 distal adenomas with HGD. The 10-year cumulative incidence of CC was 2.3%; when stratified by location, it was 4.8% for proximal vs 1.4% for distal adenomas. Proximal location was significantly associated with increased incidence of metachronous cancer (adjusted hazard ratio, 3.32; 95% CI, 2.05-5.38). CONCLUSION: Proximal location of AAs with HGD was associated with >3-fold increased incidence of metachronous CC and shorter time to diagnosis. These data suggest laterality should be considered in the treatment and follow-up of these patients.

Flexible Phenanthracene Nanotubes for Explosive Detection.

Phenanthracene nanotubes with arylene-ethynylene-butadiynylene rims and phenanthracene walls are synthesized in a modular bottom-up approach. One of the rims carries hexadecyloxy side chains, mediating the affinity to highly oriented pyrolytic graphite. Molecular dynamics simulations show that the nanotubes are much more flexible than their structural formulas suggest: In 12, the phenanthracene units act as hinges that flip the two macrocycles relative to each other to one of two possible sites, as quantum mechanical models suggest and scanning tunneling microscopy investigations prove. Unexpectedly, both theory and experiment show for 13 that the three phenanthracene hinges are deflected from the upright position, accompanied by a deformation of both macrocycles from their idealized sturdy macroporous geometry. This flexibility together with their affinity to carbon-rich substrates allows for an efficient host-guest chemistry at the solid/gas interface opening the potential for applications in single-walled carbon nanotube-based sensing, and the applicability to build new sensors for the detection of 2,4,6-trinitrotoluene via nitroaromatic markers is shown.

A Formative Evaluation of an Online Meal Kit and Grocery Platform for Supplemental Nutrition Assistance Program Recipients.

OBJECTIVE: To assess the barriers and facilitators to online food purchasing through a meal kit and grocery shopping website titled NY SNAP Express among Supplemental Nutrition Assistance Program (SNAP) beneficiaries. METHODS: A purposive sample of SNAP-eligible adults residing in New York State participated in interviews guided by the Capabilities, Opportunities, Motivations, and Behaviors Model. RESULTS: Barriers to online food purchasing among participants (n = 32) include physiological and health conditions, the weight of food, technology, language, the price of foods, transportation challenges, the stigma associated with SNAP, and concerns regarding the quantity and quality of meal kits. Facilitators include health and nutrition improvements, knowledge and skills, saving money, culturally relevant meals, increased efficiency in food purchases and preparation, and customization. CONCLUSIONS AND IMPLICATIONS: Online platforms such as NY SNAP Express have the potential to increase nutritious food access and resources among SNAP recipients; however, improvements are necessary to meet the needs of its audience.

Conditional Overall Survival After Diagnosis of Non-Metastatic Colon Cancer: Impact of Laterality, MSI, and KRAS Status.

BACKGROUND: The prognostic relevance of laterality, microsatellite instability (MSI), and KRAS status in colon cancer has been established. However, their effect on conditional overall survival (COS) remains unknown. METHODS: COS is the probability of surviving additional years after a time from diagnosis. The National Cancer Database (2010-2017) was queried for adults with non-metastatic colon cancer and known mutation status undergoing curative resection. COS was investigated at 2 years. RESULTS: Of 4838 patients, 3716 survived at least 2 years: 15% had stage I, 38% stage II, and 46% stage III disease. Fifty-nine percent had a right-sided tumor, 16% were MSI-high, and 37% were mutated KRAS (mKRAS). The proportion of patients alive at 2 years was higher for stage I compared with stage II and III (65 vs. 61 vs. 54%). The 5-year overall survival for stage I-III was 80, 76, and 67% for the initial cohort, and 90, 88, and 86% for those alive at 2 years. After adjustment, higher pathologic T and N stage, tumor deposits, and no chemotherapy were associated with worse COS (p < 0.01). While laterality and MSI status were not associated with COS, mKRAS was independently associated with decreased COS (HR 1.35, 95% CI 1.12-1.62). CONCLUSION: Patients with mKRAS had worse COS, suggesting that these mutations confer an aggressive biologic behavior, with patients remaining at higher risk of death 2 years after diagnosis. Routine evaluation of KRAS status should be considered in patients with non-metastatic disease for prognostication and to identify those who might benefit from modified surveillance protocols.

Diet-induced shifts in the gut microbiota influence anastomotic healing in a murine model of colonic surgery.

Host diet and gut microbiota interact to contribute to perioperative complications, including anastomotic leak (AL). Using a murine surgical model of colonic anastomosis, we investigated how diet and fecal microbial transplantation (FMT) impacted the intestinal microbiota and if a predictive signature for AL could be determined. We hypothesized that a Western diet (WD) would impact gut microbial composition and that the resulting dysbiosis would correlate with increased rates of AL, while FMT from healthy, lean diet (LD) donors would reduce the risk of AL. Furthermore, we predicted that surgical outcomes would allow for the development of a microbial preclinical translational tool to identify AL. Here, we show that AL is associated with a dysbiotic microbial community characterized by increased levels of Bacteroides and Akkermansia. We identified several key taxa that were associated with leak formation, and developed an index based on the ratio of bacteria associated with the absence and presence of leak. We also highlight a modifiable connection between diet, microbiota, and anastomotic healing, potentially paving the way for perioperative modulation by microbiota-targeted therapeutics to reduce AL.

Characteristics of people obtaining medication vs procedural abortions in clinical settings in the United States: Findings from the 2021-2022 Abortion Patient Survey.

OBJECTIVES: This study aimed to compare the characteristics of people obtaining medication and procedural abortions in clinical settings in the United States. STUDY DESIGN: We conducted a cross-sectional survey of people obtaining abortions at a sample of 56 US facilities between June 2021 and July 2022. We restricted analyses to patients with pregnancies less than 11 weeks' gestation presenting at 43 clinics offering both medication and procedural abortion. We conducted bivariate analyses and multivariable logistic regression to identify factors associated with obtaining a medication vs procedural abortion. RESULTS: Our analytic sample includes 4717 respondents, 57% of whom obtained a medication abortion. In bivariate analyses, individuals who identified as Asian or White, had no prior births or abortions, or were paying out of pocket were all more likely to have a medication abortion. Non-Hispanic Black individuals, those with incomes at or below the poverty level, and those paying with insurance were more likely to have a procedural abortion. Some 24% of respondents chose the facility because it offered medication abortion, but even after controlling for this proxy for method preference in a logistic regression model, Black respondents and those with poverty-level incomes were less likely to have a medication abortion. CONCLUSIONS: The findings of the study suggest that Black individuals and those with low incomes-who often face systemic barriers to care-are less likely to have medication abortions. When medication abortion is the only option available, for example, at a medication-only clinic or from an online source, these groups may be most impacted by the lack of options. IMPLICATIONS: To the extent possible, offering both medication and procedural abortion and increasing access to both types are important to meet patients' individual needs and preferences.

The Influence of the Microbiome on Anastomotic Leak.

Anastomotic leak, defined by the International Study Group of Rectal Cancer as "a communication between the intra- and extraluminal compartments owing to a defect of the integrity of the intestinal wall at the anastomosis," is one of the most devastating complications in colorectal surgery. Much work has been done to identify causes of leak; however, despite advances in surgical technique, the prevalence of anastomotic leak has remained at around 11%. The potential causative role of bacteria in the etiopathology of anastomotic leak was established in the 1950s. More recently, alterations in the colonic microbiome have been shown to affect rates of anastomotic leak. Multiple perioperative factors that alter the homeostasis of the gut microbiota community structure and function have been linked to anastomotic leak after colorectal surgery. Here, we discuss the role of diet, radiation, bowel preparation, medications including nonsteroidal anti-inflammatory drugs, morphine, and antibiotics, and specific microbial pathways that have been implicated in anastomotic leak via their effects on the microbiome.

Computational study of ground-state properties of µ2 -bridged group 14 porphyrinic sandwich complexes.

The structural properties of µ2 -bridged porphyrinic double-decker complexes are investigated and the influence of various ligands, metals, substituents, and bridging atoms on the dominant structural motif is elucidated. A variety of quantum chemical methods including semiempirical (SQM) methods and density functional theory (DFT) is assessed for the calculation of ecliptic and staggered conformational energies. Local coupled cluster (DLPNO-CCSD(T1)) data are generated for reference. The r2 SCAN-3c composite scheme as well as the B2PLYP-D4/def2-QZVPP approach are identified as reliable methods. Energy decomposition analyses (EDA) and localized molecular orbital analyses (LMO) are used to investigate the bonding situation and the nature of the inter-ligand interaction energy underlining the crucial role of attractive London dispersion interactions. Targeted modification of the bridging atom, e.g., by replacing O2- by S2- is shown to drastically change the major structural features of the investigated complexes. Further, the influence of different substituents of varying size at the phthalocyanine ligand regarding the dominant conformation is described.

Patient and provider experiences using a site-to-site telehealth model for medication abortion.

Background: In the site-to-site telehealth for medication abortion model, patients visit a health center to meet with a remote clinician using telehealth technology. This model is safe, effective, and acceptable to patients and providers. The objective of this study was to document the experiences of patients and providers using telehealth for medication abortion in Planned Parenthood health centers across different geographical contexts in the United States. Methods: We conducted in-depth interviews with Planned Parenthood medication abortion patients who either met with a clinician at the clinic via telehealth or in-person about their experiences receiving care. We also interviewed Planned Parenthood staff members about their experiences implementing telehealth for medication abortion at their health center. Results: We interviewed 29 patients who received care at Planned Parenthood health centers in five states. Both telehealth and in-person patients described positive interactions with health center staff and clinicians. The vast majority of telehealth patients said that they felt comfortable speaking with the clinician over telehealth and had no trouble using the telehealth technology. We interviewed 12 providers, including clinicians and administrative staff, who worked in seven states. Providers largely thought that telehealth for medication abortion expanded access to medication abortion. Conclusions: Across different locations, our findings indicate that patients found telehealth for medication abortion services to be highly acceptable and providers found that telehealth services may help improve medication abortion access. As the use of telehealth for medication abortion expands, future research should include additional measures of quality to ensure that services are acceptable across different identities and experiences, including age, race, gender, and income level.

Attitudes Among General Surgery Program Directors and Faculty Toward Openly Nonheterosexual Applicants.

OBJECTIVE: Historically, nonheterosexual physicians have experienced bias in medical training. While resident-focused studies have been conducted in general surgery, the views of program directors and faculty are less evident. In this study, we surveyed program directors and faculty in general surgery to assess their attitudes toward openly nonheterosexual residency applicants. DESIGN: A national, cross-sectional online survey. PARTICIPANTS: Program directors and faculty in general surgery listed on the Association of Program Directors in Surgery listserv. RESULTS: Of the 123 participants who returned the survey; 33% were faculty and 58% were program directors. The response rate was 28% for program directors and 13% for faculty. Of respondents, 68% reported having openly nonheterosexual residents in their program and 38% were aware the candidates were nonheterosexual when they ranked them. Most respondents (76%) would advise a nonheterosexual mentee to be honest about their sexuality if asked during the interview and application process for general surgery (Figure 1). Of respondents, 84% reported that knowing an applicant was nonheterosexual would not affect how they ranked them while 76% reported that their program's faculty would always feel comfortable if a nonheterosexual resident brought their partner to a residency social event. CONCLUSIONS: To our knowledge, this is the first survey of general surgery program directors regarding their attitudes toward nonheterosexual residency applicants. While a few individuals continue to hold biased beliefs, there appears to be substantial acceptance of nonheterosexual general surgery residency candidates amongst program directors and faculty who responded to our survey.

Society of Family Planning committee consensus on self-administration of subcutaneous depot medroxyprogesterone acetate (DMPA-SC).

Depot medroxyprogesterone acetate (DMPA) is a highly-effective, injectable contraceptive method that requires injections every 12 to 15 weeks. The need for return visits to a healthcare provider may present barriers to access, use, and continuation of DMPA. Studies demonstrate that self-administration of subcutaneous DMPA (DMPA-SC) outside clinical settings is safe, effective, feasible, acceptable, and can improve continuation. Based on existing evidence and potential to improve contraceptive access and autonomy, the Society of Family Planning recommends that DMPA-SC self-administration be made widely available as an additional option for patients. Provider-administered DMPA must also remain available to meet patients' individual needs and preferences.

Increased Antiaromaticity through Pentalene Connection in [n]Cyclo-1,5-dibenzopentalenes.

Conjugated nanohoops incorporating nonalternant hydrocarbons have altered optoelectronic properties compared to [n]cycloparaphenylenes or other purely aromatic hoops. We synthesized [n]cyclo-1,5-dibenzopentalenes (n = 4, 5), in which nonalternant dibenzo[a,e]pentalenes are connected through their pentalene units. This leads to an increase in antiaromatic character and low-lying LUMO energies. Calculations show puckered or entangled conformations of the precursor macrocyclic Pt-complexes. Our study proves dibenzopentalene as a versatile nonalternant building block for conjugated nanohoops with modifiable antiaromaticity and optoelectronic properties.