Multi-Omic Analysis of Esophageal Adenocarcinoma Uncovers Candidate Therapeutic Targets and Cancer-Selective Posttranscriptional Regulation.

Efforts to address the poor prognosis associated with esophageal adenocarcinoma (EAC) have been hampered by a lack of biomarkers to identify early disease and therapeutic targets. Despite extensive efforts to understand the somatic mutations associated with EAC over the past decade, a gap remains in understanding how the atlas of genomic aberrations in this cancer impacts the proteome and which somatic variants are of importance for the disease phenotype. We performed a quantitative proteomic analysis of 23 EACs and matched adjacent normal esophageal and gastric tissues. We explored the correlation of transcript and protein abundance using tissue-matched RNA-seq and proteomic data from seven patients and further integrated these data with a cohort of EAC RNA-seq data (n = 264 patients), EAC whole-genome sequencing (n = 454 patients), and external published datasets. We quantified protein expression from 5879 genes in EAC and patient-matched normal tissues. Several biomarker candidates with EAC-selective expression were identified, including the transmembrane protein GPA33. We further verified the EAC-enriched expression of GPA33 in an external cohort of 115 patients and confirm this as an attractive diagnostic and therapeutic target. To further extend the insights gained from our proteomic data, an integrated analysis of protein and RNA expression in EAC and normal tissues revealed several genes with poorly correlated protein and RNA abundance, suggesting posttranscriptional regulation of protein expression. These outlier genes, including SLC25A30, TAOK2, and AGMAT, only rarely demonstrated somatic mutation, suggesting post-transcriptional drivers for this EAC-specific phenotype. AGMAT was demonstrated to be overexpressed at the protein level in EAC compared to adjacent normal tissues with an EAC-selective, post-transcriptional mechanism of regulation of protein abundance proposed. Integrated analysis of proteome, transcriptome, and genome in EAC has revealed several genes with tumor-selective, posttranscriptional regulation of protein expression, which may be an exploitable vulnerability.

A Systematic Review on Clinical and Health-Related Quality of Life Outcomes following Total Gastrectomy in Patients with Hereditary Diffuse Gastric Cancer.

Hereditary diffuse gastric cancer (HDGC) is an autosomal-dominant syndrome associated with early onset diffuse gastric cancer. Definitive treatment is prophylactic total gastrectomy (PTG) associated with significant morbidity. Studies published from January 2000 to December 2022 reporting clinical, histopathological or health-related quality of life outcomes in HDGC patients undergoing PTG were identified. The study quality was assessed by the "Newcastle-Ottawa scale". Of the 257 articles screened, 21 were selected. A total of 353 patients were examined in 15 studies that reported surgical outcomes. The median age was 42 years old. The median major complication and mortality rates were 19.2% and 0.3%, respectively. The most common complications were wound infection at 4.8% followed by anastomotic leak and pulmonary complications at 4.5% each. Following PTG, 88.6% of patients had early lesions amongst 414 patients. The mean/median number of signet ring cell carcinoma foci in the gastrectomy specimens was from 2 to 78. All cases were stage 1 with no lymph node involvement. There was a wide range of psychosocial effects following PTG closely related to the physical symptoms. It is imperative for patients to receive comprehensive preoperative counselling to make an informed decision and be followed up under the care of a multidisciplinary team.

Impact of early enteral feed composition on the rate of chyle leak post-esophagectomy.

Patients undergoing esophagectomy are at risk of malnutrition and benefit from perioperative enteral feeding. Esophagectomy carries a risk of chyle leak, and this risk may be influenced by early enteral feed composition. We evaluated the impact of early enteral medium-chain triglyceride-rich feed on the prevalence and severity of chyle leak post-esophagectomy, length of stay, and postoperative weight change. This retrospective study included consecutive patients undergoing esophagectomy at a single center between January 2015 and December 2022. Patients received enteral feed on postoperative days 1-5 with Nutrison Energy or Protein Plus Energy ('standard') (January 2015- June 2021) or Nutrison Peptisorb Plus High Energy High Protein ('HEHP') enteral feed (June 2021 to December 2022). All patients transitioned to 'standard' supplemental jejunal feeding on postoperative day 6 onwards and were discharged on oral IDDSI level 4 diet. Patients who did not commence early enteral feeding were excluded from analysis. A total of 329 patients were included. Patients who received early HEHP feed had fewer chyle leaks (5/52; 9.6%) compared with patients who received standard feed (68/277; 24.5%, P = 0.017). The HEHP group had a shorter total length of hospital stay (P = 0.011). Weight change from preoperative baseline was equivalent in both groups at 6 weeks (P = 0.066) and 3 months (P = 0.400). In the context of routine jejunostomy use and early enteral feeding post-esophagectomy, HEHP feed on postoperative days 1-5 was associated with significantly fewer chyle leaks and shorter length of stay compared with standard feed. No difference was noted in postoperative weight change between groups.

Novel Telehealth Adaptations for Evidence-Based Outpatient Suicide Treatment: Feasibility and Effectiveness of the Crisis Care Program.

Background: Suicide rates in the United States have escalated dramatically over the past 20 years and remain a leading cause of death. Access to evidenced-based care is limited, and telehealth is well-positioned to offer novel care solutions. The Crisis Care program is a suicide-specific treatment program delivered within a national outpatient telehealth setting using a digitally adapted version of the Collaborative Assessment and Management of Suicidality (CAMS) as the framework of care. This study investigates the feasibility and preliminary effectiveness of Crisis Care as scalable suicide-specific treatment model. Methods: Patient engagement, symptom reduction, and care outcomes were examined among a cohort of patients (n = 130) over 16 weeks. The feasibility of implementation was assessed through patient engagement. Clinical outcomes were measured with PHQ-9, GAD-7, and the CAMS SSF-4 rating scales. Results: Over 85% of enrolled patients were approved for Crisis Care at intake, and 83% went on to complete at least four sessions (the minimum required to graduate). All patient subgroups experienced declines in depressive symptoms, anxiety symptoms, suicidal ideation frequency, and suicide-specific risk factors. Conclusions: Results support the feasibility and preliminary effectiveness of Crisis Care as a suicide-specific care solution that can be delivered within a stepped-care model in an outpatient telehealth setting.

Clonality, trafficking, and molecular alterations among Hprt mutant T lymphocytes isolated from control mice versus mice treated with N-ethyl-N-nitrosourea.

Mutations in T lymphocytes (T-cells) are informative quantitative markers for environmental mutagen exposures, but risk extrapolations from rodent models to humans also require an understanding of how T-cell development and proliferation kinetics impact mutagenic outcomes. Rodent studies have shown that patterns in chemical-induced mutations in the hypoxanthine-guanine phosphoribosyltransferase (Hprt) gene of T-cells differ between lymphoid organs. The current work was performed to obtain knowledge of the relationships between maturation events during T-cell development and changes in chemical-induced mutant frequencies over time in differing immune compartments of a mouse model. A novel reverse transcriptase-polymerase chain reaction based method was developed to determine the specific T-cell receptor beta (Tcrb) gene mRNA expressed in mouse T-cell isolates, enabling sequence analysis of the PCR product that then identifies the specific hypervariable CDR3 junctional region of the expressed Tcrb gene for individual isolates. Characterization of spontaneous Hprt mutant isolates from the thymus, spleen, and lymph nodes of control mice for their Tcrb gene expression found evidence of in vivo clonal amplifications of Hprt mutants and their trafficking between tissues in the same animal. Concurrent analyses of Hprt mutations and Tcrb gene rearrangements in different lymphoid tissues of control versus N-ethyl-N-nitrosourea-exposed mice permitted elucidation of the localization and timing of mutational events in T-cells, establishing that mutagenesis occurs primarily in the pre-rearrangement replicative period in pre-thymic/thymic populations. These findings demonstrate that chemical-induced mutagenic burden is determined by the combination of mutagenesis and T-cell clonal expansion, processes with roles in immune function and in the pathogenesis of autoimmune disease and cancer.

Leader and Provider Perspectives on Implementing Safe Alternatives for Teens and Youth - Acute (SAFETY-A) in Public School Districts Serving Racial/ethnic Minoritized Youth.

Racial/ethnic minoritized (REM) youth represent a high-risk group for suicide, yet there are striking disparities in their use of mental health services (MHS) even after risk is identified in schools. Prior research suggests that school-based risk assessments and hospitalization encounters can be negatively experienced by REM youth and families, thus deterring likelihood of seeking follow-up care. The Safe Alternatives for Teens and Youth-Acute (SAFETY-A) is a brief, strengths-based, cognitive-behavioral family intervention demonstrated to increase linkage to MHS when implemented in emergency departments. With its focus on strengths and family engagement, SAFETY-A may cultivate a positive therapeutic encounter suited to addressing disparities in MHS by enhancing trust and family collaboration, if appropriately adapted for schools. Thirty-seven school district leaders and frontline school MHS providers from districts serving primarily socioeconomically disadvantaged REM communities participated in key informant interviews and focus groups. First, interviews were conducted to understand usual care processes for responding to students with suicidal thoughts and behaviors, and perspectives on the strengths and disadvantages of current practices. An as-is process analysis was used to describe current practices spanning risk assessment, crisis intervention, and follow-up. Second, focus groups were conducted to solicit perceptions of the fit of SAFETY-A for these school contexts. Thematic analysis of the interviews and focus groups was used to identify multilevel facilitators and barriers to SAFETY-A implementation, and potential tailoring variables for implementation strategies across school districts.

Risk-reducing surgery for individuals with cancer-predisposing germline pathogenic variants and no personal cancer history: a review of current UK guidelines.

Identifying healthy carriers of germline pathogenic variants in high penetrance cancer susceptibility genes offers the potential for risk-reducing surgery. The NHS England National Genomic Test Directory offers germline and somatic testing to patients with certain cancers or rare and inherited diseases, or, in some cases, to their relatives. This review summarises current UK guidelines for risk-reducing surgical interventions available for individuals with no personal history of cancer, who are determined to carry germline pathogenic variants. An electronic literature search of NICE guidelines and PubMed citable articles was performed. NICE guidelines are available for bilateral mastectomy and are currently in development for risk-reducing bilateral salpingo-oophorectomy. Guidelines developed with affiliation to, or through relevant British Surgical Societies or international consensus, are available for risk-reducing hysterectomy, polypectomy, gastrectomy, and thyroidectomy. There is a disparity in the development and distribution of national guidelines for interventions amongst tumour types. Whilst we are focusing on UK guidelines, we anticipate they will be relevant much more generally and so of interest to a wider audience including where there are no national guidelines to refer to. We suggest that, as genetic testing becomes rapidly more accessible, guideline development for interventions should be more closely aligned to those for testing.

The Immunopeptidome from a Genomic Perspective: Establishing the Noncanonical Landscape of MHC Class I-Associated Peptides.

Tumor antigens can emerge through multiple mechanisms, including translation of noncoding genomic regions. This noncanonical category of tumor antigens has recently gained attention; however, our understanding of how they recur within and between cancer types is still in its infancy. Therefore, we developed a proteogenomic pipeline based on deep learning de novo mass spectrometry (MS) to enable the discovery of noncanonical MHC class I-associated peptides (ncMAP) from noncoding regions. Considering that the emergence of tumor antigens can also involve posttranslational modifications (PTM), we included an open search component in our pipeline. Leveraging the wealth of MS-based immunopeptidomics, we analyzed data from 26 MHC class I immunopeptidomic studies across 11 different cancer types. We validated the de novo identified ncMAPs, along with the most abundant PTMs, using spectral matching and controlled their FDR to 1%. The noncanonical presentation appeared to be 5 times enriched for the A03 HLA supertype, with a projected population coverage of 55%. The data reveal an atlas of 8,601 ncMAPs with varying levels of cancer selectivity and suggest 17 cancer-selective ncMAPs as attractive therapeutic targets according to a stringent cutoff. In summary, the combination of the open-source pipeline and the atlas of ncMAPs reported herein could facilitate the identification and screening of ncMAPs as targets for T-cell therapies or vaccine development.

Predictability and durability of mitral valve repair in patients with severe degenerative mitral regurgitation in medium sized centres.

INTRODUCTION: Mitral valve repair (MVr) is now the treatment of choice to correct severe degenerative mitral regurgitation (MR). Repair rates vary greatly from centre to centre, and the concept of heart valve centres of excellence has been established. OBJECTIVE: The purpose of this study was to see whether large international centre repair rates, and outcomes, are transferrable to medium-sized centres with an interest in mitral repair. METHODS: Between 2011 and 2018, a total of 346 patients underwent mitral valve surgery by a single surgeon. Of these, 238 consecutive patients had repairs, or attempted repairs for degenerative MR, and are included in this study. RESULTS: The study sample consisted of 71% male patients and had a mean age of 64.4 ± 12.3 years; 66% of the study population had concomitant procedures. The overall repair rate in this cohort is 99%. Mean follow up was 3.7 ± 1.9 years. At 5 years, the freedom from MR ≥ 3+ was 95.9 ± 1.9% and at 7 years 91.1 ± 3.8%. Freedom from reoperation at 5 years was 92.9 ± 3.7%, while the 5 years actuarial survival was 89.1 ± 3.7%. On a multivariate analysis, predischarge echo grade was associated with higher risk of future reoperation (odds ratio (OR) = 21.82, p = 0.05). Only age (OR = 1.3, p = 0.03) was predictive of long-term survival. CONCLUSIONS: In specialised medium-sized heart centres, where the surgical team have undergone specialist mitral training, favourable short- and long-term outcomes are achievable with mitral repair rates similar to those from large international centres of excellence. In these heart centres, early surgery should be considered for all patients with severe degenerative MR.

Current trends in craniofacial reconstruction.

Reconstruction of the head and neck continues to pose a variety of difficult functional and aesthetic challenges to the plastic surgeon. While the surgical treatment for midfacial and skull base tumours continues to advance, the three-dimensional reconstruction predicaments continue to increase in complexity. Reconstructive strategies of the head and neck require the restoration of intricate skeletal architecture and large volumes of both internal and external soft tissue envelopes that can withstand adjuvant therapies. Vascularized bone grafts in combination with microsurgical techniques is the current trend of most reconstruction and has replaced local and pedicle flaps as the preferred modality for large defects. This article will focus on concise areas of difficulty in craniofacial reconstruction, including mandibular, midfacial, scalp and base of skull reconstruction. As our goals now move from flap survival to refinement, more complex and innovative reconstructions are executed. The problems with each modality are examined, and the frontiers of head and neck reconstruction are explored. With the potential combination of virtual surgery and tissue engineered biotechnology, we may someday be able to expand our reconstructive capabilities beyond free tissue transfer.

Systematic review and meta-analysis comparing perioperative outcomes of emergency appendectomy performed by trainee vs trained surgeon.

BACKGROUND: Appendectomy is a benchmark operation for trainee progression, but this should be weighed against patient safety and perioperative outcomes. METHODS: Systematic literature review and meta-analysis comparing outcomes of appendectomy performed by trainees versus trained surgeons. RESULTS: Of 2086 articles screened, 29 studies reporting on 135,358 participants were analyzed. There was no difference in mortality (Odds ratio [OR] 1.08, P = 0.830), overall complications (OR 0.93, P = 0.51), or major complications (OR 0.56, P = 0.16). There was no difference in conversion from laparoscopic to open surgery (OR 0.81, P = 0.12) and in intraoperative blood loss (Mean Difference [MD] 5.58 mL, P = 0.25). Trainees had longer operating time (MD 7.61 min, P < 0.0001). Appendectomy by trainees resulted in shorter duration of hospital stay (MD 0.16 days, P = 0.005) and decreased reoperation rate (OR 0.78, P = 0.05). CONCLUSIONS: Appendectomy performed by trainees does not compromise patient safety. Due to statistical heterogeneity, further randomized controlled trials, with standardized reported outcomes, are required.

School Risk and Protective Factors of Suicide: A Cultural Model of Suicide Risk and Protective Factors in Schools.

There are known cultural variations in correlates of and symptoms related to suicide-related thoughts and behaviors; however, the majority of research that informs suicide prevention in school systems has focused on research based on Euro-American/White students. By exploring school-related risk and protective factors in ethnic-racial minoritized students, we expand existing multicultural models of suicide prevention for school settings. Specifically, this systematic literature review identified 33 studies conducted with American Indian and Alaskan Native, Hispanic and Latinx, Black and African American, and Asian American and Pacific Islander students. Findings underscore the importance of building relationships with the school community and fostering a sense of safety for students, the need to approach school-based suicide prevention and intervention with cultural considerations, and the importance of connecting students and families with providers in culturally sensitive and informed ways. Taken together, schools need to build school-family-community partnerships that promote culturally sensitive approaches to suicide prevention.

Systematic review and meta-analysis comparing perioperative outcomes of pediatric emergency appendicectomy performed by trainee vs trained surgeon.

Appendicectomy is a common pediatric surgical procedure performed by trainees and surgeons with varying reported outcomes. It is a benchmark procedure for trainee progression and training benefits should be weighed against patient safety and perioperative outcomes. This systematic review and meta-analysis investigated any differential perioperative outcomes dependent on the grade of the operating surgeon. A systematic literature review and meta-analysis were performed comparing outcomes of pediatric appendicectomy performed by trainees versus trained surgeons. Of 2,086 articles screened, 5 retrospective non-randomized comparative studies reporting on 10,019 participants were analyzed. There was no difference in overall complications (OR 0.92; 95% CI 0.76, 1.12; P = 0.42), major complications [Clavien-Dindo (CD) III/IV] (OR 1.18; 95% CI 0.71, 1.97; P = 0.52), minor complications (CD I/II) (OR 1.13; 95% CI 0.57, 2.27; P = 0.72), post-op ileus (OR 0.74; 95% CI 0.10, 5.26; P = 0.76), wound infections (OR 0.87; 95% CI 0.62, 1.21; P = 0.41), abscess formation (OR 0.58; 95% CI 0.28, 1.22; P = 0.15), operation times [Mean Difference (MD) 2.31 min; 95% CI - 4.94, 9.56; P = 0.53] and reoperation rate (OR 1.22; 95% CI 0.23, 6.42; P = 0.81). Trainees had fewer conversions to open appendicectomy (OR 0.14; 95% CI 0.02, 0.88; P = 0.04). Appendicectomy performed on pediatric patients by trainees did not compromise patient safety. LEVEL OF EVIDENCE: III.

Multiparametric High-Content Cell Painting Identifies Copper Ionophores as Selective Modulators of Esophageal Cancer Phenotypes.

Esophageal adenocarcinoma is of increasing global concern due to increasing incidence, a lack of effective treatments, and poor prognosis. Therapeutic target discovery and clinical trials have been hindered by the heterogeneity of the disease, the lack of "druggable" driver mutations, and the dominance of large-scale genomic rearrangements. We have previously undertaken a comprehensive small-molecule phenotypic screen using the high-content Cell Painting assay to quantify the morphological response to a total of 19,555 small molecules across a panel of genetically distinct human esophageal cell lines to identify new therapeutic targets and small molecules for the treatment of esophageal adenocarcinoma. In this current study, we report for the first time the dose-response validation studies for the 72 screening hits from the target-annotated LOPAC and Prestwick FDA-approved compound libraries and the full list of 51 validated esophageal adenocarcinoma-selective small molecules (71% validation rate). We then focus on the most potent and selective hit molecules, elesclomol, disulfiram, and ammonium pyrrolidinedithiocarbamate. Using a multipronged, multitechnology approach, we uncover a unified mechanism of action and a vulnerability in esophageal adenocarcinoma toward copper-dependent cell death that could be targeted in the future.

Gender and immunosuppression impact on Merkel cell carcinoma diagnosis and prognosis. A population based cohort study.

Background: Merkel cell carcinoma (MCC), a rare cutaneous neuroendocrine endocrine tumour is increasing in incidence, and continues to carry a poor prognosis. Objectives: The objectives of this study were to examine all Irish cases of MCC from 1 January 1994 over 2 decades, focusing on gender and organ transplantation recipients (OTRs). Cases were identified from the National Cancer Registry of Ireland. Covariates of interest included age, body site, period of diagnosis, deprivation-status and history of non-melanoma skin cancer (NMSC). Results: In total 314 MCC cases were identified. A female predominance was noted (53.8%). Comparison between age-standardised rates between the earliest period (1994-1996) with the latest period (2012-2014) showed an increase of 105% in total. The trend in age-standardised incidence rates were noted to be increasing significantly (p = 0.0004). Average age at diagnosis was 77.6 years (male 75.1 years, female 79.7 years). Overall, the majority of MCC cases presented on the head and neck (n = 170, 54.1%). Differences in anatomical location of MCCs were noted between genders. Males were found to be more likely to have a history of previous NMSCs (males n = 73 [57.9%], females n = 53 [42.1%]). Thirty-one percentage of patients died from MCC, average survival was 3.5 years in those who died of this malignancy. Ten organ transplant recipients developed MCC. OTR who developed MCC were diagnosed at a younger average age of 65.1 years. Standardized incidence ratio for MCC in OTR was 59.96. A higher proportion of OTR died from MCC (70%), with a shorter median survival of 0.14 years. In competing risks regression, gender was not significantly associated with risk of dying, females having a non-significantly higher hazard of dying. Organ transplant recipients and patients from less deprived areas were at greater risk of dying from MCC. Conclusions: This population based study provides epidemiological, clinical and outcome data for MCC over a 20-year period.

Use of the Portsmouth Physiological and Operative Severity Score for the Enumeration of Mortality and Morbidity ('P-POSSUM') to predict morbidity in patients undergoing surgery with reconstruction for temporal bone malignancy.

OBJECTIVE: The Portsmouth Physiological and Operative Severity Score for the Enumeration of Mortality and Morbidity ('P-POSSUM') is a two-part scoring system that includes a physiological assessment and a measure of operative severity. This study sought to determine whether risk estimates for this scoring system could be used in major head and neck reconstructive surgery. METHOD: A retrospective review was performed of patients undergoing resection for a temporal bone malignancy in a single head and neck centre in Dublin, Ireland, from 2002 to 2021. RESULTS: The mean ± standard deviation morbidity estimate calculated using the scoring system was 47.6 per cent ± 19.5 per cent. The actual rate of complications was 47 per cent. The optimal cut-off for the scoring system was calculated using the Youden index from the receiver operating characteristic curve, which was 40.5 per cent in this case. CONCLUSION: The study indicates that the Portsmouth Physiological and Operative Severity Score for the Enumeration of Mortality and Morbidity is a useful tool for predicting morbidity risk in patients undergoing head and neck resection with reconstruction for temporal bone malignancies.

Concurrent management of suppurative intracranial complications of sinusitis and acute otitis media in children.

OBJECTIVE: Intracranial complications of sinusitis and acute otitis media (AOM) are rare but life-threatening events. In children with suppurative intracranial complications, concurrent neurosurgical and otolaryngological (ORL) intervention has been recommended to optimize outcomes. The aim of this study was to investigate outcomes following concurrent neurosurgical and ORL intervention. METHODS: A retrospective cohort study of children undergoing neurosurgical intervention for intracranial complications of sinusitis or AOM in two neurosurgical centres in Ireland was conducted. RESULTS: 65 children were identified. Mean age was 11.9 years. The most prevalent symptoms were headache, pyrexia, altered level of consciousness, facial swelling, and vomiting. Subdural empyema (n = 24, 36.9%) and extradural abscess (n = 17, 26.2%) were the most common complications. 54 underwent same admission ORL intervention; 47 (87%) were performed concurrently or earlier. For rhinogenic infections, 35 (64.8%) underwent endoscopic sinus surgery (ESS), 13 (24.1%) underwent frontal sinus trephine, and 5 (9.3%) underwent maxillary sinus washout alone. For otogenic infections, 10 (90.9%) underwent mastoidectomy and 7 (63.6%) underwent tympanostomy tube placement. 19 (29.2%) had post-operative neurological deficits, of which 2 (3.1%) were permanent. Streptococcus intermedius was the most common pathogen (n = 30, 46.2%). Concurrent intervention reduced the prevalence of residual collection (p = 0.018) and the need for revision neurosurgical intervention (p = 0.039) for sinogenic complications. The same trends did not achieve statistical significance for the otogenic group. Mortality was 0%. CONCLUSION: Intracranial complications of sinusitis and AOM are best managed in a specialist centre with multidisciplinary input. Concurrent ORL and neurosurgical intervention reduces abscess recurrence and requirement for revision neurosurgery in sinogenic complications and should represent the standard of care. ESS is the ORL modality of choice in experienced hands.

The roles of school in supporting LGBTQ+ youth: A systematic review and ecological framework for understanding risk for suicide-related thoughts and behaviors.

The extant literature on suicide-related thoughts and behaviors (STB) has highlighted increased patterns of risk among specific minoritized populations, including lesbian, gay, bisexual, transgender, questioning, intersex, two spirit, and queer (LGBTQ+) youth. Compared to their heterosexual and cisgender peers, LGBTQ+ youth are at increased risk for having STB. Identity-specific stressors such as homonegativity and anti-queerness are among the unique factors posited to contribute to this risk and inhibit factors that protect against suicide. The school setting has been a focal point for suicide prevention and intervention and may also play a key role in linking students to care; however, schools also hold the potential to provide supports and experiences that may buffer against risk factors for STB in LGBTQ+ students. This systematic literature review presents findings from 44 studies examining school-related correlates of STB in LGBTQ+ students, informing an ecological approach to suicide prevention for school settings. Findings underscore the importance of school context for preventing STB in LGBTQ+ youth. Approaches that prioritize safety and acceptance of LGBTQ+ youth should span multiple layers of a student's ecology, including district and state level policies and school programs and interventions, such as Gender and Sexuality Alliances and universal bullying prevention programs. Beyond their role as a primary access point for behavioral health services, schools offer a unique opportunity to support suicide prevention by combating minority stressors through promoting positive social relationships and a safe community for LGBTQ+ students.

A comparison of transhepatic versus transperitoneal cholecystostomy for acute calculous cholecystitis: a 5-year experience.

Percutaneous cholecystostomy is a treatment for acute calculous cholecystitis used in patients where surgery is high risk or challenging either to allow for surgical optimisation or as definitive treatment. In this case series we compare the outcomes of a transhepatic versus transperitoneal approach in patients undergoing percutaneous cholecystostomy for acute calculous cholecystitis. A retrospective review of patients from 2014 to 2019 was conducted and included demographics, percutaneous cholecystostomy route, complications and outcome. Fifty-one patients were included. Percutaneous cholecystostomy was placed transhepatically in 15 cases; transperitoneal in 30 cases; 6 cases had undetermined route. The transhepatic cohort had 43.5% fewer readmissions due to biliary sepsis, 32.5% fewer drain-related complications, and were less likely to require further treatment (32.5% reduction) compared to the transperitoneal cohort. In our experience, the transhepatic route is preferred due to fewer complications, fewer readmissions and a reduction in the need for further treatment.