A systematic review of minimally invasive cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients with peritoneal malignancy.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is traditionally a maximally invasive operation with a large abdominal incision and multi-visceral resections. However, to minimize abdominal wall morbidity and improve functional recovery, some centres have adopted a minimally invasive (MI) approach in select cases. The primary aim of this systematic review and meta-analysis was to assess the evidence for safety and patient selection for minimally invasive approaches to CRS and HIPEC with curative intent. METHODS: A PRISMA-compliant systematic review was performed using three electronic databases: Ovid MEDLINE, EMBASE and Web of Science. Data regarding postoperative morbidity was meta-analysed. RESULTS: Thirteen studies met the inclusion criteria (N = 462 MI patients), all of which were retrospective in design. Six studies included an open comparison group. Pseudomyxoma peritonei, mesothelioma and ovarian carcinoma made up the majority of cases (>90%), with a PCI < 10 listed as a prerequisite to selection across all studies. On pooled analysis there was no difference in major morbidity between MI and open groups (OR 0.52 95% CI 0.18-1.46, P = 0.33). There was one perioperative death reported in the MI group. Length of stay appeared shorter in the MI group (median range MI: 4-11 v Open: 7-13 days). Short-term recurrence and overall survival between both groups also appeared no different. CONCLUSION: Minimally invasive CRS and HIPEC appears feasible and safe in appropriately selected patients. Clear histological stratification and longer term follow up is required to determine oncological safety, particularly in more aggressive tumours such as colorectal peritoneal metastases.

Corrigendum: The impact of hostile abortion legislation on the United States maternal mortality crisis: a call for increased abortion education.

[This corrects the article DOI: 10.3389/fpubh.2023.1291668.].

Comparative analyses of disease-linked missense mutations in the RNA exosome modeled in budding yeast reveal distinct functional consequences in translation.

The RNA exosome is an evolutionarily conserved exoribonuclease complex that consists of a 3-subunit cap, a 6-subunit barrel-shaped core, and a catalytic base subunit. Missense mutations in genes encoding structural subunits of the RNA exosome cause a growing family of diseases with diverse pathologies, collectively termed RNA exosomopathies. The disease symptoms vary and can manifest as neurological defects or developmental disorders. The diversity of the RNA exosomopathy pathologies suggests that the different missense mutations in structural genes result in distinct in vivo consequences. To investigate these functional consequences and distinguish whether they are unique to each RNA exosomopathy mutation, we generated a collection of in vivo models using budding yeast by introducing pathogenic missense mutations in orthologous S. cerevisiae genes. We then performed a comparative RNA-seq analysis to assess broad transcriptomic changes in each mutant model. Three of the mutant models rrp4-G226D, rrp40-W195R and rrp46-L191H, which model mutations in the genes encoding structural subunits of the RNA exosome, EXOSC2, EXOSC3 and EXOSC5 showed the largest transcriptomic differences. Further analyses revealed shared increased transcripts enriched in translation or ribosomal RNA modification/processing pathways across the three mutant models. Studies of the impact of the mutations on translation revealed shared defects in ribosome biogenesis but distinct impacts on translation. Collectively, our results provide the first comparative analysis of several RNA exosomopathy mutant models and suggest that different RNA exosomopathy mutations result in in vivo consequences that are both unique and shared across each variant, providing more insight into the biology underlying each distinct pathology.

Health Care Professional Experiences and Opinions on Depression and Suicide in People With Diabetes.

OBJECTIVE: People with diabetes have an increased risk of depression, intentional self-injury and self-harm (ISI), and suicide compared with the general population. This study aimed to explore experiences and awareness of health care professionals (HCPs) regarding depression, ISI, and suicide, and understand resource use and needs among HCPs who care for persons with diabetes (PWD). METHODS: Health care professionals who see children and/or adults with type 1 diabetes or type 2 diabetes anonymously completed an online survey about their experiences, opinions, barriers, and needs surrounding identification and care of PWD with depression, ISI, and suicide. RESULTS: One hundred twenty-nine HCPs participated. The majority were medical doctors (MDs) or advanced practice providers (APPs). Only a quarter of MDs and APPs felt very comfortable asking about ISI or suicidal ideation (SI), whereas 20% felt they had received appropriate training to support those with ISI or SI. The primary needs reported include more training on how to ask, respond, and support those expressing ISI and SI. Health care professionals reported wanting better access to resources for PWD. DISCUSSION: The HCPs tend to underestimate SI in the diabetes population and rates of training were low. Areas to address include providing education and training to HCPs to improve identification and management of ISI and suicide risk. These data can inform the development of mechanisms to improve discussions of depression and suicide and of resources to help HCPs support PWD.

Comparison of quality of life, symptom and functional outcomes following surgical treatment for colorectal neoplasia.

BACKGROUND: Colorectal surgical procedures can have a significant impact on quality-of-life (QoL), functional and symptom outcomes. This retrospective study conducted in a tertiary care center evaluated the influence of four colorectal surgical procedures on patient-reported outcome measures (PROMs). METHODS: 512 patients undergoing colorectal neoplasia surgery between June 2015 and December 2017 were identified via the Cabrini Monash Colorectal Neoplasia database. Primary outcomes measured were the mean changes in PROMs following surgery utilizing the International Consortium of Health Outcome Measures colorectal cancer (CRC) PROMs. RESULTS: 242 patients from 483 eligible patients responded (50% participation rate). Responders and non-responders were comparable in median age (72 vs. 70 years), gender (48% vs. 52% male), time from surgery (<1 and >1 year), overall stage at diagnosis and type of surgery. Respondents underwent either a right hemicolectomy, ultra-low anterior resection, abdominoperineal resection or a transanal endoscopic microsurgery/transanal minimally invasive surgery. Right hemicolectomy patients reported the best post-operative function and reduced symptoms, significantly better (P < 0.01) than ultra-low anterior resection patients who reported the worst outcomes in multiple areas (body image, embarrassment, flatulence, diarrhoea, stool frequency). Furthermore, patients undergoing an abdominoperineal resection reported the worst scores for body image, urinary frequency, urinary incontinence, buttock pain, faecal incontinence and male impotence. CONCLUSIONS: The differences in PROMs in CRC surgical procedures is demonstrable. The worst post-operative functional and symptom scores were reported after either an ultra-low anterior resection or an abdominoperineal resection. Implementation of PROMs will identify and aid early patient referral to allied health and support services.

Hydroxychloroquine for pre-exposure prophylaxis of COVID-19 in health care workers: a randomized, multicenter, placebo-controlled trial Healthcare Worker Exposure Response and Outcomes of Hydroxychloroquine (HERO-HCQ).

OBJECTIVES: To determine whether hydroxychloroquine (HCQ) is safe and effective at preventing COVID-19 infections among health care workers (HCWs). METHODS: In a 1: 1 randomized, placebo-controlled, double-blind, parallel-group, superiority trial at 34 US clinical centers, 1360 HCWs at risk for COVID-19 infection were enrolled between April and November 2020. Participants were randomized to HCQ or matched placebo. The HCQ dosing included a loading dose of HCQ 600 mg twice on day 1, followed by 400 mg daily for 29 days. The primary outcome was a composite of confirmed or suspected COVID-19 clinical infection by day 30, defined as new-onset fever, cough, or dyspnea and either a positive SARS-CoV-2 polymerase chain reaction test (confirmed) or a lack of confirmatory testing due to local restrictions (suspected). RESULTS: Study enrollment closed before full accrual due to recruitment challenges. The primary end point occurred in 41 (6.0%) participants receiving HCQ and 53 (7.8%) participants receiving placebo. No difference in the proportion of participants experiencing clinical infection (estimated difference of -1.8%, 95% confidence interval -4.6-0.9%, P = 0.20) was identified nor any significant safety issues. CONCLUSION: Oral HCQ taken as prescribed appeared safe among HCWs. No significant clinical benefits were observed. The study was not powered to detect a small but potentially important reduction in infection. TRIAL REGISTRATION: NCT04334148.

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in small bowel adenocarcinoma with peritoneal metastasis: a systematic review.

Objectives: Small bowel adenocarcinoma (SBA) with peritoneal metastasis (PM) is rare and despite treatment with systemic chemotherapy, the prognosis is poor. However, there is emerging evidence that cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) may offer a survival benefit over systemic therapy alone. This systematic review will assess the effectiveness of CRS-HIPEC for SBA-PM. Content: Three databases were searched from inception to 11/10/21. Clinical outcomes were extracted and analysed. Summary: A total of 164 cases of SBA-PM undergoing CRS-HIPEC were identified in 12 studies. The majority of patients had neoadjuvant chemotherapy (87/164, 53%) and complete cytoreduction (143/164, 87%) prior to HIPEC. The median overall survival was 9-32 months and 5-year survival ranged from 25 to 40%. Clavien-Dindo grade III/IV morbidity ranged between 19.1 and 50%, while overall mortality was low with only 3 treatment-related deaths. Outlook: CRS-HIPEC has the potential to improve the overall survival in a highly selected group of SBA-PM patients, with 5-year survival rates comparable to those reported in colorectal peritoneal metastases. However, the expected survival benefits need to be balanced against the intrinsic risk of morbidity and mortality associated with the procedure. Further multicentre studies are required to assess the safety and feasibility of CRS-HIPEC in SBA-PM to guide best practice management for this rare disease.

Major vascular reconstruction in colorectal adenocarcinoma and retroperitoneal sarcoma: A retrospective study of safety and margins in a tertiary referral centre.

BACKGROUND: The role of en bloc vascular resection and reconstruction (EVRR) is controversial in colorectal adenocarcinoma (CRC), but well-established in retroperitoneal sarcoma (RPS). Sparse data exists regarding these complex procedures. METHODS: Patients undergoing curative intent EVRR for advanced CRC and RPS between 2014 and 2021 at a tertiary centre were included. Morbidity, margins, recurrence, and survival were evaluated. RESULTS: 24 patients underwent EVRR with 48 reconstructions (11 CRC and 13 RPS). For CRC, 100% of patients underwent Iliac system reconstructions. For RPS, inferior vena cava reconstructions were the most common (69.2%). There were 2 arterial and 1 venous graft thromboses. Primary graft patency was 89.4% arterial and 93.1% venous, while secondary patency was 100% arterial and 96.5% venous at last follow up. 1 venous and 1 arterial graft required reoperation for bleeding. There were no compromised limbs. Major complications occurred in 6 patients (25.0%) with no observed difference between CRC and RPS (OR 0.43 95%CI[0.60,3.19], P = 0.41). R1 margins occurred 1 CRC (90.9%) and 3 RPS (76.9%), with no R2 resections. All vascular resection margins were clear. There were 6 CRC (50%) and 4 RPS (33.3%) recurrences. Median recurrence time was 20.9 months for CRC and 'not yet reached' for RPS. Median follow-up was 19.4 months for CRC and 21.4 months for RPS. CONCLUSION: EVRR for locally advanced CRC or RPS is safe and achieves favorable R0 resection rates. CRC patients with major vascular invasion can still be considered for curative intent surgery. Larger cohorts with longer follow up are needed to assess oncologic outcomes.

Studies of mutations of assembly factor Hit1 in budding yeast suggest translation defects as the molecular basis for PEHO syndrome.

Regulation of protein synthesis is critical for control of gene expression in all cells. Ribosomes are ribonucleoprotein machines responsible for translating cellular proteins. Defects in ribosome production, function, or regulation are detrimental to the cell and cause human diseases, such as progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy (PEHO) syndrome. PEHO syndrome is a devastating neurodevelopmental disorder caused by mutations in the ZNHIT3 gene, which encodes an evolutionarily conserved nuclear protein. The precise mechanisms by which ZNHIT3 mutations lead to PEHO syndrome are currently unclear. Studies of the human zinc finger HIT-type containing protein 3 homolog in budding yeast (Hit1) revealed that this protein is critical for formation of small nucleolar ribonucleoprotein complexes that are required for rRNA processing and 2'-O-methylation. Here, we use budding yeast as a model system to reveal the basis for the molecular pathogenesis of PEHO syndrome. We show that missense mutations modeling those found in PEHO syndrome patients cause a decrease in steady-state Hit1 protein levels, a significant reduction of box C/D snoRNA levels, and subsequent defects in rRNA processing and altered cellular translation. Using RiboMethSeq analysis of rRNAs isolated from actively translating ribosomes, we reveal site-specific changes in the rRNA modification pattern of PEHO syndrome mutant yeast cells. Our data suggest that PEHO syndrome is a ribosomopathy and reveal potential new aspects of the molecular basis of this disease in translation dysregulation.

Racial/Ethnic Disparities in Healthcare Worker Experiences During the COVID-19 Pandemic: An Analysis of the HERO Registry.

Background: The extent to which healthcare worker (HCWs) experiences during the COVID-19 pandemic vary by race or ethnicity after adjustment for confounding factors is not currently known. Methods: We performed an observational prospective cohort study of 24,769 healthcare workers from 50 U.S. states and the District of Columbia, enrolled between April 10, 2020 and June 30, 2021, and evaluated participant experiences during the COVID-19 pandemic, including testing, diagnosis with COVID-19, emotional experiences, burnout, and interest in vaccines and vaccine clinical trials. Findings: After adjustment for professional role, medical history, and community characteristics, Black and Asian participants were less likely to receive SARS-CoV-2 viral testing (adjusted odds ratio (aOR) 0·82 [0·70, 0·96], p=0·012 and aOR 0·77 [0·67, 0·89], p<0·001 respectively) than White participants. Hispanic participants were more likely to have evidence of COVID-19 infection (aOR 1·23 (1·00, 1·50, p=0·048). Black and Asian participants were less likely to report interest in a COVID-19 vaccine (aOR 0·11 [0·05, 0·25], p<0·001 and aOR 0·48 [0·27, 0·85] p=0·012). Black participants were less likely to report interest in participating in a COVID-19 vaccine trial (aOR = 0·39 [0·28, 0·54], p<0·001). Black participants were also less likely to report 3 or more daily emotional impacts of COVID-19 (aOR = 0·66 [0·53, 0·82], p=<0·001). Black participants were additionally less likely to report burnout (aOR = 0·66 ([0·49, 0·95], p=0·025). Interpretation: In a large, national study of healthcare workers, after adjustment for individual and community characteristics, race/ethnicity disparities in COVID-19 outcomes persist. Future work is urgently needed to understand precise mechanisms behind these disparities and to develop and implement targeted interventions to improve health equity for healthcare workers. Funding: This work was funded by the Patient-Centered Outcomes Research Institute (PCORI), Contract # COVID-19-2020-001.

Late life anxiety and depression symptoms, and suicidal behaviors in racial/ethnic minority older adults in community-based organizations and community clinics in the U.S.

OBJECTIVE: Late life anxiety and depression represent a significant source of disability, with racial/ethnic minority older adults in the U.S. showing marked disparities in healthy aging. Community-based organizations (CBOs) and community clinics serve these populations for preventive care, yet few identify their mental health service needs. We examine the association between race/ethnicity and risk of mild-to-severe symptoms of anxiety and depression, and suicidal behaviors in minority older adults. METHOD: Data come from the multisite randomized controlled trial Building Community Capacity for Disability Prevention for Minority Elders, which screened 1,057 adults (45.5% Asian, 26.8% Latinx, 15.0% non-Latinx Black, 8.5% non-Latinx White, and 4.2% American Indian) aged 60 + years at CBOs and clinics in Massachusetts, New York, Florida, and Puerto Rico. Screened participants completed the Generalized Anxiety Disorder-7 (GAD-7) for anxiety symptoms, the Geriatric Depression Scale-15 (GDS-15) for depression symptoms, and the Paykel Suicide Risk Questionnaire for suicidal behaviors. RESULTS: 28.1% of older adults reported mild-to-severe anxiety symptoms, 30.1% reported mild-to-severe depression symptoms, and 4.3% reported at least one suicidal behavior. Compared to non-Latinx Whites, Latinxs had higher odds of mild-to-severe anxiety and depression symptoms and one or more suicidal behaviors, and Asians had higher odds of mild-to-severe depression symptoms only. CONCLUSIONS: There is an urgent need to improve outreach for screening and preventive mental health care for minority older adults. Expanding outreach and community-based capacity to identify and treat minority older adults with mental health conditions represents an opportunity to prevent disability. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Feasibility of Spotlight Consultations Tool in Routine Care: Real-World Evidence.

BACKGROUND: Burnout in people with diabetes and healthcare professionals (HCPs) is at an all-time high. Spotlight AQ, a novel "smart" adaptive patient questionnaire, is designed to improve consultations by rapidly identifying patient priorities and presenting these in the context of best-practice care pathways to aid consultations. We aimed to determine Spotlight AQ's feasibility in routine care. MATERIALS AND METHODS: The Spotlight prototype tool was trialed at three centers: two UK primary care centers and one US specialist center (June-September 2020). Participants with type 1 (T1D) or type 2 diabetes (T2D) completed the questionnaire prior to their routine consultations. Results were immediately available and formed the basis of the clinical discussion and decision-making within the clinic visit. RESULTS: A convenience sample of 49 adults took part, n=31 T1D, (n=18 female); and n=18 T2D (n=10 male, n=4 female, n=4 gender unreported). Each identified two priority concerns. "Psychological burden of diabetes" was the most common priority concern (T1D n = 27, 87.1%) followed by "gaining more skills about particular aspects of diabetes" (T1D n=19, 61.3%), "improving support around me" (n=8, 25.8%) and "diabetes-related treatment issues" (n=8, 25.8%). Burden of diabetes was widespread as was lack of confidence around self-management. Similarly, psychological burden of diabetes was the primary concern for participants with T2D (n=18,100%) followed by "gaining more skills about aspects of diabetes" (n=7, 38.9%), "improving support around me" (n=7, 38.9%) and "diabetes-related treatment issues" (n=4; 22.2%). CONCLUSIONS: Spotlight AQ is acceptable and feasible for use in routine care. Gaining more skills and addressing the psychological burden of diabetes are high-priority areas that must be addressed to reduce high levels of distress.

"If I could survive without eating, it would be a huge relief": Development and initial validation of the Fear of Food Questionnaire.

BACKGROUND: Fear of food and behavioral avoidance of specific foods, food groups, and food related social situations can substantially reduce health related quality of life in individuals with a wide range of conditions that affect appetite, eating behavior, and digestion, including irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), vomit and choking phobias, and food allergies/sensitivities. When this avoidance leads to weight/nutritional and/or psychosocial impairment, the diagnostic criteria for Avoidant/restrictive food intake disorder (ARFID) are met. Fear of food is an important target for interventions designed to improve psychosocial functioning and quality of life in such individuals. The purpose of this research was to develop and validate a novel measure of fear of food. METHODS: Participants (n = 1138) were recruited from ongoing clinical trials for both IBD and IBS, from Amazon's Mechanical Turk, from Reddit support forums for IBS, IBD, and vomit phobia, and from an undergraduate subject pool. Exploratory and confirmatory factor analysis, Pearson's correlations, one-way ANOVA, and intraclass correlation coefficients were used to assess the validity and reliability of the Fear of Food Questionnaire. RESULTS: The final 18 item questionnaire showed excellent internal consistency, test-retest reliability, convergent validity, discriminative (known groups) validity, as well as good factor structure. Fear of food was highly correlated with visceral hypersensitivity, catastrophizing, GI symptom severity and health related quality of life, as well as with self-reported Fear-ARFID symptoms. Individuals meeting study criteria for Fear-ARFID reported the highest scores relative to control and other analogue clinical groups. CONCLUSION: The Fear of Food Questionnaire appears to be reliable and valid across populations and may be a valuable tool in the assessment and treatment of Fear-ARFID.

Design of the Healthcare Worker Exposure Response and Outcomes (HERO) research platform.

BACKGROUND: The SARS CoV-2 virus has caused one of the deadliest pandemics in recent history, resulting in over 170 million deaths and global economic disruption. There remains an urgent need for clinical trials to test therapies for treatment and prevention. DESIGN: An online research platform was created to support a registry community of healthcare workers (HCWs) to understand their experiences and conduct clinical studies to address their concerns. The first study, HERO-HCQ, was a double-blind, multicenter, randomized, pragmatic trial to evaluate the superiority of hydroxychloroquine (HCQ) vs placebo for pre-exposure prophylaxis (PrEP) of COVID-19 clinical infection in HCWs. Secondary objectives were to assess the efficacy of HCQ in preventing viral shedding of COVID-19 among HCWs and to assess the safety and tolerability of HCQ. METHODS: HCWs joined the Registry and were pre-screened for trial interest and eligibility. Trial participants were randomized 1:1 to receive HCQ or placebo. On-site baseline assessment included a COVID-19 nasopharyngeal PCR and blood serology test. Weekly follow-up was done via an online portal and included screening for symptoms of COVID-19, self-reported testing, adverse events, and quality of life assessments. The on-site visit was repeated at Day 30. DISCUSSION: The HERO research platform offers an approach to rapidly engage, screen, invite and enroll into clinical studies using a novel participant-facing online portal interface and remote data collection, enabling limited onsite procedures for conduct of a pragmatic clinical trial. This platform may be an example for future clinical trials of common conditions to enable more rapid evidence generation.