The Impact of Bariatric Surgery on Coronary Microvascular Function Assessed Using Automated Quantitative Perfusion CMR.

BACKGROUND: Coronary microvascular function is impaired in patients with obesity, contributing to myocardial dysfunction and heart failure. Bariatric surgery decreases cardiovascular mortality and heart failure, but the mechanisms are unclear. OBJECTIVES: The authors studied the impact of bariatric surgery on coronary microvascular function in patients with obesity and its relationship with metabolic syndrome. METHODS: Fully automated quantitative perfusion cardiac magnetic resonance and metabolic markers were performed before and 6 months after bariatric surgery. RESULTS: Compared with age- and sex-matched healthy volunteers, 38 patients living with obesity had lower stress myocardial blood flow (MBF) (P = 0.001) and lower myocardial perfusion reserve (P < 0.001). A total of 27 participants underwent paired follow-up 6 months post-surgery. Metabolic abnormalities reduced significantly at follow-up including mean body mass index by 11 ± 3 kg/m2 (P < 0.001), glycated hemoglobin by 9 mmol/mol (Q1-Q3: 4-19 mmol/mol; P < 0.001), fasting insulin by 142 ± 131 pmol/L (P < 0.001), and hepatic fat fraction by 5.6% (2.6%-15.0%; P < 0.001). Stress MBF increased by 0.28 mL/g/min (-0.02 to 0.75 mL/g/min; P = 0.003) and myocardial perfusion reserve by 0.13 (-0.25 to 1.1; P = 0.036). The increase in stress MBF was lower in those with preoperative type 2 diabetes mellitus (0.1 mL/g/min [-0.09 to 0.46 mL/g/min] vs 0.75 mL/g/min [0.31-1.25 mL/g/min]; P = 0.002). Improvement in stress MBF was associated with reduction in fasting insulin (beta = -0.45 [95% CI: -0.05 to 0.90]; P = 0.03). CONCLUSIONS: Coronary microvascular function is impaired in patients with obesity, but can be improved significantly with bariatric surgery. Improvements in microvascular function are associated with improvements in insulin resistance but are attenuated in those with preoperative type 2 diabetes mellitus.

Prevention of Ovarian Cancer: Where are We Now and Where are We Going?

PURPOSE OF REVIEW: To describe current and future strategies to reduce the burden of ovarian cancer through prevention. RECENT FINDINGS: Current strategies in genetic testing are missing a substantial number of individuals at risk, representing a missed opportunity for ovarian cancer prevention. Past efforts at screening and early detection have thus far failed to improve ovarian cancer mortality, and novel techniques are needed. Surgical prevention is highly effective, but surgical menopause from oophorectomy has significant side effects. Novel surgical strategies aimed at reducing risk while minimizing these harms are currently being studied. To maximize ovarian cancer prevention, a multi-pronged approach is needed. We propose that more inclusive and accurate genetic testing to identify more individuals at risk, novel molecular screening and early detection, surgical prevention that maximizes quality of life while reducing risk, and broader adoption of targeted and opportunistic salpingectomy will together reduce the burden of ovarian cancer.

Pressure injury pain over time among nursing home residents.

OBJECTIVE: Examine pressure injury (PrI) pain severity, stability, and current treatment of PrI pain among nursing home (NH) residents using two assessment tools and a descriptive cohort study design. BACKGROUND: PrI pain affects quality of life of NH residents yet, best assessment methods, stability of PrI pain, and how to take care of the pain are not well known. METHODS: Data collected from 33 residents with PrI (stages 1-4) from 4 NHs. All PrI were staged and assessed using the Bates-Jensen Wound Assessment Tool (BWAT) to determine severity. Verbal Response Scale (VRS) and Pain Assessment in Advanced Dementia (PAINAD) were used to assess general and PrI pain 3 times a day for two days within one week. Data classified as: no, mild, moderate, or severe pain. Proportions of participants with different levels of PrI pain were calculated. T tests were conducted to examine differences across time; VRS and PAINAD were examined for agreement. RESULTS: Participants were 74 % female, 49 % white, 58 % cognitively intact, 58 % functionally dependent, and had mean age of 82 years old. The majority (52 %; n = 17) were full thickness PrI, stage 3 (n = 5), stage 4 (n = 7), unstageable (n = 5). The majority of participants (82 %; n = 27) reported PrI pain on at least one of six assessments over the two days; with 57 % mild, 26 % moderate and 16 % severe pain. More severe pain occurred in afternoon. No differences existed across days. Although there was a positive relationship between VRS and PAINAD in pain assessments (r = 0.38, P<.05), the agreement between the two scales, as indicated by Cohen's kappa (K = 0.19, p=.28), was found to be poor. Of those with PrI pain, 22 % had pain documented in the Minimum Data Set (MDS). Only 42 % of participants who reported PrI pain received pain medication within 12 h of initial pain assessment. Out of 28 participants who received routine pain medication for general pain, 18 of them reported experiencing no pain. CONCLUSION: While VRS and PAINAD scores exhibited a relationship, their agreement was limited. Documentation of PrI pain on the Minimum Data Set (MDS) was found to be inadequate. Notably, 40 % of participants reported higher levels of PrI pain in the afternoon, suggesting this time may be opportune for PrI pain assessment and management. Interestingly, participants who received medication for general pain did not report PrI pain, suggesting that treatment of general pain may effectively alleviate PrI pain symptoms.

The GIBACHT fellowship: a multilateral initiative for strengthening capacity in biosafety and biosecurity towards pandemic preparedness.

The German Biosecurity Programme was launched in 2013 with the aim to support partner countries overcome biological threats including natural outbreaks or the intentional misuse of highly pathogenic agents. As part of this programme, this paper describes the development and implementation of a multilateral biosafety and biosecurity training initiative, called 'Global Partnership Initiated Biosecurity Academia for Controlling Health Threats' (GIBACHT). To achieve its objectives, GIBACHT implemented a blended-learning approach with self-directed, distance-based learning phases and three training-of-trainer workshops. The programme follows Kirkpatrick's model of learning to guarantee sustainable effects of improved knowledge and skills. One hundred nine fellows from 26 countries have been trained in seven cohorts. Many GIBACHT alumni have established additional biosafety/biosecurity trainings in their home countries. The knowledge exchange is strengthened by the implementation of a Moodle-based alumni network. GIBACHT has the potential to contribute to strengthening the capacities of partner countries in Africa, the Middle East, and South and Central Asia to respond and build resilience to biological threats.

Efficacy and safety of once-weekly semaglutide 2·4 mg versus placebo in people with obesity and prediabetes (STEP 10): a randomised, double-blind, placebo-controlled, multicentre phase 3 trial.

BACKGROUND: There are currently limited data regarding the effect of semaglutide 2·4 mg in individuals with obesity and prediabetes in clinical trials. We aimed to assess the efficacy and safety of semaglutide 2·4 mg for weight management and glycaemic control in participants with obesity and prediabetes. METHODS: STEP 10 was a randomised, double-blind, parallel-group, phase 3 trial done across 30 trial sites in Canada, Denmark, Finland, Spain, and the UK and included participants aged 18 years or older with a BMI of 30 kg/m2 or higher and prediabetes according to UK National Institute for Health and Care Excellence criteria (defined as having at least one of the following at screening: HbA1c of 6·0-6·4% [42-47 mmol/mol] or fasting plasma glucose [FPG] of 5·5-6·9 mmol/L). Participants were randomly assigned (2:1) to once-weekly subcutaneous semaglutide 2·4 mg or placebo with diet and physical activity counselling for 52 weeks, followed by a 28-week off-treatment period. Primary endpoints were percentage change in bodyweight and proportion of participants reverting to normoglycaemia (HbA1c <6·0% [<42 mmol/mol] and FPG <5·5 mmol/L) at week 52 (assessed in all randomly assigned participants by intention to treat). Selective safety data were collected for participants who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT05040971, and is complete. FINDINGS: Between Sept 16 and Dec 29, 2021, 138 participants were randomly assigned to semaglutide 2·4 mg and 69 to placebo. 147 (71%) were female and 60 (29%) were male; 183 (88%) were White. All randomly assigned participants received at least one dose of study drug. Baseline mean age was 53 years (SD 11), bodyweight 111·6 kg (22·2), BMI 40·1 kg/m2 (6·9), waist circumference 120·1 cm (14·7), HbA1c 5·9% (0·3; 41·3 mmol/mol [3·0]), and FPG 5·9 mmol/L (0·6). There was a significantly greater reduction in bodyweight with semaglutide 2·4 mg than with placebo at week 52 (-13·9% [SD 0·7] vs -2·7% [0·6]; estimated treatment difference -11·2% [95% CI -13·0 to -9·4]; p<0·0001). Greater proportions of participants reverted to normoglycaemia at week 52 with semaglutide 2·4 mg than with placebo (103 [81%] of 127 vs nine [14%] of 64; odds ratio 19·8 [95% CI 8·7 to 45·2]; p<0·0001). Serious adverse events occurred in 12 (9%) participants receiving semaglutide 2·4 mg versus six (9%) receiving placebo. Adverse events leading to treatment discontinuation occurred in eight (6%) participants in the semaglutide 2·4 mg group versus one (1%) participant in the placebo group. No new safety signals were reported. INTERPRETATION: Semaglutide 2·4 mg provided superior reduction in bodyweight and reversion to normoglycaemia versus placebo in participants with obesity and prediabetes. The safety and tolerability profile was consistent with previous studies and with the GLP-1 receptor agonist class. These findings support the potential use of semaglutide 2·4 mg as a treatment option for individuals with obesity and prediabetes to achieve reversion to normoglycaemia. FUNDING: Novo Nordisk. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

Increased TP53 somatic evolution in peritoneal washes of individuals with BRCA1 germline mutations.

BACKGROUND: Individuals with germline BRCA1 and BRCA2 pathogenic variants (BRCA carriers) are at high risk of developing high grade serous ovarian carcinoma (HGSC). HGSC is predominantly driven by TP53 mutations, but mutations in this gene are also commonly found in non-cancerous tissue as a feature of normal human aging. We hypothesized that HGSC predisposition in BRCA carriers may be related to increased TP53 somatic evolution, which could be detectable by ultra-deep sequencing of TP53 mutations in gynecological liquid biopsies. METHODS: Duplex sequencing was used to identify TP53 mutations with high sensitivity in peritoneal washes and cervical liquid-based cytology (LBC) collected at surgery from 60 individuals including BRCA1 and BRCA2 carriers, and non-carriers. TP53 mutation pathogenicity was compared across groups and with TP53 cancer mutations. RESULTS: TP53 mutations were more abundant in cervical LBC than in peritoneal washes but increased with age in both sample types. In peritoneal washes, but not in cervical LBC, pathogenic TP53 mutation burden was increased in BRCA1 carriers compared to non-carriers, independently of age. Five individuals shared identical pathogenic TP53 mutations in peritoneal washes and cervical LBC, but not in blood. CONCLUSIONS: Ultra-deep sequencing of TP53 mutations in peritoneal washes collected at surgery reveals increased burden of pathogenic TP53 mutations in BRCA1 carriers. This excess of pathogenic TP53 mutations might be linked to the elevated risk of HGSC in these individuals. In some patients, concordant TP53 mutations were found in peritoneal washes and cervical LBCs, but the cell of origin remains unknown and deserves further investigation.

Decreasing Intraoperative Skin Damage in Prone-Position Surgeries.

OBJECTIVE: To determine if subepidermal moisture (SEM) measures help detect and prevent intraoperative acquired pressure injuries (IAPIs) for prone-position surgery. METHODS: In this clinical trial of patients (n = 39 preintervention, n = 48 intervention, 100 historical control) undergoing prone-position surgery, researchers examined the use of multidimensionally flexible silicone foam (MFSF) dressings applied preoperatively to patients' face, chest, and iliac crests. Visual skin assessments and SEM measures were obtained preoperatively, postoperatively, and daily for up to 5 days or until discharge. Electronic health record review included demographic, medical, and surgery data. RESULTS: Of the 187 total participants, 76 (41%) were women. Participants' mean age was 61.0 ± 15.0 years, and 9.6% were Hispanic (n = 18), 9.6% were Asian (n = 18), 6.9% were Black or African American (n = 13), and 73.8% were White (n = 138). Participants had a mean Scott-Triggers IAPI risk score of 1.5 ± 1.1. Among those with no erythema preoperatively, fewer intervention participants exhibited postoperative erythema on their face and chest than did preintervention participants. Further, fewer intervention participants had SEM-defined IAPIs at all locations in comparison with preintervention participants. The MFSF dressings overcame IAPI risk factors of surgery length, skin tone, and body mass index with fewer IAPIs in intervention participants. CONCLUSIONS: Patients undergoing prone-position surgeries developed fewer IAPIs, and SEM measures indicated no damage when MFSF dressings were applied to sites preoperatively. The SEM measures detected more damage than visual assessment.

A rapid review of motives and barriers for living substance of human origin donation and an extended typology.

Our objective is to review motives and barriers for non-reproductive, living substance of human origin (SoHO) donation, and to extend existing typologies beyond blood. The expansion of SoHO collection is currently unmatched by increased living donors. Thus, there is a critical need to understand how to effectively recruit and retain donors to ensure a sustainable supply of SoHO. We undertook a rapid review and narrative synthesis of published, peer-reviewed literature reporting on motives and/or barriers for living SoHO donation (whole-blood, blood products [2009-2023], bone marrow/stem cells, cord blood, organ, human breast milk, intestinal microbiota [2000-2023]). Results were interpreted through directed qualitative content analysis using an extended typology of motives/barriers largely drawn from blood donation research, and subsequently refined based on results to be inclusive of other SoHO. 234 articles with 237 studies met review criteria. Most were quantitative (74.3%), conducted in Western countries (63.8%), focused on blood donation (64.2%), reported motives and barriers (51.9%) and did not examine differences by donor characteristics or history (74%). We present a revised typology inclusive of motives/barriers for donation of substances beyond blood. This shows while broader motives and barriers are shared across substances donated, there are critical differences at the subcategory level that may account for heterogeneity in results of prior interventions. The nuances in how broad categories of motives and barriers manifest across different SoHO are critical for blood collection agencies to consider as they attempt to expand collection of products beyond whole-blood, plasma, and platelets. WHAT IS KNOWN ABOUT THE TOPIC?: Blood collection agencies (BCAs) continue to expand SoHO product collection beyond whole-blood, plasma, and platelets. The demand for SoHO is currently unmatched by increased living donors. The need to understand how to recruit new and retain existing living donors to ensure a sustainable supply of SoHO remains critical. However, there is no available synthesis of the factors, such as motives/facilitators and barriers/deterrents, to inform our understanding. WHAT IS NEW?: Comprehensively reviewed evidence for motives and barriers of willing/actual donors and nondonors across all types of non-reproductive living SoHO donation. Explored variations in motives and barriers based on substance, donor history and demographic differences (gender, age, ethnicity or culture). Extended typology of motives and barriers inclusive of all non-reproductive living SoHO, beyond solely whole-blood and blood products. Identified that while there are commonalities in the overarching motive and barrier categories across substances (e.g., prosocial motivation, low self-efficacy), within these broader constructs there are differences at the subcategory level (e.g., low-self efficacy was about eligibility, lifestyle barriers, or lack/loss of financial or material resources depending on the substance donated) that are crucial for development of future interventions and for BCAs to consider as they expand SoHO product collection. Highlighted the continued focus on motives and barriers for whole-blood and blood product donation to the exclusion of other, particularly newer, SoHO; lack of qualitative work for newer SoHO; and lack of consideration of differences based on donor characteristics (especially ethnicity/culture) and donor history, which limits our understanding. WHAT ARE THE KEY QUESTIONS FOR FUTURE WORK ON THE TOPIC?: What are the motives and barriers (in both qualitative and quantitative studies) for donation of newer SoHO such as stem cells, cord blood, human milk, and intestinal microbiota? Are there differences in motives and barriers within and across SoHO that are informed by individual and contextual-level factors? How can we develop interventions that respond to the nuances of motives and barriers present across different forms of SoHO that are effective in encouraging new and maintaining continuing donors?

A rapid review of strategies to manage low iron levels in adults donating whole-blood: A focus on donor behaviour.

In recognition of the impact of whole-blood donation on body iron stores, there has been an increased focus assessing the efficacy of strategies to minimise the risk of iron deficiency (ID). Whilst donor behaviour is an important determinant of success, this literature is yet to be fully synthesised to help guide blood collection agencies when implementing these strategies into routine practice. This rapid review identifies strategies for management of low iron, how they have been communicated to donors, donor compliance with advice, donor use of external health services and their effect on donor retention. Web of Science, Medline, CINAHL and Wiley online library databases were searched from 2012 to November 2023, with 29 studies meeting inclusion criteria. Five iron management strategies were identified: oral iron supplementation (IS), education, dietary advice, lengthening inter-donation interval and switching donation type. Most studies (n = 16) focused on IS, with only four reporting how they communicated this to donors. Donor use of IS was high in controlled research environments but has not been evaluated when implemented into routine practice. None of the four studies on dietary advice included findings on donor acceptability. The proportion of donors consulting their doctor about a low iron result or their risk of ID was found to be suboptimal. However, in general, the identified strategies and communications had a positive effect on donor retention. More evidence is needed on how to increase donor knowledge and awareness of donation-related risk of ID as well as to identify how to effectively communicate strategies to donors to ensure optimal acceptability and use.

Bariatric and general surgical procedures in obese patients with a history of venous thromboembolism and concurrent anticoagulation therapy.

OBJECTIVE: The objective of this study was to examine the use and outcomes of perioperative anticoagulation (AC) in obese patients with a known history of venous thromboembolism event (VTE). METHOD: A retrospective review of a prospective database for patients with a VTE history undergoing bariatric and general surgery at a single center (1/2008-12/2017) was performed. Factors assessed included demographics, surgical details, and outcomes. RESULTS: Sixty-five patients underwent 76 procedures: 46 females (71%); mean age 51 years (range 26-73), mean weight 284 pounds (range 110-558), mean body mass index 45 (range 19-87). Comorbidities include hypertension (60%), gastroesophageal reflux disease (54%), osteoarthritis (49%), obstructive sleep apnea (45%), and diabetes (37%). Operations: 22 general surgeries (29%), 20 sleeve gastrectomies (26%), 12 revisions/conversions (16%), 12 Roux-en-Y gastric bypasses (16%), and 10 gastric bands (13%). Modalities: 67% laparoscopic, 28% robotic, and 5% open. Twenty-two patients (34%) had a pre-operative inferior vena cava filter placed with no complications. The mean length of stay was 4.4 days (range 1-31). Complications: seven 30-day readmissions (9%), one 30-day reoperation (1%), and two 90-day VTEs (3%). Thirty-day readmissions: four for inability to tolerate PO, two for small bowel obstruction, and one for symptomatic anastomotic ulcer. CONCLUSIONS: In our patients, post-operative AC could be started without an increased risk of bleeding in patients with a history of VTE undergoing bariatric surgery.

OBJETIVO: Examinar el uso y los resultados de la anticoagulación perioperatoria en pacientes bariátricos con antecedentes de tromboembolia venosa (TEV). MÉTODO: Revisión retrospectiva (base de datos prospectiva) de pacientes sometidos a cirugía general y bariátrica (1/2008-12/2017). Se evaluaron datos demográficos, detalles quirúrgicos y resultados. RESULTADOS: Sesenta y cinco pacientes se sometieron a 76 procedimientos: 46 mujeres (71%), edad media 51 años (rango: 26-73), peso medio 284 libras (rango: 110-558), índice de masa corporal medio 45 (rango: 19-87). Comorbilidad: hipertensión (60%), enfermedad por reflujo gastroesofágico (54%), osteoartritis (49%), apnea obstructiva del sueño (45%), diabetes (37%). Operaciones: 22 cirugía general (29%), 20 gastrectomías en manga (26%), 12 revisiones/conversiones (16%), 12 Y-de-Roux (16%), 10 bandas gástricas (13%). Modalidades: 67% laparoscópica, 28% robótica, 5% abierta. A 22 pacientes (34%) se les colocó un filtro de vena cava inferior preoperatorio sin complicaciones. La estancia media fue de 4.4 días (rango: 1-31). Complicaciones: 7 reingresos a los 30 días (9%), 1 reoperación a los 30 días (1%), 2 TEV a los 90 días (3%). Reingresos a los 30 días: 4 por incapacidad para tolerar la vía oral, 2 obstrucciones de intestino delgado y 1 úlcera anastomótica sintomática. CONCLUSIONES: En nuestros casos, la anticoagulación posoperatoria pudo iniciarse sin aumento del riesgo de sangrado en pacientes con antecedentes de TVE sometidos a cirugía bariátrica.

Protocol for the development and validation of a clinical measurement tool for fear of disease progression and recurrence in cardiac patients.

Introduction: One in two cardiac patients fear having another heart event or their heart condition getting worse. Research in other chronic illnesses demonstrates that screening for fear of progression and recurrence is vital for adequately addressing such concerns in clinical care. The current project aims to develop and validate a measure for fear of progression and recurrence in cardiac patients. Methods: The Fear of Cardiac Recurrence and Progression Scale (FCRP) will be developed through a multistep process. An initial item pool will be generated through a review of the literature and existing measures and consultation with and feedback from key informants. The item pool will be tested in a sample of over 250 adults who have ever had an acute coronary event, undergone cardiac surgery, or a chronic cardiac condition. Exploratory factor analysis will be used to identify the underlying factors, and Rasch analysis will be used to reduce the number of items. A short form version of the FCRP will be developed for use as a brief screening tool, informed by clinical relevance and Rasch psychometric indices. Discussion: While many cardiac patients experience fears related to the progression or recurrence of their illness, there remains the need for a validated tool with which these concerns can be identified and measured. It is expected that the design and validation of the FCRP will aid identification of cardiac patients suffering from clinically significant levels of fear of progression and recurrence and facilitate the design of tailored psychological interventions to target these fears.

Navigating the Aftermath: A Comprehensive Scoping Review on Follow-up Strategies After Kidney-sparing Surgery for Upper Tract Urothelial Carcinoma.

Background and objective: Upper tract urothelial carcinoma (UTUC) can be managed efficiently and safely through kidney-sparing surgery (KSS) in selected patient groups. However, the most effective and efficient postoperative surveillance strategy remains undetermined. We aimed to provide a comprehensive synopsis of the follow-up strategies and survival outcomes in patients diagnosed with UTUC treated by KSS. Methods: Following the systematic methodology outlined in the Preferred Reporting Items for Systematic Reviews and Meta-analyses Extension for Scoping Reviews, we conducted searches in four databases (MEDLINE [Ovid], Embase [Ovid], Cochrane Library, and Web of Science) up until December 11, 2023. Key findings and limitations: A total of 3121 articles underwent screening, of which 19 were selected for inclusion in this review. The follow-up schedules after KSS exhibited considerable variability among the included studies. Diagnostic modalities employed consisted of computed tomography urography (present in 84% of protocols), X urography (21%), ultrasound (21%), thoracic imaging (26%), voided urine cytology (89%), selective upper tract cytology (5.3%), cystoscopy (84%), and ureterorenoscopy (53%) at varying frequencies. At 5 yr of follow-up, the reported recurrence-free survival rate ranged from 30% to 86%, overall survival was 50-92%, and metastasis-free survival was 77-90%. Conclusions and clinical implications: This review unveils significant heterogeneity in clinical practices and survival outcomes, indicating disparities between real-world approaches and guideline recommendations. The lack of consensus on follow-up schemes is evident, emphasising the necessity for future initiatives aimed at developing a comprehensive protocol. Patient summary: This review shows significant heterogeneity in follow-up strategies after kidney-sparing surgery for upper tract urothelial carcinoma. A lack of evidence contributes to discrepancies between guidelines and real-world approaches. Thus, future endeavours should aim at establishing a comprehensive protocol.

Streamlining Research Metrics Compilation Reports: An Automated Approach Using Scopus and Clarivate APIs.

This article examines the development and implementation of a customized Python script utilizing the Elsevier Scopus and Clarivate Web of Science Journal Citation Reports Application Programming Interfaces (APIs). The aim was to streamline and expedite the labor-intensive process of collecting research metrics, which were traditionally compiled manually by librarians at the University of Miami Miller School of Medicine Louis Calder Memorial Library. The script significantly reduces the time and effort required to generate comprehensive reports on research productivity, thereby enabling more efficient resource allocation and aiding in faculty evaluations.

The extracellular serine protease from Staphylococcus epidermidis elicits a type 2-biased immune response in atopic dermatitis patients.

Background: Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease with skin barrier defects and a misdirected type 2 immune response against harmless antigens. The skin microbiome in AD is characterized by a reduction in microbial diversity with a dominance of staphylococci, including Staphylococcus epidermidis (S. epidermidis). Objective: To assess whether S. epidermidis antigens play a role in AD, we screened for candidate allergens and studied the T cell and humoral immune response against the extracellular serine protease (Esp). Methods: To identify candidate allergens, we analyzed the binding of human serum IgG4, as a surrogate of IgE, to S. epidermidis extracellular proteins using 2-dimensional immunoblotting and mass spectrometry. We then measured serum IgE and IgG1 binding to recombinant Esp by ELISA in healthy and AD individuals. We also stimulated T cells from AD patients and control subjects with Esp and measured the secreted cytokines. Finally, we analyzed the proteolytic activity of Esp against IL-33 and determined the cleavage sites by mass spectrometry. Results: We identified Esp as the dominant candidate allergen of S. epidermidis. Esp-specific IgE was present in human serum; AD patients had higher concentrations than controls. T cells reacting to Esp were detectable in both AD patients and healthy controls. The T cell response in healthy adults was characterized by IL-17, IL-22, IFN-γ, and IL-10, whereas the AD patients' T cells lacked IL-17 production and released only low amounts of IL-22, IFN-γ, and IL-10. In contrast, Th2 cytokine release was higher in T cells from AD patients than from healthy controls. Mature Esp cleaved and activated the alarmin IL-33. Conclusion: The extracellular serine protease Esp of S. epidermidis can activate IL-33. As an antigen, Esp elicits a type 2-biased antibody and T cell response in AD patients. This suggests that S. epidermidis can aggravate AD through the allergenic properties of Esp.

Pharmacotherapy for older people with obesity.

Rates of obesity continue to rise, including in older adults. Use of medication for obesity in the elderly has been considered controversial, due to concerns around potential progression of age-related sarcopenia and a general lack of evidence for its use in this age group. Within this review, we describe the general considerations when prescribing obesity pharmacotherapy for older adults living with obesity. We evaluate in detail the anti-obesity medications currently licenced in Europe, with emphasis on the available efficacy, safety and cardiovascular outcome data gathered from study of older people. Finally, we discuss future directions and avenues of research.

Cost-Effectiveness of Unselected Multigene Germline and Somatic Genetic Testing for Epithelial Ovarian Cancer.

BACKGROUND: Parallel panel germline and somatic genetic testing of all patients with ovarian cancer (OC) can identify more pathogenic variants (PVs) that would benefit from PARP inhibitor (PARPi) therapy, and allow for precision prevention in unaffected relatives with PVs. In this study, we estimate the cost-effectiveness and population impact of parallel panel germline and somatic BRCA testing of all patients with OC incorporating PARPi therapy in the United Kingdom and the United States compared with clinical criteria/family history (FH)-based germline BRCA testing. We also evaluate the cost-effectiveness of multigene panel germline testing alone. METHODS: Microsimulation cost-effectiveness modeling using data from 2,391 (UK: n=1,483; US: n=908) unselected, population-based patients with OC was used to compare lifetime costs and effects of panel germline and somatic BRCA testing of all OC cases (with PARPi therapy) (strategy A) versus clinical criteria/FH-based germline BRCA testing (strategy B). Unaffected relatives with germline BRCA1/BRCA2/RAD51C/RAD51D/BRIP1 PVs identified through cascade testing underwent appropriate OC and breast cancer (BC) risk-reduction interventions. We also compared the cost-effectiveness of multigene panel germline testing alone (without PARPi therapy) versus strategy B. Unaffected relatives with PVs could undergo risk-reducing interventions. Lifetime horizon with payer/societal perspectives, along with probabilistic/one-way sensitivity analyses, are presented. Incremental cost-effectiveness ratio (ICER) and incremental cost per quality-adjusted life year (QALY) gained were compared with £30,000/QALY (UK) and $100,000/QALY (US) thresholds. OC incidence, BC incidence, and prevented deaths were estimated. RESULTS: Compared with clinical criteria/FH-based BRCA testing, BRCA1/BRCA2/RAD51C/RAD51D/BRIP1 germline testing and BRCA1/BRCA2 somatic testing of all patients with OC incorporating PARPi therapy had a UK ICER of £51,175/QALY (payer perspective) and £50,202/QALY (societal perspective) and a US ICER of $175,232/QALY (payer perspective) and $174,667/QALY (societal perspective), above UK/NICE and US cost-effectiveness thresholds in the base case. However, strategy A becomes cost-effective if PARPi costs decrease by 45% to 46% or if overall survival with PARPi reaches a hazard ratio of 0.28. Unselected panel germline testing alone (without PARPi therapy) is cost-effective, with payer-perspective ICERs of £11,291/QALY or $68,808/QALY and societal-perspective ICERs of £6,923/QALY or $65,786/QALY. One year's testing could prevent 209 UK BC/OC cases and 192 deaths, and 560 US BC/OC cases and 460 deaths. CONCLUSIONS: Unselected panel germline and somatic BRCA testing can become cost-effective, with a 45% to 46% reduction in PARPi costs. Regarding germline testing, unselected panel germline testing is highly cost-effective and should replace BRCA testing alone.

Healthcare cost expenditure for robotic versus laparoscopic liver resection: a bottom-up economic evaluation.

BACKGROUND: Minimally invasive liver surgery (MILS) is increasingly performed via the robot-assisted approach but may be associated with increased costs. This study is a post-hoc comparison of healthcare cost expenditure for robotic liver resection (RLR) and laparoscopic liver resection (LLR) in a high-volume center. METHODS: In-hospital and 30-day postoperative healthcare costs were calculated per patient in a retrospective series (October 2015-December 2022). RESULTS: Overall, 298 patients were included (143 RLR and 155 LLR). Benefits of RLR were lower conversion rate (2.8% vs 12.3%, p = 0.002), shorter operating time (167 min vs 198 min, p = 0.044), and less blood loss (50 mL vs 200 mL, p < 0.001). Total per-procedure costs of RLR (€10260) and LLR (€9931) were not significantly different (mean difference €329 [95% bootstrapped confidence interval (BCI) €-1179-€2120]). Lower costs with RLR due to shorter surgical and operating room time were offset by higher disposable instrumentation costs resulting in comparable intraoperative costs (€5559 vs €5247, mean difference €312 [95% BCI €-25-€648]). Postoperative costs were similar for RLR (€4701) and LLR (€4684), mean difference €17 [95% BCI €-1357-€1727]. When also considering purchase and maintenance costs, RLR resulted in higher total per-procedure costs. DISCUSSION: In a high-volume center, RLR can have similar per-procedure cost expenditure as LLR when disregarding capital investment.

"Catheter replacement in catheter-associated urinary tract infection: current state of evidence ".

PURPOSE: Catheter associated urinary tract infection (CAUTI) is the most common healthcare associated infection. A significant knowledge gap exists regarding the necessity of catheter replacement as part of CAUTI treatment. Current guidelines recommend replacement for faster recovery and to prevent recurrences, but adherence is low. In this systematic review, we aimed to assess the available evidence regarding catheter replacement for CAUTI. MATERIALS AND METHODS: Eligible studies investigated the effect of catheter replacement in CAUTI on clinical outcomes and/or recurrence rates, irrespective of catheter type or setting. We searched electronic literature databases from inception to October 15th, 2023. Information was extracted regarding setting, eligibility criteria, definition of CAUTI, timing of replacement, and outcomes. RESULTS: Of the 257 identified studies, four were considered relevant and included. Two were randomized controlled trials (RCT) and two were observational studies. One RCT showed higher rates of clinical recovery and lower recurrence rates in the replacement group, while results of the other RCT favoured retainment, with a lower recurrence rate in the retainment group, although longer antimicrobial treatment in this group. Two observational studies were inconclusive. CONCLUSIONS: Current guidelines rely heavily on recommendations from a single study, emphasizing the need for further research. The burden of catheter replacement, including patient discomfort and resource impact, warrants careful consideration. A randomized trial is essential to provide more evidence on the effect of catheter replacement on clinical outcomes including CAUTI recurrence.