Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy in cN0 Breast Cancer: Impact of HER2-Positive Status on Survival.

Objective: High rates of negative sentinel lymph node biopsy (SLNB) in clinically node-negative (cN0) breast cancer (BC) after neoadjuvant chemotherapy (NAC) have been described. These results are associated with triple-negative (TNBC) and human epidermal growth factor receptor 2 (HER2+) subtypes achieving pathologic complete response (pCR). This study evaluates predictive variables and survival in order to assess the possible omission of SLNB after NAC. Materials and Methods: Prospective study of women with cN0 BC treated with NAC and subsequent surgery, between April 2010 and May 2021. SLNB technique included, performing axillary lymphadenectomy in the absence of detection or SLNB-positivity. Multivariable logistic regression was used for analysis of NAC-response and SLNB-results in molecular subtypes: HR-/HER2+, TNBC, HR+/HER2- and HR+/HER2+. Kaplan-Meyer and log-rank were used for survival analysis. Results: A total of 179 patients (50.5±10.1 years) were included. Of these, 39.7% achieved pCR (ypT0/Tis). HR-negative subtypes had higher pCR rates (HR-/HER2+: 59.4%; TNBC: 53.4%), with no cases of SLNB-positive. With residual disease, HR-/HER2+ and TNBC showed low rates of SLNB-positivity (6.7% and 10.3%) versus HR+ (HR+/HER2+: 20%; HR+/HER2-: 44%; p<0.001). Multivariable analysis identified independent predictors of SLNB-negativity (p<0.0001) to be: HR- [odds ratio (OR)=0.15; 95% confidence interval (CI): 0.06-0.37; p = 0.0001], HER2+ (OR=0.34; 95% CI: 0.14-0.81; p = 0.015) and high-grade Nottingham (OR=0.42; 95% CI: 0.18-0.99; p = 0.048). Disease-free survival showed worse outcomes with SLNB-positivity (p<0.0001), HR+/HER2- (p = 0.0277), larger tumor size (p = 0.002) and residual disease after NAC (p<0.0001). Conclusion: Patient selection based on NAC response, molecular subtype, and survival outcomes is a priority for establishing individualized therapeutic strategies after NAC. Molecular subtypes with higher pCR rates and lower rates of SLNB-positivity could benefit from non-invasive strategies that include omission of SLNB.

Spatially preserved multi-region transcriptomic subtyping and biomarkers of chemoimmunotherapy outcome in extensive-stage small cell lung cancer.

BACKGROUND: Transcriptomic subtyping holds promise for personalized therapy in extensive-stage small-cell lung cancer (ES-SCLC). In this study, we aimed to assess intratumoral transcriptomic subtype diversity and to identify biomarkers of long-term chemoimmunotherapy benefit in human ES-SCLC. PATIENTS AND METHODS: We analyzed tumor samples from 58 ES-SCLC patients enrolled in two multicenter single-arm phase IIIb studies evaluating front-line chemoimmunotherapy in Spain: n=32 from the IMfirst trial, and n=26 from the CANTABRICO trial. We utilized the GeoMxTM DSP system to perform multi-region transcriptomic analysis. For subtype classification, we performed hierarchical clustering using the relative expression of ASCL1 (SCLC-A), NEUROD1 (SCLC-N), POU2F3 (SCLC-P), and YAP1 (SCLC-Y). RESULTS: Subtype distribution was similar between both cohorts, except for SCLC-P, not identified in the CANTABRICO_DSP cohort. A total of 44% of the patients in both cohorts had tumors with multiple co-existing transcriptional subtypes. Transcriptional subtypes or subtype heterogeneity were not associated with outcomes. Most potential targets did not show subtype-specific expression. Consistently in both cohorts, tumors from patients with long-term benefit (time to progression ³12 months) contained an IFNg-dominated mRNA profile, including enhanced capacity for antigen presentation. Hypoxia and glycolytic pathways were associated with resistance to chemoimmunotherapy. CONCLUSIONS: This work suggests that intratumoral heterogeneity, inconsistent association with outcome, and unclear subtype-specific target expression might be significant challenges for subtype-based precision oncology in SCLC. Pre-existing IFNg-driven immunity and mitochondrial metabolism seem correlates of long-term efficacy in this study, although the absence of a chemotherapy control arm precludes concluding that these are predictive features specific for immunotherapy.

Higher Synovial Immunohistochemistry Reactivity of IL-17A, Dkk1, and TGF-ß1 in Patients with Early Psoriatic Arthritis and Rheumatoid Arthritis Could Predict the Use of Biologics.

BACKGROUND: Delay in diagnosis and therapy in patients with arthritis commonly leads to progressive articular damage. The study aimed to investigate the immunohistochemical reactivity of synovial cytokines associated with inflammation and the bone erosives/neoformatives processes among individuals diagnosed with psoriatic arthritis (PsA), rheumatoid arthritis (RA), osteoarthritis (OA), and radiographic axial spondyloarthritis (r-axSpA), with the intention of identifying potential biomarkers. METHODS: Specimens were collected from the inflamed knee joints of patients referred for arthroscopic procedures, and the synovial tissue (ST) was prepared for quantifying protein expression through immunohistochemical analysis (% expressed in Ratio_Area-Intensity) for TGF-ß1, IL-17A, Dkk1, BMP2, BMP4, and Wnt5b. The collected data underwent thorough analysis and examination of their predictive capabilities utilising receiver operating characteristic (ROC) curves. RESULTS: Valid synovial tissue samples were acquired from 40 patients for IHC quantification analysis. Initially, these patients had not undergone treatment with biologics. However, after 5 years, 4 out of 13 patients diagnosed with PsA and two out of nine patients diagnosed with RA had commenced biologic treatments. Individuals with early PsA who received subsequent biologic treatment exhibited significantly elevated IHC reactivity in ST for TGF-ß1 (p = 0.015). Additionally, patients with both PsA and RA who underwent biologic therapy displayed increased IHC reactivity for IL-17A (p = 0.016), TGF-ß1 (p = 0.009), and Dkk1 (p = 0.042). ROC curve analysis of IHC reactivity for TGF-ß1, Dkk1, and IL-17A in the synovial seems to predict future treatment with biologics in the next 5 years with the area under the curve (AUC) of a combined sum of the three values: AUC: 0.828 (95% CI: 0.689-0.968; p 0.005) S 75% E 84.4%. CONCLUSIONS: Higher synovial immunohistochemistry reactivity of IL-17A, Dkk1, and TGF-ß1 in patients with early psoriatic arthritis and rheumatoid arthritis may serve as potential indicators for predicting the necessity of utilising biologic treatments.

Spiritual well-being, faith, meaning in life, peace, and purpose in life for cancer-related fatigue: systematic review with meta-analysis and meta-regressions.

BACKGROUND: Cancer-related fatigue is associated with spiritual distress. Spiritual well-being, characterized by the presence of factors such as meaning in life or purpose in life, seems to play an important role in the management of symptoms of cancer. Currently, the number of studies evaluating the association between cancer-related fatigue and spiritual well-being is increasing and no systematic review has been conducted. AIM: To summarize the association between cancer-related fatigue and spiritual well-being, faith, meaning in life, peace, and purpose in life. DESIGN: A systematic review with meta-analysis. DATA SOURCES: The CINAHL, Embase, PsycINFO, and PubMed databases were searched from inception to 9 October 2023. We considered studies evaluating the cross-sectional or longitudinal association between cancer-related fatigue and the spiritual factors above mentioned. The Joanna Briggs Institute Checklist for Analytical Cross-Sectional Studies and the Quality in Prognosis Studies tool assessed the methodological quality of cross-sectional and longitudinal studies, respectively. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system rated the certainty of evidence. Meta-analyses, meta-regressions, subgroup meta-analyses, and sensitivity analyses were conducted. RESULTS: A total of 13 studies were included and no longitudinal findings were found. One meta-analysis showed that cancer-related fatigue may be negatively correlated with spiritual well-being (r = - 0.37 (95%CI - 0.44 to - 0.28) p < 0.01). In addition, another meta-analysis found the correlation between cancer-related fatigue and faith was not statistically significant (r = - 0.25 (95%CI - 0.66 to 0.28) p = 0.36). CONCLUSIONS: Cancer-related fatigue may be correlated with spiritual well-being. However, the certainty of evidence was very low across the meta-analyzed outcomes. IMPLICATIONS FOR CANCER SURVIVORS: A negative correlation was observed between spiritual well-being and cancer-related fatigue.

Enduring Consensus Guidelines for Cervical Cancer Screening and Management: Introduction to the Scope and Process.

OBJECTIVES: The Enduring Consensus Cervical Cancer Screening and Management Guidelines (Enduring Guidelines) effort is a standing committee to continuously evaluate new technologies and approaches to cervical cancer screening, management, and surveillance. METHODS AND RESULTS: The Enduring Guidelines process will selectively incorporate new technologies and approaches with adequate supportive data to more effectively improve cancer prevention for high-risk individuals and decrease unnecessary procedures in low-risk individuals. This manuscript describes the structure, process, and methods of the Enduring Guidelines effort. Using systematic literature reviews and primary data sources, risk of precancer will be estimated and recommendations will be made based on risk estimates in the context of established risk-based clinical action thresholds. The Enduring Guidelines process will consider health equity and health disparities by assuring inclusion of diverse populations in the evidence review and risk assessment and by developing recommendations that provide a choice of well-validated strategies that can be adapted to different settings. CONCLUSIONS: The Enduring Guidelines process will allow updating existing cervical cancer screening and management guidelines rapidly when new technologies are approved or new scientific evidence becomes available.

Recommendations for Use of p16/Ki67 Dual Stain for Management of Individuals Testing Positive for Human Papillomavirus.

OBJECTIVES: The Enduring Consensus Cervical Cancer Screening and Management Guidelines Committee developed recommendations for dual stain (DS) testing with CINtec PLUS Cytology for use of DS to triage high-risk human papillomavirus (HPV)-positive results. METHODS: Risks of cervical intraepithelial neoplasia grade 3 or worse were calculated according to DS results among individuals testing HPV-positive using data from the Kaiser Permanente Northern California cohort and the STudying Risk to Improve DisparitiES study in Mississippi. Management recommendations were based on clinical action thresholds developed for the 2019 American Society for Colposcopy and Cervical Pathology Risk-Based Management Consensus Guidelines. Resource usage metrics were calculated to support decision-making. Risk estimates in relation to clinical action thresholds were reviewed and used as the basis for draft recommendations. After an open comment period, recommendations were finalized and ratified through a vote by the Consensus Stakeholder Group. RESULTS: For triage of positive HPV results from screening with primary HPV testing (with or without genotyping) or with cytology cotesting, colposcopy is recommended for individuals testing DS-positive. One-year follow-up with HPV-based testing is recommended for individuals testing DS-negative, except for HPV16- and HPV18-positive results, or high-grade cytology in cotesting, where immediate colposcopy referral is recommended. Risk estimates were similar between the Kaiser Permanente Northern California and STudying Risk to Improve DisparitiES populations. In general, resource usage metrics suggest that compared with cytology, DS requires fewer colposcopies and detects cervical intraepithelial neoplasia grade 3 or worse earlier. CONCLUSIONS: Dual stain testing with CINtec PLUS Cytology is acceptable for triage of HPV-positive test results. Risk estimates are portable across different populations.

Metabolic Recovery with the Persistence of Proinflammatory Leucocyte Dysfunction After Bariatric Intervention for Obesity.

PURPOSE: A suitable option for severe obesity treatment is a surgical approach. After surgery, metabolic markers and weight frequently return to adequate values; however, concerning systemic inflammatory mediators, the results are inconsistent. Furthermore, it has been suggested that leucocyte function may be affected even after weight normalization. This study aimed to determine if the surgical treatment of obesity influences the production of cytokines by LPS-stimulated as a function of leucocytes. MATERIALS AND METHODS: We performed a cross-sectional study that investigated the production of cytokines in response to lipopolysaccharide (LPS) along a kinetic of simulation by leucocytes recovered from individuals with normal weight (NW, n = 8), persons living with obesity (Ob, n = 7), persons living with obesity and diabetes mellitus (Ob-DM, n = 17), and persons that used to live with obesity who underwent bypass surgery (fOb + bypass, n = 8) and recover normal weigh. RESULTS: IL-6 levels were significantly higher in the Ob and fOb + bypass groups than in NW (p = 0.043). IL-10 secretion without LPS was significantly higher in the NW group than in the other groups explored (p < 0.05). When exposed to LPS, the IL-10 levels increased in all groups except the NW group. As also observed for IL-18 and IL-33, the secretion curve of the fOb + bypass group was more similar to the Ob group, even when they had reached normal weight, as opposed to the NW group. CONCLUSION: Our results show that in patients with fOb + bypass, inflammatory and anti-inflammatory cytokine production dynamics remain disrupted even with improved metabolic control and normal weight recovery.

Early hospital discharge through prediction of post-thyroidectomy hypoparathyroidism.

INTRODUCTION: Hypoparathyroidism is the most common postsurgical complication of total thyroidectomy. Furthermore, it is the main cause of prolonged hospitalisation after this procedure. OBJECTIVE: To predict the probability of post-thyroidectomy hypocalcaemia according to the levels of intact parathyroid hormone (iPTH), as well as to determine the needs for treatment with exogenous calcium according to the levels of serum calcium (Ca). MATERIALS AND METHODS: Retrospective study was carried out on patients who underwent total thyroidectomy between January 2017 and January 2020 at Los Arcos del Mar Menor University Hospital (HULAMM). iPTH and Ca levels ​​were measured at 4, 24 and 48 h after the surgery. Follow-up was 6 months. RESULTS: Ninety-four patients were operated on. Temporary and permanent postoperative hypoparathyroidism percentages were, respectively, 51.06% and 6.38%. iPTH level 24 h after the procedure was the most reliable predictor of post-thyroidectomy temporary hypoparathyroidism (Area Under the ROC Curve (AUC) = 0.933, p < .001). iPTH levels ​​≥29 pg/mL predicted normal parathyroid metabolism. CONCLUSIONS: The combined values of iPTH and Ca levels 24 h after thyroidectomy seems to be a reliable, safe and efficient method to control the post-thyroidectomy hypoparathyroidism. Our protocol could reduce the hospital stay of patients at low risk of hypocalcaemia, allowing them to be discharged from the hospital on the first postoperative morning and identifying patients at high risk of hypocalcaemia early.

The prevalence of anxiety and depression in cancer around the world: An overview of systematic reviews evaluating 128 meta-analyses.

BACKGROUND: This overview of systematic reviews with meta-analysis summarized the prevalence of anxiety and depression in different types of tumors around the world. METHODS: The quality of reviews was assessed. The degree of overlap between reviews was calculated. The regional prevalence of anxiety and depression was shown in the main text based on the World Health Organization regions. RESULTS: Twenty-five reviews including 128 meta-analyses of interest were selected. The pooled prevalence of anxiety in breast tumors was in Africa (19 %), the Americas (38 %), Eastern Mediterranean (56 %), Europe (38 %), South-East Asia (42 %), and Western Pacific (26 %). The pooled prevalence of depression in breast tumors was in Africa (40 %), the Americas (23-25 %), Eastern Mediterranean (49-51 %), Europe (27-29 %), South-East Asia (23-33 %), Western Pacific (29 %). The pooled prevalence of depression in digestive tumors was in the Americas (4-44 %), Eastern Mediterranean (42 %), Europe (20-27 %), South-East Asia (66 %), and Western Pacific (24-40 %). The pooled national prevalence of anxiety and depression was mainly evaluated in China and Iran. LIMITATIONS: Important methodological issues were identified. For example, no reviews judged the certainty of evidence. CONCLUSIONS: The Eastern Mediterranean region showed the highest prevalence of anxiety and depression for breast tumors. The South-East Asian region showed the highest prevalence of depression for digestive tumors. In these regions, many countries are considered low-income and middle-income countries. Further research funding would help increase the investigation on this topic, which may allow the development of preventive strategies that reduce the prevalence of anxiety and depression.

Novel insight into the lipid network of plasma extracellular vesicles reveal sex-based differences in the lipidomic profile of alcohol use disorder patients.

BACKGROUND: Alcohol use disorder (AUD) is one of the most common psychiatric disorders, with the consumption of alcohol considered a leading cause of preventable deaths worldwide. Lipids play a crucial functional role in cell membranes; however, we know little about the role of lipids in extracellular vesicles (EVs) as regulatory molecules and disease biomarkers. METHODS: We employed a sensitive lipidomic strategy to characterize lipid species from the plasma EVs of AUD patients to evaluate functional roles and enzymatic activity networks to improve the knowledge of lipid metabolism after alcohol consumption. We analyzed plasma EV lipids from AUD females and males and healthy individuals to highlight lipids with differential abundance and biologically interpreted lipidomics data using LINEX2, which evaluates enzymatic dysregulation using an enrichment algorithm. RESULTS: Our results show, for the first time, that AUD females exhibited more significant substrate-product changes in lysophosphatidylcholine/phosphatidylcholine lipids and phospholipase/acyltransferase activity, which are potentially linked to cancer progression and neuroinflammation. Conversely, AUD males suffer from dysregulated ceramide and sphingomyelin lipids involving sphingomyelinase, sphingomyelin phosphodiesterase, and sphingomyelin synthase activity, which relates to hepatotoxicity. Notably, the analysis of plasma EVs from AUD females and males demonstrates enrichment of lipid ontology terms associated with "negative intrinsic curvature" and "positive intrinsic curvature", respectively. CONCLUSIONS: Our methodological developments support an improved understanding of lipid metabolism and regulatory mechanisms, which contribute to the identification of novel lipid targets and the discovery of sex-specific clinical biomarkers in AUD.

Alcohol use disorder (AUD) is one of the most common psychiatric disorders, with the consumption of alcohol considered a leading cause of preventable deaths worldwide. Lipids play a crucial functional role in cell membranes; however, we know little about the role of lipids in extracellular vesicles (EVs) as regulatory molecules and disease biomarkers. We employed a sensitive lipidomic strategy to characterize lipid species from the plasma EVs of AUD patients to evaluate functional roles and enzymatic activity networks to improve the knowledge of lipid metabolism after alcohol consumption. We analyzed plasma EV lipids from AUD females and males and healthy individuals to highlight lipids with differential abundance and biologically interpreted lipidomics data using LINEX², which evaluates enzymatic dysregulation using an enrichment algorithm. Our results show, for the first time, that AUD females exhibited more significant substrate-product changes in lysophosphatidylcholine/phosphatidylcholine lipids and phospholipase/acyltransferase activity, which are potentially linked to cancer progression and neuroinflammation. Conversely, AUD males suffer from dysregulated ceramide and sphingomyelin lipids involving sphingomyelinase, sphingomyelin phosphodiesterase, and sphingomyelin synthase activity, which relates to hepatotoxicity. Notably, the analysis of plasma EVs from AUD females and males demonstrates enrichment of lipid ontology terms associated with "negative intrinsic curvature" and "positive intrinsic curvature", respectively. Our methodological developments support an improved understanding of lipid metabolism and regulatory mechanisms, which contribute to the identification of novel lipid targets and the discovery of sex-specific clinical biomarkers in AUD.

Introduction of Breast Implants through the Abdominal Route: Analysis of a Cohort.

BACKGROUND: Simultaneous breast reshaping and abdominoplasty offer patients the opportunity to undergo body reshaping in a single surgical session involving one anesthesia induction and one incision. In Latin America, abdominal implant placement is an infrequently used technique, likely because there is little evidence on its efficacy and safety. This study aimed to evaluate the efficacy and safety of implant placement through the abdominal route. METHODS: A retrospective cohort was analyzed, including 350 records of patients who underwent abdominal breast implants from 2013 to 2021 with a minimum follow-up of 1 year. The procedure was performed under epidural anesthesia. RESULTS: No intraoperative complications were reported. After a minimum 12-month follow-up, complications were detected in 5% of cases; the most frequent was asymmetry (4.6%), followed by abdominal migration and one case of symmastia. During the follow-up period, no capsular contracture was detected in any case. A satisfaction percentage of 98.1% was obtained. The only independent factor associated with complications was distance from the sternal notch to the nipple-areola complex greater than 21 cm. CONCLUSION: In this case series, mammaplasty with abdominal implant placement was an effective and safe procedure, with reduced risk of infection or capsular contracture and no scarring in or near the breasts for patients with properly selected comorbidities. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Acceptance and Commitment Therapy for Chronic Pain: An Overview of Systematic Reviews with Meta-Analysis of Randomized Clinical Trials.

This overview of reviews aimed to summarize the evidence from systematic reviews and meta-analyses of randomized clinical trials of the efficacy of acceptance and commitment therapy (ACT) for adults with chronic pain in relation to pain intensity, pain-related functioning, quality of life, and psychological factors. The Cumulative Index of Nursing and Allied Health Literature (CINAHL), Embase, PsycINFO, PubMed, and the Cochrane Library databases were searched from inception to July 2, 2023. AMSTAR 2 was used to assess the methodological quality of systematic reviews. The overlap among reviews was calculated. Nine reviews comprising 84 meta-analyses of interest were included. At post-treatment, some meta-analyses mainly showed that ACT can reduce depression symptoms, anxiety symptoms, psychological inflexibility, and pain catastrophizing; and can improve mindfulness, pain acceptance, and psychological flexibility. At three-month follow-up, ACT can reduce depression symptoms and psychological inflexibility, as well as improve pain-related functioning and psychological flexibility. At six-month follow-up, ACT can improve mindfulness, pain-related functioning, pain acceptance, psychological flexibility, and quality of life. At six-twelve-month follow-up, ACT can reduce pain catastrophizing and can improve pain-related functioning. Some methodological and clinical issues are identified in the reviews, such as a very high overlap between systematic reviews, the fact that the certainty of the evidence is often not rated and specific details needed to replicate the interventions reviewed are often not reported. Overall, however, randomized clinical trials and systematic reviews show that ACT can improve outcomes related to chronic pain (eg, pain-related functioning). Future systematic reviews should address the methodological and clinical concerns identified here to produce higher-quality findings. PERSPECTIVE: Despite certain methodological and clinical issues, randomized clinical trials and systematic reviews of ACT appear to show that it can improve outcomes related to chronic pain (eg, psychological factors).

Association between endogenous plasma beta-hydroxy-beta-methylbutyrate levels and frailty in community-dwelling older people.

BACKGROUND: Frailty is a key element in healthy ageing in which muscle performance plays a main role. Beta-hydroxy-beta-methylbutyrate (HMB) supplementation has shown favourable effects in modulating protein synthesis, improving muscle mass and function in interventional studies. Decreased age-related endogenous HMB levels have been shown in previous studies. The aim of the present study is to assess whether there is an association between endogenous plasma HMB levels and frailty. METHODS: Data from 1290 subjects (56.98% women; mean ± standard deviation age 74.6 ± 5.95 years) from the Toledo Study for Healthy Aging were obtained. Participants had their frailty status qualified according to Fried's Frailty Phenotype (FFP) score and the Frailty Trait Scale in its 12-domain version (FTS-12). Plasma HMB levels were analysed by an ultrahigh-performance liquid chromatography tandem mass spectrometry. Differences between groups (frail vs. non-frail) were tested using Mann-Whitney U test, Kruskal-Wallis test and chi-squared test. The association between HMB and frailty was assessed by multivariate linear and logistic regressions when frailty was analysed as continuous and binary, respectively. Models were adjusted by age, gender, comorbidity, body composition and protein intake. RESULTS: HMB levels were lower in those aged ≥75 years than in those aged 65-74 years, with an inverse linear relationship between age and HMB levels (ß = -0.031; P = 0.018), mainly accounted by males (ß = -0.062; P = 0.002). HMB levels were higher in men (0.238 ± 0.065 vs. 0.193 ± 0.051 ng/mL; P ≤ 0.001). HMB levels were significantly lower in frail than in non-frail individuals: 0.204 ± 0.058 versus 0.217 ± 0.063 ng/dL (P = 0.001) according to the FFP and 0.203 ± 0.059 versus 0.219 ± 0.063 ng/mL (P < 0.001) according to FTS-12. These differences showed a dose-dependent profile when we compared them by quintiles of HMB (P for trend: 0.022; 0.012 and 0.0004, respectively, for FFP, FTS-12 binary and FTS-12 continuous). Variables associated with low HMB levels were body mass index, strength, exhaustion and weight loss. Frailty was associated with HMB levels in all the adjusted models, including the fully adjusted ones, no matter the tool used (odds ratio: 0.45 [0.26, 0.77] for FFP and 0.36 [0.20, 0.63] for FTS-12 binary; ß = -4.76 [-7.29, -2.23] for FTS-12 score). This association was also observed when the analyses were done by quintiles, showing such association since Q4 (FFP), Q2 (FTS-12 binary) and Q3 (FTS-12 score). The associations were observed in the whole sample and in each gender. CONCLUSIONS: There is an inverse association between HMB levels and frailty status. These findings support the design of targeted clinical trials to evaluate the effect of HMB supplementation in older frail people with low HMB levels.

Safety of biologic therapy in combination with methotrexate in moderate to severe psoriasis: a cohort study from the BIOBADADERM registry.

BACKGROUND: Safety is an important consideration in decisions on treatment for patients with moderate-to-severe psoriasis and the study of drug safety is the main purpose of the BIOBADADERM registry. The combination of a biologic agent and a conventional systemic drug [generally methotrexate (MTX)] is a common treatment in clinical practice. However, there is a paucity of evidence from real-world practice on the safety of such combination regimens in the treatment of psoriasis. OBJECTIVES: The primary objective of this study was to ascertain whether the use of regimens combining biologic drugs with MTX in the management of moderate-to-severe psoriasis increases the risk of adverse events (AEs) or serious AEs (SAEs). We compared monotherapy using tumour necrosis factor (TNF), interleukin (IL)-17 and IL-23 inhibitors with the use of the same drugs in combination with MTX. METHODS: Using data from the BIOBADADERM registry, we compared biologic monotherapies with therapies that were combined with MTX. We estimated adjusted incidence rate ratios (aIRR) using a random effects Poisson regression with 95% confidence intervals for all AEs, SAEs, infections and serious infections and other AEs by system organ class. RESULTS: We analysed data from 2829 patients and 5441 treatment cycles, a total of 12 853 patient-years. The combination of a biologic with MTX was not associated with statistically significant increases in overall risk of AEs or SAEs in any treatment group. No increase in the total number of infections or serious infections in patients receiving combined therapy was observed for any group. However, treatment with a TNF inhibitor combined with MTX was associated with an increase in the incidence of gastrointestinal AEs (aIRR 2.50, 95% CI 1.57-3.98; P < 0.002). CONCLUSIONS: The risk of AEs and SAEs was not significantly increased in patients with moderate-to-severe psoriasis receiving different classes of biologic drugs combined with MTX compared with those on biologic monotherapy.

2019 ASCCP Risk-Based Management Consensus Guidelines: Updates Through 2023.

ABSTRACT: This Research Letter summarizes all updates to the 2019 Guidelines through September 2023, including: endorsement of the 2021 Opportunistic Infections guidelines for HIV+ or immunosuppressed patients; clarification of use of human papillomavirus testing alone for patients undergoing observation for cervical intraepithelial neoplasia 2; revision of unsatisfactory cytology management; clarification that 2012 guidelines should be followed for patients aged 25 years and older screened with cytology only; management of patients for whom colposcopy was recommended but not completed; clarification that after treatment for cervical intraepithelial neoplasia 2+, 3 negative human papillomavirus tests or cotests at 6, 18, and 30 months are recommended before the patient can return to a 3-year testing interval; and clarification of postcolposcopy management of minimally abnormal results.

Consensus document of the Spanish Society of Paediatric Infectious Diseases and the Advisory Committee on Vaccines of the Spanish Association of Pediatrics for vaccination of immunosuppressed individuals.

The number of people with immunosuppression is increasing considerably due to their greater survival and the use of new immunosuppressive treatments for various chronic diseases. This is a heterogeneous group of patients in whom vaccination as a preventive measure is one of the basic pillars of their wellbeing, given their increased risk of contracting infections. This consensus, developed jointly by the Sociedad Española de Infectología Pediátrica (Spanish Society of Pediatric Infectious Diseases) and the Advisory Committee on Vaccines of the Asociación Española de Pediatría (Spanish Association of Paediatrics), provides guidelines for the development of a personalised vaccination schedule for patients in special situations, including general recommendations and specific recommendations for vaccination of bone marrow and solid organ transplant recipients, children with inborn errors of immunity, oncologic patients, patients with chronic or systemic diseases and immunosuppressed travellers.

Rotation of the c-Ring Promotes the Curvature Sorting of Monomeric ATP Synthases.

ATP synthases are proteins that catalyse the formation of ATP through the rotatory movement of their membrane-spanning subunit. In mitochondria, ATP synthases are found to arrange as dimers at the high-curved edges of cristae. Here, a direct link is explored between the rotatory movement of ATP synthases and their preference for curved membranes. An active curvature sorting of ATP synthases in lipid nanotubes pulled from giant vesicles is found. Coarse-grained simulations confirm the curvature-seeking behaviour of rotating ATP synthases, promoting reversible and frequent protein-protein contacts. The formation of transient protein dimers relies on the membrane-mediated attractive interaction of the order of 1.5 kB T produced by a hydrophobic mismatch upon protein rotation. Transient dimers are sustained by a conic-like arrangement characterized by a wedge angle of θ ≈ 50°, producing a dynamic coupling between protein shape and membrane curvature. The results suggest a new role of the rotational movement of ATP synthases for their dynamic self-assembly in biological membranes.

Psychological and spiritual interventions to enhance meaning in adults diagnosed with cancer: a systematic review with meta-analysis and meta-regression.

OBJECTIVE: To summarize the evidence on the effectiveness that psychological and/or spiritual interventions may have to change the levels of meaning, measured with the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale (FACIT-Sp), in adults diagnosed with cancer. METHODS: Systematic review with meta-analysis and meta-regression. CINAHL (via EBSCOhost), Embase, PubMed, PsycINFO (via ProQuest), and the Cochrane Library were searched from inception to 21st October 2022. Manual searches were conducted. Only randomized clinical trials (RCTs) were included. The risk of bias was assessed with the Cochrane Risk of Bias tool 2. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach was used to judge the certainty of the evidence. RESULTS: Eight RCTs were included (N = 1682). Although some individual studies showed positive effects to enhance meaning using mindfulness or dignity therapy, the overall and individual meta-analyses showed a lack of effect of psychological and spiritual interventions in comparison to comparator interventions (MD (95%CI) = -0.19 (-0.45 to 0.06), p = 0.11, Tau2 = 0.0015, I2 = 2%). Publication bias was undetected (Egger's test = 0.35). Furthermore, no RCTs were judged to have a low risk of bias and the overall certainty of the evidence was judged as low. Meta-regression and subgroups meta-analyses also found possible sources of heterogeneity such as some cancer characteristics, the educational stage, or the religious affiliation. CONCLUSIONS: Despite some RCTs may show promising results following mindfulness or dignity therapy, no effects were observed in the meta-analysis. Moreover, important methodological and clinical concerns precluded us to make sound clinical recommendations with the available evidence. OPEN SCIENCE FRAMEWORK DOI REGISTRATION: https://doi.org/10.17605/OSF.IO/4YMTK .