Universal Genetic Testing for Newly Diagnosed Invasive Breast Cancer.

Importance: Between 5% and 10% of breast cancer cases are associated with an inherited germline pathogenic or likely pathogenic variant (GPV) in a breast cancer susceptibility gene (BCSG), which could alter local and systemic therapy recommendations. Traditional genetic testing criteria misses a proportion of these cases. Objective: To evaluate the prevalence and clinicopathological associations of GPVs in 2 groups of BCSGs among an ethnically diverse cohort of women with newly diagnosed breast cancer. Design, Setting, and Participants: This cross-sectional study, conducted at 3 Montreal hospitals between September 2019 and April 2022, offered universal genetic counseling and testing to all women with a first diagnosis of invasive breast cancer. Women were offered an obligatory primary panel of BRCA1, BRCA2, and PALB2 (B1B2P2) and an optional secondary panel of 14 additional BCSGs. Eligible participants were women 18 years of age or older who received a diagnosis of a first primary invasive breast cancer not more than 6 months before the time of referral to the study. Data were analyzed from November 2023 to June 2024. Results: Of 1017 referred patients, 805 were eligible and offered genetic counseling and testing, and 729 of those 805 (90.6%) consented to be tested. The median age at breast cancer diagnosis was 53 years (range, 23-91 years), and 65.4% were White and of European ancestry. Fifty-four GPVs were identified in 53 patients (7.3%), including 39 patients (5.3%) with B1B2P2 and 15 patients (2.1%) with 6 of the 14 secondary panel BCSGs (ATM, BARD1, BRIP1, CHEK2, RAD51D, and STK11). On multivariable analysis, clinical factors independently associated with B1B2P2-positive status included being younger than 40 years of age at diagnosis (odds ratio [OR], 6.83; 95% CI, 2.22-20.90), triple-negative breast cancer (OR, 3.19; 95% CI, 1.20-8.43), high grade disease (OR, 1.68; 95% CI, 1.05-2.70), and family history of ovarian cancer (OR, 9.75; 95% CI, 2.65-35.85). Of 39 B1B2P2-positive patients, 13 (33.3%) were eligible for poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors. Conclusions and Relevance: In this cross-sectional universal genetic testing study of women with newly diagnosed invasive breast cancer, the prevalence of GPVs was 7.3%, with 5.3% of patients testing positive for B1B2P2. Among B1B2P2-women women, one-third were eligible for PARP inhibitors.

Learning, internalisation and integration of the COVID-19 pandemic in healthcare workers: A qualitative document analysis.

The COVID-19 pandemic triggered an unprecedented health crisis that impacted healthcare systems worldwide. This study explores how Spanish healthcare workers learned, internalised and integrated values and work behaviours during the COVID-19 pandemic and their impact on the personal sphere. This documentary research, using images, narratives and audiovisual content, was framed within the interpretative hermeneutic paradigm. Categories and subcategories emerged after a final theoretical sampling that focused on the analysis. Data triangulation between researchers favoured theoretical saturation. A total of 117 images and 27 texts were selected. The analysis identified three stages: bewilderment, seeking functionality in the chaos and integrating chaos into care. The data reflects how the need for security and knowledge, and the exhaustion and frustration caused by the initial working conditions, prompted adaptive responses. These responses involved focusing on problem-solving and strengthening group sentiments and solidarity. Subsequently, the data indicates the acceptance of new structural, organisational and communication aspects. The findings of the analysis will contribute towards finding a framework that can help understand community health crisis events.

The Relationship Between Loneliness, Social Isolation, and Inflammatory Bowel Disease: A Narrative Review.

BACKGROUND: There is clear evidence that loneliness and social isolation have profound health consequences. Documenting the associations of loneliness and social isolation with inflammatory bowel disease (IBD) symptoms, disease severity, and treatment outcomes could meaningfully improve health and quality of life in patients with IBD. PURPOSE: The purpose of this narrative review was to synthesize the empirical evidence on the associations of loneliness and social isolation with IBD symptoms, disease severity, and treatment outcomes. METHODS: Articles were identified through systematic database searches. Quantitative studies that enrolled patients with IBD were included if they examined one of the following outcomes: (a) loneliness or social isolation or (b) IBD-related symptoms, disease severity, or treatment outcomes. RESULTS: We identified 1,816 articles after removing duplicates. Of the 18 studies that met the inclusion criteria, 15 were cross-sectional and 3 were longitudinal. Overall, studies found that loneliness was associated with greater disease activity, functional gastrointestinal symptoms, IBD illness stigma, depressive symptoms, daily IBD symptom burden, reduced resilience, and poorer quality of life. Social isolation was associated with higher prevalence of IBD hospitalizations, premature mortality, and depression. CONCLUSIONS: Findings suggest that loneliness and social isolation are associated with poorer health and quality of life in patients with IBD. Prospective cohort studies examining the biobehavioral mechanisms accounting for the associations of loneliness and social isolation with IBD-related outcomes are needed to guide the development of psychological interventions for individuals living with IBD.

This article explores the connection between loneliness, social isolation, and health outcomes in people with inflammatory bowel disease (IBD). While loneliness and social isolation are known to negatively impact health in other chronic diseases, their specific effects within IBD have been far less studied. This study conducted a narrative review and found that loneliness is linked to more severe IBD symptoms, including increased disease activity, greater gastrointestinal distress, and lower quality of life. Similarly, social isolation is associated with higher rates of IBD-related hospitalizations, depression, and reduced coping abilities. These findings highlight the importance of addressing loneliness and social isolation in patients with IBD. Doing so may be key to developing psychological interventions that improve the well-being and health of those living with IBD.

Imaging the adsorption sites of organic molecules on metallic surfaces by an adaptive tunnelling current feedback.

Atomic force microscopy (AFM) allows submolecular resolution imaging of organic molecules deposited on a surface by using CO-functionalized qPlus sensors under ultrahigh vacuum and low temperature conditions. However, the experimental determination of the adsorption sites of these organic molecules requires the precise identification of the atomic structure of the surface on which they are adsorbed. Here, we develop an automation method for AFM imaging that provides in a single image both, submolecular resolution on organic molecules and atomic resolution on the surrounding metallic surface. The method is based on an adaptive tunnelling current feedback system that is regulated according to the response of the AFM observables, which guarantees that both the molecules and the surface atoms are imaged under optimum conditions. Therewith, the approach is suitable for imaging adsorption sites of several adjacent and highly mobile molecules such as 2-iodotriphenylene on Ag(111) in a single scan. The proposed method with the adaptive feedback system facilitates statistical analysis of molecular adsorption geometries and could in the future contribute to autonomous AFM imaging as it adapts the feedback parameters depending on the sample properties.

Preventing Cognitive Decline in Older Latino Adults With HIV Through a Culturally Tailored Health Promotion Intervention: Protocol for a Single-Arm Pilot Trial.

BACKGROUND: Older Latino adults with HIV are at increased risk for mild cognitive impairment and earlier onset of aging-related cognitive decline. Improvements in cognitive functioning and cognitive outcomes are possible among people with HIV who adopt health promotion behaviors. However, health promotion interventions for older Latino adults with HIV have not been extensively used or widely recognized as viable treatment options. Happy Older Latinos are Active (HOLA) is a multicomponent, health promotion intervention that is uniquely tailored for older Latino adults with HIV. OBJECTIVE: This study aims to (1) determine the feasibility and acceptability of an adapted version of HOLA aimed at improving cognitive functioning among older Latino adults with HIV; (2) explore whether HOLA will produce changes in cognitive functioning; (3) explore whether HOLA will produce changes in activity, psychosocial functioning, or biomarkers of cognition; and (4) explore whether changes in activity, psychosocial functioning or cognitive biomarkers correlate with changes in cognition, while accounting for genetic risk for dementia. METHODS: A single-arm pilot trial with 30 Latino (aged 50 years and older) men and women with HIV was conducted to assess feasibility, acceptability, and preliminary effects on cognition. Participants were assessed at 2 time points (baseline and postintervention) on measures of neurocognitive and psychosocial functioning. In addition, blood samples were collected to determine biomarkers of cognition at baseline and postintervention. Successful recruitment was defined as meeting 100% of the targeted sample (N=30), with 20% (n=6) or less of eligible participants refusing to participate. Adequate retention was defined as 85% (n=25) or more of participants completing the postintervention assessment and acceptability was defined as 80% (n=38) or more of sessions attended by participants. RESULTS: Participant recruitment began on February 22, 2022, and was completed on August 15, 2022. The last study visit took place on February 20, 2023. Data analysis is currently ongoing. CONCLUSIONS: Encouraging findings from this exploratory study may provide a blueprint for scaling up the HOLA intervention to a larger cohort of older Latino adults with HIV who may be currently experiencing or are at risk for HIV-related cognitive challenges. TRIAL REGISTRATION: ClinicalTrials.gov NCT04791709; https://clinicaltrials.gov/study/NCT04791709. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/55507.

Obesity and the gut microbiota: implications of neuroendocrine and immune signaling.

Obesity is a major health challenge due to its high prevalence and associated comorbidities. The excessive intake of a diet rich in fat and sugars leads to a persistent imbalance between energy intake and energy expenditure, which increases adiposity. Here, we provide an update on relevant diet-microbe-host interactions contributing to or protecting from obesity. In particular, we focus on how unhealthy diets shape the gut microbiota and thus impact crucial intestinal neuroendocrine and immune system functions. We describe how these interactions promote dysfunction in gut-to-brain neuroendocrine pathways involved in food intake control and postprandial metabolism and elevate the intestinal proinflammatory tone, promoting obesity and metabolic complications. In addition, we provide examples of how this knowledge may inspire microbiome-based interventions, such as fecal microbiota transplants, probiotics, and biotherapeutics, to effectively combat obesity-related disorders. We also discuss the current limitations and gaps in knowledge of gut microbiota research in obesity.

Substance use moderates relationships between apolipoprotein E genotype, hepatitis C, cognition, and depression in Miami Adult Studies on HIV (MASH) participants.

The impact of APOE on HIV and HCV disease course, cognition, and memory has been understudied in minoritized populations. This study examined whether scores on cognition and depression measures differed by APOE ε4 carrier status while considering HCV and HIV seropositivity and whether these measures were moderated by substance use. A retrospective analysis examined cognitive and psychological data from participants (n = 493) in the Miami Adult Studies on HIV (MASH) cohort. APOE genotyping was performed on banked blood samples. Multiple linear regression was employed to examine differences across participants living with and without HIV and/or HCV and by APOE ε4 genotype. APOE ε4 carriers living with HCV who used cannabis had higher depression scores than non-ε4 carriers, while nonusers had fewer depressive symptoms. APOE ε4 carriers living with HCV had better cognition scores after adjusting for cocaine, opiate, and cannabis use than non-ε4 carriers. Scores on cognitive and depression measures did not differ between APOE ε4 carriers and non-ε4 carriers in participants living with HIV, and substance use did not moderate this relationship. This study was the first of its kind to examine substance use as a moderator for cognition and depression among individuals with HIV and/or HCV stratified by APOE genotype. Findings support further research evaluating the frequency and duration of 1) domains of cognitive functioning impacted by APOE genotype relevant to substance use and 2) the influence of substance use on cognitive and depressive outcomes among adults living with HIV and HCV, HIV, or HCV.

Traditional Cardiovascular Risk Factors Associated with Diagonal Earlobe Crease (Frank Sign) in Mexican Adults: Aging, Obesity, Arterial Hypertension, and Being Male Are the Most Important.

Introduction: Cardiovascular risk factors such as obesity, type 2 diabetes, hypertension, smoking, and dyslipidemia enfold heart disease morbimortality. Diagonal earlobe crease has been proposed as a prognostic marker of extension and severity of illness in patients with acute coronary syndrome. But its usefulness remains unclear in patients with or without coronary disease. Methods: A case-control study was carried out on a total of 805 patients with and without cardiovascular risk factors or acute coronary syndrome. Univariate and multivariate binary logistic regression analyses were used to determine the probability of having diagonal earlobe crease with the presence of cardiovascular risk factors and acute coronary syndrome. Data were summarized as odds ratio with 95% confidence intervals and P values. Results: An unadjusted (univariate) analysis showed that being male, being older than 55 years, obesity, type 2 diabetes mellitus, arterial hypertension, smoking, and dyslipidemia, as well as having acute coronary syndrome, were associated with the presence of diagonal earlobe crease. The multivariate analysis showed that men (OR 1.6, 95% IC 1.1-2.4, P=0.007), being over 55 years old (OR 4.8, 95% IC 3.2-7.2, P < 0.001), being obese (OR 2.1, 95% IC 1.4-3.1, P < 0.001), having arterial hypertension (1.5, 95% IC 1.1-2.3, P=0.025), or suffering from acute coronary syndrome (OR 5.3, 95% IC 2.5-11.1, P < 0.001), were independent factors associated with diagonal earlobe crease. The rest of cardiovascular risk factors were not relevant in the multivariate model. Conclusions: In Mexican adults, having an acute coronary syndrome is not the only factor associated with diagonal earlobe crease but also being a man, older than 55 years, having high blood pressure and obesity. Diagonal earlobe crease may simply be caused by changes in the skin and connective tissues of the ears because of the aging process, obesity, and/or being male. These factors, by themselves, enfold cardiovascular risk due to well-known pathophysiological causes.

Updating and profiling the natural product-likeness of Latin American compound libraries.

Compound databases of natural products play a crucial role in drug discovery and development projects and have implications in other areas, such as food chemical research, ecology and metabolomics. Recently, we put together the first version of the Latin American Natural Product database (LANaPDB) as a collective effort of researchers from six countries to ensemble a public and representative library of natural products in a geographical region with a large biodiversity. The present work aims to conduct a comparative and extensive profiling of the natural product-likeness of an updated version of LANaPDB and the individual ten compound databases that form part of LANaPDB. The natural product-likeness profile of the Latin American compound databases is contrasted with the profile of other major natural product databases in the public domain and a set of small-molecule drugs approved for clinical use. As part of the extensive characterization, we employed several chemoinformatics metrics of natural product likeness. The results of this study will capture the attention of the global community engaged in natural product databases, not only in Latin America but across the world.

Proteomic snapshot of saliva samples predicts new pathways implicated in SARS-CoV-2 pathogenesis.

BACKGROUND: Information on the microbiome's human pathways and active members that can affect SARS-CoV-2 susceptibility and pathogenesis in the salivary proteome is very scarce. Here, we studied a unique collection of samples harvested from April to June 2020 from unvaccinated patients. METHODS: We compared 10 infected and hospitalized patients with severe (n = 5) and moderate (n = 5) coronavirus disease (COVID-19) with 10 uninfected individuals, including non-COVID-19 but susceptible individuals (n = 5) and non-COVID-19 and nonsusceptible healthcare workers with repeated high-risk exposures (n = 5). RESULTS: By performing high-throughput proteomic profiling in saliva samples, we detected 226 unique differentially expressed (DE) human proteins between groups (q-value ≤ 0.05) out of 3376 unambiguously identified proteins (false discovery rate ≤ 1%). Major differences were observed between the non-COVID-19 and nonsusceptible groups. Bioinformatics analysis of DE proteins revealed human proteomic signatures related to inflammatory responses, central cellular processes, and antiviral activity associated with the saliva of SARS-CoV-2-infected patients (p-value ≤ 0.0004). Discriminatory biomarker signatures from human saliva include cystatins, protective molecules present in the oral cavity, calprotectins, involved in cell cycle progression, and histones, related to nucleosome functions. The expression levels of two human proteins related to protein transport in the cytoplasm, DYNC1 (p-value, 0.0021) and MAPRE1 (p-value, 0.047), correlated with angiotensin-converting enzyme 2 (ACE2) plasma activity. Finally, the proteomes of microorganisms present in the saliva samples showed 4 main microbial functional features related to ribosome functioning that were overrepresented in the infected group. CONCLUSION: Our study explores potential candidates involved in pathways implicated in SARS-CoV-2 susceptibility, although further studies in larger cohorts will be necessary.

Geriatrics and artificial intelligence in Spain (Ger-IA project): talking to ChatGPT, a nationwide survey.

PURPOSE: The purposes of the study was to describe the degree of agreement between geriatricians with the answers given by an AI tool (ChatGPT) in response to questions related to different areas in geriatrics, to study the differences between specialists and residents in geriatrics in terms of the degree of agreement with ChatGPT, and to analyse the mean scores obtained by areas of knowledge/domains. METHODS: An observational study was conducted involving 126 doctors from 41 geriatric medicine departments in Spain. Ten questions about geriatric medicine were posed to ChatGPT, and doctors evaluated the AI's answers using a Likert scale. Sociodemographic variables were included. Questions were categorized into five knowledge domains, and means and standard deviations were calculated for each. RESULTS: 130 doctors answered the questionnaire. 126 doctors (69.8% women, mean age 41.4 [9.8]) were included in the final analysis. The mean score obtained by ChatGPT was 3.1/5 [0.67]. Specialists rated ChatGPT lower than residents (3.0/5 vs. 3.3/5 points, respectively, P < 0.05). By domains, ChatGPT ​​scored better (M: 3.96; SD: 0.71) in general/theoretical questions rather than in complex decisions/end-of-life situations (M: 2.50; SD: 0.76) and answers related to diagnosis/performing of complementary tests obtained the lowest ones (M: 2.48; SD: 0.77). CONCLUSION: Scores presented big variability depending on the area of knowledge. Questions related to theoretical aspects of challenges/future in geriatrics obtained better scores. When it comes to complex decision-making, appropriateness of the therapeutic efforts or decisions about diagnostic tests, professionals indicated a poorer performance. AI is likely to be incorporated into some areas of medicine, but it would still present important limitations, mainly in complex medical decision-making.

Loneliness, Methamphetamine Use, and Cardiovascular Risk Factors Among Sexual Minority Men in the COVID-19 Era.

BACKGROUND: Important gaps exist in our understanding of loneliness and biobehavioral outcomes among sexual minority men (SMM), such as faster HIV disease progression. At the same time, SMM who use methamphetamine are approximately one-third more likely than non-users to develop cardiovascular disease. This study examined associations of loneliness, stimulant use, and cardiovascular risk in SMM with and without HIV. METHOD: Participants were enrolled from August 2020 to February 2022 in a 6-month prospective cohort study. The study leveraged self-report baseline data from 103 SMM, with a subset of 56 SMM that provided a blood sample to measure markers of cardiovascular risk. RESULTS: Loneliness showed negative bivariate associations with total cholesterol and LDL cholesterol in the cardiometabolic subsample (n = 56). SMM with methamphetamine use (t(101) = 2.03, p < .05; d = .42) and those that screened positive for a stimulant use disorder (t(101) = 2.07, p < .05; d = .46) had significantly higher mean loneliness scores. In linear regression analyses, negative associations of loneliness with LDL and total cholesterol were observed only among SMM who used methamphetamine. CONCLUSION: We observed lower cholesterol in SMM reporting loneliness and methamphetamine use. Thus, in addition to the observed associations of loneliness with cholesterol, there are important medical consequences of methamphetamine use including cardiovascular risk, higher HIV acquisition risk and progression, as well as stimulant overdose death. This cross-sectional study underscores the need for clinical research to develop and test interventions targeting loneliness among SMM with stimulant use disorders.

Opioid-Sparing Nonsteroid Anti-inflammatory Drugs Protocol in Patients Undergoing Intramedullary Nailing of Tibial Shaft Fractures: A Randomized Control Trial.

INTRODUCTION: Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective analgesics commonly used in fracture management. Although previously associated with delayed fracture healing, multiple studies have demonstrated their safety, with minimal risks of fracture healing. Given the current opioid crisis in the United States, alternate pain control modalities are essential to reduce opioid consumption. This study aims to determine whether the combination of oral acetaminophen and intravenous ketorolac is a viable alternative to opioid-based pain management in closed tibial shaft fractures treated with intramedullary nailing. METHODS: We conducted a randomized controlled trial evaluating postoperative pain control and opioid consumption in patients with closed tibial shaft fractures who underwent intramedullary nailing. Patients were randomized into an NSAID-based pain control group (52 patients) and an opioid-based pain control group (44 patients). Visual analog scale (VAS) scores and morphine milligram equivalents (MMEs) were evaluated at 12-hour postoperative intervals during the first 48 hours after surgery. Nonunion and delayed healing rates were recorded for both groups. RESULTS: A statistically significant decrease in MMEs was noted at every measured interval (12, 24, 36, and 48 hours) in the NSAID group compared with the opioid group ( P -value 0.001, 0.001, 0.040, 0.024, respectively). No significant change in visual analog scale scores was observed at 12, 36, and 48 hours between both groups ( P -value 0.215, 0.12, and 0.083, respectively). A significant decrease in VAS scores was observed at the 24-hour interval in the NSAID group compared with the opioid group ( P -value 0.041). No significant differences in union rates were observed between groups ( P -value 0.820). DISCUSSION: Using an NSAID-based postoperative pain protocol led to a decrease in opioid consumption without affecting pain scores or union rates. Owing to the minimal risk of short-term NSAID use, their role in the perioperative management of tibia shaft fractures is justified, especially when they reduce opioid consumption markedly. LEVEL OF EVIDENCE: Therapeutic Level I.

Barriers to Accessing and Engaging in HIV Preventive Care and Pre-Exposure Prophylaxis Experienced by Transgender Women in Florida.

BACKGROUND: PrEP, a biomedical HIV prevention option, continues to be underutilized among transgender women who could benefit from sustained use, especially women of color and those who identify as Latina and/or reside in the southeastern US. OBJECTIVE: We explored the barriers and facilitators experienced by transgender women who live in Florida regarding accessing, using, and/or staying on PrEP. METHODS: In-depth interviews and focus groups were conducted in either Spanish or English with adult transgender women living in Florida (N = 22). The interviews were audio-recorded, transcribed, and coded in ATLAS.ti using thematic analyses. RESULTS: The mean age of the participants was 42.2 years. Among the participants, 73% were Hispanic/Latina, 59% were foreign-born, and approximately one-third were living with HIV (but had past experience with PrEP). Transgender women cited the following barriers to accessing or considering PrEP: (1) costs and benefits of PrEP use; (2) under-representation in clinical trials resulting in unknown or misinformation regarding PrEP side effects; (3) chronic poverty; and (4) trauma and discrimination. Other stressors, such as behavioral healthcare needs, were identified. CONCLUSIONS: Our analysis revealed interlocking systems of oppression like transphobia, discrimination, and misgendering, which were common barriers experienced by our participants. These synergistically epidemic (i.e., syndemic) barriers contributed to their feelings of being systematically excluded in social spaces, research, public health planning and policies, laws, and social programs related to PrEP. These structural barriers are impediments to HIV preventive care but also act as a source of stress that contributes to mental health problems, financial vulnerability, substance abuse, and other deleterious health outcomes.

The Value of Subjective Olfactometry as a Predictive Biomarker of Neurodegenerative Diseases: A Systematic Review.

BACKGROUND: Olfactory disorders (ODs) are reported to be an early non-motor sign before the onset of deterioration in neurodegenerative diseases (NDs) such as Alzheimer's and Parkinson's. This systematic revision aims to review the current literature and the value of subjective olfactometry (SO) in the early diagnosis of cognitive decline and NDs. METHODS: A systematic literature review was conducted following the PRISMA framework. Four different authors reviewed six different databases. The main variables analyzed were olfactory function and cognitive status. The quality of results was evaluated using the Oxford Centre of Evidence-based Medicine Levels. RESULTS: Twenty-one cross-sectional and cohort studies and six meta-analyses were included. Most of them found an association between ODs and NDs. A prevalence of ODs greater than 80% was shown in Parkinson's disease, proportional to the severity of symptoms. In Alzheimer's, ODs were associated with early diagnosis and prognosis. All SO tests employed in the literature showed enough predictive value to correlate with early stages of cognitive decline. CONCLUSIONS: SO should be considered a pivotal tool when diagnosing NDs due to their association with early symptoms and prognosis. However, in the current literature, no firm consensus exists on the optimal SO tests and protocols that should be applied to the study of NDs, which prevents the interpretability and comparability of results among studies.

Long-Term Clinical Outcomes in Patients with Chronic Rhinosinusitis with Nasal Polyps Associated with Expanded Types of Endoscopic Sinus Surgery.

(1) Background: Surgical criteria for chronic rhinosinusitis with nasal polyps (CRSwNP) remain unresolved. This study addresses these discrepancies by comparing the clinical outcomes of expanded-functional endoscopic sinus surgeries (E-FESS) with more-limited FESS (L-FESS). (2) Methods: A database was analyzed retrospectively to compare surgical outcomes in CRSwNP patients who underwent E-FESS versus those subjected to L-FESS. Quality of life, endoscopic and radiological outcomes were compared at the baseline and two years after surgery. The clinical status of the responder was defined when a minimal clinically important difference of 12 points in SNOT-22 change was achieved. (3) Results: A total of 274 patients met the inclusion criteria and were analyzed; 111 underwent E-FESS and 163 were subjected to L-FESS. Both groups exhibited significant clinical improvements, although a greater magnitude of change in SNOT-22 (14.8 ± 4.8, p = 0.002) was shown after E-FESS. Higher significant improvements for endoscopic and radiological scores and lower surgical revision rates were also noted in the E-FESS group. (4) Conclusions: E-FESS provides better clinical outcomes and reduced revision surgery rates when compared to L-FESS in CRSwNP patients two years after surgery, irrespective of any comorbidity. Further randomized prospective studies are needed to comprehensively contrast these results.

Electroacupuncture efficacy in diabetic polyneuropathy: Study protocol for a double-blinded randomized controlled multicenter clinical trial.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is the most common complication of type 2 diabetes mellitus (T2DM); its diagnosis and treatment are based on symptomatic improvement. However, as pharmacological therapy causes multiple adverse effects, the implementation of acupunctural techniques, such as electroacupuncture (EA) has been suggested as an alternative treatment. Nonetheless, there is a lack of scientific evidence, and its mechanisms are still unclear. We present the design and methodology of a new clinical randomized trial, that investigates the effectiveness of EA for the treatment of DPN. METHODS: This study is a four-armed, randomized, controlled, multicenter clinical trial (20-week intervention period, plus 12 weeks of follow-up after concluding intervention). A total of 48 T2DM patients with clinical signs and symptoms of DPN; and electrophysiological signs in the Nerve Conduction Study (NCS); will be treated by acupuncture specialists in outpatient units in Mexico City. Patients will be randomized in a 1:1 ratio to one of the following four groups: (a) short fibre DPN with EA, (b) short fibre DPN with sham EA, (c) axonal DPN with EA and (d) axonal DPN with sham EA treatment. The intervention will consist of 32 sessions, 20 min each, per patient over two cycles of intervention of 8 weeks each and a mid-term rest period of 4 weeks. The primary outcome will be NCS parameters, and secondary outcomes will include DPN-related symptoms and pain by Michigan Neuropathy Screening Instrument (MNSI), Michigan Diabetic Neuropathy Score (MDNS), Dolour Neuropatique Score (DN-4), Semmes-Westein monofilament, Numerical Rating Scale (NRS) for pain assessment, and the 36-item Short Form Health Survey (SF-36). To measure quality of life and improve oxidative stress, the inflammatory response; and genetic expression; will be analysed at the beginning and at the end of treatment. DISCUSSION: This study will be conducted to compare the efficacy of EA versus sham EA combined with conventional diabetic and neuropathic treatments if needed. EA may improve NCS, neuropathic pain and symptoms, oxidative stress, inflammatory response, and genetic expression, and it could be considered a potential coadjutant treatment for the management of DPN with a possible remyelinating effect. TRIAL REGISTRATION: ClinicalTrials.gov. NCT05521737 Registered on 30 August 2022. International Clinical Trials Registry Platform (ICTRP) ISRCTN97391213 Registered on 26 September 2022 [2b].

Tissue-specific early and late activated lymphocytes immunophenotype in chronic rhinosinusitis with nasal polyps.

KEY POINTS: T-cell activation in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) is enriched by late cytotoxic T cells. The proportion of early and intermediate activated cytotoxic T cells decreases in nasal polyps of patients with CRSwNP. Our results identify late activated cytotoxic T cells as potential biomarkers or therapeutic targets for patients with CRSwNP.