Insulin resistance potentiates the effect of remnant cholesterol on cardiovascular mortality in individuals without diabetes.

BACKGROUND AND AIMS: Remnant cholesterol (RC) and insulin resistance (IR) have been independently associated with cardiovascular risk. Here, we evaluated the role of IR and RC on cardiovascular disease (CVD) mortality. METHODS: We conducted an analysis of 16,113 individuals ≥20 years without diabetes from the National Health and Nutrition Examination Survey (NHANES-III/IV). RC levels were calculated using total cholesterol, non-HDL-c, and LDL-c; IR was defined as HOMA2-IR≥2.5 and CVD mortality as a composite of cardiovascular and cerebrovascular mortality. Multiple linear regression was used to assess the relationship between HOMA2-IR and RC and Cox regression models to assess their joint role in CVD mortality. Causally ordered mediation models were used to explore the mediating role of IR in RC-associated CVD mortality. RESULTS: We identified an association between higher HOMA2-IR and higher RC levels. The effect of IR on CVD mortality was predominant (HR 1.32, 95%CI 1.18-1.48) and decreased at older ages (HR 0.934, 95%CI 0.918-0.959) compared to RC (HR 0.983, 95%CI 0.952-1.014). Higher risk of CVD mortality was observed in individuals with IR but normal RC (HR 1.37, 95%CI 1.25-1.50) and subjects with IR and high RC (HR 1.24, 95%CI 1.13-1.37), but not in subjects without IR but high RC. In mediation models, HOMA2-IR accounted for 78.2% (95%CI 28.11-98.89) of the effect of RC levels on CVD mortality. CONCLUSIONS: Our findings suggest that RC potentiates the risk of CVD mortality through its effect on whole-body insulin sensitivity, particularly among younger individuals.

London Protocol under water-perfused HRM in a healthy population, towards novel 3D manometric parameters in an evaluation of anorectal functional disorders.

BACKGROUND/AIM: London Protocol (LP) and Classification allied to high-resolution manometry (HRM) technological evolution has updated and enhanced the diagnostic armamentarium in anorectal disorders. This study aims to evaluate LP reproducibility under water-perfused HRM, provide normal data and new parameters based on 3D and healthy comparison studies under perfusional HRM. METHODS: Fifty healthy (25 F) underwent water-perfused 36 channel HRM based on LP at resting, squeeze, cough, push, and rectal sensory. Additional 3D manometric parameters were: pressure-volume (PV) 104mmHg2.cm (resting, short and long squeeze, cough); highest and lowest pressure asymmetry (resting, short squeeze, and cough). Complementary parameters (CP) were: resting (mean pressure, functional anal canal length); short squeeze (mean and maximum absolute squeeze pressure), endurance (fatigue rate, fatigue rate index, capacity to sustain); cough (anorectal gradient pressure); push (rectum-anal gradient pressure, anal canal relaxation percent); recto-anal inhibitory reflex (anal canal relaxation percent). RESULTS: No difference to genders: resting (LP, CP, and 3D); short squeeze (highest pressure asymmetry); endurance (CP); cough (CP, highest and lowest pressure asymmetry); push (gradient pressure); rectal sensory. Higher pressure in men: short squeeze (maximum incremental, absolute, and mean pressure, PV, lowest pressure asymmetry); long squeeze (PV); cough (anal canal and rectum maximum pressure, anal canal PV); push (anal canal and rectum maximum pressure). Anal canal relaxation was higher in women (push). CONCLUSIONS: LP reproducibility is feasible under water-perfused HRM, and comparative studies could bring similarity to dataset expansion. Novel 3D parameters need further studies with healthy and larger data to be validated and for disease comparisons. KEY POINTS: • London Protocol and Classification allied with the technological evolution of HRM (software and probes) has refined the diagnostic armamentarium in anorectal disorders. • Novel 3D and deepening the analysis of manometric parameters before the London Classification as a contributory diagnostic tool. • Comparison of healthy volunteers according to the London Protocol under a perfusional high-resolution system could establish equivalence points.

Diabetes subgroups and sociodemographic inequalities in Mexico: a cross-sectional analysis of nationally representative surveys from 2016 to 2022.

Background: Differences in the prevalence of four diabetes subgroups have been reported in Mexico compared to other populations, but factors that may contribute to these differences are poorly understood. Here, we estimate the prevalence of diabetes subgroups in Mexico and evaluate their correlates with indicators of social disadvantage using data from national representative surveys. Methods: We analyzed serial, cross-sectional Mexican National Health and Nutrition Surveys spanning 2016, 2018, 2020, 2021, and 2022, including 23,354 adults (>20 years). Diabetes subgroups (obesity-related [MOD], severe insulin-deficient [SIDD], severe insulin-resistant [SIRD], and age-related [MARD]) were classified using self-normalizing neural networks based on a previously validated algorithm. We used the density-independent social lag index (DISLI) as a proxy of state-level social disadvantage. Findings: We identified 4204 adults (median age: 57, IQR: 47-66, women: 64%) living with diabetes, yielding a pooled prevalence of 16.04% [95% CI: 14.92-17.17]. When stratified by diabetes subgroup, prevalence was 6.62% (5.69-7.55) for SIDD, 5.25% (4.52-5.97) for MOD, 2.39% (1.95-2.83) for MARD, and 1.27% (1.00-1.54) for SIRD. SIDD and MOD clustered in Southern Mexico, whereas MARD and SIRD clustered in Northern Mexico and Mexico City. Each standard deviation increase in DISLI was associated with higher odds of SIDD (OR: 1.12, 95% CI: 1.06-1.12) and lower odds of MOD (OR: 0.93, 0.88-0.99). Speaking an indigenous language was associated with higher odds of SIDD (OR: 1.35, 1.16-1.57) and lower odds of MARD (OR 0.58, 0.45-0.74). Interpretation: Diabetes prevalence in Mexico is rising in the context of regional and sociodemographic inequalities across distinct diabetes subgroups. SIDD is a subgroup of concern that may be associated with inadequate diabetes management, mainly in marginalized states. Funding: This research was supported by Instituto Nacional de Geriatría in Mexico.

Optimizing cryopreservation conditions for use of fucosylated human mesenchymal stromal cells in anti-inflammatory/immunomodulatory therapeutics.

Mesenchymal stem/stromal cells (MSCs) are being increasingly used in cell-based therapies due to their broad anti-inflammatory and immunomodulatory properties. Intravascularly-administered MSCs do not efficiently migrate to sites of inflammation/immunopathology, but this shortfall has been overcome by cell surface enzymatic fucosylation to engender expression of the potent E-selectin ligand HCELL. In applications of cell-based therapies, cryopreservation enables stability in both storage and transport of the produced cells from the manufacturing facility to the point of care. However, it has been reported that cryopreservation and thawing dampens their immunomodulatory/anti-inflammatory activity even after a reactivation/reconditioning step. To address this issue, we employed a variety of methods to cryopreserve and thaw fucosylated human MSCs derived from either bone marrow or adipose tissue sources. We then evaluated their immunosuppressive properties, cell viability, morphology, proliferation kinetics, immunophenotype, senescence, and osteogenic and adipogenic differentiation. Our studies provide new insights into the immunobiology of cryopreserved and thawed MSCs and offer a readily applicable approach to optimize the use of fucosylated human allogeneic MSCs as immunomodulatory/anti-inflammatory therapeutics.

The role of PCSK9 in metabolic dysfunction-associated steatotic liver disease and its impact on bariatric surgery outcomes.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely tied to obesity. The degree ranges from steatosis (MASL) and steatohepatitis (MASH) to liver cirrhosis. PCSK9 controls cholesterol and lipid particle transport to the liver. PCSK9 might interfere with the pathophysiology of MASLD and bariatric surgery (BS) outcomes of patients with MASLD. OBJECTIVES: Evaluate the relationship between serum and hepatic PCSK9 levels with the degree of MASLD and the metabolic outcome of BS. SETTING: University Hospital, Spain. METHODS: A total of 110 patients with obesity undergoing BS were classified according to liver histology as controls, MAS, and MASH. PCSK9 levels in serum were measured before and 6 months after BS using enzyme-linked immunosorbent assay. PCSK9 protein and mRNA levels in liver tissue were analyzed by immunohistochemistry and reverse transcriptase-polymerase chain reaction, respectively. RESULTS: Hepatic PCSK9 protein levels were diminished in MASL and MASH compared with patients without MASLD and showed a strong negative association with MASLD severity scores. Liver PCSK9 mRNA was higher in MASH compared with controls and MASL and showed positive associations with MASLD severity scores. There were no differences in serum PCSK9 pre or postBS between the groups. Pre- and postsurgery serum PCSK9 positively correlated with cholesterol fold-changes and body mass index (BMI), cholesterol, and low-density lipoprotein -cholesterol fold-changes, respectively. PCSK9 fold-change positively correlated with BMI changes and was the sole variable explaining BMI fold changes in a regression model. CONCLUSIONS: PCSK9 mRNA and protein in the liver might be associated with the degree of MASLD. Serum PCSK9 may be associated with cholesterol and/or BMI fold changes. Serum changes of PCSK9 after BS could explain BMI loss outcome.

Transcriptomic Profiling of Pleural Effusions: Differences in Malignant and Infectious Fluids.

Background and Objectives: Different cellular and molecular processes are involved in the production of malignant and infectious pleural effusions. However, the underlying mechanisms responsible for these differences or their consequences remain incompletely understood. The objective of this study was to identify differences in gene expression in pleural exudates of malignant and infectious aetiology and establish the possible different biological processes involved in both situations. Materials and Methods: RNA transcriptomic analysis was performed on 46 pleural fluid samples obtained during diagnostic thoracocenteses from 46 patients. There were 35 exudates (19 malignant and 16 infectious effusions) and 11 transudates that were used as a reference control group. Differential gene expression analysis for both exudative groups was identified. An enrichment score using the Human Kegg Orthology database was used for establishing the biological processes associated with malignant and infectious pleural effusions. Results: When comparing malignant exudates with infectious effusions, 27 differentially expressed genes with statistical significance were identified. Network analysis showed ten different biological processes for malignant and for infectious pleural effusions. In malignant fluids, processes related to protein synthesis and processing predominate. In infectious exudates, biological processes in connection with ATP production prevail. Conclusions: This study demonstrates differentially expressed genes in malignant and infectious pleural effusions, which could have important implications in the search for diagnostic or prognostic biomarkers. In addition, for the first time, biological processes involved in these two causes of pleural exudates have been described.

Radiotherapy Enhances Metastasis Through Immune Suppression by inducing PD-L1 and MDSC in distal sites.

PURPOSE: Radiotherapy (RT) is a widely employed anti-cancer treatment. Emerging evidence suggests that RT can elicit both tumor-inhibiting and tumor-promoting immune effects. This study is to investigate immune suppressive factors of radiotherapy. EXPERIMENTAL DESIGN: We used a heterologous two-tumor model in which adaptive concomitant immunity was eliminated. RESULTS: Through analysis of PD-L1 expression and MDSC frequencies using patient PBMC and murine two-tumor and metastasis model, we report that local irradiation can induce a systemic increase in MDSCs, as well as PD-L1 expression on DCs and myeloid cells, and thereby increase the potential for metastatic dissemination in distal, non-irradiated tissue. In a mouse model using two distinct tumors, we found that PD-L1 induction by ionizing radiation (IR) was dependent on elevated chemokine CXCL10 signaling. Inhibiting PD-L1 or MDSCs can potentially abrogate RT-induced metastasis and improve clinical outcomes for patients receiving RT. CONCLUSIONS: Blockade of PD-L1/CXCL10 axis or MDSC infiltration during radiation can enhance abscopal tumor control and reduce metastasis.

INFLUENCE OF NEOADJUVANT THERAPY ON THE RATIO OF LYMPH NODES.

BACKGROUND: To evaluate the relationship between the ratio of affected lymph nodes (LNR) and clinical and anatomopathological variables in patients with rectal adenocarcinoma submitted or not to neoadjuvant chemoradiotherapy. METHODS: The LNR was determined by dividing the number of compromised LNR by the total number of LNR dissected in the surgical specimen. Patients were divided into two groups: with QRT and without QRT. In each group, the relationship between LNR and the following variables was evaluated: degree of cell differentiation, depth of invasion in the rectal wall, angiolymphatic /perineural invasion, degree of tumor regression and occurrence of metastases. The LNR was evaluated in patients with more than 1, LNR (LNR >12) or less (LNR<12) in the surgical specimen with overall survival (OS) and disease-free survival (DFS). The results were expressed as the mean with the respective standard deviation. Qualitative variables were analyzed using Fisher's exact test, while quantitative variables were analyzed using the Kruskal -Wallis and Mann-Whitney tests. The significance level was 5%. RESULTS: We evaluated 282 patients with QRT and 114 without QRT, between 1995-2011. In the QRT Group, LNR showed a significant association with mucinous tumors (P=0.007) and degree of tumor regression (P=0.003). In both groups, LNR was associated with poorly differentiated tumors (P=0.001, P=0.02), presence of angiolymphatic invasion (P<0.0001 and P=0.01), perineural (P=0.0007, P=0.02), degree of rectal wall invasion (T3>T2; P<0.0001, P=0.02); Compromised LNR (P<0.0001, P<0.01), metastases (P<0.0001, P<0.01). In patients with QRT, LNR<12 was associated with DFS (5.889; 95%CI1.935-19.687; P=0.018) and LNR>12 with DFS and OS (17.984; 95%CI5.931-54.351; P<0.001 and 10.286; 95%CI 2.654-39.854; P=0.007, respectively). CONCLUSION: LNR was associated with histological aspects of poor prognosis, regardless of the use of QRT. In the occurrence of less than 12 evaluated LNR, the LNR was associated only with the DFS. BACKGROUND: • Assessment of the lymph nodes during pathological analysis of the surgical specimen is crucial to determine treatment and prognosis. BACKGROUND: • Neoadjuvance therapy reduces the number of lymph nodes, being lower than recommended, therefore the lymph node ratio can be an alternative analysis for a better prognosis.

Comparison of Clinical Outcomes in Patients with Active Cancer Receiving Rivaroxaban or Low-Molecular-Weight Heparin: The OSCAR-UK Study.

BACKGROUND: In most patients with cancer-associated venous thromboembolism (CT), essentially those not at high risk of bleeding, guidelines recommend treatment with direct oral anticoagulants as an alternative to low-molecular-weight heparins (LMWHs). Population-based studies comparing these therapies are scarce. OBJECTIVES: To compare the risk of venous thromboembolism (VTE) recurrences, significant bleeding, and all-cause mortality in patients with CT receiving rivaroxaban or LMWHs. PATIENTS/METHODS: Using UK Clinical Practice Research Datalink data from 2013 to 2020, we generated a cohort of patients with first CT treated initially with either rivaroxaban or LMWH. Patients were observed 12 months for VTE recurrences, significant bleeds (major bleeds or clinically relevant nonmajor bleeding requiring hospitalization), and all-cause mortality. Overlap weighted sub-distribution hazard ratios (SHRs) compared rivaroxaban with LMWH in an intention-to-treat analysis. RESULTS: The cohort consisted of 2,259 patients with first CT, 314 receiving rivaroxaban, and 1,945 LMWH, mean age 72.4 and 66.9 years, respectively. In the 12-month observational period, 184 person-years following rivaroxaban and 1,057 following LMWH, 10 and 66 incident recurrent VTE events, 20 and 102 significant bleeds, and 10 and 133 deaths were observed in rivaroxaban and LMWH users, respectively. The weighted SHR at 12 months for VTE recurrences in rivaroxaban compared with LMWH were 0.80 (0.37-1.73); for significant bleeds 1.01 (0.57-1.81); and for all-cause mortality 0.49 (0.23-1.06). CONCLUSION: Patients with CT, not at high risk of bleeding, treated with either rivaroxaban or LMWH have comparable effectiveness and safety outcomes. This supports the recommendation that rivaroxaban is a reasonable alternative to LMWH for the treatment of CT.

Balancing trade-offs: Enhanced carbon assimilation and productivity with reduced nutritional value in a well-watered C4 pasture under a warmer CO2-enriched atmosphere.

The concentration of atmospheric CO2 and temperature are pivotal components of ecosystem productivity, carbon balance, and food security. In this study, we investigated the impacts of a warmer climate (+2 °C above ambient temperature) and an atmosphere enriched with CO2 (600 ppm) on gas exchange, antioxidant enzymatic system, growth, nutritive value, and digestibility of a well-watered, managed pasture of Megathyrsus maximus, a tropical C4 forage grass, under field conditions. Elevated [CO2] (eC) improved photosynthesis and reduced stomatal conductance, resulting in increased water use efficiency and plant C content. Under eC, stem biomass production increased without a corresponding increase in leaf biomass, leading to a smaller leaf/stem ratio. Additionally, eC had negative impacts on forage nutritive value and digestibility. Elevated temperature (eT) increased photosynthetic gains, as well as stem and leaf biomass production. However, it reduced P and K concentration, forage nutritive value, and digestibility. Under the combined conditions of eC and eT (eCeT), eT completely offset the effects of eC on the leaf/stem ratio. However, eT intensified the effects of eC on photosynthesis, leaf C concentration, biomass accumulation, and nutritive value. This resulted in a forage with 12% more acid detergent fiber content and 28% more lignin. Additionally, there was a decrease of 19% in crude protein leading to a 15% decrease in forage digestibility. These changes could potentially affect animal feeding efficiency and feedback climate change, as ruminants may experience an amplification in methane emissions. Our results highlight the critical significance of conducting multifactorial field studies when evaluating plant responses to climate change variables.

IMPACT OF THE COVID-19 PANDEMIC ON THE EMERGENCY SURGICAL TREATMENT OF COLORECTAL CANCER.

BACKGROUND: Colorectal cancer (CRC) is the most common malignancy of the gastrointestinal tract and the third most common type of cancer worldwide. The COVID-19 pandemic, during the years 2020 and 2022, increased the difficulties in offering adequate early diagnosis and treatment to CRC patients worldwide. During this period, it was only possible to treat patients who evolved with complications, mainly intestinal obstruction and perforation. AIMS: To assess the impact of the COVID-19 pandemic on the treatment of patients with CRC. METHODS: A review of data from a total of 112 patients undergoing emergency surgical treatment due to complications of CRC was carried out. Of these, 78 patients underwent emergency surgery during the COVID-19 pandemic (2020/2021), and 34 were treated before the pandemic (2018/2019). Ethnic aspects, clinical symptoms, laboratory tests, histopathological variables, intra and postoperative complications, and 90-day postoperative follow-up were compared between the two groups. RESULTS: Between the years 2018 and 2019, 79.4% (27/34) of patients had intestinal obstruction, while 20.6% (7/34) had intestinal perforation. During the period of the COVID-19 pandemic (2020/2021), 1.3% (1/78) of patients underwent surgery due to gastrointestinal bleeding, 6.4% (5/78) due to intestinal perforation, and 92.3% (72/78) due to intestinal obstruction. No statistically significant differences were recorded between the two groups in ethnic aspects, laboratory tests, type of complications, number of lymph nodes resected, compromised lymph nodes, TNM staging, pre or intraoperative complications, length of stay, readmission, or mortality rate. When considering postoperative tumor staging, among patients operated on in 2018/2019, 44.1% were classified as stage III and 38.2% as stage IV, while during the pandemic period, 28.2% presented stage III and 51.3% stage IV, also without a statistically significant difference between the two periods. Patients operated on during the pandemic had higher rates of vascular, lymphatic and perineural invasion. CONCLUSIONS: The COVID-19 pandemic increased the rate of complications related to CRC when comparing patients treated before and during the pandemic. Furthermore, it had a negative impact on histopathological variables, causing worse oncological prognoses in patients undergoing emergency surgery.

Retinal response to systemic inflammation differs between sexes and neurons.

Background: Neurological dysfunction and glial activation are common in severe infections such as sepsis. There is a sexual dimorphism in the response to systemic inflammation in both patients and animal models, but there are few comparative studies. Here, we investigate the effect of systemic inflammation induced by intraperitoneal administration of lipopolysaccharide (LPS) on the retina of male and female mice and determine whether antagonism of the NLRP3 inflammasome and the extrinsic pathway of apoptosis have protective effects on the retina. Methods: A single intraperitoneal injection of LPS (5 mg/kg) was administered to two months old C57BL/6J male and female mice. Retinas were examined longitudinally in vivo using electroretinography and spectral domain optical coherence tomography. Retinal ganglion cell (RGC) survival and microglial activation were analysed in flat-mounts. Retinal extracts were used for flow cytometric analysis of CD45 and CD11b positive cells. Matched plasma and retinal levels of proinflammatory cytokines were measured by ELISA. Retinal function and RGC survival were assessed in animals treated with P2X7R and TNFR1 antagonists alone or in combination. Results: In LPS-treated animals of both sexes, there was transient retinal dysfunction, loss of vision-forming but not non-vision forming RGCs, retinal swelling, microglial activation, cell infiltration, and increases in TNF and IL-1ß. Compared to females, males showed higher vision-forming RGC death, slower functional recovery, and overexpression of lymphotoxin alpha in their retinas. P2X7R and TNFR1 antagonism, alone or in combination, rescued vision-forming RGCs. P2X7R antagonism also rescued retinal function. Response to treatment was better in females than in males. Conclusions: Systemic LPS has neuronal and sex-specific adverse effects in the mouse retina, which are counteracted by targeting the NLRP3 inflammasome and the extrinsic pathway of apoptosis. Our results highlight the need to analyse males and females in preclinical studies of inflammatory diseases affecting the central nervous system.

Exploratory analysis of the economically justifiable price of nirsevimab for healthy late-preterm and term infants in Colombia.

INTRODUCTION: Respiratory syncytial virus infection is the leading cause of lower respiratory infection globally. Recently, nirsevimab has been approved to prevent respiratory syncytial virus (RSV) infection. This study explores the economically justifiable price of nirsevimab for preventing RSV infection in Colombia's children under 1 year of age. MATERIALS AND METHODS: A static model was developed using the decision tree microsimulation to estimate the quality-adjusted costs and life years of two interventions: a single intramuscular dose of nirsevimab versus not applying nirsevimab. This analysis was made during a time horizon of 1 year and from a societal perspective. RESULTS: The annual savings in Colombia associated with this cost per dose ranged from U$ 2.5 to 4.1 million. Based on thresholds of U$ 4828, U$ 5128, and U$ 19 992 per QALY evaluated in this study, we established economically justifiable drug acquisition prices of U$ 21.88, U$ 25.04, and U$ 44.02 per dose of nirsevimab. CONCLUSION: the economically justifiable cost for nirsevimab in Colombia is between U$ 21 to U$ 44 per dose, depending on the willingness to pay used to decide its implementation. This result should encourage more studies in the region that optimize decision-making processes when incorporating this drug into the health plans of each country.

Prevalence and determinants of post-acute sequelae after SARS-CoV-2 infection (Long COVID) among adults in Mexico during 2022: a retrospective analysis of nationally representative data.

Background: Post-acute sequelae after SARS-CoV-2 infection (PASC) remains a concerning long-term complication of COVID-19. Here, we aimed to characterize the epidemiology of PASC in Mexico during 2022 and identify potential associations of covariates with PASC prevalence using nationally representative data. Methods: We analyzed data from the 2022 Mexican National Health and Nutrition Survey (ENSANUT) from 24,434 participants, representing 85,521,661 adults ≥20 years. PASC was defined using both the National Institute for Health and Care Excellence (NICE) definition and a PASC score ≥12. Estimates of PASC prevalence were stratified by age, sex, rural vs. urban setting, social lag quartiles, number of reinfections, vaccination status and periods of predominance of SARS-CoV-2 circulating variants. Determinants of PASC were assessed using log-binomial regression models adjusted by survey weights. Findings: Persistent symptoms after SARS-CoV-2 infection were reported by 12.44% (95% CI 11.89-12.99) of adults ≥20 years in Mexico in 2022. The most common persistent symptoms were fatigue, musculoskeletal pain, headache, cough, loss of smell or taste, fever, post-exertional malaise, brain fog, anxiety, and chest pain. PASC was present in 21.21% (95% CI 19.74-22.68) of subjects with previously diagnosed COVID-19. Over 28.6% of patients with PASC reported symptoms persistence ≥6 months and 14.05% reported incapacitating symptoms. Higher PASC prevalence was associated with SARS-CoV-2 reinfections, depressive symptoms and living in states with high social lag. PASC prevalence, particularly its more severe forms, decreased with COVID-19 vaccination and for infections during periods of Omicron variant predominance. Interpretation: PASC remains a significant public health burden in Mexico as the COVID-19 pandemic transitions into endemic. Promoting SARS-CoV-2 reinfection prevention and booster vaccination may be useful in reducing PASC burden. Funding: This research was supported by Instituto Nacional de Geriatría in Mexico.

Multidisciplinary Treatment in Patients with Craniofacial, Neurocognitive, and Neuromuscular Disorders with Obstructive Sleep Apnea: A Systematic Review of the Literature.

Obstructive sleep apnea (OSA) is a respiratory disorder that has a high prevalence in patients with craniofacial, neurocognitive, and neuromuscular disorders. Currently, the treatments for this population are diverse and depend on the individual conditions of the patient and the severity of the case. However, there are no multidisciplinary dental treatment guidelines. The aim of the present study was to determine the multidisciplinary dental treatment alternatives in patients with craniofacial, neurocognitive, and neuromuscular disorders with a diagnosis of OSA through evidence-based medicine. A systematic review of the literature has been performed by searching scientific articles in the PubMed, Cochrane, Ovid, ScienceDirect and Scopus databases, through controlled and uncontrolled language. Articles were classified according to the level of evidence and grades of recommendation through the Scottish Intercollegiate Guidelines Network. A total of 19,439 references were identified, of which 15 articles met the predetermined requirements to be included in the investigation. The articles included for this systematic review showed that mandibular distraction osteogenesis and adenotonsilectomy are the first-choice therapies for craniofacial and neurocognitive disorders. However, for neuromuscular disorders, the findings reported were not enough to provide information about surgical or nonsurgical alternatives. Despite the reported high frequency of OSA in those children with craniofacial, neurocognitive, and neuromuscular disorders, the evidence on the surgical and nonsurgical therapeutic success for OSA in these patients is scarce. It is necessary to perform future studies to investigate successful therapies for OSA in children. [Pediatr Ann. 2024;53(2):e62-e69.].

Adherence to a healthy lifestyle behavior composite score and cardiometabolic risk factors in Spanish children from the CORALS cohort.

To assess the associations between the adherence to a composite score comprised of 6 healthy lifestyle behaviors and its individual components with several cardiometabolic risk factors in Spanish preschool children. Cross-sectional analyses were conducted in 938 participants included in the CORALS cohort aged 3-6 years. Six recognized healthy lifestyle behaviors (breastfeeding, sleep duration, physical activity, screentime, adherence to the Mediterranean diet, and eating speed) were assessed in a composite score. Multiple linear and logistic regression models were fitted to assess the associations with cardiometabolic risk factors (weight status, waist circumference, fat mass index, blood pressure, fasting plasma glucose, and lipid profile). In the adjusted multiple linear and logistic regression models, compared with the reference category of adherence to the healthy lifestyle behavior composite score, those participants in the category of the highest adherence showed significant decreased prevalence risk of overweight or obesity [OR (95% CI), 0.4 (0.2, 0.6)] as well as significant lower waist circumference, fat mass index (FMI), systolic blood pressure and fasting plasma glucose concentration [ß (95% CI), - 1.4 cm (- 2.5, - 0.4); - 0.3 kg/m2 (- 0.5, - 0.1); and - 3.0 mmHg (- 5.2, - 0.9); - 1.9 mg/dL (- 3.5, - 0.4), respectively]. Slow eating speed was individually associated with most of the cardiometabolic risk factors.   Conclusions: Higher adherence to the healthy lifestyle behavior composite score was associated with lower waist circumference, FMI, other cardiometabolic risk factors, and risk of overweight or obesity in Spanish preschool children. Further studies are required to confirm these associations. What is Known: • Lifestyle is a well-recognized etiologic factor of obesity and its comorbidities. • Certain healthy behaviors such as adhering to a healthy diet, increasing physical activity, and decreasing screentime are strategies for prevention and treatment of childhood obesity. What is New: • Higher adherence to the healthy lifestyle behavior composite score to 6 healthy behaviors (breastfeeding, sleep duration, physical activity, screentime, eating speed, and adherence to the Mediterranean diet) was associated with decreased adiposity, including prevalence risk of overweight or obesity, and cardiometabolic risk in preschool children. • Slow eating and greater adherence to the Mediterranean diet were mainly associated to lower fasting plasma and serum triglycerides concentration, respectively.

Time-restricted eating and supervised exercise for improving hepatic steatosis and cardiometabolic health in adults with obesity: protocol for the TEMPUS randomised controlled trial.

INTRODUCTION: Metabolic dysfunction-associated steatotic liver disease is a major public health problem considering its high prevalence and its strong association with extrahepatic diseases. Implementing strategies based on an intermittent fasting approach and supervised exercise may mitigate the risks. This study aims to investigate the effects of a 12-week time-restricted eating (TRE) intervention combined with a supervised exercise intervention, compared with TRE or supervised exercise alone and with a usual-care control group, on hepatic fat (primary outcome) and cardiometabolic health (secondary outcomes) in adults with obesity. METHODS AND ANALYSIS: An anticipated 184 adults with obesity (50% women) will be recruited from Granada (south of Spain) for this parallel-group, randomised controlled trial (TEMPUS). Participants will be randomly designated to usual care, TRE alone, supervised exercise alone or TRE combined with supervised exercise, using a parallel design with a 1:1:1:1 allocation ratio. The TRE and TRE combined with supervised exercise groups will select an 8-hour eating window before the intervention and will maintain it over the intervention. The exercise alone and TRE combined with exercise groups will perform 24 sessions (2 sessions per week+walking intervention) of supervised exercise combining resistance and aerobic high-intensity interval training. All participants will receive nutritional counselling throughout the intervention. The primary outcome is change from baseline to 12 weeks in hepatic fat; secondary outcomes include measures of cardiometabolic health. ETHICS AND DISSEMINATION: This study was approved by Granada Provincial Research Ethics Committee (CEI Granada-0365-N-23). All participants will be asked to provide written informed consent. The findings will be disseminated in scientific journals and at international scientific conferences. TRIAL REGISTRATION NUMBER: NCT05897073.

In-hospital outcomes of septal myectomy vs. alcohol septal ablation for hypertrophic cardiomyopathy with outflow tract obstruction: An update and insights from the national inpatient sample from 2011 to 2019.

Septal Myectomy (SM) and Alcohol Septal Ablation (ASA) improve symptoms in patients with Hypertrophic Cardiomyopathy with outflow tract obstruction (oHCM). However, outcomes data in this population is predominantly from specialized centers. The National Inpatient Database was queried from 2011 to 2019 for relevant international classification of diseases (ICD)-9 and -10 diagnostic and procedural codes. We compared baseline characteristics and in-hospital outcomes of patients with oHCM who underwent SM vs ASA. A p-value < 0.001 was considered statistically significant. We identified 15,119 patients with oHCM who underwent septal reduction therapies, of whom 57.4% underwent SM, and 42.6% underwent ASA. Patients who underwent SM had higher all-cause mortality (OR: 1.8 (1.3-2.5)), post-procedure ischemic stroke (OR: 2.3 (1.7-3.2)), acute kidney injury (OR: 1.4 (1.2-1.7)), vascular complications (OR: 3.6 (2.3-5.3)), ventricular septal defect (OR: 4.4 (3.2-6.1)), cardiogenic shock (OR: 1.7 (1.3-2.3)), sepsis (OR: 3.2 (1.9-5.4)), and left bundle branch block (OR: 3.5 (3-4)), compared to ASA. Patients who underwent ASA had higher post-procedure complete heart block (OR: 1.3 (1.1-1.4)), right bundle branch block (OR: 6.3 (5-7.7)), ventricular tachycardia (OR: 2.2 (1.9-2.6)), supraventricular tachycardia (OR: 1.6 (1.4-2)), and more commonly required pacemaker insertion (OR: 1.4 (1.3-1.7)) (p < 0.001 for all) compared to SM. This nationwide analysis evidenced that patients undergoing SM had higher in-hospital mortality and periprocedural complications than ASA; however, those undergoing ASA had more post-procedure conduction abnormalities and pacemaker implantation. The implications of these findings warrant further investigation regarding patient selection strategies for these therapies.