Diurnal control of H3K27me1 deposition shapes expression of a subset of cell cycle and DNA damage response genes.

Rhythmic oscillation of biological processes helps organisms adapt their physiological responses to the most appropriate time of the day. Chromatin remodeling has been described as one of the molecular mechanisms controlling these oscillations. The importance of these changes in transcriptional activation as well as in the maintenance of heterochromatic regions has been widely demonstrated. However, little is still known on how diurnal changes can impact the global status of chromatin modifications and, hence, control gene expression. In plants, the repressive mark H3K27me1, deposited by ARABIDOPSIS TRITHORAX-RELATED PROTEIN 5 and 6 (ATXR5 and 6) methyltransferases, is largely associated with transposable elements but also covers lowly expressed genes. Here we show that this histone modification is preferentially deposited during the night. In euchromatic regions, it is found along the bodies of DNA damage response genes (DDR), where it is needed for their proper expression. The absence of H3K27me1 translates into an enhanced expression of DDR genes that follows a rhythmic oscillation pattern. This evidences a link between chromatin modifications and their synchronization with the diurnal cycle in order to accurately modulate the activation of biological processes to the most appropriate time of the day.

Transcriptomic alterations in APP/PS1 mice astrocytes lead to early postnatal axon initial segment structural changes.

Alzheimer´s disease (AD) is characterized by neuronal function loss and degeneration. The integrity of the axon initial segment (AIS) is essential to maintain neuronal function and output. AIS alterations are detected in human post-mortem AD brains and mice models, as well as, neurodevelopmental and mental disorders. However, the mechanisms leading to AIS deregulation in AD and the extrinsic glial origin are elusive. We studied early postnatal differences in AIS cellular/molecular mechanisms in wild-type or APP/PS1 mice and combined neuron-astrocyte co-cultures. We observed AIS integrity alterations, reduced ankyrinG expression and shortening, in APP/PS1 mice from P21 and loss of AIS integrity at 21 DIV in wild-type and APP/PS1 neurons in the presence of APP/PS1 astrocytes. AnkyrinG decrease is due to mRNAs and protein reduction of retinoic acid synthesis enzymes Rdh1 and Aldh1b1, as well as ADNP (Activity-dependent neuroprotective protein) in APP/PS1 astrocytes. This effect was mimicked by wild-type astrocytes expressing ADNP shRNA. In the presence of APP/PS1 astrocytes, wild-type neurons AIS is recovered by inhibition of retinoic acid degradation, and Adnp-derived NAP peptide (NAPVSIPQ) addition or P2X7 receptor inhibition, both regulated by retinoic acid levels. Moreover, P2X7 inhibitor treatment for 2 months impaired AIS disruption in APP/PS1 mice. Our findings extend current knowledge on AIS regulation, providing data to support the role of astrocytes in early postnatal AIS modulation. In conclusion, AD onset may be related to very early glial cell alterations that induce AIS and neuronal function changes, opening new therapeutic approaches to detect and avoid neuronal function loss.

Systematic preoperative approach for bariatric surgery, perioperative results, and economic impact.

Introduction: Obesity is a complex systemic condition, involving numerous anatomical and metabolic changes. Therefore, a comprehensive preoperative assessment is essential for each patient contemplating bariatric surgery. Objetive: This study presents the findings of a proposed protocol designed to streamline the pre-anesthesia consultation process. Our aim was to compare the efficiency and costs of consultations guided by the protocol with those conducted without a specific strategy. The secondary outcomes assessed included postoperative (PO) length of hospital stay and surgical duration. Matherial and methods: We conducted a retrospective cross-sectional analysis involving 206 clinical cases. Statistical analyses, including the chi-squared test, Student's t-test, and Mann-Whitney U test, were utilized based on the type of variables. Results: The results showed a significant reduction in the costs, pre-anesthesia consultation duration, time spent in the recovery unit, and the need for referrals. However, no statistically significant differences were observed in the delay before surgery and length of hospital stays, measured in days. Conclusion: This algorithm offers a promising approach for optimizing perioperative management in bariatric surgery, demonstrating its effectiveness in cutting costs and reducing the need for referrals.

Subclassification of obesity for precision prediction of cardiometabolic diseases.

Obesity and cardiometabolic disease often, but not always, coincide. Distinguishing subpopulations within which cardiometabolic risk diverges from the risk expected for a given body mass index (BMI) may facilitate precision prevention of cardiometabolic diseases. Accordingly, we performed unsupervised clustering in four European population-based cohorts (N ≈ 173,000). We detected five discordant profiles consisting of individuals with cardiometabolic biomarkers higher or lower than expected given their BMI, which generally increases disease risk, in total representing ~20% of the total population. Persons with discordant profiles differed from concordant individuals in prevalence and future risk of major adverse cardiovascular events (MACE) and type 2 diabetes. Subtle BMI-discordances in biomarkers affected disease risk. For instance, a 10% higher probability of having a discordant lipid profile was associated with a 5% higher risk of MACE (hazard ratio in women 1.05, 95% confidence interval 1.03, 1.06, P = 4.19 × 10-10; hazard ratio in men 1.05, 95% confidence interval 1.04, 1.06, P = 9.33 × 10-14). Multivariate prediction models for MACE and type 2 diabetes performed better when incorporating discordant profile information (likelihood ratio test P < 0.001). This enhancement represents an additional net benefit of 4-15 additional correct interventions and 37-135 additional unnecessary interventions correctly avoided for every 10,000 individuals tested.

Efficacy and Cognitive Outcomes of Gamma Knife Radiosurgery in Glioblastoma Management for Elderly Patients.

BACKGROUND: Gamma Knife Radiosurgery (GKRS), a specific type of Stereotactic Radiosurgery (SRS), has developed as a significant modality in the treatment of glioblastoma, particularly in conjunction with standard chemotherapy. The goal of this study is to evaluate the efficacy of combining GKRS with surgical resection and chemotherapy in enhancing therapeutic effects for glioblastoma patients aged 55 years and older. METHODS: This prospective clinical study, conducted in accordance with the STROBE guidelines, involved 49 glioblastoma patients aged 55 years and older, treated between January 2013 and January 2023. Data were collected prospectively, and strict adherence to the STUPP protocol was maintained. Only patients who conformed to the STUPP protocol were included in the analysis. Due to concerns regarding the cognitive impairment associated with conventional radiotherapy, and at the patients' request, a radiosurgery plan was offered. Radiosurgery was administered for 4-8 weeks following surgical resection. Any patients who had not received previous radiotherapy received open surgical tumor removal, followed by GKRS along with adjuvant chemotherapy. RESULTS: In this prospective clinical study of 49 glioblastoma patients aged 55 years and older, the average lifespan post-histopathological diagnosis was established at 22.3 months (95% CI: 12.0-28.0 months). The median time before disease progression was 14.3 months (95% CI: 13.0-29.7 months). The median duration until the first recurrence after treatment was 15.2 months, with documented cases varying between 4 and 33 months. The Gamma Knife Radiosurgery (GKRS) treatment involved a median marginal recommended dose of 12.5 Gy, targeting an average volume of 5.7 cm3 (range: 1.6-39 cm3). Local recurrence occurred in 21 patients, while distant recurrence was identified in 8 patients. Within the cohort, 34 patients were subjected to further therapeutic approaches, including reoperation, a second GKRS session, the administration of bevacizumab and irinotecan, and PCV chemotherapy. A cognitive function assessment revealed that the patients treated with GKRS experienced significantly less cognitive decline compared to the historical controls, who were treated with conventional radiotherapy. The median MMSE scores declined by 1.9 points over 12 months, and the median MoCA scores declined by 2.9 points. CONCLUSION: This study demonstrates that Gamma Knife Radiosurgery (GKRS), when integrated with surgical resection and adjuvant chemotherapy, offers a substantial benefit for glioblastoma patients aged 55 years and older. The data reveal that GKRS not only prolongs overall survival and progression-free survival but also significantly reduces cognitive decline compared to conventional radiotherapy. These findings underscore the efficacy and safety of GKRS, advocating for its incorporation into standard treatment protocols for older glioblastoma patients. The potential of GKRS to improve patient outcomes while preserving cognitive function is compelling and warrants further research to optimize and confirm its role in glioblastoma management.

Facilitators and barriers to perform physical activity in patients post-heart transplantation: a qualitative study.

AIM: Most patients experience barriers for becoming physical active post-heart transplantation. Therefore, identifying barriers and facilitators can help healthcare professionals in developing physical activity programs. This study aimed to explore the physical activity experiences, perceived barriers, and facilitators to perform physical activity of patients' post-heart transplantation. METHODS AND RESULTS: A qualitative study was carried out using in-depth semi-structured interviews on 24 patients post-heart transplantation from October to December 2022. The data were analyzed using an inductive strategy for finding emerging themes. NVivo 12.0 software was used to analyze the data. The physical activity experiences included that (1) patients felt that they had to adapt to a new situation after the heart transplantation, (2) walking was a popular physical activity preferably outdoors, (3) participants preferred to perform physical activity regularly with others, and (4) they felt better since they perform physical activity. The facilitators were: (1) Desire to live; (2) Experiencing physical benefits; (3) Being physically active with others; (4) Use of mobility assistive devices resources. The barriers were: (1) Feeling not being able to perform former physical activity; (2) Complications and experiencing symptoms post-heart transplantation; (3) Unfavourable climate. CONCLUSIONS: Patients post-heart transplantation have various facilitators influencing their post-transplant experience to perform physical activity. Key facilitators include the desire to live, physical benefits, social activity, and external support. Yet, they also face barriers like lost abilities, post-transplant complications, and environmental challenges.

Bone Marrow and Metabolic Bone Disease.

The bone marrow represents one of the largest organs in the body, with a relevant metabolic role that continues to be investigated. Numerous studies have focused on marrow adipose tissue (MAT). Evidence indicates that the bone marrow adipocytes do not only work as storage tissue but also consist of endocrine and paracrine cells, with the potential to contribute to local and systemic metabolism. MAT plays a role in bone health through its interaction with the other components of bone. Many metabolic disorders (osteoporosis, obesity, diabetes) have a complex and still not well-established or understood relationship with bone health. This article surveys the literature on the relationship of bone marrow and metabolic disorders, and how it is being studied using imaging techniques, with a special focus on bone health.

Imaging of Body Composition.

Body composition is now recognized to have a major impact on health and disease. Imaging enables its analysis in an objective and quantitative way through diverse techniques such as dual-energy X-ray absorptiometry, computed tomography, magnetic resonance imaging, and ultrasonography. This review article first surveys the methodological aspects underpinning the use of these modalities to assess body composition, highlighting their strengths and limitations as well as the set of parameters that they measure and their clinical relevance. It then provides an update on the main applications of body composition imaging in current practice, with a focus on sarcopenia, obesity, lipodystrophies, cancer, and critical care. We conclude by considering the emerging role of artificial intelligence in the analysis of body composition, enabling the extraction of numerous metrics with the potential to refine prognostication and management across a number of pathologies, paving the way toward personalized medicine.

Efficacy and safety of levosimendan in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: The LEVOCEST trial.

BACKGROUND: Primary angioplasty is the standard procedure for patients with ST-segment elevation myocardial infarction (STEMI). However, myocardial reperfusion results in additional cell damage. Levosimendan, due to its pleiotropic effects, may be a therapeutic alternative to prevent this damage. The objective of this study was to evaluate whether this drug can reduce infarct size in patients with STEMI. METHODS: Patients were randomized to receive a 24-h infusion of either levosimendan (0.1 µg/kg/min) or placebo after the primary angioplasty. The main objective was to assess the size of the infarct by cardiac resonance at 30 days and 6 months after the event. Other variables such as left ventricular ejection fraction (LVEF) and adverse ventricular remodeling (AVR) were assessed by speckle-tracking echocardiography and magnetic resonance. Major adverse cardiovascular events (MACE) were also collected. RESULTS: 157 patients were analysed (levosimendan, n = 79; placebo, n = 78). We found that after 6 months, patients treated with levosimendan had a greater reduction in infarct size (13.19% ± 9.5% vs.11.79% ± 9%, p = 0.001), compared with those in the placebo group (13.35% ± 7.1% vs. 13.43% ± 7.8%, p = 0.38). There were no significant differences in MACE between both groups. CONCLUSIONS: Levosimendan is a safe and effective therapeutic option for reducing infarct size in patients with STEMI.

Eggplant latent viroid is located in the chloroplasts and nuclei of eggplant infected cells.

Viroids that belong to genera Avsunviroid and Pelamovirod (family Avsunviroidae) replicate and accumulate in the chloroplasts of infected cells. In this report, we confirmed by RNA in situ hybridization using digoxigenin-UTP-labelled riboprobes that the positive strands of eggplant latent viroid (ELVd), the only member of genus Elaviroid within the family Avsunviroidae, also accumulate in the chloroplasts of infected cells. However, comparison of ELVd in situ hybridization signals with those from bona fide chloroplastic and nuclear non-coding RNAs, such as chloroplast 5S rRNA and U1 small nuclear RNA, supports the notion that this viroid is also present in the nuclei of infected cells. These results suggest that the subcellular localization of viroids within the family Avsunviroidae may be more complex than previously assumed with dynamic presence in several compartments during the infectious cycle.

Efficacy of the Sub-Urethral Transobturator KIM System® for Female Urinary Incontinence: Long Term Results.

Background/Objectives: Female stress urinary incontinence (SUI) surgical treatment has changed since its beginning. Selecting materials that promote constructive tissue remodelling helps to maintain continence after surgery and minimizes complications. To analyze the long-term urinary continence results in women who underwent SUI surgical correction using the transobturator mid-urethral sling KIM system® (Knotless Incontinence Mesh) and analyze the complications associated with this SUI treatment. Materials and Methods: Prospective study of the first 1000 patients undergoing SUI surgery with the Contasure KIM® sling between April 2007 and December 2018. Results and complications were recorded. Group A represented 94.2% of the sample and were the continent patients after surgery (GA = 942), while Group B accounted for incontinent patients after surgery (5.8%) (GB = 58). Results: The mean age at operation was 60 years. Eutocic deliveries (p = 0.0022), high blood pressure (p = 0.0190), anxiety (p = 0.0084), hemorrhoidectomies (p = 0.0016) and hysterectomies (p = 0.0002) were higher in GB. No differences between groups were found regarding body mass index (GA 26.50; GB 26.93) (p = 0.220649), food or drug allergies (p = 0.0.6547), dystocia (p = 0.2365), diabetes mellitus (p = 0.1715), pelvic surgery (p = 0.8842), other surgery (p = 0.8801) or concomitant treatments that would have an impact on bladder function. Correction of SUI was achieved in 94.2% of cases. Continence persisted over time in 97.98% of continent patients at 4-year follow-up and 90.90% of patients at last follow-up. Mesh caused erosion of the urethra in 0.3% of patients and extruded to the vagina in 0.42%. De novo urinary urgency (2.8%), significant chronic pain (3.6%) and urinary tract infections (3.0%) after surgery were lower than complications reported in reviewed publications. Pain was treated with medication, and all patients were pain-free at the one-year follow-up visit. Conclusions: The mid-urethral transobturator sling KIM system® has good initial and long-term results in patients with stress urinary incontinence, with a low recurrence rate and minimal complications.

Axillary nerve: what anesthesiologists and pain physicians should know.

Innervation of the shoulder joint is complex and remains poorly understood among regional anesthesiologists and chronic pain specialists. Current literature supports the important contribution of the axillary nerve to the total innervation of the shoulder, as well as its blockade for perioperative pain and denervation for chronic shoulder pain. However, a description of the entire course of the axillary nerve, the corresponding optimal targets, and the sonoanatomy pertinent to pain intervention is lacking. This educational article discusses in detail the functional anatomy and sonographic identification of possible windows for axillary nerve intervention. We discuss the contribution, extent, and type of innervation the axillary nerve provides to the shoulder joint, which is often misunderstood. Ultimately, this article serves to stimulate thoughts and ideas for future research in an area where literature is scarce.

Avatrombopag in immune thrombocytopenia: A real-world study of the Spanish ITP Group (GEPTI).

Avatrombopag is the newest thrombopoietin receptor agonist (TPO-RA) approved to treat immune thrombocytopenia (ITP). Real-world evidence regarding effectiveness/safety is limited. The Spanish ITP Group (GEPTI) performed a retrospective study with patients starting avatrombopag for the first time. A total of 268 ITP patients were recruited. The median (interquartile range [IQR]) follow-up time was 47.5 (30.4-58.9) weeks. Among the 193 patients with baseline platelet counts <50 × 109/L, 174 (90.1%) of them achieved response (PC ≥50 × 109/L), and 113 (87.6%) of the 129 who persisted on avatrombopag at last visit had platelet levels above such threshold. Results were similar when only those patients switching to avatrombopag due to previous treatment failure were considered (n = 104). Patients reached response in 13 (7-21) days. Among patients with baseline levels ≥50 × 109/L, 73/75 (97.3%) reported response, which was maintained by 53 (94.6%) of the 56 who continued on avatrombopag at the end of the study. Loss-of-response was always <10%. ITP duration did not influence response. Approximately 79% (34/43) of heavily pretreated (≥4 lines) patients with baseline platelet counts <50 × 109/L switching after previous failure achieved PC ≥50 × 109/L. Previous use of eltrombopag and/or romiplostim did not influence response, regardless of whether previous TPO-RA(s) succeeded or failed. Avatrombopag allowed dose-reduction/suspension of corticosteroids in 40/50 (80.0%) patients with baseline platelet counts <50 × 109/L. Overall, 40/268 (14.9%) thrombocytosis and 12/268 (4.5%) thromboembolic events were reported. Our real-world cohort supports the use of avatrombopag to manage ITP, regardless of disease severity and treatment history.

Shared Pathophysiology of Inflammatory Bowel Disease and Psoriasis: Unraveling the Connection.

Psoriasis (PS) and inflammatory bowel disease (IBD) are immune-mediated chronic conditions that share pathophysiological processes, including immune system dysfunction, microbiome dysbiosis, and inflammatory pathways. These pathways result in increased turnover of epithelial cells and compromised barrier function. The assessment of the literature suggests that immunopathogenic mechanisms, such as tumor necrosis factor (TNF)-α signaling and IL-23/IL-17 axis dysregulation, are shared by PS and IBD. Clinical characteristics and diagnostic approaches overlap significantly, and advances in biomarker identification benefit both conditions. Current treatments, namely biologics that target TNF-α, IL-17, and IL-23, show promising results in decreasing inflammation and controlling symptoms. Precision medicine approaches are prioritized in prospective therapeutic procedures to tailor pharmaceuticals based on specific biomarkers, perhaps improving outcomes and minimizing side effects. This study thoroughly examines and evaluates the body of research on PS and IBD. Several papers were examined to compile data on clinical features, diagnosis, therapies, pathophysiology, epidemiology, and potential future therapeutic developments. The selection of articles was based on three methodological qualities: relevance and addition to the knowledge of IBD and PS. The retrieved data were combined to provide a coherent summary of the state of the knowledge and to spot new trends. The overview of the latest studies demonstrates that both PS and IBD share pathophysiological foundations and therapeutic approaches. With a spotlight on particular biomarkers, advances in precision medicine provide a promising path toward enhancing therapeutic effectiveness and minimizing side effects.

Time in range and mean glucose cut-off points for reduction of fetal outcomes in pregnant women with type 1 diabetes using automated insulin delivery systems.

AIM: In pregnant women with Type 1 Diabetes (T1D), achieving a lower recommended time in range (TIRp,63-140 mg/dl) could have an impact on fetal outcomes. To determine the TIRp and mean glucose cut-off point associated with better fetal outcomes in pregnant women using automated insulin delivery (AID) systems. METHODS: A prospective cohort of pregnant women with T1D, using AID systems and followed-up in Latin America was analyzed. Optimal TIRp and mean glucose cut-off points for predicting large for gestational age (LGA) were determined using the Liu method. Fetal outcomes were evaluated for the identified cut-off point and the one recommended by guidelines (TIRp > 70 %). RESULTS: Sixty-two patients were included (mean age 31.9 ± 5.9 years, HbA1c 7.57 %±1.29 %, TIRp 59.8 %±14.6 %). 27.5 % on advanced hybrid closed loop systems (AHCL). LGA (50 vs 17.9 %,p = 0.010) and hyperbilirubinemia (45 % vs 11.8 %,p = 0.016) were more common in patients with TIRp < 59.1 %. Optimal cut-off of TIRp in the second trimester for predicting LGA was < 59.1 % (sensitivity 75 %, specificity 61 %) with an AUC of 0.68(CI 0.48-0.88). Optimal cut-off for mean glucose was 133 mg/dL (sensitivity 69 %, specificity 70 %) with an AUC of 0.70(CI 0.51-0.88) in the same trimester. Better metabolic control during the third trimester was seen in the AHCL users compared to other devices. CONCLUSIONS: TIRp > 59.1 % and mean glucose < 133 mg/dl in the second trimester, is associated with lower fetal outcomes of large for gestational age. One of the strategies that would improve TIRp is the early use of AHCL systems. Further studies are needed before a strong recommendation can be made.

Gastric perforation and generalized peritonitis due to heterotopic pancreas, an unusual case report.

INTRODUCTION: Heterotopic pancreas is the presence of normal pancreatic tissue that is in an anatomical site different from the pancreas. CASE REPORT: Adolescent who was admitted to the emergency room due to intense, generalized abdominal pain, which did not go away with anything, was exacerbated with movements, 24 h later vomiting that occurred as soon as he ate food was added, and severe and progressive abdominal distention, reason for admission to the service of emergencies. He had no significant family or personal medical history. On physical examination, he was found to be sick with a painful appearance, pale, sweaty, feverish, with tachycardia, he complained of intense pain, distended abdomen, with loss of hepatic dullness, with involuntary muscular resistance, with positive rebound sign, absent peristalsis. Laboratory studies were taken that reported anemia, leukocytosis and neutrophilia, blood chemistry, electrolytes, and coagulation times within normal limits; abdominal x-rays showed subdiaphragmatic free air. DISCUSSION: The prevalence of pancreatic heterotopia in the literature varies from 0.6 % in autopsy series to 14 %, however, the increasingly frequent use of upper gastrointestinal endoscopy and endoscopic ultrasound allows early diagnosis, since whether directed or incidentally, which avoids serious complications such as gastric perforation, because it is unusual for it to occur as in this clinical case. Specifically in the stomach, involvement of the submucosa layer has been described in 73 %, muscular layer in 17 % and subserosa in 10 % of cases respectively. In cases where the disease is in an asymptomatic stage, it can be treated conservatively; it seems to be more common in men, as in our case, than in women. CONCLUSION: In patients with chronic epigastric pain, it is essential to rule out conditions such as heterotopic pancreas, to avoid serious complications such as perforation.

DLK1 and DLK2, two non-canonical ligands of NOTCH receptors, differentially modulate the osteogenic differentiation of mesenchymal C3H10T1/2 cells.

BACKGROUND: C3H10T1/2 is a mesenchymal cell line capable of differentiating into osteoblasts, adipocytes and chondrocytes. The differentiation of these cells into osteoblasts is modulated by various transcription factors, such as RUNX2. Additionally, several interconnected signaling pathways, including the NOTCH pathway, play a crucial role in modulating their differentiation into mature bone cells. We have investigated the roles of DLK1 and DLK2, two non-canonical inhibitory ligands of NOTCH receptors, in the osteogenic differentiation of C3H10T1/2 cells. RESULTS: Our results corroborate existing evidence that DLK1 acts as an inhibitor of osteogenesis. In contrast, we demonstrate for the first time that DLK2 enhances this differentiation process. Additionally, our data suggest that NOTCH2, 3 and 4 receptors may promote osteogenesis, as indicated by their increased expression during this process, whereas NOTCH1 expression, which decreases during cell differentiation, might inhibit osteogenesis. Moreover, treatment with DAPT, a NOTCH signaling inhibitor, impeded osteogenic differentiation. We have confirmed the increase in ERK1/2 MAPK and p38 MAPK phosphorylation in C3H10T1/2 cells induced to differentiate to osteoblasts. Our new findings reveal increased ERK1/2 MAPK phosphorylation in differentiated C3H10T1/2 cells with a decrease in DLK1 expression or an overexpression of DLK2, which is coincident with the behavior of those transfectants where we have detected an increase in osteogenic differentiation. Additionally, p38 MAPK phosphorylation increases in differentiated C3H10T1/2 cells with reduced DLK1 levels. CONCLUSIONS: Our results suggest that DLK1 may inhibit osteogenesis, while DLK2 may promote it, by modulating NOTCH signaling and the phosphorylation of ERK1/2 and p38 MAPK pathways. Given the established inhibitory effect of DLK proteins on NOTCH signaling, these new insights could pave the way for developing future therapeutic strategies aimed at treating bone diseases.

Effectiveness of pain medication tapering in chronic pain patients: a systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis aimed to inventory all outcome measures that are affected by tapering in chronic noncancer pain and to investigate the effectiveness of tapering. METHODS: A literature search was conducted from inception to April 2024 in MEDLINE via PubMed, Web of Science, SCOPUS, EMBASE, and PsycINFO. RESULTS: The initial database search identified 3969 articles, which were screened by two independent reviewers. Studies evaluating pain medication tapering in adults with chronic noncancer pain were eligible for inclusion. In total, 57 and 34 articles were included in the systematic review and meta-analysis, respectively. Risk of bias assessment demonstrated poor, fair, and good quality in 30, 24, and three studies, respectively. Pain intensity was the most reported outcome measure, as reported in 28 studies. Furthermore, a random-effect three-level meta-analysis was performed. An overall effect size of 0.917 (95% confidence interval 0.61-1.22; P<0.001) was found, indicating a beneficial effect of tapering. In addition, a statistically significant improvement was demonstrated after tapering for pain intensity, headache disability, the number of headache days per month, anxiety, depression, the number of pills consumed per month, the number of days with medication intake per month, pain catastrophising, and pain interference. No statistically significant effect was observed for physical functioning, mental health-related quality of life, opioid use, pain self-efficacy, and physical health-related quality of life. CONCLUSIONS: This systematic review revealed a broad range of outcome measures affected by tapering. Owing to the high risk of bias of the included articles, the results of this meta-analysis must be interpreted with caution. SYSTEMATIC REVIEW PROTOCOL: CRD42023416343 (PROSPERO).

Association Between Tidal Volume in Invasive Mechanical Ventilation and Mortality in Children With Extracorporeal Membrane Oxygenation.

Mechanical ventilation (MV) strategies in children on extracorporeal membrane oxygenation (ECMO) have not been studied much and the ventilatory parameters to avoid greater lung damage are still unclear. Our objective was to determine the relationship between conventional tidal volume (4-8 ml/kg, CTV) versus low tidal volume (<4 ml/kg, LTV) and mortality in children with MV at the beginning of ECMO. This was a retrospective cohort study that included 101 (10.9 months interquartile range [IQR]: 6.0-24.0) children. Children with LTV had greater odds of hospital mortality (adjusted odds ratio [aOR]: 2.45; 95% confidence interval [CI]: 1.05-5.71; p = 0.03) regardless of age, reason for ECMO, and disease severity, as well as a longer duration of MV after ECMO. We found no differences between the groups in other MV settings. The CTV group required fewer fibrobronchoscopies than patients with LTV (aOR: 0.38; 95% CI: 0.15-0.99; p = 0.04). We found that a tidal volume (VT) lower than 4 ml/kg at the onset of ECMO support in children with MV was associated with higher odds of mortality, longer post-decannulation ventilation, and a greater need for fibrobronchoscopies. Lung-protective bundles in patients with ECMO and MV should consider the VT to maintain plateau and driving pressure that avoid major lung injury caused by MV.