OBJECTIVE: To better understand the presentation and clinical needs of the under-characterized extreme end of the congenital titinopathy severity spectrum.
METHODS: We comprehensively analyzed the clinical, imaging, pathology, autopsy, and genetic findings in 15 severely affected individuals from 11 families.
RESULTS: Prenatal features included hypokinesia or akinesia and growth restriction. Six pregnancies were terminated. Nine infants were born at or near term with severe-to-profound weakness and required resuscitation. Seven died following withdrawal of life support. Two surviving children require ongoing respiratory support. Most cohort members had at least 1 disease-causing variant predicted to result in some near-normal-length titin expression. The exceptions, from 2 unrelated families, had homozygous truncating variants predicted to induce complete nonsense mediated decay. However, subsequent analyses suggested that the causative variant in each family had an additional previously unrecognized impact on splicing likely to result in some near-normal-length titin expression. This impact was confirmed by minigene assay for 1 variant.
INTERPRETATION: This study confirms the clinical variability of congenital titinopathy. Severely affected individuals succumb prenatally/during infancy, whereas others survive into adulthood. It is likely that this variability is because of differences in the amount and/or length of expressed titin. If confirmed, analysis of titin expression could facilitate clinical prediction and increasing expression might be an effective treatment strategy. Our findings also further-support the hypothesis that some near-normal-length titin expression is essential to early prenatal survival. Sometimes expression of normal/near-normal-length titin is due to disease-causing variants having an additional impact on splicing. ANN NEUROL 2025;97:611-628.
METHODOLOGY: A multicenter, prospective study of consecutive adults with IBS who underwent a hydrogen breath test (HBT) (glucose, 75 g; lactose, 25 g; or fructose, 25 g) was conducted. The proportion of patients who tested positive for glucose, fructose and lactose HBT were evaluated. The symptom severity, psychology, and quality of life of subjects with SIBO were compared with those having LM and/or FM. Independent factors associated with severe IBS (IBS-symptom severity scale: IBS-SSS > 300) were explored.
RESULTS: A total of 116 subjects were included (median age 56 years, male 35.3%). Of these, 23.3% (27/116), 85.7% (24/28), and 44.4% (16/36) of them tested positive for glucose, lactose, and fructose HBT, respectively. Among those with a positive HBT (n = 65), patients with SIBO were more likely to have the diarrhea-predominant subtype of IBS (77.8% vs. 47.4%, p = 0.014). Severe IBS was associated with SIBO, compared with LM/FM (SIBO: 36.4% vs. LM: 9.1%/FM 13.3%, p = 0.016). With multivariate analysis, SIBO (OR 5.25, p = 0.028) and depression (OR 5.59, p = 0.030) were independently associated with severe IBS.
CONCLUSION: Although LM and FM commonly co-exist in IBS, their clinical relevance appears to be less significant than that of SIBO. The connection between SIBO with depression reinforces the importance of the microbiome-gut-brain axis in IBS.
METHODS: The systematic review protocol was registered on PROSPERO on July 26, 2023 (CRD42023445166). The research articles related to the immunogenicity, efficacy, or safety of malaria or TB vaccines that were published between January 1, 2012, and August 31, 2023, were searched on three databases: Web of Science (WoS), PubMed, and ClinicalTrials.gov.
RESULTS: A total of 2342 articles were obtained, 50 of which met the inclusion criteria. 28 (56%) articles reported on malaria vaccine attributes, while 22 (44%) articles reported on TB vaccines. In both cases, the major challenges in sub-Saharan African clinical trials were immunogenicity and efficacy, rather than safety.
CONCLUSION: Factors such as population characteristics, pathogen genetic diversity, vaccine nature, strategy, and formulation were associated with slow progress of the malaria and TB vaccine candidates in sub-Saharan African clinical trials.
OBJECTIVE: This study aims to review the external and internal load performed by soccer referees in high-level competitions, to identify changes in these indicators over different periods as the competition progresses, and to analyze the standards for dividing speed zones and heart rate zones.
METHODS: Web of Science, PubMed, Scopus, and EBSCOhost were thoroughly searched. Grey literature sources and Google Scholar were also consulted, with a focus on analysing and comparing the physical demands of soccer referees at different phases of high-level matches.
RESULTS: A total of 14 manuscripts were included in this review. Studies revealed that the total distance (TD) covered by referees during a full match ranged from 9 to 12 km. High-intensity running (HIR) constituted 2.0-18.7% of TD, accounting for approximately 38% of total time (TT). Referees reached 80-100% of their maximal heart rate during matches. The standards for dividing speed zones and heart rate zones varied among the selected studies.
DISCUSSION: This systematic review aimed to provide a comprehensive overview of referees' physical demands (e.g., TD, HIR, and HR) to offer practitioners valuable biological data for training and competition preparation. The lack of uniform criteria for dividing speed and heart rate zones limits data collection, thereby affecting the reporting of distances covered at different exercise intensities.
METHODS: A panel of 41 experts, that regularly use nICP systems for guiding TBI care, was established. Three scoping and four systematic reviews with meta-analysis were performed summarizing the current global-literature evidence. A modified Delphi method was applied for the development of recommendations. An in-person meeting with group discussions and voting was conducted. Strong recommendations were defined for an agreement of at least 85%. Weak recommendations were defined for an agreement of 75-85%.
RESULTS: A total of 34 recommendations were provided (32 Strong, 2 Weak) divided into three domains: general consideration for nICP use, management of ICP using nICP methods and thresholds of nICP tools for escalating/de-escalating treatment. We developed four clinical algorithms for escalating treatment and heatmaps for de-escalating treatment.
CONCLUSIONS: Using a mixed-method approach involving literature review and an in-person consensus by experts, a set of recommendations designed to assist clinicians managing TBI patients using nICP systems plus clinical assessment, in the presence or absence of brain imaging, were built. Further clinical studies are required to validate the potential use of these recommendations in the daily clinical practice.
PURPOSE: The primary goal of osteoporosis management is to prevent fragility fractures, which occur from falls from standing height or less in individuals over fifty. However, the management of bone health optimization is often neglected in patients undergoing elective surgeries, such as arthroplasty and spinal surgeries. The objective of this article is to link all these three conditions into a TRIAD so that surgeons and physicians can collaborate more effectively, utilizing similar principles and strategies for better management.
METHODOLOGY: Clinical approaches based on country-specific guidelines are commonly used to manage osteoporosis. However, skeletal assessments are rarely conducted before or after elective procedures, leading to overlooked conditions such as osteoporosis, osteopenia, and fragility fracture risk factors. These three conditions are illustrated from the patient case study shown, to highlight the importance of not neglecting bone health optimization in high risk individuals undergoing elective surgery, with underlying osteopenia and multiple risk factors who sustained fragility fracture intraoperatively.
RESULT: Patients undergoing elective surgeries often have their bone health neglected, leading to a higher incidence of complications such as aseptic loosening and peri-prosthetic fractures due to poor bone quality and density. Bone health assessment and optimization therefore is essential in patients with osteoporosis, osteopenia with clinical risk factors, and patients with history of fragility fracture, to ensure implants sit on bone with good density and quality to minimize the complications.
CONCLUSION: By combining osteoporosis, fragility fractures, and bone health optimization into a TRIAD, "Lee's TRIAD," surgeons and physicians can collaborate more effectively, utilizing similar principles and strategies for better management.
OBJECTIVE: This study aimed to synthesize current literature on digital solutions for CVD prevention, identify the key components of effective digital interventions, and highlight critical research gaps to inform the development of sustainable strategies for CVD prevention.
METHODS: Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we conducted a comprehensive search in Web of Science, Scopus, and PubMed to identify original English-language studies published between January 2000 and May 2024 that examined primary or secondary CVD prevention through digital solutions. The exclusion criteria included: telephone-only interventions, abstract-only publications, methodology-focused studies without primary data, studies without participants or specific groups, and studies with no follow-up period. The literature search used the string with terms like "digital health," "mHealth," "mobile health," "text message," "short message service," "SMS," "prevention," "prevent," "cardiovascular disease," "CVD," etc. Study bias was assessed using the RoB 2 (Cochrane Collaboration) and the ROBINS-I tool (Cochrane Collaboration). Data on prevention components, prevention types, study design, population, intervention, follow-up duration, personnel, and delivery settings were extracted.
RESULTS: A total of 2871 studies were identified through the search. After excluding ineligible studies, 30 studies remained, including 24 randomized controlled trials. The reviewed digital solutions for CVD prevention focused on baseline assessment (29/30, 97%), physical activity counseling (18/30, 60%), tobacco cessation (14/30, 47%), blood pressure management (13/30, 43%), and medication adherence (10/30, 33%). The technologies used were categorized into 3 types, smartphones and wearables (16/30, 53%), email and SMS communications (12/30, 40%), and websites or web portals (3/30, 10%). The majority of the study outcomes addressed blood pressure (14/30, 47%), exercise capacity (12/30, 40%), weight (12/30, 40%), and lipid profile (11/30, 37%), while fewer focused on nicotine dependence (9/30, 30%), medication use (8/30, 27%), quality of life (7/30, 23%), dietary habits (5/30, 17%), intervention adherence (4/30, 13%), waist circumference (4/30, 13%), and blood glucose levels (2/30, 7%).
CONCLUSIONS: Digital solutions can address challenges in traditional CVD prevention by improving preventive behaviors and monitoring health indicators. However, most evaluated interventions have focused on medication use, quality of life, dietary habits, adherence, and waist circumference. Further studies are needed to assess the long-term impact of more comprehensive interventions on key cardiovascular outcomes.