Effect of CMV Mismatch on Heart Transplant Outcomes Using a Surveillance and Preemptive Strategy.

PURPOSE: The aim of the study was to determine outcomes after heart transplantation for cytomegalovirus (CMV) mismatched patients (D+/R-) who underwent a surveillance and preemptive therapy protocol, compared to nonmismatch patients. METHODS: A review of patient records from January 2010 to December 2020 with follow-up to October 2023 was done. The protocol consisted weekly surveillance with CMV PCR starting 4 weeks after transplant continuing up until the patient seroconverts or up to 3 months posttransplant if the patient does not seroconvert. Valganciclovir was given for 2 weeks to those who seroconverted. RESULTS: Two hundred and twenty-one patients were included, and 23% were mismatched patients. Overall survival was not different between CMV groups (p = NS). Causes of death and morbidities were also not significantly different (p = NS). Sixty-six percent of mismatch patients seroconverted, and there was also a significantly older donor age in the seroconverted patients compared to nonseroconverted patients (41 ± 11 vs. 29 ± 12 years, p < 0.005), indicating a higher risk donor profile. A multivariate Cox regression including donor age showed that there was no increase in mortality in the seroconverted mismatches compared to nonmismatch patients (p = NS). CONCLUSIONS: There is no significant increased mortality or morbidity using a CMV surveillance and preemptive therapy protocol. The effect of donor age on seroconversion of mismatches requires further validation.

Association between human leukocyte antigen class II-DR-DQ and narcolepsy: a case control study.

STUDY OBJECTIVES: Narcolepsy is a neurologic disorder characterized by irresistible sleep attacks. Although its etiology is unknown, it is strongly associated with genetic variances in the human leukocyte antigen (HLA) complex. We investigated the association of HLA class II-DR-DQ alleles in a sample of patients with narcolepsy-cataplexy (narcolepsy type 1; NT1) and patients with narcolepsy without cataplexy (narcolepsy type 2; NT2) with a control group. Additionally, we compared demographic, clinical, and laboratory characteristics of patients with narcolepsy with or without the DQB1*06:02 allele. METHODS: This case control study included 21 patients with NT1 (56.8%), 16 patients with NT2 (43.2%), and 100 controls. Sequence-based typing identified HLA-DRB1 alleles, and HLA-DQB1 typing was done using PCR-Sequence-Specific Oligonucleotide. Allele and haplotype frequencies were calculated by direct counting. Nocturnal polysomnography and Multiple Sleep Latency Test were performed in all participants. RESULTS: In the NT1 group, only one allele had a significantly higher frequency than in the NT2 group: DQB1*06:02 (61.9% vs. 18.8%;). Compared to controls, DQB1*06:02 (61.9% vs. 18.0% in controls) and DRB1*15:01(47.6% vs. 8.0%), had higher frequencies in patients with NT1. Multiple analyses showed that patients with NT1 had an increased chance of being HLA-DQB1*06:02 positive. HLA-DRB1*15:01-DQA1*01:02-DQB1*06:02 haplotype is associated with NT1 in our Brazilian patients. PSG was identified in DQB1*06:02 positive subgroup REM sleep latency (REML) ≤ 15 minutes, and all patients had two or more sleep-onset REM periods (SOREMPs) at MSLT. CONCLUSIONS: This study showed a strong association between HLA DQB1*06:02 and the haplotype HLA-DRB1*15:01-DQA1*01:02-DQB1*06:02 in patients with NT1. Patients with DQB1*0602 allele showed shorter REMLs at PSG. These results reinforce the suggestion of DQB1 genotyping as relevant to narcolepsy screening.

GPS Suitability for Physical Frailty Assessment.

The ageing of the population needs the automation of patient monitoring. The objective of this is twofold: to improve care and reduce costs. Frailty, as a state of increased vulnerability resulting from several diseases, can be seen as a pandemic for older people. One of the most common detection tests is gait speed. This article compares the gait speed measured outdoors using smartphones with that measured using manual tests conducted in medical centres. In the experiments, the walking speed was measured over a straight path of 80 m. Additionally, the speed was measured over 2.4 m in the middle of the path, given that this is the minimum distance used in medical frailty tests. To eliminate external factors, the participants were healthy individuals, the weather was good, and the path was flat and free of obstacles. The results obtained are promising. The measurements taken with common smartphones over a straight path of 80 m are within the same order of error as those observed in the manual tests conducted by practitioners.

Dynamic Contrast-Enhanced Magnetic Resonance Lymphangiography for Diagnosis and Treatment of Chylopericardium After Cardiac Transplantation.

Chylopericardium is a rare complication after cardiac transplantation. We report a case of a 69-year-old woman with persistent chylopericardium after a heart transplantation due to Chagas disease. Failure of conservative treatment led to dynamic contrast-enhanced magnetic resonance lymphangiography and percutaneous radiologic intervention of the lymphatic leakage and symptoms resolution.

Case report and presentation of a new classification system for hip acetabular and periacetabular ossifications and calcifications.

This report describes a rare case in which double calcifications of the acetabular labrum and rectus femoris occurred concomitantly in a middle-aged female patient who was treated successfully with surgical intervention via hip arthroscopy. Contribution: This case highlights the existence of various types of calcifications around the acetabulum, with a proposed new classification system for acetabular and periacetabular rim ossifications.

Practical tool to identify Spasticity-Plus Syndrome amongst patients with multiple sclerosis. Algorithm development based on a conjoint analysis.

Introduction: The Spasticity-Plus Syndrome (SPS) in multiple sclerosis (MS) refers to a combination of spasticity and other signs/symptoms such as spasms, cramps, bladder dysfunction, tremor, sleep disorder, pain, and fatigue. The main purpose is to develop a user-friendly tool that could help neurologists to detect SPS in MS patients as soon as possible. Methods: A survey research based on a conjoint analysis approach was used. An orthogonal factorial design was employed to form 12 patient profiles combining, at random, the eight principal SPS signs/symptoms. Expert neurologists evaluated in a survey and a logistic regression model determined the weight of each SPS sign/symptom, classifying profiles as SPS or not. Results: 72 neurologists participated in the survey answering the conjoint exercise. Logistic regression results of the survey showed the relative contribution of each sign/symptom to the classification as SPS. Spasticity was the most influential sign, followed by spasms, tremor, cramps, and bladder dysfunction. The goodness of fit of the model was appropriate (AUC = 0.816). Concordance between the experts' evaluation vs. model estimation showed strong Pearson's (r = 0.936) and Spearman's (r = 0.893) correlation coefficients. The application of the algorithm provides with a probability of showing SPS and the following ranges are proposed to interpret the results: high (> 60%), moderate (30-60%), or low (< 30%) probability of SPS. Discussion: This study offers an algorithmic tool to help healthcare professionals to identify SPS in MS patients. The use of this tool could simplify the management of SPS, reducing side effects related with polypharmacotherapy.

Arrhythmias and cardiac MRI associations in patients with established cardiac dystrophinopathy.

AIMS: Some patients with cardiac dystrophinopathy die suddenly. Whether such deaths are preventable by specific antiarrhythmic management or simply indicate heart failure overwhelming medical therapies is uncertain. The aim of this prospective, cohort study was to describe the occurrence and nature of cardiac arrhythmias recorded during prolonged continuous ECG rhythm surveillance in patients with established cardiac dystrophinopathy and relate them to abnormalities on cardiac MRI. METHODS AND RESULTS: A cohort of 10 patients (36.3 years; 3 female) with LVEF<40% due to Duchenne (3) or Becker muscular (4) dystrophy or Duchenne muscular dystrophy-gene carrying effects in females (3) were recruited, had cardiac MRI, ECG signal-averaging and ECG loop-recorder implants. All were on standard of care heart medications and none had prior history of arrhythmias.No deaths or brady arrhythmias occurred during median follow-up 30 months (range 13-35). Self-limiting episodes of asymptomatic tachyarrhythmia (range 1-29) were confirmed in 8 (80%) patients (ventricular only 2; ventricular and atrial 6). Higher ventricular arrhythmia burden correlated with extent of myocardial fibrosis (extracellular volume%, p=0.029; native T1, p=0.49; late gadolinium enhancement, p=0.49), but not with LVEF% (p=1.0) on MRI and atrial arrhythmias with left atrial dilatation. Features of VT episodes suggested various underlying arrhythmia mechanisms. CONCLUSIONS: The overall prevalence of arrhythmias was low. Even in such a small sample size, higher arrhythmia counts occurred in those with larger scar burden and greater ventricular volume, suggesting key roles for myocardial stretch as well as disease progression in arrhythmogenesis. These features overlap with the stage of left ventricular dysfunction when heart failure also becomes overt. The findings of this pilot study should help inform the design of a definitive study of specific antiarrhythmic management in dystrophinopathy. TRIAL REGISTRATION NUMBER: ISRCTN15622536.

Managing multiple sclerosis in individuals aged 55 and above: a comprehensive review.

Multiple Sclerosis (MS) management in individuals aged 55 and above presents unique challenges due to the complex interaction between aging, comorbidities, immunosenescence, and MS pathophysiology. This comprehensive review explores the evolving landscape of MS in older adults, including the increased incidence and prevalence of MS in this age group, the shift in disease phenotypes from relapsing-remitting to progressive forms, and the presence of multimorbidity and polypharmacy. We aim to provide an updated review of the available evidence of disease-modifying treatments (DMTs) in older patients, including the efficacy and safety of existing therapies, emerging treatments such as Bruton tyrosine kinase (BTKs) inhibitors and those targeting remyelination and neuroprotection, and the critical decisions surrounding the initiation, de-escalation, and discontinuation of DMTs. Non-pharmacologic approaches, including physical therapy, neuromodulation therapies, cognitive rehabilitation, and psychotherapy, are also examined for their role in holistic care. The importance of MS Care Units and advance care planning are explored as a cornerstone in providing patient-centric care, ensuring alignment with patient preferences in the disease trajectory. Finally, the review emphasizes the need for personalized management and continuous monitoring of MS patients, alongside advocating for inclusive study designs in clinical research to improve the management of this growing patient demographic.

Salt-rich versus salt-poor structural scenarios in the central Northern Calcareous Alps: implications for the Hallstatt facies and early Alpine tectonic evolution (Eastern Alps, Austria).

One of the most remarkable features of the central Northern Calcareous Alps (Eastern Alps, Austria) is the widespread presence of Upper Triassic deep-water carbonates (the Hallstatt facies) and Permo-Triassic evaporites resting on deep-water Middle Jurassic strata and their underlying Upper Triassic shallow-water carbonate platform successions. The Hallstatt facies and accompanying evaporites have been classically interpreted to originate either from a location south of the time-equivalent carbonate platforms, or to have been deposited in deeper water seaways within the broad platform domain. To date, this dispute has been addressed mostly through the analysis of Triassic and Jurassic facies distribution in map view, which, however, is subject to some degree of ambiguity and subjectivity. In this contribution we present, for the first time, sequentially restored regional cross-sections through the central Northern Calcareous Alps to understand the implications of the contrasting paleogeographic models. We present (a) an interpretation based on a highly allochthonous origin of the Triassic deep-water units and (b) an interpretation based on their relative autochthony in which we incorporate the potential influence of salt tectonics in the central NCA. The restored cross-sections provide a framework within which the alternative scenarios and their paleogeographic implications can be better understood. Through this analysis we propose that salt tectonics in the central NCA can provide a valid explanation for apparent inconsistencies in the relative autochthony scenario and thus constitutes a reasonable alternative to the currently accepted allochthony scenario.

Identification of a Potential Entry-Fusion Complex Based on Sequence Homology of African Swine Fever and Vaccinia Virus.

African swine fever virus (ASFV) belongs to the family of Asfarviridae, part of the group of nucleocytoplasmic large DNA viruses (NCLDV). Little is known about the internalization of ASFV in the host cell and the fusion membrane events that take place at early stages of the infection. Poxviruses, also members of the NCLDV and represented by vaccinia virus (VACV), are large, enveloped, double-stranded DNA viruses. Poxviruses were considered unique in having an elaborate entry-fusion complex (EFC) composed of 11 highly conserved proteins integrated into the membrane of mature virions. Recent advances in methodological techniques have again revealed several connections between VACV EFC proteins. In this study, we explored the possibility of an analogous ASFV EFC by identifying ten candidate proteins exhibiting structural similarities with VACV EFC proteins. This could reveal key functions of these ASFV proteins, drawing attention to shared features between the two virus families, suggesting the potential existence of an ASFV entry-fusion complex.

Preventive interventions for children and adolescents of parents with mental illness: A systematic review.

BACKGROUND: Children of parents with mental disorders have a relatively high risk of developing a mental illness or behavioural disorder. OBJECTIVE: The aim of this systematic review was to evaluate the efficacy of preventive psychotherapeutic interventions in children of parents with mental illness. In particular, the development of mental illness and/or psychological symptomatology in this population was assessed. METHOD: This qualitative systematic review looked at interventions targeting children aged 4-18 years without a diagnosed mental disorder, alone or with their families, with a parent with a diagnosed mental disorder. The protocol was pre-registered in Open Science Framework. A total of 1255 references were retrieved from MEDLINE, PsychArticles, PsycINFO, Springer Link, Science Direct, Scopus and WOS databases, and 12 references from grey literature. This search was replicated by an external reviewer. RESULTS: Fifteen studies involving 1941 children and 1328 parents were included. Interventions were based on cognitive-behavioural and/or psychoeducational components, including six randomized controlled trials. Internalizing symptomatology was assessed in 80% of the studies, externalizing and prosocial behaviour in 47%, and coping style in 33%. Only two studies measured the future risk of developing a mental disorder (ORs of 2.37 and 6.6). There was variability in the format of the intervention (group; family) as well as in the type of intervention and its duration (from one session to 12 sessions). CONCLUSIONS: Interventions for children of parents with mental disorder were clinically and statistically significant, especially in preventing internalizing symptomatology at one-year follow-up, with effect sizes ranging from d = -0.28 to 0.57 (95% CI).

Risk of complications after a non-ST segment elevation acute myocardial infarction in a Latin-American cohort: An application of the ACTION ICU score.

BACKGROUND: European Society of Cardiology (ESC) guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation (NSTEMI) recommend Intensive Care Unit (ICU) surveillance during the first 24-48 h. Interestingly, the in-hospital mortality of NSTEMI patients has consistently decreased, giving some patients the option to be managed in general hospital wards. The ACTION ICU score has been proposed to identify high-risk patients with NSTEMI and guide the selective risk-based need for ICU care. OBJECTIVE: To evaluate the usefulness of the ACTION ICU score to predict patients' risk of developing complications requiring ICU care in a Latin-American cohort with NSTEMI. METHODS: We applied the ACTION ICU score in a retrospective cohort. A composite primary outcome included: cardiorespiratory arrest, shock, high-grade atrio-ventricular block, respiratory failure, stroke, or death. The predictive performance of this model was estimated with a conditional multivariable logistic regression analysis. RESULTS: Of 1,062 patients with NSTEMI, the primary outcome was present in 75 patients (7.1%), and 1,019 (96%) were admitted to ICU. The most common event was respiratory failure (4.0%), followed by cardiogenic shock (3.7%), and cardiac arrest (1.7%). The presence of heart failure signs or symptoms had the highest association with the primary outcome (OR:2.16; 95%CI:1.61-2.92). The best cut-off point for this population was 3 (complications risk: 4.0%, SEN:96%, SP:15.4%, NPV:98.1%, PPV:7.9%). CONCLUSION: The ACTION ICU score may be a promising tool to identify the need for ICU care in Latin-American patients with NSTEMI. Furthermore, additional research is needed to evaluate the cost-effectiveness of this strategy.

Durable ventricular assist device in Spain (2007-2020). First report of the REGALAD registry.

INTRODUCTION AND OBJECTIVES: This report presents the clinical characteristics, outcomes and complications of all consecutive patients implanted with a long-term mechanical circulatory support device in Spain between 2007 and 2020. METHODS: Analysis of the Spanish Registry of durable ventricular assist devices (REGALAD) including data form Spanish centers with a mechanical circulatory support program. RESULTS: During the study period, 263 ventricular assist devices were implanted in 22 hospitals. The implanted device was an isolated continuous-flow left ventricular assist device in 182 patients (69%), a pulsatile-flow device (58 isolated left ventricular and 21 biventricular) in 79 (30%), and a total artificial heart in 2 patients (1%). The strategy of the implant was as bridge to heart transplant in 78 patients (30%), bridge to candidacy in 110 (42%), bridge to recovery in 3 (1%) and destination therapy in 72 patients (27%). Overall survival at 6, 12 and 24 months was 79%, 74% and 69%, respectively, and was better in continuous-flow left ventricular assist devices (84%, 80%, and 75%). The main adverse events related to this therapy were infections (37% of patients), bleeding (35%), neurological (29%), and device malfunction (17%). CONCLUSIONS: Durable ventricular assist devices have emerged in Spain in the last few years as a useful therapy for patients with advanced heart failure. As in other international registries, the current trend is to use continuous-flow intracorporeal left ventricular devices, which are associated with better results. Adverse events continue to be frequent and severe.

Emplacement and associated sedimentary record of the Jurassic submarine salt allochthon of the Wurzeralm (Eastern Alps, Austria).

A fossil salt sheet emplaced in the Jurassic in submarine conditions is described in the Eastern Alps of Austria, providing unique insights into the emplacement of similar submarine structures and their potential control on depositional systems. The salt sheet is a plug-fed extrusion emplaced due to squeezing of a salt diapir under compression. The preserved mylonitic shear fabric in the evaporites indicates radial, south-directed emplacement of the salt sheet. Tectono-sedimentary relationships record the evolution of the salt structure, from initial diapiric growth, to salt sheet extrusion and posterior collapse. Syn-extrusion sediments record the variable bathymetry of the extruding salt sheet, with reefal carbonates building up on the crestal bulge while their deeper water equivalents accumulated on the extruding salt lobe. This is the first description of a salt allochthon still linked to its source diapir in the Eastern Alps.

On the emergence of the correlation between life expectancy and the variance in the age at death.

Recent empirical studies have found various patterns in the correlations between lifespan inequality and life expectancy in modern human populations. However, it is unclear how general these regularities are. Here we establish three theorems that provide theoretical foundations for such regularities. We show that for populations with a finite maximum lifespan ω, and under certain continuity assumptions, the variance in the age at death is bounded by a function of lifespan that has a maximum and tends to zero as life expectancy tends to zero and ω. We show how the change in said variance is determined by a particular interplay between the coefficient of variation and the mean age in the population. These results lead to three hypotheses-a three-phased pattern of change for the correlation between the variance and life expectancy, a particular shape of the associated variance function, and that survival curve Type is one driver of the pattern. We illustrate those hypotheses empirically via a study of the 10 countries in the Human Mortality Database with the oldest available data. Our results elucidate the emergence of the aforementioned correlation patterns and provide demographically meaningful conditions under which those correlations reverse.

Advancing Key Gaps in the Knowledge of Plasmodium vivax Cryptic Infections Using Humanized Mouse Models and Organs-on-Chips.

Plasmodium vivax is the most widely distributed human malaria parasite representing 36.3% of disease burden in the South-East Asia region and the most predominant species in the region of the Americas. Recent estimates indicate that 3.3 billion of people are under risk of infection with circa 7 million clinical cases reported each year. This burden is certainly underestimated as the vast majority of chronic infections are asymptomatic. For centuries, it has been widely accepted that the only source of cryptic parasites is the liver dormant stages known as hypnozoites. However, recent evidence indicates that niches outside the liver, in particular in the spleen and the bone marrow, can represent a major source of cryptic chronic erythrocytic infections. The origin of such chronic infections is highly controversial as many key knowledge gaps remain unanswered. Yet, as parasites in these niches seem to be sheltered from immune response and antimalarial drugs, research on this area should be reinforced if elimination of malaria is to be achieved. Due to ethical and technical considerations, working with the liver, bone marrow and spleen from natural infections is very difficult. Recent advances in the development of humanized mouse models and organs-on-a-chip models, offer novel technological frontiers to study human diseases, vaccine validation and drug discovery. Here, we review current data of these frontier technologies in malaria, highlighting major challenges ahead to study P. vivax cryptic niches, which perpetuate transmission and burden.

A new Algorithm for Detecting Clinical High Risk of Psychosis in Adolescents.

BACKGROUND: The delimitation of the clinical high risk of psychosis (CHRp) is characterized by the wide variety of symptoms assessed from different approaches from the onset of psychosis. This study aimed to create a systematic procedure for an effective and accurate earlydetection of CHRp in educational settings. METHOD: A representative sample of 1,824 adolescents (average age, 15.79; 53.8%, women) was used to develop an online assessment system and a new 3-track, 3-level algorithm that combines symptoms of the main risk approaches: ultra-high risk (UHR), basic symptoms (BS), and anomalies in the subjective self-experience (ASE) with functional deficit. RESULTS: The acceptability and feasibility of the online screening system were confirmed by the data. Of the total participants, 68 (3.7%) were identified as high-risk and 417 (22.9%) were identified as moderate, which also supports the functionality of the proposed algorithm. CONCLUSIONS: The system indicates a dynamic model of progression of the different symptoms in the early stages of psychosis, and it may constitute a first line of identification for severe mental disorders in young people in the earliest stages, allowing application of initial preventive measures.

Quantizing Chaplygin Hamiltonizable nonholonomic systems.

In this article we develop a quantization procedure for Chaplygin Hamiltonizable nonholonomic systems-mechanical systems subject to non-integrable velocity constraints whose reduced mechanics is Hamiltonian after a suitable time reparametrization-using Poincaré transformations and geometric quantization. We illustrate the theory developed through examples and discuss potential applications to the study of the quantum mechanics of nanovehicles.