Novel heterozygous STUB1 gene mutation causes SCA48 in a Hungarian patient

Spinocerebellar ataxia type 48 (SCA48) is an autosomal dominantly inherited disease characterized by gait and limb ataxia, cerebellar dysarthria, cognitive impairment, psychiatric abnormalities and variable types of movement disorders. To date, more than 30 STUB1 gene (NM_005861.4) mutations have been described in the genetic background of SCA48.The aim of this short report was to demonstrate the first Hungarian SCA48 patient caused by a novel STUB1 missense mutation (c.788G>C, p.Arg263Pro). The characteristics of detailed neurological phenotype, brain MRI and genetic assessment are presented and compared to previously published cases. The most important neurological findings of the patient were gait ataxia, dysarthria, cognitive decline and psychiatric problems including depression, anxiety and mild impulsivity. The brain MRI demonstrated cerebellar atrophy with posterolateral predominance and frontal lobe cortical atrophy. Clinical exome sequencing examination identified the above-mentioned missense variant located in the significant ubiquitinase domain of the CHIP protein.In this paper the first Hungarian SCA48 patient was described with characteristic neuropsychiatric signs and brain MRI abnormalities, due to a novel STUB1 gene missense mutation

Early changes in laboratory parameters are predictors of mortality and ICU admission in patients with COVID-19 : a systematic review and meta-analysis

Despite the growing knowledge of the clinicopathological features of COVID-19, the correlation between early changes in the laboratory parameters and the clinical outcomes of patients is not entirely understood. In this study, we aimed to assess the prognostic value of early laboratory parameters in COVID-19. We conducted a systematic review and meta-analysis based on the available literature in five databases. The last search was on July 26, 2020, with key terms related to COVID-19. Eligible studies contained original data of at least ten infected patients and reported on baseline laboratory parameters of patients. We calculated weighted mean differences (WMDs) for continuous outcomes and odds ratios (ORs) with 95% confidence intervals. 93 and 78 studies were included in quantitative and qualitative syntheses, respectively. Higher baseline total white blood cell count (WBC), C-reactive protein (CRP), lactate-dehydrogenase (LDH), creatine kinase (CK), D-dimer and lower absolute lymphocyte count (ALC) (WMDALC = - 0.35 × 109/L [CI - 0.43, - 0.27], p < 0.001, I2 = 94.2%; < 0.8 × 109/L, ORALC = 3.74 [CI 1.77, 7.92], p = 0.001, I2 = 65.5%) were all associated with higher mortality rate. On admission WBC, ALC, D-dimer, CRP, LDH, and CK changes could serve as alarming prognostic factors. The correct interpretation of laboratory abnormalities can guide therapeutic decisions, especially in early identification of potentially critical cases. This meta-analysis should help to allocate resources and save lives by enabling timely intervention

Predominant neurological phenotype in a Hungarian family with two novel mutations in the XPA gene-case series

The prevalence of xeroderma pigmentosum (XP) is quite low in Europe, which may result in a delay in determining the appropriate diagnosis. Furthermore, some subtypes of XP, including XPA, may manifest themselves with quite severe neurological symptoms in addition to the characteristic dermatological lesions. Accordingly, the aim of the current study is to highlight the predominant neurological aspects of XPA, as well as mild-to-moderate dermatological signs in a Hungarian family with 5 affected siblings.The symptoms of the Caucasian male proband started to develop at 13-14 years of age with predominantly cerebellar, hippocampal, and brainstem alterations. His elder sister and three younger brothers all presented similar, but less expressed neurological signs. The diagnostic work-up, including clinical exome sequencing, revealed 2 novel compound heterozygous mutations (p.Gln146_Tyr148delinsHis, p.Arg258TyrfsTer5) in the XPA gene. Surprisingly, only mild-to-moderate dermatological alterations were observed, and less severe characteristic ophthalmological and auditory signs were detected.In summary, we present the first family with genetically confirmed XPA in the Central-Eastern region of Europe, clearly supporting the notion that disturbed function of the C-terminal region of the XPA protein contributes to the development of age-dependent neurologically predominant signs. This case series may help clinicians recognize this rare disorder

LIFEStyle, prevention and risk of Acute PaNcreatitis (LIFESPAN): protocol of a multicentre and multinational observational case-control study

Introduction Acute pancreatitis (AP) is a life-threatening inflammatory disease of the exocrine pancreas which needs acute hospitalisation. Despite its importance, we have significant lack of knowledge whether the lifestyle factors elevate or decrease the risk of AP or influence the disease outcome. So far, no synthetising study has been carried out examining associations between socioeconomic factors, dietary habits, physical activity, chronic stress, sleep quality and AP. Accordingly, LIFESPAN identifies risk factors of acute pancreatitis and helps to prepare preventive recommendations for lifestyle elements. Methods and analysis LIFESPAN is an observational, multicentre international case–control study. Participating subjects will create case and control groups. The study protocol was designed according to the SPIRIT guideline. Patients in the case group (n=1700) have suffered from AP (alcohol-induced, n=500; biliary, n=500; hypertriglyceridemiainduced, n=200; other, n=500); the control group subjects have no AP in their medical history. Our study will have three major control groups (n=2200): hospital-based (n=500), population-based (n=500) and aetiology-based (alcohol, n=500; biliary, n=500 and hypertriglyceridemia, n=200). All of them will be matched to the case group individually by gender, age and location of residence. Aggregately, 3900 subjects will be enrolled into the study. The study participants will complete a complex questionnaire with the help of a clinical research administrator/study nurse. Analysis methods include analysis of the continuous and categorical values. Ethics and dissemination The study has obtained the relevant ethical approval (54175-2/2018/EKU) and also internationally registered (ISRCTN25940508). After obtaining the final conclusions, we will publish the data to the medical community and will also disseminate our results via open access

Recurrent acute pancreatitis prevention by the elimination of alcohol and cigarette smoking (REAPPEAR): protocol of a randomised controlled trial and a cohort study

Background/objectives Acute recurrent pancreatitis (ARP) due to alcohol and/or tobacco abuse is a preventable disease which lowers quality of life and can lead to chronic pancreatitis. The REAPPEAR study aims to investigate whether a combined patient education and cessation programme for smoking and alcohol prevents ARP. Methods and analysis The REAPPEAR study consists of an international multicentre randomised controlled trial (REAPPEAR-T) testing the efficacy of a cessation programme on alcohol and smoking and a prospective cohort study (REAPPEAR-C) assessing the effects of change in alcohol consumption and smoking (irrespective of intervention). Daily smoker patients hospitalised with alcohol-induced acute pancreatitis (AP) will be enrolled. All patients will receive a standard intervention priorly to encourage alcohol and smoking cessation. Participants will be subjected to laboratory testing, measurement of blood pressure and body mass index and will provide blood, hair and urine samples for later biomarker analysis. Addiction, motivation to change, socioeconomic status and quality of life will be evaluated with questionnaires. In the trial, patients will be randomised either to the cessation programme with 3-monthly visits or to the control group with annual visits. Participants of the cessation programme will receive a brief intervention at every visit with direct feedback on their alcohol consumption based on laboratory results. The primary endpoint will be the composite of 2-year all-cause recurrence rate of AP and/or 2-year all-cause mortality. The cost-effectiveness of the cessation programme will be evaluated. An estimated 182 participants will be enrolled per group to the REAPPEAR-T with further enrolment to the cohort