Summary
Objective The aim of this study was to group patients with MODY (maturity‐onset diabetes of the young) according to the genetic alterations underlying the disease and to investigate their ...clinical characteristics.
Patients and methods Molecular analysis of GCK (MODY2), HNF‐1α (MODY3), HNF‐4α (MODY1) and HNF‐1β (MODY5) genes was performed by DNA sequencing in 95 unrelated index probands (47M/48F; mean age 9·9 ± 5·2 years) with clinical diagnosis of MODY. After classification into MODY subtypes according to the genetic alterations, clinical characteristics were compared between the groups.
Results Seventy‐six families were shown to carry mutations in GCK (34 of them previously unreported), eight families presented HNF‐1α mutations, and a large genomic rearrangement in HNF‐1β was found in a family. No alteration was found in HNF‐4α. Thus, relative frequencies in the group studied were 80% MODY2, 8·5% MODY3 and 1% MODY5. Comparison of clinical parameters according to genetic status showed significant differences between MODY2 and MODY3 patients in age at diagnosis (9·4 ± 5·4 years vs. 12·7 ± 4·6 years), diagnosis (impaired glucose tolerance vs. diabetes), diagnostic test used (OGTT vs. fasting glucose), treatment (diet and exercise vs. insulin/oral antidiabetic agents) and birth weight (2·96 ± 0·44 kg vs. 3·40 ± 0·67 kg).
Conclusion Almost 90% of the MODY cases in the group studied are explained by mutations in the major genes GCK (MODY2) and HNF‐1α(MODY3), although differences in the relative prevalence of each form could be partly due to patient referral bias (paediatric vs. adult). In general, patients with MODY2 were diagnosed at an earlier age in life than MODY3 patients and had a milder form of diabetes. Moreover, the majority of patients with MODY2 mutations were treated with diet whereas half of MODY3 patients received pharmacological treatment.
Patients with coronavirus disaese 2019 (COVID-19) can develop a cytokine release syndrome that eventually leads to acute respiratory distress syndrome requiring invasive mechanical ventilation (IMV). ...Because IL-6 is a relevant cytokine in acute respiratory distress syndrome, the blockade of its receptor with tocilizumab (TCZ) could reduce mortality and/or morbidity in severe COVID-19.
We sought to determine whether baseline IL-6 serum levels can predict the need for IMV and the response to TCZ.
A retrospective observational study was performed in hospitalized patients diagnosed with COVID-19. Clinical information and laboratory findings, including IL-6 levels, were collected approximately 3 and 9 days after admission to be matched with preadministration and postadministration of TCZ. Multivariable logistic and linear regressions and survival analysis were performed depending on outcomes: need for IMV, evolution of arterial oxygen tension/fraction of inspired oxygen ratio, or mortality.
One hundred forty-six patients were studied, predominantly males (66%); median age was 63 years. Forty-four patients (30%) required IMV, and 58 patients (40%) received treatment with TCZ. IL-6 levels greater than 30 pg/mL was the best predictor for IMV (odds ratio, 7.1; P < .001). Early administration of TCZ was associated with improvement in oxygenation (arterial oxygen tension/fraction of inspired oxygen ratio) in patients with high IL-6 (P = .048). Patients with high IL-6 not treated with TCZ showed high mortality (hazard ratio, 4.6; P = .003), as well as those with low IL-6 treated with TCZ (hazard ratio, 3.6; P = .016). No relevant serious adverse events were observed in TCZ-treated patients.
Baseline IL-6 greater than 30 pg/mL predicts IMV requirement in patients with COVID-19 and contributes to establish an adequate indication for TCZ administration.
Abstract
COVID-19 has overloaded national health services worldwide. Thus, early identification of patients at risk of poor outcomes is critical. Our objective was to analyse SARS-CoV-2 RNA detection ...in serum as a severity biomarker in COVID-19. Retrospective observational study including 193 patients admitted for COVID-19. Detection of SARS-CoV-2 RNA in serum (viremia) was performed with samples collected at 48–72 h of admission by two techniques from Roche and Thermo Fischer Scientific (TFS). Main outcome variables were mortality and need for ICU admission during hospitalization for COVID-19. Viremia was detected in 50–60% of patients depending on technique. The correlation of Ct in serum between both techniques was good (intraclass correlation coefficient: 0.612; p < 0.001). Patients with viremia were older (p = 0.006), had poorer baseline oxygenation (PaO
2
/FiO
2
; p < 0.001), more severe lymphopenia (p < 0.001) and higher LDH (p < 0.001), IL-6 (p = 0.021), C-reactive protein (CRP; p = 0.022) and procalcitonin (p = 0.002) serum levels. We defined "relevant viremia" when detection Ct was < 34 with Roche and < 31 for TFS. These thresholds had 95% sensitivity and 35% specificity. Relevant viremia predicted death during hospitalization (OR 9.2 3.8–22.6 for Roche, OR 10.3 3.6–29.3 for TFS; p < 0.001). Cox regression models, adjusted by age, sex and Charlson index, identified increased LDH serum levels and relevant viremia (HR = 9.87 4.13–23.57 for TFS viremia and HR = 7.09 3.3–14.82 for Roche viremia) as the best markers to predict mortality. Viremia assessment at admission is the most useful biomarker for predicting mortality in COVID-19 patients. Viremia is highly reproducible with two different techniques (TFS and Roche), has a good consistency with other severity biomarkers for COVID-19 and better predictive accuracy.
Summary
Objective The aim of this study was to characterize glucokinase (GCK) alterations in maturity‐onset diabetes of the young 2 (MODY2)‐suspected patients and to investigate their clinical ...characteristics in relation to the parental origin of the mutation.
Patients and methods We studied a group of 57 unrelated Spanish patients presenting with MODY2 phenotype. Patients without mutation in the coding region of the GCK gene were screened for rearrangements by Multiplex Ligation‐dependent Probe Amplification (MLPA). After classification according to the parental origin of the mutation, clinical characteristics were compared between the groups.
Results We detected a point mutation or small deletion or insertion of the GCK gene in 47 patients (82·5%); 19 mutations were novel. In addition, we found a whole‐gene deletion by MLPA. Patients carrying a GCK gene defect and those with MODY of unknown genetic origin shows similar phenotypes.
Comparison of clinical parameters according to the origin of the mutation did not show any differences in the birth weight (BW) nor in age at diagnosis. Patients who inherited the mutation from the father had higher fasting glucose levels at diagnosis.
Conclusion Although the presence of haploinsufficiency of GCK is not a common cause of MODY2, gene dose analysis should be performed when no mutation is found.
Strict maternal euglycaemia can contribute to intrauterine growth restriction and low BW when the foetus has inherited the GCK mutation from the mother. As foetal genotype in generally is not known, serial foetal abdominal scans may act as a surrogate for this.
Functional neurological disorders (FND) are a frequent reason for visits in neurology. However, specific training on these disorders during undergraduate and residency training is limited. This study ...assesses the knowledge, attitude and exposure of medical students to FNDs before completing their medical degree.
We conducted a 15-item survey to explore understanding, exposure and attitudes towards FNDs among sixth-year medical students at four Spanish universities.
A total of 118 students (mean age 23.6 ± 1.2 years; 71.2% female) returned the survey. Of these, 88 (74.6%) were aware of the concept of FNDs and 78 (66.1%) had studied them in psychiatry classes. The term 'psychosomatic' was chosen by 54.1% of the students as the most appropriate term to refer to these disorders, and 111 (94.1%) believed that a history of sexual or physical abuse was common among FND patients. Fifty-seven students (48.3%) assumed that the diagnosis of FND was mostly a clinical diagnosis of exclusion and 63 (53.4%) indicated that it is managed only by psychiatry. One hundred and one students (85.6%) considered that adequate training on FNDs is an important aspect of their medical training.
Medical students are aware of the existence of FNDs, but their preferred terminology, as well as the perceived aetiological factors, reflect that the historical view of these disorders is still deeply rooted. Medical students feel that they should receive adequate education on FNDs from specialists in neurology and psychiatry as part of their training.
•Feeding dystonia, trunk spasms, head-drops and orolingual mutilations are distinctive features of ChAc.•Severe dysarthria and dysphagia were considered the most limiting aspects of ChAc during early ...stages of the disease.•Hyperkinetic movements give way to parkinsonism during follow up.•Ten years after diagnosis only 50% of patients retain self-care abilities.
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