Homozygosity for a novel large deletion in SLC29A3 in a patient with H syndrome

H syndrome (OMIM 6027820) is a novel form of histiocytosis affecting multiple organs with peculiar cutaneous manifestations. It is an autosomal recessive genodermatosis caused by pathogenic mutations in SLC29A3 that encodes the human equilibrative nucleoside transporter, hENT3. The cutaneous manifestations can mimic other sclerodermoid conditions. We present a 15-year-old boy diagnosed with H syndrome with typical clinical features and homozygosity for a novel pathogenic mutation.     

Syndrome of the trephined: clinical spectrum,risk factors,and impact of cranioplasty on neurologic recovery in a prospective cohort

Syndrome of the trephined (SoT) is an underrecognized complication after decompressive craniectomy. We aimed to investigate SoT incidence, clinical spectrum, risk factors, and the impact of the cranioplasty on neurologic recovery. Patients undergoing a large craniectomy (>?80 cm²) and cranioplasty were prospectively evaluated using modified Rankin score (mRS), cognitive (attention/processing speed, executive function, language, visuospatial), motor (Motricity Index, Jamar dynamometer, postural score, gait assessment), and radiologic evaluation within four days before and after a cranioplasty. The primary outcome was SoT, diagnosed when a neurologic improvement was observed after the cranioplasty. The secondary outcome was a good neurologic outcome (mRS 0–3) 4 days and 90 days after the cranioplasty. Logistic regression models were used to evaluate the risk factors for SoT and the impact of cranioplasty timing on neurologic recovery. We enrolled 40 patients with a large craniectomy; 26 (65%) developed SoT and improved after the cranioplasty. Brain trauma, hemorrhagic lesions, and shifting of brain structures were associated with SoT. After cranioplasty, a shift towards a good outcome was observed within 4 days (p?=?0.025) and persisted at 90 days (p?=?0.005). Increasing delay to cranioplasty was associated with decreased odds of improvement when adjusting for age and baseline disability (odds ratio 0.96; 95% CI, 0.93–0.99, p?=?0.012). In conclusion, SoT is frequent after craniectomy and interferes with neurologic recovery. High suspicion of SoT should be exercised in patients who fail to progress or have a previous trauma, hemorrhage, or shifting of brain structures. Performing the cranioplasty earlier was associated with improved and quantifiable neurologic recovery.

Graphical abstract

     

特发性脊柱侧凸患者椎旁肌结蛋白和波形蛋白的特征表达

目的:研究表明,结蛋白和波形蛋白可反映肌肉损伤再生的情况,同时结蛋白可反应肌力的大小。比较特发性和先天性脊柱侧凸患者顶椎处凹凸两侧椎旁肌形态和结蛋白及波行蛋白的表达,探讨椎旁肌在特发性脊柱侧凸发生发展中的作用。方法:①选择2005-07/2006-11间南方医科大学南方医院脊柱骨病科收治的部分特发性脊柱侧凸患者12例,Cobb角平均73.8°;先天性脊柱侧凸患者5例,Cobb角平均36.0°;腰椎间盘突出症患者2例和胸腰椎管内占位性病变患者3例作为正常对照。所有患者年龄均在10～20岁。②对脊柱侧凸患者顶椎凹凸两侧及正常对照组患者椎旁肌进行活检,术前均签署知情同意书。③采用光镜和电镜下观察椎旁肌的形态改变;SP法分别对光镜切片的结蛋白和波行蛋白进行免疫组织化学染色,在光镜下观察蛋白表达;应用图像分析系统测量结蛋白免疫组织化学染色后反应椎旁肌蛋白表达强弱的吸光度(A)。结果:22例患者全部进入结果分析。①椎旁肌组织形态:特发性脊柱侧凸患者椎旁肌在光镜及电镜下均有病变,凹侧椎旁肌病变较重,凸侧椎旁肌相对正常。②结蛋白免疫组织化学的阳性表达:结蛋白在各组椎旁肌中均有不同程度的表达,组间比较差别显著(P<0.01)。特发性脊柱侧凸及先天性脊柱侧凸患者椎旁肌在顶椎凸侧比正常组结蛋白表达稍强(0.2727±0.0478,0.2768±0.0372,0.2429±0.0272,P<0.05),特发性脊柱侧凸及先天性脊柱侧凸患者椎旁肌在顶椎凹侧相对于正常组表达减弱(0.1898±0.0258,0.1869±0.0306,0.2429±0.0272,P<0.05)。③波行蛋白免疫组织化学的阳性表达:各组间椎旁肌肌纤维内均无波形蛋白表达。特发性脊柱侧凸与先天性脊柱侧凸患者同侧椎旁肌两组间在形态和结蛋白及波行蛋白表达无明显差别(P>0.05)。结论:特发性脊柱侧凸患者椎旁肌内波形蛋白表达均为阴性,提示椎旁肌不存在再生现象。与先天性脊柱侧凸类似,特发性脊柱侧凸患者椎旁肌结蛋白表达凸侧增强及凹侧减弱为继发性改变。     

The value of ECG changes in risk stratification of COVID‐19 patients

BackgroundThere is growing evidence of cardiac injury in COVID‐19. Our purpose was to assess the prognostic value of serial electrocardiograms in COVID‐19 patients.MethodsWe evaluated 269 consecutive patients admitted to our center with confirmed SARS‐CoV‐2 infection. ECGs available at admission and after 1 week from hospitalization were assessed. We evaluated the correlation between ECGs findings and major adverse events (MAE) as the composite of intra‐hospital all‐cause mortality or need for invasive mechanical ventilation. Abnormal ECGs were defined if primary ST‐T segment alterations, left ventricular hypertrophy, tachy or bradyarrhythmias and any new AV, bundle blocks or significant morphology alterations (e.g., new Q pathological waves) were present.ResultsAbnormal ECG at admission (106/216) and elevated baseline troponin values were more common in patients who developed MAE (p = .04 and p = .02, respectively). Concerning ECGs recorded after 7 days (159), abnormal findings were reported in 53.5% of patients and they were more frequent in those with MAE (p = .001). Among abnormal ECGs, ischemic alterations and left ventricular hypertrophy were significantly associated with a higher MAE rate. The multivariable analysis showed that the presence of abnormal ECG at 7 days of hospitalization was an independent predictor of MAE (HR 3.2; 95% CI 1.2–8.7; p = .02). Furthermore, patients with abnormal ECG at 7 days more often required transfer to the intensive care unit (p = .01) or renal replacement therapy (p = .04).ConclusionsPatients with COVID‐19 should receive ECG at admission but also during their hospital stay. Indeed, electrocardiographic alterations during hospitalization are associated with MAE and infection severity.     

Molecular combing reveals complex 4q35 rearrangements in Facioscapulohumeral dystrophy

Facioscapulohumeral dystrophy (FSHD), one of the most common hereditary neuromuscular disorders, is associated with a complex combination of genetic variations at the subtelomeric 4q35 locus. As molecular diagnosis relying on Southern blot (SB) might be challenging in some cases, molecular combing (MC) was recently developed as an additional technique for FSHD diagnosis and exploration of the genomic organization of the 4q35 and 10q26 regions. In complement to the usual SB, we applied MC in a large cohort of 586 individuals with clinical FSHD. In 332 subjects, the two 4q alleles were normal in size, allowing exclusion of FSHD1 while we confirmed FSHD1 in 230 patients. In 14 patients from 10 families, we identified a recurrent complex heterozygous rearrangement at 4q35 consisting of a duplication of the D4Z4 array and a 4qA haplotype, irresolvable by the SB technique. In five families, we further identified variations in the SMCHD1 gene. Impact of the different mutations was tested using a minigene assay and we analyzed DNA methylation after sodium bisulfite modification and NGS sequencing. We discuss the involvement of this rearrangement in FSHD since all mutations in SMCHD1 are not associated with D4Z4 hypomethylation and do not always segregate with the disease.