Subxiphoid robot-assisted complete resection for postchemotherapy primary mediastinal yolk sac tumour.

The standard treatment for primary mediastinal yolk sac tumour involves neoadjuvant chemotherapy followed by residual tumour resection, typically performed through a median sternotomy or a thoracotomy. However, in this case, a 16-year-old patient with a large anterior mediastinal tumour underwent less invasive, subxiphoid, robot-assisted surgery using a 4-arm da Vinci Xi system with CO2 insufflation at 8 mmHg. The tumour, located in the right thymic lobe, was dissected using a technique similar to blunt dissection, bipolar electrocautery and vessel sealer. Pericardiotomy was performed suspecting tumour invasion, with the thickened pericardial border incised circularly from the left side. Preservation of the right phrenic nerve involved careful separation from the densely adherent tumour. A pulmonary wedge resection was also performed using a stapler. The pericardial defect was reconstructed using an expanded polytetrafluoroethylene sheet, sutured together with nylon threads, and the resected tumour was extracted with a retrieval bag. This subxiphoid robot-assisted approach is a minimally invasive option for malignant mediastinal tumours.

Breakpoint analysis for cytogenetically balanced translocation revealed unexpected complex structural abnormalities and suggested the position effect for MEF2C.

Many disease-causing genes have been identified by determining the breakpoints of balanced chromosomal translocations. Recent progress in genomic analysis has accelerated the analysis of chromosomal translocation-breakpoints at the nucleotide level. Using a long-read whole-genome sequence, we analyzed the breakpoints of the cytogenetically balanced chromosomal translocation t(5;15)(q21;26.3), which was confirmed to be of de novo origin, in a patient with a neurodevelopmental disorder. The results showed complex rearrangements with seven fragments consisting of five breakpoint-junctions (BJs). Four of the five BJs showed microhomologies of 1-3-bp, and only one BJ displayed a signature of blunt-end ligation, indicating chromothripsis as the underlying mechanism. Although the BJs did not disrupt any disease-causing gene, the clinical features of the patient were compatible with MEF2C haploinsufficiency syndrome. Complex rearrangements were located approximately 2.5-Mb downstream of MEF2C. Therefore, position effects were considered the mechanism of the occurrence of MEF2C haploinsufficiency syndrome.

A Case of Acute Encephalopathy Associated with Acute Focal Bacterial Nephritis.

Acute encephalopathy is a syndrome characterized by an acute onset of disturbance of consciousness. Many acute encephalopathies are caused by viral infections; however, they can also be a result of bacterial infections. Acute focal bacterial nephritis (AFBN) can cause neurological symptoms, such as irritation, unconsciousness, and seizures. In some cases, AFBN-associated acute encephalopathy has also been reported. This report describes the first case of acute encephalopathy with AFBN without significant findings on brain MRI. The patient was a 3-year-old male, who had two episodes of febrile seizures at the ages of 1 and 2 years. He developed disturbance of consciousness, irritability, excitability, and neck stiffness on the day after admission. There were no abnormal findings on brain MRI; however, a generalized high-voltage slow wave was noted on electroencephalography (EEG). His urinary sediment count was elevated, and Morganella morganii and Enterococcus faecalis were detected in the urinary culture. A diagnosis of acute encephalopathy with urinary tract infection (UTI) was made. Intravenous (IV) antibiotics were administered to treat the UTI, while methylprednisolone pulse therapy and IV immunoglobulin were administered to treat acute encephalopathy. Additionally, AFBN was detected in both kidneys on contrast-enhanced CT. The patient received a second course of methylprednisolone pulse therapy due to the persistent high voltage slow wave noted on the EEG on day 8. Furthermore, contrast-enhanced CT revealed AFBN in both kidneys. The final diagnosis was acute encephalopathy with AFBN; however, we had initially diagnosed febrile seizures associated with UTI. It should be noted that acute encephalopathy is associated with AFBN.

Mutation in the STXBP1 Gene Associated with Early Onset West Syndrome: A Case Report and Literature Review.

Syntaxin-binding protein1 (STXBP1) is a member of the Sec1/Munc18-1 protein family, which comprises important regulators of the secretory and synaptic vesicle fusion machinery underlying hormonal and neuronal transmission, respectively. STXBP1 pathogenic variants are associated with multiple neurological disorders. Herein, we present the case of a Japanese girl with a mutation in the STXBP1 gene, who was born at 40 weeks without neonatal asphyxia. At 15 days old, she developed epilepsy and generalized seizures. Around 88 days old, she presented with a series of nodding spasms, with the seizure frequency gradually increasing. Interictal EEG indicated hypsarrhythmia and she presented with developmental regression. At 1.5 years old, genetic testing was performed and mutational analysis revealed an STXBP1 gene mutation (c.875G > A: p.Arg292His). Accordingly, she was diagnosed with developmental and epileptic encephalopathy, presenting West syndrome's clinical characteristics caused by the STXBP1 gene mutation. Although drug treatment has reduced the frequency of epileptic seizures, her development has remained regressive. The relationship between the location and type of genetic abnormality and the phenotype remains unclear. Future studies should investigate the genotype−phenotype correlation and the underlying pathophysiology to elucidate the causal relationships among the multiple phenotype-determining factors.

Recurrent de novo pathogenic variant of WASF1 in a Japanese patient with neurodevelopmental disorder with absent language and variable seizures.

A recurrent de novo pathogenic variant of WASF1, NM_003931:c.1516C>T [p.Arg506*], was identified in a 6-year-old female Japanese patient with severe developmental delay, hypotonia, hyperkinetic behavior, and distinctive facial features. The initial report of five adult patients with WASF1 variants was the only previous report regarding variants of this gene; this is the second such report, reaffirming that rare but recurrent truncating variants of WASF1 are associated with severe neurodevelopmental disorders.

HECW2-related disorder in four Japanese patients.

The HECT, C2, and WW domain containing E3 ubiquitin protein ligase 2 gene (HECW2) is involved in protein ubiquitination. Several genes associated with protein ubiquitination have been linked to neurodevelopmental disorders. HECW2-related disorder has been established through the identification of de novo variants in HECW2 in patients with neurodevelopmental disorders with hypotonia, seizures, and absent language. Recently, we identified novel HECW2 variants in four Japanese patients with neurodevelopmental disorders. Regarding motor development, two of the patients cannot walk, whereas the other two can walk with an unsteady gait, owing to hypotonia. All HECW2 variants, including those that were previously reported, are missense, and no loss-of-function variants have been identified. Most of the identified variants are located around the HECT domain. These findings suggest that the dominant negative effects of missense variants around the HECT domain may be the mechanism underlying HECW2-related disorder.

Efficacy of preoperative inhaled LAMA/LABA combinations in patients with lung cancer and untreated COPD.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with a high incidence of postoperative pulmonary complications (PPCs). When untreated COPD is found before lung cancer surgery, we have been actively intervening therapeutically with inhaled long-acting muscarinic antagonist (LAMA)/long-acting ß2-agonist (LABA) combinations. We investigated the efficacy of preoperative LAMA/LABA treatment. METHODS: We reviewed data from 261 patients who underwent pulmonary resection for primary lung cancer. Of these, 59 patients showed unrecognized obstructive ventilatory impairment on respiratory function testing. We administered inhaled drugs for 38 patients, of whom 22 patients treated with LAMA/LABA combinations and diagnosed with COPD were retrospectively analyzed regarding improvement of respiratory function and postoperative course. RESULTS: Median duration of LAMA/LABA treatment was 19.5 days (interquartile range (IQR), 10.5-28.3 days). Percentage predicted vital capacity (%VC) (pretreatment: 95.6%, IQR 91.9-111.7 vs. posttreatment 102.8%, IQR 92.3-113.0), forced expiratory volume in 1 s (FEV1) (1.76 L, 1.43-2.12 vs. 2.00 L, 1.78-2.40), forced VC (FVC) (2.96 L, 2.64-3.47 vs. 3.22 L, 2.95-3.74) and percentage predicted FEV1 (80.1%, 68.4-97.0 vs. 91.6%, 80.3-101.9) were all significantly improved (P<0.05 each). FEV1/FVC tended to be improved, but not significantly. No significant difference in improvement of respiratory function was seen between short-term (≤2 weeks) and normal-term (>2 weeks) treatment. PPCs occurred in 4 of 22 patients (18.2%), showing no significant difference compared to patients with COPD previously treated with inhaled drugs (2/20; 10.0%). CONCLUSIONS: Respiratory function is improved by preoperative LAMA/LABA treatment even in the short term. Starting treatment allows even COPD patients diagnosed on preoperative screening to experience the same frequency of PPCs as previously treated patients.

HPeV3-associated acute encephalitis/encephalopathy among Japanese infants.

OBJECTIVE: The current study aimed to identify and compare the clinical characteristics of human parechovirus type 3 (HPeV3)-associated acute encephalitis/encephalopathy (HPeV3E/E) between infants with abnormal brain magnetic resonance imaging (MRI) findings (typical, or MRI-positive HPeV3E/E) and those with MRI-negative findings (MRI-negative HPeV3E/E). METHODS: This is a retrospective study on patients with HPeV3 infection, and a two-step questionnaire survey performed on 837 hospitals in Japan between 2014 and 2016. RESULTS: We identified 240 infants with HPeV3 infection, of which 34 had been clinically-diagnosed HPeV3E/E (cHPeV3E/E). However, detailed clinical data were provided by 32 of the 34 patients. Among these 32, 23 had undergone MRI and were categorized into two groups, MRI-positive (n = 17) and -negative (n = 6). There were no significant intergroup differences in clinical lab results or symptoms, except for gastrointestinal symptoms that were only present in the MRI-negative patients. The MRI-positive group showed white matter involvement on brain MRI during the acute phase, and 8 patients presented with lesions on follow-up MRI. Furthermore, 4 (50%) of the 8 patients had neurological sequelae. CONCLUSION: Clinical characteristics of cHPeV3E/E patients with and without lesions on brain MRI showed no significant differences. Therefore, considering the difficulty in distinguishing febrile infants with cHPeV3E/E from those with a sepsis-like illness, during an HPeV3 infection epidemic, it is imperative to frequently perform brain MRI in febrile infants presenting with severe disease for the early diagnosis of HPeV3E/E presenting with brain lesions.