Laparoscopic Findings of Rare Pediatric Inguinal Hernias

Pediatric inguinal hernias are caused to the patency of the processus vaginalis (PPV). The principle for the repair of indirect inguinal hernias in children consists of complete ligation of the PPV. Laparoscopic percutaneous extraperitoneal closure (LPEC) has spread rapidly since it was reported by some groups from around 1998, and the number of institutions adopting this method as a standard procedure for pediatric inguinal hernia is increasing in Japan. Since the closure of PPV by laparoscopic surgery is popular, rare hernias in children can be observed from the abdominal cavity. We present the laparoscopic findings of rare pediatric inguinal hernias and report their experience

The influence of various distractions prior to upper gastrointestinal endoscopy : a prospective randomized controlled study

Background Although many patients still have anxiety about upper gastrointestinal (GI) endoscopy, there have been few reports on the influence of distractions for a person who is going to undergo upper GI endoscopy soon. This study was a prospective randomized controlled study investigating the influence of distractions, such as auditive and visual distractions using subjective and objective assessments including autonomic nervous function prior to upper GI endoscopy. Methods 206 subjects who underwent upper GI endoscopy as regular health check-ups were divided randomly into 4 groups prior to upper GI endoscopy; group 1 (control group), group 2 (auditive group), group 3 (visual group), and group 4 (combination group). We measured vital signs, autonomic nervous function, profile of mood state (POMS), and the impression for upper GI endoscopy pre- and post-distraction in the 4 groups. Results There was no significant difference in vital signs between 5 and 15 min after sitting in group 1, however, several vital signs in all distraction groups improved significantly after distraction (Pulse rate (P): p <  0.001 in group 4; blood pressure: p <  0.05 in group 2, 3, 4) and the rate of decrease in P and diastolic blood pressure was highest in group 4 (p <  0.001). Several scores of POMS and the impression for upper GI endoscopy post-distraction improved significantly compared to pre-distraction between distraction groups and the satisfaction for distraction was highest in group 4 (p <  0.01). Regarding autonomic nerve function, the low- frequency power/ high- frequency power ratio post-distraction was significantly lower than that pre-distraction in all distraction groups (p <  0.001). Conclusions Although auditive distraction alone and visual distraction alone were effective, a combination distraction was more effective than any other distraction by subjective and objective assessments. These distractions, which were simple and safe, may play an assistive role in the stability of physical and psychological conditions prior to upper GI endoscopy. Trial registration This trial was registered in the University Hospital Medical Information Network (UMIN) Clinical Trials Registry as UMIN000022801 ( https://www.umin.ac.jp/ctr/ ). Registered on 10 July 2016

Potential use of lenvatinib for patients with unresectable hepatocellular carcinoma including after treatment with sorafenib : Real-world evidence and in vitro assessment via protein phosphorylation array

The efficacy and safety of lenvatinib (LEN) as a second/third-line treatment for unresectable hepatocellular carcinoma (HCC) after sorafenib (SOR) therapy remains unknown. We evaluated the outcomes of second/third-line LEN treatment, investigated the sensitivity of a SOR-resistant HCC cell line (PLC/PRF5-R2) to LEN, and assessed their signal transduction pathways by protein array analysis. We retrospectively enrolled 57 patients with unresectable HCC. Fifty-three radiologically evaluated patients comprised 34 molecular-targeted agent (MTA)-naive (first-line), nine intolerant to SOR (second-line), and 10 resistant to regorafenib (third-line). The objective response rates (ORRs) were 61.8% in first-line, 33.3% in second-line, and 20.0% in third-line groups. The overall survival (OS) in the first-line was significantly longer than that in the third-line group (p < 0.05). Patients with better liver functional reserves (child score, ALBI grade) exhibited higher ORR and longer OS. The IC50 of LEN against PLC/PRF5-R2 was significantly higher than that against PLC/PRF5. LEN significantly inhibited more LEN-related signal transduction pathways in PLC/PRF5 than in PLC/PRF5-R2 cells. This suggests that LEN is active and safe as a second/third-line treatment for unresectable HCC. LEN seems more effective for patients with HCC with better hepatic reserve functions or before MTA-resistance is acquired because of the partial cross-resistance to SOR

Cesium Implant for Tongue Carcinoma with a Thickness of 1.5 cm or More: Cases Successfully Treated with a Modified Manchester System

∙The authors have no financial conflicts of interest. Purpose: Deciding on treatment carcinoma of the tongue when the tumor has a thickness of 1.5 cm or more is difficult. Surgery often requires wide resection and re-construction, leading to considerable functional impairment. A cesium implant is an attractive option, but according to the Manchester System, a two plane implant is needed. Materials and Methods: According to the textbook, a tumor is sandwiched between the needles, which are implanted at the edge of the tumor. This may cause an unnecessarily high dose to the outer surface of the tongue, which sometimes leads to a persistent ulcer. To avoid this complication, we invented a modified implantation method, and applied the method to five consecutive patients. Results: With a minimum follow-up of 2 years, all primary tumors in 5 consecutive patients have been controlled. No complications occurred in soft tissu

Impact of functional studies on exome sequence variant interpretation in early-onset cardiac conduction system diseases

Aims The genetic cause of cardiac conduction system disease (CCSD) has not been fully elucidated. Whole-exome sequencing (WES) can detect various genetic variants; however, the identification of pathogenic variants remains a challenge. We aimed to identify pathogenic or likely pathogenic variants in CCSD patients by using WES and 2015 American College of Medical Genetics and Genomics (ACMG) standards and guidelines as well as evaluating the usefulness of functional studies for determining them. Methods and Results We performed WES of 23 probands diagnosed with early-onset (&amp;lt;65 years) CCSD and analyzed 117 genes linked to arrhythmogenic diseases or cardiomyopathies. We focused on rare variants (minor allele frequency &amp;lt; 0.1%) that were absent from population databases. Five probands had protein truncating variants in EMD and LMNA which were classified as “pathogenic” by 2015 ACMG standards and guidelines. To evaluate the functional changes brought about by these variants, we generated a knock-out zebrafish with CRISPR-mediated insertions or deletions of the EMD or LMNA homologs in zebrafish. The mean heart rate and conduction velocities in the CRISPR/Cas9-injected embryos and F2 generation embryos with homozygous deletions were significantly decreased. Twenty-one variants of uncertain significance were identified in 11 probands. Cellular electrophysiological study and in vivo zebrafish cardiac assay showed that 2 variants in KCNH2 and SCN5A, 4 variants in SCN10A, and 1 variant in MYH6 damaged each gene, which resulted in the change of the clinical significance of them from “Uncertain significance” to “Likely pathogenic” in 6 probands. Conclusions Of 23 CCSD probands, we successfully identified pathogenic or likely pathogenic variants in 11 probands (48%). Functional analyses of a cellular electrophysiological study and in vivo zebrafish cardiac assay might be useful for determining the pathogenicity of rare variants in patients with CCSD. SCN10A may be one of the major genes responsible for CCSD. Translational Perspective Whole-exome sequencing (WES) may be helpful in determining the causes of cardiac conduction system disease (CCSD), however, the identification of pathogenic variants remains a challenge. We performed WES of 23 probands diagnosed with early-onset CCSD, and identified 12 pathogenic or likely pathogenic variants in 11 of these probands (48%) according to the 2015 ACMG standards and guidelines. In this context, functional analyses of a cellular electrophysiological study and in vivo zebrafish cardiac assay might be useful for determining the pathogenicity of rare variants, and SCN10A may be one of the major development factors in CCSD

Association of CCR2-CCR5 Haplotypes and CCL3L1 Copy Number with Kawasaki Disease, Coronary Artery Lesions, and IVIG Responses in Japanese Children

BACKGROUND: The etiology of Kawasaki Disease (KD) is enigmatic, although an infectious cause is suspected. Polymorphisms in CC chemokine receptor 5 (CCR5) and/or its potent ligand CCL3L1 influence KD susceptibility in US, European and Korean populations. However, the influence of these variations on KD susceptibility, coronary artery lesions (CAL) and response to intravenous immunoglobulin (IVIG) in Japanese children, who have the highest incidence of KD, is unknown. METHODOLOGY/PRINCIPAL FINDINGS: We used unconditional logistic regression analyses to determine the associations of the copy number of the CCL3L1 gene-containing duplication and CCR2-CCR5 haplotypes in 133 Japanese KD cases [33 with CAL and 25 with resistance to IVIG] and 312 Japanese controls without a history of KD. We observed that the deviation from the population average of four CCL3L1 copies (i.e., <or>four copies) was associated with an increased risk of KD and IVIG resistance (adjusted odds ratio (OR)=2.25, p=0.004 and OR=6.26, p=0.089, respectively). Heterozygosity for the CCR5 HHF*2 haplotype was associated with a reduced risk of both IVIG resistance (OR=0.21, p=0.026) and CAL development (OR=0.44, p=0.071). CONCLUSIONS/SIGNIFICANCE: The CCL3L1-CCR5 axis may play an important role in KD pathogenesis. In addition to clinical and laboratory parameters, genetic markers may also predict risk of CAL and resistance to IVIG

キョウクウ センパ ニヨル ノウキョウ ガッペイ オ ミトメタ セイジュクガタ ジュウカク キケイシュ ノ 1レイ

症例は16 歳女性,咳嗽,発熱,左前胸部痛を主訴に来院.胸部CT にて内部不均一な径7 cm の前縦隔腫瘍及び左舌区・下葉の完全無気肺を確認,また,MRI にて前縦隔腫瘍内に脂肪組織と同一の吸収域を認め,成熟型奇形腫穿破による膿胸と診断.膿胸に対し胸腔内繊維素溶解療法,ドレナージ及び抗生剤にて加療,膿胸改善を確認した上で,前縦隔腫瘍摘出術施行,病理にて嚢胞性成熟型奇形腫と診断した.病理組織にて膵類似の腺組織を確認,穿破の原因として,腫瘍内膵酵素の存在が考えられた.成熟型縦隔奇形腫は穿破により重篤な合併症発生の危険性があり,また経過中悪性転化する可能性もあることから,早期の外科治療が重要と考えられた.A 16-year-old female visited our hospital, complaining ofcough, fever, and left precordial pain. Chest computed tomographyshowed a heterogeneous anterior mediastinal tumormeasuring 7 cm in diameter and complete atelectasis inthe lingula and lower lobe of the left lung. Magnetic resonanceimaging also showed an area of intensity identical tothat of adipose tissue in the anterior mediastinal tumor.Thus, empyema due to rupture of a mature teratoma wasdiagnosed. The empyema was treated with intra-pleural fibrinolytictherapy, drainage, and antibiotics. After confirmingresolution of the empyema, we resected the anteriormediastinal tumor and pathologically diagnosed it as cysticmature teratoma. Histopathological examination showedglandular tissue resembling the pancreas, suggesting thatthe rupture had been caused by pancreatic enzymes in thetumor. Mediastinal mature teratoma carries a risk of seriouscomplications developing due to rupture and the possibilityof malignant transformation during the diseasecourse. Thus, early surgical treatment is important

COVID-19 vaccine effectiveness against severe COVID-19 requiring oxygen therapy, invasive mechanical ventilation, and death in Japan: A multicenter case-control study (MOTIVATE study).

INTRODUCTION: Since the SARS-CoV-2 Omicron variant became dominant, assessing COVID-19 vaccine effectiveness (VE) against severe disease using hospitalization as an outcome became more challenging due to incidental infections via admission screening and variable admission criteria, resulting in a wide range of estimates. To address this, the World Health Organization (WHO) guidance recommends the use of outcomes that are more specific to severe pneumonia such as oxygen use and mechanical ventilation. METHODS: A case-control study was conducted in 24 hospitals in Japan for the Delta-dominant period (August-November 2021; "Delta") and early Omicron (BA.1/BA.2)-dominant period (January-June 2022; "Omicron"). Detailed chart review/interviews were conducted in January-May 2023. VE was measured using various outcomes including disease requiring oxygen therapy, disease requiring invasive mechanical ventilation (IMV), death, outcome restricting to "true" severe COVID-19 (where oxygen requirement is due to COVID-19 rather than another condition(s)), and progression from oxygen use to IMV or death among COVID-19 patients. RESULTS: The analysis included 2125 individuals with respiratory failure (1608 cases [75.7%]; 99.2% of vaccinees received mRNA vaccines). During Delta, 2 doses provided high protection for up to 6 months (oxygen requirement: 95.2% [95% CI:88.7-98.0%] [restricted to "true" severe COVID-19: 95.5% {89.3-98.1%}]; IMV: 99.6% [97.3-99.9%]; fatal: 98.6% [92.3-99.7%]). During Omicron, 3 doses provided high protection for up to 6 months (oxygen requirement: 85.5% [68.8-93.3%] ["true" severe COVID-19: 88.1% {73.6-94.7%}]; IMV: 97.9% [85.9-99.7%]; fatal: 99.6% [95.2-99.97]). There was a trend towards higher VE for more severe and specific outcomes. CONCLUSION: Multiple outcomes pointed towards high protection of 2 doses during Delta and 3 doses during Omicron. These results demonstrate the importance of using severe and specific outcomes to accurately measure VE against severe COVID-19, as recommended in WHO guidance in settings of intense transmission as seen during Omicron