TF-FED for Gas-containing HNP at L5-S

The vacuum phenomenon is often observed in degenerative disc disease, whereas gas-containing disc herniation is relatively rare. Full-endoscopic discectomy at the lumbar spine level via a transforaminal approach, which was established and subsequently refined over the last two decades, requires only an 8-mm skin incision and causes minimal damage to the paravertebral muscles. Foraminoplasty, performed with a high-speed drill, is a useful technique to enlarge the foramen, especially when applied at the L5-S1 level, where the trajectory is limited because of anatomical structures such as the iliac crest. Here, we report a case of gas-containing lumbar disc herniation at L5-S1 that was successfully treated by transforaminal full-endoscopic discectomy. The patient was a 62-year-old man with low back pain and pain in the plantar aspect of the right great toe. Magnetic resonance and computed tomography scans demonstrated gas-containing lumbar disc herniation at L5-S1 on the right. Following foraminoplasty, transforaminal full-endoscopic lumbar discectomy was successfully performed under local anesthesia. The patient’s symptoms improved immediately after the surgery. Transforaminal full-endoscopic surgery can be effective and minimally invasive even when performed for gas-containing disc herniation

Low Back Pain and Lumbar Degeneration

Background: Baseball is one of the most popular sports in Asia. It is known that baseball can easily lead to back pain. However, there has been no survey of low back pain (LBP) and lumbar disc degeneration in Japanese professional baseball players to date. Purpose: To investigate the cause of LBP and lumbar degeneration in professional Japanese baseball players. Study Design: Cross-sectional study; Level of evidence, 3. Methods: We retrospectively reviewed the medical records of Japanese professional baseball players with LBP who visited our hospital. Data were collected from July 2018 to April 2021. We also investigated whether the results differed between players in their 20s and 30s or between pitchers and fielders. Data analysis was performed using the chi-square test. Results: We surveyed 32 professional baseball players. The most frequent causes of LBP among players in their 20s (n = 21) were lumbar disc herniation (LDH; 57%) and spondylolysis (24%). Of the players with spondylolysis, 50% had adult-onset spondylolysis. Players in their 30s (n = 11) most commonly had discogenic pain (55%) as well as LDH and facet joint arthritis (each 18%). The incidence of lumbar intervertebral disc degeneration was significantly higher in players in their 30s (91%) than those in their 20s (14%), as was the incidence of Schmorl nodes and Modic type 1 changes. There was no significant difference in the cause of LBP or the incidence of lumbar intervertebral disc degeneration between pitchers and fielders (P = .59). Conclusion: Among professional baseball players in their 20s, lumbar degeneration was less common, and they most frequently developed diseases less related to degeneration, such as LDH. However, among players in their 30s, lumbar degeneration was more advanced, and degenerative diseases such as discogenic pain occurred more frequently. Research on training methods could lead to the prevention of LBP. Our data may be applicable to other professional athletes and will contribute to diagnosis and treatment

Full-endoscopic Intradiscal Surgery: State of the Art

Two types of full-endoscopic intradiscal surgery have been described in the literature. The first is full-endoscopic thermal annuloplasty, which was introduced in 2004 for discogenic pain. The proposed pain generator is a high signal intensity zone or a toxic annular tear, which can be treated by full-endoscopic thermal annuloplasty using a bipolar radio-pulse device. The second is full-endoscopic disc cleaning surgery, which is more recent and has been used to treat intractable chronic low back pain due to type 1 Modic change. In this review, we describe the current status of full-endoscopic intradiscal surgery

Prevalence and predictors of direct discharge home following hospitalization of patients with serious adverse events managed by the rapid response system in Japan: a multicenter, retrospective, observational study

Aim: The rapid response system (RRS) is an in-hospital medical safety system. To date, not much is known about patient disposition after RRS activation, especially discharge home. This study aimed to investigate the prevalence, characteristics, and outcomes of patients with adverse events who required RRS activation. Methods: Retrospective data from the In-Hospital Emergency Registry in Japan collected from April 2016 to November 2020 were eligible for our analysis. We divided patients into Home Discharge, Transfer, and Death groups. The primary outcome was the prevalence of direct discharge home, and independently associated factors were determined using multivariable logistic regression. Results: We enrolled 2,043 patients who met the inclusion criteria. The prevalence of discharge home was 45.7%; 934 patients were included in the Home Discharge group. Age (adjusted odds ratio [AOR] 0.96; 95% confidence interval [CI], 0.95-0.97), malignancy (AOR 0.69; 95% CI, 0.48-0.99), oxygen administration before RRS (AOR 0.49; 95% CI, 0.36-0.66), cerebral performance category score on admission (AOR 0.38; 95% CI, 0.26-0.56), do not attempt resuscitation order before RRS (AOR 0.17; 95% CI, 0.10-0.29), RRS call for respiratory failure (AOR 0.50; 95% CI, 0.34-0.72), RRS call for stroke (AOR 0.12; 95% CI, 0.03-0.37), and intubation (AOR 0.20; 95% CI, 0.12-0.34) were independently negative, and RRS call for anaphylaxis (AOR 15.3; 95% CI, 2.72-86.3) was positively associated with discharge home. Conclusion: Less than half of the in-hospital patients under RRS activation could discharge home. Patients' conditions before RRS activation, disorders requiring RRS activation, and intubation were factors that affected direct discharge home

Characterisation of Ppy-lineage cells clarifies the functional heterogeneity of pancreatic beta cells in mice

Aims/hypothesis Pancreatic polypeptide (PP) cells, which secrete PP (encoded by the Ppy gene), are a minor population of pancreatic endocrine cells. Although it has been reported that the loss of beta cell identity might be associated with beta-to-PP cell-fate conversion, at present, little is known regarding the characteristics of Ppy-lineage cells. Methods We used Ppy-Cre driver mice and a PP-specific monoclonal antibody to investigate the association between Ppy-lineage cells and beta cells. The molecular profiles of endocrine cells were investigated by single-cell transcriptome analysis and the glucose responsiveness of beta cells was assessed by Ca2+ imaging. Diabetic conditions were experimentally induced in mice by either streptozotocin or diphtheria toxin. Results Ppy-lineage cells were found to contribute to the four major types of endocrine cells, including beta cells. Ppy-lineage beta cells are a minor subpopulation, accounting for 12–15% of total beta cells, and are mostly (81.2%) localised at the islet periphery. Unbiased single-cell analysis with a Ppy-lineage tracer demonstrated that beta cells are composed of seven clusters, which are categorised into two groups (i.e. Ppy-lineage and non-Ppy-lineage beta cells). These subpopulations of beta cells demonstrated distinct characteristics regarding their functionality and gene expression profiles. Ppy-lineage beta cells had a reduced glucose-stimulated Ca2+ signalling response and were increased in number in experimental diabetes models. Conclusions/interpretation Our results indicate that an unexpected degree of beta cell heterogeneity is defined by Ppy gene activation, providing valuable insight into the homeostatic regulation of pancreatic islets and future therapeutic strategies against diabetes

Programmed Chemotherapy for Patients with Metastatic Unresectable Gastric Cancer

BACKGROUND: Recent advances in the treatment of metastatic unresectable gastric cancers (MGC) include the development of new antitumor drugs and new regimens for their use. However, the selection of individually designed regimens by gastric cancer (GC) subtype remains problematic. Here, we investigated the clinical usefulness of programmed chemotherapy. METHODOLOGY/PRINCIPAL FINDINGS: MGC patients were classified into three groups by clinical condition. We implemented a chemotherapy program consisting of S-1 combination regimens. Median survival time (MST) of level 1 patients was 416 days (95% CI: 313-506 days), with an overall response rate of 47%. MSTs of level 2 and 3 patients were 208 (95% CI: 153-287 days) and 95 days (95% CI: 28-136 days), respectively. Grade 3-4 toxicities were neutropenia in 12% and anorexia in 6%. All treatment- related toxicities were resolved, and no treatment-related deaths occurred. CONCLUSIONS/SIGNIFICANCE: This program provided reasonable selection of case-matching regimens and may improve the survival of patients with MGC. Further, it may represent the first clinical tool to provide efficient chemotherapy course selection for MGC. Ongoing analysis of newly developed drugs and regimens will allow the efficacy of this chemotherapy program to be improved

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection