Platypnoea-orthodeoxia syndrome in COVID-19 pneumonia patients: An observational study

This retrospective observational study aimed to assess the clinical characteristics of platypnea-orthodeoxia syndrome in patients with coronavirus disease 2019 (COVID-19) treated using mechanical ventilation or highflow nasal canula. We analyzed 42 consecutive patients with COVID-19 from January 2020 to March 2022. The primary outcomes were the incidence of platypnea-orthodeoxia syndrome, the time with required long-term oxygen therapy, and short-term prognosis. Additionally, we examined the relationships between platypneaorthodeoxia syndrome and COVID-19 severity, the time with long-term oxygen therapy, and short-term prognosis. Of the 42 included patients, 15 (35.7 %) had platypnea-orthodeoxia syndrome. Although mortality was not significantly different between both groups, the oxygen withdrawal rate in the platypnea-orthodeoxia syndrome group was significantly lower than that in the group without this syndrome. Clinical staff should be aware of the possibility of platypnea-orthodeoxia syndrome during positional changes in patients with COVID-19. Recognizing POS can improve early detection, countermeasures, and safety during physiotherapy.Respiratory Investigation, 62(2), pp. 291-294; 2024journal articl

Usefulness and safety of 0.4% sodium hyaluronate solution as a submucosal fluid "cushion" for endoscopic resection of colorectal mucosal neoplasms: A prospective multi-center open-label trial

<p>Abstract</p> <p>Background</p> <p>Sodium hyaluronate (SH) solution has been used for submucosal injection in endoscopic resection to create a long-lasting submucosal fluid "cushion". Recently, we proved the usefulness and safety of 0.4% SH solution in endoscopic resection for gastric mucosal tumors. To evaluate the usefulness of 0.4% SH as a submucosal injection solution for colorectal endoscopic resection, we conducted an open-label clinical trial on six referral hospitals in Japan.</p> <p>Methods</p> <p>A prospective multi-center open-label study was designed. A total of 41 patients with 5–20 mm neoplastic lesions localized in the colorectal mucosa at six referral hospitals in Japan in a single year period from December 2002 to November 2003 were enrolled and underwent endoscopic resection with SH. The usefulness of 0.4% SH was assessed by the <it>en bloc </it>complete resection and the formation and maintenance of mucosal lesion-lifting during endoscopic resection. Safety was evaluated by analyzing adverse events during the study period.</p> <p>Results</p> <p>The usefulness rate was high (82.5%; 33/40). The following secondary outcome measures were noted: 1) steepness of mucosal lesion-lifting, 75.0% (30/40); 2) intraoperative complications, 10.0% (4/40); 3) time required for mucosal resection, 6.7 min; 4) volume of submucosal injection, 6.8 mL and 5) ease of mucosal resection, 87.5% (35/40). Two adverse events of bleeding potentially related to 0.4% SH were reported.</p> <p>Conclusion</p> <p>Using 0.4% SH solution enabled sufficient lifting of a colorectal intramucosal lesion during endoscopic resection, reducing the need for additional injections and the risk of perforation. Therefore, 0.4% SH may contribute to the reduction of complications and serve as a promising submucosal injection solution due to its potentially superior safety in comparison to normal saline solution.</p

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

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

All-sky search for continuous gravitational waves from isolated neutron stars in the early O3 LIGO data

We report on an all-sky search for continuous gravitational waves in the frequency band 20-2000 Hz and with a frequency time derivative in the range of [-1.0,+0.1]×10-8 Hz/s. Such a signal could be produced by a nearby, spinning and slightly nonaxisymmetric isolated neutron star in our Galaxy. This search uses the LIGO data from the first six months of Advanced LIGO's and Advanced Virgo's third observational run, O3. No periodic gravitational wave signals are observed, and 95% confidence-level (C.L.) frequentist upper limits are placed on their strengths. The lowest upper limits on worst-case (linearly polarized) strain amplitude h0 are ∼1.7×10-25 near 200 Hz. For a circularly polarized source (most favorable orientation), the lowest upper limits are ∼6.3×10-26. These strict frequentist upper limits refer to all sky locations and the entire range of frequency derivative values. For a population-averaged ensemble of sky locations and stellar orientations, the lowest 95% C.L. upper limits on the strain amplitude are ∼1.4×10-25. These upper limits improve upon our previously published all-sky results, with the greatest improvement (factor of ∼2) seen at higher frequencies, in part because quantum squeezing has dramatically improved the detector noise level relative to the second observational run, O2. These limits are the most constraining to date over most of the parameter space searched

Constraints on dark photon dark matter using data from LIGO's and Virgo's third observing run

We present a search for dark photon dark matter that could couple to gravitational-wave interferometers using data from Advanced LIGO and Virgo's third observing run. To perform this analysis, we use two methods, one based on cross-correlation of the strain channels in the two nearly aligned LIGO detectors, and one that looks for excess power in the strain channels of the LIGO and Virgo detectors. The excess power method optimizes the Fourier Transform coherence time as a function of frequency, to account for the expected signal width due to Doppler modulations. We do not find any evidence of dark photon dark matter with a mass between $m_{\rm A} \sim 10^{-14}-10^{-11}$ eV/$c^2$, which corresponds to frequencies between 10-2000 Hz, and therefore provide upper limits on the square of the minimum coupling of dark photons to baryons, i.e. $U(1)_{\rm B}$ dark matter. For the cross-correlation method, the best median constraint on the squared coupling is $\sim1.31\times10^{-47}$ at $m_{\rm A}\sim4.2\times10^{-13}$ eV/$c^2$; for the other analysis, the best constraint is $\sim 2.4\times 10^{-47}$ at $m_{\rm A}\sim 5.7\times 10^{-13}$ eV/$c^2$. These limits improve upon those obtained in direct dark matter detection experiments by a factor of $\sim100$ for $m_{\rm A}\sim [2-4]\times 10^{-13}$ eV/$c^2$, and are, in absolute terms, the most stringent constraint so far in a large mass range $m_A\sim$ $2\times 10^{-13}-8\times 10^{-12}$ eV/$c^2$.Comment: 20 pages, 7 figure

GWTC-3:compact binary coalescences observed by LIGO and Virgo during the second part of the third observing run

The third Gravitational-Wave Transient Catalog (GWTC-3) describes signals detected with Advanced LIGO and Advanced Virgo up to the end of their third observing run. Updating the previous GWTC-2.1, we present candidate gravitational waves from compact binary coalescences during the second half of the third observing run (O3b) between 1 November 2019, 15∶00 Coordinated Universal Time (UTC) and 27 March 2020, 17∶00 UTC. There are 35 compact binary coalescence candidates identified by at least one of our search algorithms with a probability of astrophysical origin astro&gt;0.5. Of these, 18 were previously reported as low-latency public alerts, and 17 are reported here for the first time. Based upon estimates for the component masses, our O3b candidates with astro&gt;0.5 are consistent with gravitational-wave signals from binary black holes or neutron-star–black-hole binaries, and we identify none from binary neutron stars. However, from the gravitational-wave data alone, we are not able to measure matter effects that distinguish whether the binary components are neutron stars or black holes. The range of inferred component masses is similar to that found with previous catalogs, but the O3b candidates include the first confident observations of neutron-star–black-hole binaries. Including the 35 candidates from O3b in addition to those from GWTC-2.1, GWTC-3 contains 90 candidates found by our analysis with astro&gt;0.5 across the first three observing runs. These observations of compact binary coalescences present an unprecedented view of the properties of black holes and neutron stars