Current guidelines recommend using nirmatrelvir-ritonavir for coronavirus disease 2019 (COVID-19) treatment, but its potential drug interactions and contraindications limit its applicability in ...certain categories of patients. The aim of the study was to evaluate the real-world effectiveness of molnupiravir and nirmatrelvir-ritonavir in managing COVID-19 among hospitalized patients.
We conducted a retrospective cohort study among hospitalized COVID-19 patients who received molnupiravir or nirmatrelvir-ritonavir and did not require baseline supplemental oxygen from February 2022 to January 2023. We compared the effectiveness of molnupiravir and nirmatrelvir-ritonavir with a focus on disease progression.
The study included 401 high-risk, hospitalized adult COVID-19 patients who received molnupiravir or nirmatrelvir-ritonavir. No significant difference was found in disease progression, the composite outcome of disease progression (4.0% vs. 1.4%,
= 0.782), and O
supplementation via nasal prong (21.8% vs. 14.8%,
= 0.115) between the patients treated with molnupiravir and those treated with nirmatrelvir-ritonavir. This finding was similar after 1:1 propensity-score matching. In the multivariate analysis, molnupiravir treatment was not significantly associated with progression to severe disease.
In conclusion, our findings suggest that similar to nirmatrelvir-ritonavir, molnupiravir has a distinct potential role in COVID-19 treatment, transcending its current perceived status as only a secondary option.
Mutations affecting RNA splicing factors are the most common genetic alterations in myelodysplastic syndrome (MDS) patients and occur in a mutually exclusive manner. The basis for the mutual ...exclusivity of these mutations and how they contribute to MDS is not well understood. Here we report that although different spliceosome gene mutations impart distinct effects on splicing, they are negatively selected for when co-expressed due to aberrant splicing and downregulation of regulators of hematopoietic stem cell survival and quiescence. In addition to this synthetic lethal interaction, mutations in the splicing factors SF3B1 and SRSF2 share convergent effects on aberrant splicing of mRNAs that promote nuclear factor κB signaling. These data identify shared consequences of splicing-factor mutations and the basis for their mutual exclusivity.
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•Mutations in SF3B1 and SRSF2 have a synthetic lethal interaction•Mutations in RNA splicing factors are not tolerated in a homozygous state•Mutations in SF3B1 and SRSF2 have distinct effects on pre-mRNA splicing•Both SF3B1 and SRSF2 mutations result in hyperactive NF-κB signaling
Lee et al. report that SF3B1 and SRSF2 mutations elicit distinct effects on splicing and are synthetically lethal due to the cumulative impact on hematopoietic stem cell survival and quiescence. These mutations share convergent effects on promoting NF-κB signaling to drive myelodysplastic syndrome.
The study aimed to determine the pattern of fever resolution among febrile patients undergoing treatment for acute pyelonephritis (APN) and prove that switching therapy based solely on persistent ...fever beyond 72 hours of antibiotics treatment may be unwarranted.For the purpose of this study, non-responders were defined as those patients who had a persistent fever over 72 hours after the initiation of antibiotic therapy. Responders were defined as those patients who became afebrile in less than 72 hours after the initiation of antibiotic therapy. Clinical cure was defined as the complete resolution of all symptoms during antibiotic therapy without recurrence during the follow-up period.A total of 843 female patients with uncomplicated community-acquired APN met all inclusion criteria. The non-responder group comprised of 248 patients (29%), and the remaining patients constituted the responder group. The median initial C-reactive protein level was higher (15.6 mg/dl vs 12.6 md/dl, P < .001) and bacteremia was more frequent (31% vs 40%, P = .001) in the non-responder group. Escherichia coli (E. coli) was the most common pathogen in both groups; there was no significant difference between the groups in the etiology of APN. Antimicrobial resistance and extended spectrum β-lactamase producing strains had an increasing trend in the non-responder group but there was no significant difference between the groups.This study shows that it is difficult to identify patients at risk of uncomplicated community-acquired APN by antibiotic-resistant pathogens based exclusively on persistent fever. Patients with a prolonged fever for more than 72 hours show similar antibiotic susceptibility patterns and are not associated with adverse treatment outcomes. Therefore, switching of current antibiotics to broad-spectrum antibiotics should be reserved in this patient population until antibiotic susceptibility test results are available.
•Retrospective study of mild-to-moderate COVID-19, including the Delta variant.•Patient deterioration was reduced with regdanvimab versus standard of care.•The efficacy of regdanvimab was maintained ...against the more virulent Delta variant.•The adverse events observed during the study were generally mild and transient.
To evaluate the efficacy and safety of regdanvimab, a neutralizing antibody, in patients with mild-to-moderate SARS-CoV-2 including against the Delta variant.
A single-center, retrospective, observational cohort study in adults with confirmed COVID-19. The primary end point was the proportion of patients deteriorating with peripheral oxygen saturation <90% in room air, requiring supplemental oxygen therapy above high flow, or experiencing mortality due to COVID-19 up to day 28.
A total of 722 patients were eligible; 418 received regdanvimab and 304 received standard of care (SoC), of whom 71.1% (297/418, regdanvimab) and 37.8% (115/304, SoC) were infected with the Delta variant. The proportion of patients with a primary end point event was significantly lower with regdanvimab than SoC (3.1% vs 9.9%; difference: -6.8 95% confidence interval: -10.9, -2.8; P = 0.0002). A similar trend was observed in the Delta variant subgroup (regdanvimab, 2.7% vs SoC, 7.0%; difference -4.3 95% confidence interval: -10.8, 0.2; P = 0.0827). The secondary efficacy end points supported the primary analysis findings in the overall cohort and Delta variant subgroup. No new safety signals were identified.
Regdanvimab demonstrated clinical efficacy in the overall cohort and may provide a clinical benefit for patients with mild-to-moderate COVID-19 infected with the Delta variant.
A rapid outbreak of monkeypox is ongoing in non-endemic countries since May 2022. We report the first case of monkeypox in the Republic of Korea. This occurred in a 34-year-old male patient who ...traveled to Europe in June 2022. On the day of his return to the Republic of Korea (June 21, 2022), the patient presented with a genital lesion. The results of the monkeypox real-time polymerase chain reaction tests were positive in the penile ulcer, oropharyngeal and nasopharyngeal specimens. The patient subsequently developed fever and skin rash after hospital admission. Careful history taking along physical examination should be conducted in the patients who have epidemiologic risk factors for monkeypox. Moreover, appropriate specimens should be obtained from lesions and tested for the monkeypox virus.
Serologic diagnosis is one of the most widely used diagnostic methods for Q fever, but the window period in antibody response of 2 to 3 weeks after symptom onset results in significant diagnostic ...delay. We investigated the diagnostic utility of Q fever PCR from formalin-fixed liver tissues in Q fever patients with acute hepatitis.
We reviewed the clinical and laboratory data in patients with Q fever hepatitis who underwent liver biopsy during a 17-year period, and whose biopsied tissues were available. We also selected patients who revealed granuloma in liver biopsy and with no Q fever diagnosis within the last 3 years as control. Acute Q fever hepatitis was diagnosed if two or more of the following clinical, serologic, or histopathologic criteria were met: (1) an infectious hepatitis-like clinical feature such as fever (≥ 38°C) with elevated hepatic transaminase levels; (2) exhibition of a phase II immunoglobulin G (IgG) antibodies titer by IFA of ≥ 1:128 in single determination, or a four-fold or greater rise between two separate samples obtained two or more weeks apart; (3) histologic finding of biopsy tissue showing characteristic fibrin ring granuloma.
A total of 11 patients with acute Q fever hepatitis were selected and analyzed. Of the 11 patients, 3 (27%) had exposure to zoonotic risk factors and 7 (63%) met the serologic criteria. Granulomas with either circumferential or radiating fibrin deposition were observed in 10 cases on liver biopsy and in 1 case on bone marrow biopsy. 8 (73%) revealed positive Coxiella burnetii PCR from their formalin-fixed liver tissues. In contrast, none of 10 patients with alternative diagnosis who had hepatic granuloma revealed positive C. burnetii PCR from their formalin-fixed liver tissues.
Q fever PCR from formalin-fixed liver tissues appears to be a useful adjunct for diagnosing Q fever hepatitis.
Recent zoonotic outbreaks, such as Zika, Middle East respiratory syndrome and Ebola, have highlighted the need for rapid and accurate diagnostic assays that can be used to aid pathogen control. Q ...fever is a zoonotic disease caused by the transmission of Coxiella burnetii that can cause serious illness in humans through aerosols and is considered a potential bioterrorism agent. However, the existing assays are not suitable for the detection of this pathogen due to its low levels in real samples. We here describe a rapid bio‐optical sensor for the accurate detection of Q fever and validate its clinical utility. By combining a bio‐optical sensor, that transduces the presence of the target DNA based on binding‐induced changes in the refractive index on the waveguide surface in a label‐free and real‐time manner, with isothermal DNA amplification, this new diagnostic tool offers a rapid (<20 min), 1‐step DNA amplification/detection method. We confirmed the clinical sensitivity (>90%) of the bio‐optical sensor by detecting C. burnetii in 11 formalin‐fixed, paraffin‐embedded liver biopsy samples from acute Q fever hepatitis patients and in 16 blood plasma samples from patients in which Q fever is the cause of fever of unknown origin.
Schematic representation of the 3 detection methods including the conventional assays and the bio‐optical sensor for formalin‐fixed, paraffin‐embedded tissue and blood plasma samples. The bio‐optical sensor can simultaneously amplify and detect the target DNA in a label‐free and real‐time manner (#1). The conventional assays (end‐point and real‐time PCRs) are composed of DNA amplification and detection step separately (#2 and #3)
Perfluoro methyl vinyl ether (C3F6O) is a promising alternative gas to SF6 for switching applications in the power industry. We measured the total electron scattering cross section (TCS) of C3F6O in ...the intermediate energy region from 15 to 90 eV using a magnetized electron beam apparatus. The overall TCS values were less than 20.8 × 10−16 cm2 within the measuring energy region. The measured and observed TCS exhibited some features, a steep increase before 30 eV, the highest value near 30 eV, and a gradual decrease after 30 eV. The total uncertainty was evaluated as 3.5–8.5%, depending on the incident electron energies. These first measurement data of C3F6O are useful for understanding both the discharging characteristics and identifying the insulation properties and arc-extinguishing.
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•First C3F6O TCS in the intermediate-energy region from 15 to 90 eV was measured.•Overall TCS values of C3F6O were less than 20.8 × 10−16 cm2 within measuring energy region.•TCS of C3F6O has some features within the electron energy region.•Add some explanations for interpreting the formation of stable negative ion by electron collision.•Add comparison opinions on the use of insulating gas with SF6 and C3F6O.•Data useful for understanding the discharging characteristics as well as the insulation properties and arc-extinguishing.
Purpose
The incidence of
Klebsiella pneumoniae
pyogenic liver abscesses (KP-PLA) is increasing. However, its diagnosis and treatment are often delayed, leading to complications. In this study, we ...aimed to retrospectively compare computed tomographic (CT) features of KP-PLAs with those of abscesses caused by other bacterial pathogens (non-KP-PLAS) and to further identify prognostic factors for PLA.
Methods
Data of 219 study patients including clinical presentation, comorbid conditions, metastatic infection, treatment duration, and mortality were retrospectively collated. CT characteristics of abscesses were recorded. Etiology was established by pus and/or blood culture. The differentiating CT features and clinical findings were compared between the monomicrobial KP-PLA and non-KP-PLA groups. Furthermore, factors related to in-hospital case fatality were analyzed.
Results
Multivariate analysis identified thin-walled abscesses, absent rim enhancement, metastatic infection, and absence of underlying biliary tract disease as significant predictors of KP-PLA. With 3/4 criteria applied in combination, a specificity of 96.5% was achieved for KP-PLA diagnosis. The in-hospital mortality rate was 3.7%. Multivariate analysis revealed that diabetes mellitus (
P
= 0.031), multiple abscesses (
P
= 0.026), internal gas bubble (
P
= 0.041), metastatic infection (
P
= 0.004), and septic shock (
P
= 0.002) were significantly associated with mortality.
Conclusion
Thin-walled abscess, metastatic infection, absence of rim enhancement, and absence of underlying biliary tract disease are potentially useful CT findings for early KP-PLA diagnosis.
Here, we present an overview of how a tertiary hospital responded to maintain necessary activities and protect patients and staff from the coronavirus disease (COVID-19) outbreak.
Gil Medical Center, ...a tertiary hospital in Incheon, has operated a special response team since January 21, 2020. All visitors were assessed for body temperature and respiratory symptoms, and screened for recent overseas travel. Suspected COVID-19 patients were taken to a screening clinic. All febrile patients with or without respiratory symptoms were taken to a respiratory safety clinic. An isolation ward, which consisted of 10 negative-pressure rooms, was used to treat confirmed cases. More than 120 beds were prepared for the outbreak, and patients with pneumonia were preemptively isolated.
By May 5, 480 960 visitors were assessed at the control station, 3350 patients visited the triage center, and 1794 were treated in the respiratory safety clinic. Seventeen confirmed cases were admitted to the negative isolation ward, and 350 patients with pneumonia were preemptively isolated. A total of 2977 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction tests were performed.
While tertiary hospitals play an important role in treating both COVID-19 patients and non-COVID-19 patients, hospital staff have to protect themselves from unexpected in-hospital transmission. A multifaceted response must be undertaken to protect tertiary hospitals and their staff during the COVID-19 epidemic.