ABSTRACT
BACKGROUND: Recent advancements in advanced non-small-cell lung cancer (NSCLC) treatment have significantly improved primary therapy outcomes owing to the emergence of various molecular targeted therapies and immune checkpoint inhibitors (ICIs). However, for Kirsten rat sarcoma viral antigen (KRAS) mutations, molecular targeted drugs, such as sotorasib, are not applicable as first-line treatments, and the optimal primary treatment remains unclear. Therefore, we aimed to investigate the efficacy of ICI combination therapy as first-line treatment for KRAS-mutant NSCLC. METHODS: We conducted a systematic search for phase 3 randomized controlled trials (RCTs) that presented data on KRAS mutation status in advanced NSCLC. The primary endpoints were progression-free survival (PFS) and overall survival (OS). A random-effects network meta-analysis was conducted to perform direct and indirect comparisons among treatment groups. RESULTS: Six RCTs were eligible for inclusion. In the network meta-analysis for KRAS-mutant NSCLC, Chemo + bevacizumab (Bev) + ICI was associated with improved PFS (hazard ratio [HR] 0.38, 95% confidence interval [CI] 0.22-0.64), followed by Chemo + ICI + ICI (HR 0.66, 95% CI 0.47-0.93) and Chemo + ICI (HR 0.67, 95% CI 0.49-0.91). The most beneficial effect on OS was observed with Chemo + Bev + ICI (HR 0.50, 95% CI 0.34-0.73), followed by Chemo + ICI + ICI (HR 0.64, 95% CI 0.48-0.87) and Chemo + ICI (HR 0.72, 95% CI 0.56-0.92). Regarding OS in wild-type KRAS, ICI + ICI (HR 0.73, 95% CI 0.50-1.07) produced the most favorable effects, followed by Chemo + ICI (HR 0.79, 95% CI 0.63-0.99). CONCLUSION: The efficacy of Chemo + Bev + ICI is potentially high for improving PFS and OS in KRAS-mutant NSCLC. In advanced NSCLC, the presence or absence of KRAS mutations may need to be considered when administering first-line treatment.
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Echinococcosis, caused by Echinococcus spp., often affects the lungs and liver, and spinal involvement is rare. Echinococcus multilocularis is prevalent in Japan, particularly in Hokkaido. We herein report a rare case of spinal echinococcosis in a 31-year-old woman who was diagnosed in Tokyo. Spinal echinococcosis is uncommon and often leads to misdiagnoses. The patient likely contracted the disease via contaminated fresh produce transported from an endemic region. This study emphasizes the diagnostic challenges of spinal echinococcosis in non-endemic regions and highlights the public health concerns related to the spread of infections in non-endemic areas.
ABSTRACT
Extracorporeal blood purification with polymyxin B immobilized fiber column direct hemoperfusion (PMX-DHP), is reported to be effective in treating COVID-19 pneumonitis with oxygen demand. This multicenter prospective study evaluated the efficacy and safety of PMX-DHP in oxygen-requiring patients with COVID-19 admitted between September 28, 2020, and March 31, 2022. The primary endpoint was the percentage of clinical improvement 15 days after treatment. The secondary endpoint was the percentage of worsened disease status. Data from the COVID-19 patient registry were used for the synthetic control group. The improvement rate on Day 15 did not differ between PMX-treated patients and controls; however, the deterioration rate was 0.38 times lower in the PMX-treated group, and the death rates on Day 29 were 0 and 11.1% in the PMX-treated and control groups, respectively. The PMX group showed a 0.73 times higher likelihood for reduced intensive care demand, as 16.7% of PMX-treated patients and 22.8% of controls worsened. After treatment blood oxygenation improved, urinary ß2-microglobulin and liver-type fatty acid-binding protein showed significant decreases, and IL-6 decreased once during treatment but did not persist. In this study, PMX treatment effectively prevented the worsening of COVID-19 pathology, accompanied by improved oxygenation. PMX treatment to remove activated cells may effectively improve patient outcomes.
Subject(s)
COVID-19 , Hemoperfusion , Polymyxin B , Humans , COVID-19/therapy , Polymyxin B/administration & dosage , Polymyxin B/therapeutic use , Male , Female , Hemoperfusion/methods , Middle Aged , Aged , Prospective Studies , SARS-CoV-2/isolation & purification , Treatment Outcome , Oxygen , Oxygen Inhalation Therapy/methods , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/administration & dosageSubject(s)
Aneurysm, False , Embolization, Therapeutic , Humans , Aneurysm, False/therapy , Bronchial Arteries , RuptureABSTRACT
BACKGROUND: While the prevalence of severe cases and mortality rate of coronavirus disease 2019 (COVID-19) appear to be reducing, the clinical characteristics and severity of hospitalized patients with asthma and COVID-19 remain largely unknown. This study aimed to examine the association of asthma with COVID-19 severity and mortality risk. METHODS: Data from the Japanese COVID-19 Registry Database were used to investigate the association between COVID-19 and asthma. This study focused on patients hospitalized for COVID-19 in 690 facilities from January 31, 2020, to December 31, 2022. Multivariate analysis using logistic regression was conducted to assess whether asthma, compared with other conditions, represents a risk factor for mortality and invasive mechanical ventilation after COVID-19. RESULTS: In total, 72,582 patients with COVID-19 were included in the analysis, of whom, 3731 were diagnosed with asthma. From January 2020 to June 2021, asthma showed no significant association with an increase in mortality (OR 0.837, 95% CI 0.639-1.080, p = 0.184) or invasive mechanical ventilation events (OR 1.084, 95% CI 0.878-1.326, p = 0.440). An analysis conducted after July 2021 yielded similar results. For patients with asthma, factors such as age, body-mass index, sex, and chronic kidney disease increased the risk of mechanical ventilation. However, non-vaccination status and high blood pressure increased the risk of mechanical ventilation during the second half of the study. CONCLUSION: Patients with asthma did not have an increased risk of mortality or mechanical ventilation due to COVID-19. However, patients with asthma had a higher risk of more severe COVID-19 due to factors such as advancing age, elevated body-mass index, chronic kidney disease, and non-vaccination.
Subject(s)
Asthma , COVID-19 , Renal Insufficiency, Chronic , Humans , COVID-19/epidemiology , COVID-19/complications , Asthma/epidemiology , Asthma/therapy , Asthma/complications , Respiration, Artificial , Risk Factors , Renal Insufficiency, Chronic/complicationsABSTRACT
This study aimed to evaluate diagnostic accuracy of SARS-CoV-2 RNA detection in saliva samples treated with a guanidine-based or guanidine-free inactivator, using nasopharyngeal swab samples (NPS) as referents. Based on the NPS reverse transcription-polymerase chain reaction (RT-PCR) results, participants were classified as with or without COVID-19. Fifty sets of samples comprising NPS, self-collected raw saliva, and saliva with a guanidine-based, and guanidine-free inactivator were collected from each group. In patients with COVID-19, the sensitivity of direct RT-PCR using raw saliva and saliva treated with a guanidine-based and guanidine-free inactivator was 100.0%, 65.9%, and 82.9%, respectively, with corresponding concordance rates of 94.3% (κ=88.5), 82.8% (κ=64.8), and 92.0% (κ=83.7). Among patients with a PCR Ct value of <30 in the NPS sample, the positive predictive value for the three samples was 100.0%, 80.0%, and 96.0%, respectively. The sensitivity of SARS-CoV-2 RNA detection was lower in inactivated saliva than in raw saliva and lower in samples treated with a guanidine-based than with a guanidine-free inactivator. However, in individuals contributing to infection spread, inactivated saliva showed adequate accuracy regardless of the inactivator used. Inactivators can be added to saliva samples collected for RT-PCR to reduce viral transmission risk while maintaining adequate diagnostic accuracy.
Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Guanidine , SARS-CoV-2/genetics , RNA, Viral/genetics , Reverse Transcriptase Polymerase Chain Reaction , Reverse Transcription , Saliva , COVID-19/diagnosis , Guanidines , Nasopharynx , Specimen Handling , COVID-19 TestingABSTRACT
AIM: Several studies have shown the efficacy and safety of low-molecular-weight heparin use in coronavirus disease 2019 (COVID-19), but that of unfractionated heparin (UFH) has not been investigated. We investigated the prevalence of bleeding complications during UFH administration, its impact on mortality, and the risk factors of bleeding outcomes associated with UFH. METHODS: This retrospective cohort study was conducted at a single-center tertiary care hospital, including hospitalized patients with COVID-19. The primary outcomes were measured as the prevalence of bleeding complications during hospitalization, and the secondary outcomes were thromboembolic events and 60-day mortality rates. Logistic regression analysis and propensity score matching were used to assess risk factors for bleeding complications and their impact on mortality. RESULTS: Among 1035 included patients, 516 patients were treated with UFH. Twelve (2.3%) patients in the UFH group experienced major bleeding. The prevalence of major bleeding in patients treated with therapeutic-dose UFH was 9.2%. Logistic regression analysis showed that age ≥ 60 years (adjusted odds ratio [aOR], 3.89; 95% confidence interval [CI], 1.01-15.0; Pï¼.05) and COVID-19 severity (aOR, 35.9; 95% CI, 4.57-282; Pï¼.05) were associated with major bleeding complications. After propensity score matching, 11 major and 11 non-major bleeding cases (including minor bleeding) were matched. The 60-day cumulative mortality rate between the two groups did not differ significantly (P=.13, log-rank test). CONCLUSIONS: The incidence of major bleeding in COVID-19 patients using therapeutic-dose UFH was relatively high. Critical COVID-19 and older age were risk factors for bleeding complications.
Subject(s)
Anticoagulants , COVID-19 , Hemorrhage , Heparin , Humans , Male , Female , Japan/epidemiology , Retrospective Studies , Hemorrhage/epidemiology , Hemorrhage/chemically induced , COVID-19/epidemiology , COVID-19/complications , COVID-19/mortality , Heparin/adverse effects , Aged , Middle Aged , Incidence , Anticoagulants/adverse effects , Risk Factors , SARS-CoV-2 , COVID-19 Drug Treatment , Aged, 80 and over , Thromboembolism/epidemiology , Thromboembolism/etiologyABSTRACT
Delays in clearance and rapid evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported in immunocompromised patients. We encountered a case of recurrent, multi-mutational SARS-CoV-2 infection in a 40-year-old man with severe immunodeficiency due to Good syndrome. The patient had not received the SARS-CoV-2 vaccination. In August 2021, he was first admitted to the hospital owing to coronavirus disease 2019 (COVID-19) pneumonia and was administered dexamethasone, remdesivir, and baricitinib. Although his fever and respiratory condition improved once, chest computed tomography (CT) revealed extensive diffuse consolidation and ground-glass opacities (GGOs), and both methylprednisolone pulse therapy and tocilizumab yielded a limited effect. After a third course of remdesivir without immunosuppressants or steroids, the patient recovered, and he tested negative for SARS-CoV-2. On day 272 since the clinical onset, he was readmitted with dyspnea and mild fever due to a COVID-19 recurrence. He was infected with the Delta variant (AY.29), despite the Omicron (BA.2) variant being predominant at that time. During this admission, additional remdesivir and casirivimab/imdevimab yielded marked effects, and the SARS-CoV-2 quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) tests rapidly returned negative. Phylogenetic analysis demonstrated the accumulation of mutations, including those yielding remdesivir resistance, throughout the SARS-CoV-2 genome. Appropriate use of antivirals and monoclonal antibodies may aid in the recovery of patients with COVID-19 and immunodeficiency and in preventing the emergence of multi-mutational SARS-CoV-2 variants.
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We demonstrate a technique that generates frequency-entangled photon pairs with strong polarization correlation by using a single-period nonlinear crystal and single pass configuration. The technique is based on the simultaneous occurrence of two spontaneous parametric down-conversion processes satisfying independent type-II collinear quasi-phase matching conditions in periodically poled stoichiometric lithium tantalate. The generated photon pairs exhibit non-degenerate Hong-Ou-Mandel interference, indicating the presence of quantum entanglement in the frequency domain. This method provides a light source capable of wide-range quantum sensing and quantum imaging or high-dimensional quantum processing.
ABSTRACT
Some cases of bronchial asthma are refractory to conventional therapies. As the pathogenesis of bronchial asthma has been clarified, new treatments, such as bronchial thermoplasty and biological drugs, have been developed. Tezepelumab, an anti-thymic stromal lymphopoietin antibody, has been reported to inhibit the exacerbation of severe asthma; however, its adverse effects on glucose metabolism have not yet been reported. We encountered a case of weight gain and worsening glycemic management in a patient with type 2 diabetes and refractory bronchial asthma after the initiation of tezepelumab treatment. It has been reported that the overexpression of thymic stromal lymphopoietin in mice resulted in an enhanced release of free fatty acids from adipose tissues and the liver; thus, the administration of anti-thymic stromal lymphopoietin antibodies in the present case might have caused obesity, fatty liver and lower glucose tolerance.
Subject(s)
Antibodies, Monoclonal, Humanized , Asthma , Diabetes Mellitus, Type 2 , Humans , Animals , Mice , Diabetes Mellitus, Type 2/drug therapy , Weight Gain , Obesity/complications , Asthma/drug therapy , CytokinesABSTRACT
EG.5.1 is a subvariant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron XBB variant that is rapidly increasing in prevalence worldwide. However, the pathogenicity, transmissibility, and immune evasion properties of isolates of EG.5.1 are largely unknown. Here, we show that there are no obvious differences in growth ability and pathogenicity between EG.5.1 and XBB.1.5 in hamsters. We also demonstrate that, like XBB.1.5, EG.5.1 is transmitted more efficiently between hamsters compared to its predecessor, BA.2. In contrast, unlike XBB.1.5, we detect EG.5.1 in the lungs of four of six exposed hamsters, suggesting that the virus properties of EG.5.1 are different from those of XBB.1.5. Finally, we find that the neutralizing activity of plasma from convalescent individuals against EG.5.1 was slightly, but significantly, lower than that against XBB.1.5 or XBB.1.9.2. Our data suggest that the different virus properties after transmission and the altered antigenicity of EG.5.1 may be driving its increasing prevalence over XBB.1.5 in humans.
Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Cricetinae , Humans , Immune Evasion , Morphogenesis , Antibodies, NeutralizingABSTRACT
During an earlier multicenter, open-label, randomized controlled trial designed to evaluate the effectiveness of high-dose inhaled ciclesonide in patients with asymptomatic or mild coronavirus disease 2019 (COVID-19), we observed that worsening of shadows on CT without worsening of clinical symptoms was more common with ciclesonide. The present study sought to determine if an association exists between worsening CT shadows and impaired antibody production in patients treated with inhaled ciclesonide. Eighty-nine of the 90 patients in the original study were prospectively enrolled. After exclusions, there were 36 patients each in the ciclesonide and control groups. We analyzed antibody titers against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid protein at various time points. Changes in viral load during treatment were compared. There was no significant difference in age, sex, body mass index, background clinical characteristics, or symptoms between the two groups. Although evaluation on day 8 suggested a greater tendency for worsening shadows on CT in the ciclesonide group (p = 0.072), there was no significant difference between them in the ability to produce antibodies (p = 0.379) or the maximum antibody titer during the clinical course. In both groups, worsening CT shadows and higher viral loads were observed on days 1-8, suggesting ciclesonide does not affect clearance of the virus (p = 0.134). High-dose inhaled ciclesonide did not impair production of antibodies against SARS-CoV-2 or affect elimination of the virus, suggesting that this treatment can be used safely in patients with COVID-19 patients who use inhaled steroids for asthma and other diseases.
Subject(s)
Asthma , COVID-19 , Pregnenediones , Humans , SARS-CoV-2 , Pregnenediones/therapeutic useABSTRACT
We have developed a sensor for simultaneous measurement of atomic force microscopy (AFM) and scanning tunneling microscopy (STM) under liquid environments. The sensor, which is based on the qPlus sensor, is equipped with an insulated conductive tip. Owing to its electrical insulation except for the tip apex, the developed sensor enabled simultaneous detection of tip-sample interaction force and tunneling current, suppressing the Faradaic leakage current. As a fundamental demonstration, we performed simultaneous AFM/STM imaging in an electrolyte solution by using the developed sensor.
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A 50-year-old Japanese woman with advanced breast cancer presented with productive cough and dyspnea while she was receiving a sixth cycle of chemotherapy including atezolizumab. Chest computed tomography revealed bronchiolitis and transbronchial lung cryobiopsy revealed eosinophilic bronchiolitis. Corticosteroid therapy successfully resolved her symptoms. Eosinophilic bronchiolitis is a rare but important immune-related adverse event; herein, we discuss its diagnosis and possible pathophysiology.
Subject(s)
Bronchiolitis , Immune Checkpoint Inhibitors , Female , Humans , Middle Aged , Immune Checkpoint Inhibitors/adverse effects , Bronchiolitis/drug therapy , Lung/pathology , Dyspnea/pathology , Cough/pathologyABSTRACT
The coronavirus disease 2019 (COVID-19) pandemic has affected the world for over 3 years. Treatment options have improved substantially during this period, including antiviral drugs, antibody drugs, immune-based agents, and vaccination. While these improvements have reduced mortality rates in patients with COVID-19, some patients still develop severe illness. In this review, we aimed to provide an overview of treatments for patients with severe COVID-19 from study reports and clinical experience. We discussed the treatments from two perspectives: respiratory care and drug treatments. In the respiratory care section, we discussed the usefulness of high-flow nasal cannula therapy and non-invasive ventilation as an alternative to invasive ventilation. In the drug treatments section, we focused on three classes for severe COVID-19 treatment: antiviral drugs, immune-based agents, and anticoagulation therapy. We did not discuss antibody drugs and vaccination, as they are not used for severe COVID-19 treatment.
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Quantum correlation is a key concept characterizing the properties of quantum light sources and is important for developing quantum applications with superior performance. In particular, it enables photon pairs that are widely separated in the frequency domain, one in the visible region, the other in the infrared region, to be used for quantum infrared sensing without direct detection of infrared photons. Here, simultaneous multiwavelength and broadband phase matching in a nonlinear crystal could provide versatile photon-pairs source for broadband infrared quantum sensing. This paper describes direct generation and detection of two quantum-correlated photon pairs produced via simultaneous phase-matched processes in periodic crystals. These simultaneous photon pairs provide a correlated state with two frequency modes in a single pass. To confirm the correlation, we constructed an infrared-photon counting system with two repetition-synchronized fiber lasers. We performed coincidence measurements between two pairs, 980 nm and 3810 nm, and 1013 nm and 3390 nm, which yielded coincidence-to-accidental ratios of 6.2 and 6.5, respectively. We believe that our novel correlated light source with two separate pairs in the visible and infrared region complements a wide-range of multi-dimensional quantum infrared processing applications.
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A 70-year-old man began to cough. Chest X-ray showed a tumor in the center, pleural effusion on the left side, and diffuse granular shadows on the right side. Chest computed tomography (CT) showed bronchial wall thickening and numerous granular shadows. We suspected diffuse panbronchiolitis. Thus, transbronchial lung biopsy (TBLB) and transbronchial lung cryobiopsy (TBLC) were performed. The tissue size obtained was 1 mm by TBLB and 6 mm at 5 seconds by TBLC. Histological analysis of the TBLB specimen showed lymphocyte infiltration, no fibrosis in Hematoxylin-eosin (HE) staining, and no elastic fibers in Elastica van Gieson (EVG) staining. On the other hand, TBLC specimens showed inflammatory cell infiltration and fibrosis around the bronchioles in HE staining and hypertrophy of elastic fibers in EVG staining. It was diagnosed as diffuse panbronchiolitis (DPB) from clinical and pathological findings. Cryobiopsy is useful in diagnosing DPB as well as interstitial pneumonia and lung cancer.
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Thoracoscopy under local anaesthesia is effective for the diagnosis of tuberculous pleurisy (TP), mesothelioma and pleural metastases of lung cancer, etc. It has recently been reported that cryobiopsy is useful for obtaining sufficient tissue, achieving a greater depth, and avoiding crush artefact than biopsy forceps. However, the utility of the tissue obtained by cryobiopsy for culture for diagnosing TP is unknown. We compared positivity rates of tissue culture obtained by biopsy forceps and cryobiopsy in seven TP patients. The median tissue size was 2 mm by biopsy forceps and 6 mm by cryobiopsy. The pathological diagnostic rate of pleural tissue was 85.7% with biopsy forceps and 100% with cryobiopsy. However, the positivity rate of tissue culture was 57.1% with biopsy forceps and 28.5% with cryobiopsy. Since rapid freezing with a cryoprobe makes it difficult for bacteria to grow, it is possible that cryobiopsy might not be useful for obtaining a tissue culture in TP cases. However, since the sample size of this study was small, analysis of more cases is required to confirm our results.
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A 41-year-old man presented with chronic cough and chest pain. Laboratory tests revealed anemia, inflammation, hypoalbuminemia, polyclonal hypergammaglobulinemia, and elevated interleukin-6 levels. Computed tomography revealed diffuse bilateral pulmonary nodules and multicentric lymphadenopathy. Histopathology of the pulmonary nodule resembled pulmonary hyalinizing granuloma (PHG), whereas lymph node histopathology was consistent with idiopathic multicentric Castleman disease (iMCD). The patient was diagnosed with iMCD involving PHG-like pulmonary nodules. Little is known about the association between these two diseases, and the present case provides insights regarding the relationship between PHG and iMCD.