High-Speed Three-Dimensional Scanning Force Microscopy Visualization of Subnanoscale Hydration Structures on Dissolving Calcite Step Edges.

Hydration at solid-liquid interfaces plays an essential role in a wide range of phenomena in biology and in materials and Earth sciences. However, the atomic-scale dynamics of hydration have remained elusive because of difficulties associated with their direct visualization. In this work, a high-speed three-dimensional (3D) scanning force microscopy technique that produces 3D images of solid-liquid interfaces with subnanoscale resolution at a rate of 1.6 s per 3D image was developed. Using this technique, direct 3D images of moving step edges were acquired during calcite dissolution in water, and hydration structures on transition regions were visualized. A Ca(OH)2 monolayer was found to form along the step edge as an intermediate state during dissolution. This imaging process also showed that hydration layers extended from the upper terraces to the transition regions to stabilize adsorbed Ca(OH)2. This technique provides information that cannot be obtained via conventional 1D/2D measurement methods.

Characterization of anisotropic pore structure and dense selective layer of capillary membranes for long-term ECMO by cross-sectional ion-milling method.

Since the COVID-19 pandemic of 2020-2023, extracorporeal membrane oxygenator (ECMO) has attracted considerable attention worldwide. It is expected that ECMO with long-term durability is put into practical use in order to prepare for next emerging infectious diseases and to facilitate manufacturing for novel medical devices. Polypropylene (PP) and polymethylpentene (PMP) capillary membranes are currently the mainstream for gas exchange membrane for ECMO. ECMO support days for COVID-19-related acute hypoxemic respiratory failure have been reported to be on average for 14 or 24 days. It is necessary to improve opposing functions such that promoting the permeation of oxygen and carbon dioxide and inhibiting the permeation of water vapor or plasma to develop sufficient durability for long-term use. For this purpose, accurately controlling the anisotropy of the pore structure of the entire cross section and functions of capillary membrane is significant. In this study, we focused on the cross-sectional ion-milling (CSIM) method, to precisely clarify the pore structure of the entire cross section of capillary membrane for ECMO, because there is less physical stress on the porous structure applied during the preparation of cross-sectional samples of porous capillary membranes. We attempted to observe the cross sections of commercially available PMP membranes using the CSIM method. As a result, we succeeded in fabricating fine-scale flat cross-sectional samples of PMP capillary membranes. The pore structures and the degree of anisotropy of the cross sections are quantitatively clarified. The achievements and the approaches of this study are being applied to the development of next-generation gas exchange membranes.

Aspiration pneumonia after SARS-CoV-2 Omicron infection frequently induced physical functional decline in Japan.

Introduction. Nursing and healthcare-associated pneumonia (NHCAP) mainly occurs in older people whose physical functions have declined, and it is the most common type of pneumonia in Japan, a super-ageing society. In older people who meet NHCAP criteria, respiratory tract infections are often accompanied by aspiration pneumonia.Gap statement. The SARS-CoV-2 Omicron variant frequently causes aspiration pneumonia and has induced a decline in physical function.Aim. To clarify functional outcomes at 1 year after hospital discharge in SARS-CoV-2 Omicron-related NHCAP cases.Methodology. We compared the functional outcomes between 259 patients with primary SARS-CoV-2 pneumonia and 223 patients with aspiration pneumonia.Results. Functional decline rates for calculating the Barthel index at the time of hospital discharge were higher in the aspiration pneumonia group than the primary SARS-CoV-2 pneumonia group [114 patients (51.6%) vs 70 patients (27.0%), P<0.0001]. Of 114 patients with aspiration pneumonia who had a decline in physical function at the time of hospital discharge, 91 (79.8%) still showed functional decline 1 year later. In contrast, 9.3% of patients had functional decline at 1 year after hospital discharge in the primary SARS-CoV-2 pneumonia group, which was significantly lower than in the aspiration pneumonia group.Conclusions. The Omicron variant showed decreased infectivity in the lungs and was less pathogenic compared with the Delta and former variants. However, physicians should recommend SARS-CoV-2 vaccination and non-pharmaceutical interventions, depending on the presence or absence of applicable criteria for NHCAP, even when the predominant strain is the Omicron variant.

Efficacy of ensitrelvir for cough due to COVID-19 Omicron variant in medical healthcare workers.

We evaluated the efficacy of ensitrelvir for the treatment of cough due to coronavirus disease 2019 Omicron variant in medical healthcare workers. A total of 633 patients were registered in this study: 206 patients chose ensitrelvir and 427 patients chose symptomatic treatment. Difference in score changes using the Leicester Cough Questionnaire between groups was 3.17 on day 4, 3.24 on day 7, and 2.46 on day 14. The analysis demonstrated a significant difference at all time points.

Invalidity of JRS atypical pneumonia prediction score in Omicron variant of COVID-19 pneumonia.

BACKGROUND: We evaluated whether the Japanese Respiratory Society (JRS) atypical pneumonia prediction score can be adapted for the diagnosis of COVID-19 pneumonia due to Omicron BA.1, BA.2, and BA.5 subvariants. METHODS: We enrolled a total of 547 patients with community-acquired COVID-19 pneumonia. Of the COVID-19 pneumonia patients, 198 cases were the Omicron BA.1 subvariant, 127 cases were the Omicron BA.2 subvariant, and 222 cases were the Omicron BA.5 subvariant. Patients with extremely severe pneumonia were excluded and finally 524 patients were analyzed. RESULTS: Rates of conformity for the six predictors were identical among the three Omicron groups, and high rates of conformity were observed in the following predictors: adventitious sounds; etiological agent; and a peripheral WBC count. The sensitivities of the diagnosis of atypical pneumonia in patients with COVID-19 pneumonia based on four or more predictors were 49.0% in the BA.1 subvariant group, 58.1% in the BA.2 subvariant group, and 51.0% in the BA.5 subvariant group. The diagnostic sensitivities for Omicron BA.1, BA.2, and BA.5 subvariant groups were 96.6%, 100%, and 96.4% for non-elderly (aged <60 years) patients and 28.4%, 29.7%, and 34.2% for elderly (aged ≥60 years) patients, respectively. CONCLUSIONS: In Omicron variant of COVID-19, the JRS atypical pneumonia prediction score is a useful tool for distinguishing between COVID-19 pneumonia and bacterial pneumonia only in patients aged <60 years.

Functional decline at 1 year in hospitalized elderly pneumonia with SARS-CoV-2 Omicron variant: Comparison with the ancestral strain and Alpha variant.

In the SARS-CoV-2 Omicron period, the pattern of pneumonia changed from primarily viral pneumonia to pneumonia mixed with bacteria in the elderly. We investigated functional outcomes at 1 year after hospital discharge in patients with primary Omicron pneumonia and pneumonia mixed with bacteria, mainly aspiration pneumonia. Functional decline rates calculated using the Barthel Index at 1 year after hospital discharge were significantly higher in the pneumonia mixed with bacteria group than the primary viral pneumonia group (42.6% vs. 20.5%, p < 0.0001). It is necessary to consider early rehabilitation and treatment in elderly patients even when the predominant strain is the Omicron variant.

Is the JRS atypical pneumonia prediction score useful in detecting COVID-19 pneumonia under nursing or healthcare settings?

BACKGROUND: SARS-CoV-2 causes frequent outbreaks in elderly care facilities that meet the criteria for nursing and healthcare-associated pneumonia (NHCAP). We evaluated whether the Japanese Respiratory Society (JRS) atypical pneumonia prediction score could be adapted to the diagnosis of nursing and healthcare acquired COVID-19 (NHA-COVID-19) with pneumonia. METHODS: We analyzed 516 pneumonia patients with NHA-COVID-19 and compared them with 1505 pneumonia patients with community-associated COVID-19 (CA-COVID-19). NHA-COVID-19 patients were divided into six groups; 80 cases had the ancestral strain, 76 cases had the Alfa variant, 30 cases had the Delta variant, 120 cases had the Omicron subvariant BA.1, 53 cases had the Omicron subvariant BA.2, and 157 cases had the Omicron subvariant BA.5. RESULTS: The sensitivities of the diagnosis of atypical pneumonia in patients with NHA-COVID-19 based on four or more predictors were 22.8 % in the ancestral strain group, 32.0 % in the Alfa variant group, 34.5 % in the Delta variant group, 23.1 % in the BA.1 subvariant group, 32.7 % in the BA.2 subvariant group, and 30.4 % in the BA.5 subvariant group. The diagnostic sensitivity for the presumptive diagnosis of atypical pneumonia was significantly lower for NHA-COVID-19 than for CA-COVID-19 (28.2 % vs 64.1 %, p < 0.0001). CONCLUSIONS: Our present study demonstrated that the JRS atypical pneumonia prediction score is not a useful tool in elderly patients even if there is a lot of atypical pneumonia in the NHCAP group. The caution is necessary that JRS atypical pneumonia prediction score was not fully applied to prediction for NHA-COVID-19 pneumonia.

Nursing and healthcare-associated pneumonia due to SARS-CoV-2 Omicron variant.

BACKGROUND: There were many differences in the clinical characteristics between nursing and healthcare-associated pneumonia (NHCAP) and community-acquired pneumonia (CAP) due to the SARS-CoV-2 ancestral strain, Alpha variant and Delta variant. With the replacement of the Delta variant by the Omicron variant, the Omicron variant showed decreased infectivity to lung and was less pathogenic. We investigated the clinical differences between NHCAP and CAP due to the Omicron variant. METHODS: We analyzed 516 NHCAP and 547 CAP patients with COVID-19 pneumonia. Of 516 patients with COVID-19 NHCAP, 330 cases were the Omicron variant (120 cases were BA.1, 53 cases were BA.2, and 157 cases were BA.5 subvariants) and 186 cases were non-Omicron variants. RESULTS: The median age, frequency of comorbid illness, rates of intensive care unit (ICU) stay, and mortality rate were significantly higher in Omicron patients with NHCAP than in those with CAP. Rates of ICU stay and in-hospital mortality were significantly higher in NHCAP patients with non-Omicron variants compared with those in the Omicron variant group. No clinical differences were observed in patients with NHCAP among the Omicron BA.1, BA.2, and BA.5 subvariant groups. CONCLUSIONS: The present study supported that the NHCAP category is necessary not only for bacterial pneumonia but also viral pneumonia. It is necessary to consider prevention and treatment strategies depending on the presence or absence of applicable criteria for NHCAP.

Sulfamethoxazole-trimethoprim for pneumocystis pneumonia prophylaxis, causes of discontinuation and thrombocytopenia observed during administration: A single-center retrospective study.

INTRODUCTION: The development of pneumocystis pneumonia (PCP) has recently become a growing concern; thus, its prevention has become increasingly important. Sulfamethoxazole-trimethoprim (ST) is a cost-effective first-line and prophylactic treatment for PCP. However, ST administration criteria for PCP prophylaxis remain unclear and are often discontinued because of adverse events (AEs). In this study, we aimed to investigate the causes of ST discontinuation and the associated AEs using objective data. METHODS: We retrospectively analyzed the data of 162 patients admitted to Kansai Medical University Hospital between January 2018 and December 2020, who received ST for PCP prophylaxis. We compared clinical characteristics, laboratory data, and incidence of AEs between ST non-discontinuation and ST discontinuation groups. Additionally, we divided the patients into non-developing and developing thrombocytopenia (≥ Grade 1) groups based on the investigation results. RESULTS: No patients developed PCP while receiving ST. The most common causes of ST discontinuation were thrombocytopenia (37%), liver dysfunction (20%), and rash (18%). Multivariate analysis revealed thrombocytopenia (≥ Grade 1) as a factor significantly associated with ST discontinuation. Furthermore, we identified three factors correlated with thrombocytopenia (≥ Grade 1): age ≥50 years, lymphocyte count <1000/µL, and platelet count <180,000/µL. CONCLUSIONS: Patients with the aforementioned factors are at higher risk of developing thrombocytopenia (≥ Grade 1) during ST administration for PCP prophylaxis. Therefore, platelet count monitoring is essential to enhance safety and efficacy of ST treatment. Nonetheless, further research is warranted to explore additional implications and interventions.

Comparison of pneumonia severity scores for COVID-19 patients with the Omicron variant.

INTRODUCTION: We demonstrated that there was a significant relationship between the severity measured using the A-DROP scoring system and the mortality rate in patients with COVID-19 community-acquired pneumonia (CAP) in the ancestral strain, Alpha variant, and Delta variant. We investigated the usefulness of the A-DROP scoring system in SARS-CoV-2 Omicron variant CAP and compared it with severity scores, the Pneumonia Severity Index (PSI) and CURB-65 score. METHODS: We analyzed a total of 547 patients with COVID-19 CAP Omicron variant; 198 cases were the BA.1 subvariant, 127 cases were the BA.2 subvariant, and 222 cases were the BA.5 subvariant, respectively. RESULTS: The mortality rates in patients with COVID-19 CAP among the three Omicron subvariants were identical in each pneumonia severity group. The mortality rate in patients with the Omicron variant was 0 % in patients classified with mild disease, 0.6 % in those with moderate disease, 10.4 % in those with severe disease, and 34.8 % in those with extremely severe disease. The mortality rate in patients with COVID-19 CAP increased depending on the severity classified according to the A-DROP system in each of the Omicron subvariants (Cochran-Armitage trend test; p < 0.001). The values of the area under the curve in Receiver Operating Characteristic analysis for prediction of 30-day mortality was 0.881, 0.879, and 0.863 for A-DROP, PSI, and CURB-65, respectively. There were no significant differences in the predictive ability of each pneumonia severity score. CONCLUSIONS: Our results demonstrated that the A-DROP scoring system is useful for predicting mortality in patients with COVID-19 CAP.

Efficacy of Gefapixant, a P2X3 Antagonist, for Refractory Atopic Cough.

Cough, a frequent symptom encountered in clinical practice, often has a considerable impact on patients' lives. There is an urgent need to investigate more potent antitussive treatments for chronic refractory cough, particularly atopic cough, which is a major cause of chronic refractory cough in Japan. Previous studies have shown that eosinophilic tracheobronchitis with hypersensitivity to sensory nerve C-fibers is the pathophysiology of atopic cough. Gefapixant is a first-in-class P2X3 antagonist that has recently become available for clinical use in patients with refractory coughs. A 64-year-old female non-smoker presented to our hospital with a complaint of chronic intractable cough due to atopic cough. Addition of gefapixant (90 mg/day) to her previous treatment improved her distressing cough, despite the partial efficacy of many other drugs. The findings of this case demonstrate that P2X3 inhibition is a viable therapeutic option for patients with chronic refractory cough caused by atopic cough. This case report offers valuable information regarding currently available treatment options for refractory chronic refractory cough caused by atopic cough. There remains an urgent need to clarify the disease entities presenting with chronic cough that can be effectively treated by inhibiting P2X3.

Aetiological agents of adult community-acquired pneumonia in Japan: systematic review and meta-analysis of published data.

OBJECTIVE: Epidemiological information is essential in providing appropriate empiric antimicrobial therapy for pneumonia. This study aimed to clarify the epidemiology of community-acquired pneumonia (CAP) by conducting a systematic review of published studies in Japan. DESIGN: Systematic review. DATA SOURCE: PubMed and Ichushi web database (January 1970 to October 2022). ELIGIBILITY CRITERIA: Clinical studies describing pathogenic micro-organisms in CAP written in English or Japanese, excluding studies on pneumonia other than adult CAP, investigations limited to specific pathogens and case reports. DATA EXTRACTION AND SYNTHESIS: Patient setting (inpatient vs outpatient), number of patients, concordance with the CAP guidelines, diagnostic criteria and methods for diagnosing pneumonia pathogens as well as the numbers of each isolate. A meta-analysis of various situations was performed to measure the frequency of each aetiological agent. RESULTS: Fifty-six studies were included and 17 095 cases of CAP were identified. Pathogens were undetectable in 44.1% (95% CI 39.7% to 48.5%). Streptococcus pneumoniae was the most common cause of CAP requiring hospitalisation or outpatient care (20.0% (95% CI 17.2% to 22.8%)), followed by Haemophilus influenzae (10.8% (95% CI 7.3% to 14.3%)) and Mycoplasma pneumoniae (7.5% (95% CI 4.6% to 10.4%)). However, when limited to CAP requiring hospitalisation, Staphylococcus aureus was the third most common at 4.9% (95% CI 3.9% to 5.8%). Pseudomonas aeruginosa was more frequent in hospitalised cases, while atypical pathogens were less common. Methicillin-resistant S. aureus accounted for 40.7% (95% CI 29.0% to 52.4%) of S. aureus cases. In studies that used PCR testing for pan-respiratory viral pathogens, human enterovirus/human rhinovirus (9.4% (95% CI 0% to 20.5%)) and several other respiratory pathogenic viruses were detected. The epidemiology varied depending on the methodology and situation. CONCLUSION: The epidemiology of CAP varies depending on the situation, such as in the hospital versus outpatient setting. Viruses are more frequently detected by exhaustive genetic searches, resulting in a significant variation in epidemiology.

Efficacy of gefapixant, a P2X3 antagonist, for lung cancer-related cough: a case report.

Cough is a frequent symptom accompanied by lung cancer. More potent antitussive treatment for this complex and distressing symptom is required, but anti-cancer chemotherapy cannot fully manage the cough. Inhibition of vagal nerves might control coughing in patients with troublesome lung cancer-related cough and P2X3 inhibitory therapy may be useful for targeting neuronal function. We report the case of a woman in her late 70s who never smoked and had advanced lung cancer. She visited our hospital complaining of serious deterioration of a non-productive cough. She was diagnosed with relapse of lung cancer, but she requested 2-week anti-tussive therapy before second-line chemotherapy. Gefapixant (P2X3 antagonist) add-on at a dose of 90 mg/day (45 mg twice daily as the usual dosage in Japan) improved her cough as indicated by an improvement in the visual analog scale for cough from 70 to 20 mm and in the Japanese version of the Leicester Cough Questionnaire from 8.2 to 16.3, despite a deterioration in lung cancer after 2 weeks. There are no current guidelines for cough accompanied by lung cancer; however, our findings suggest that P2X3 inhibition is a potent therapeutic option for lung cancer-related cough.

Clinical Efficacy of the Neutralizing Antibody Therapy Sotrovimab in Patients with SARS-CoV-2 Omicron BA.1 and BA.2 Subvariant Infections.

Sotrovimab, an antibody active against severe acute respiratory syndrome coronavirus 2 that neutralizes antibodies, reduced the risk of COVID-19-related hospitalization or death in studies conducted before the emergence of the Omicron variant. The objective of this study is to evaluate the clinical efficacy of sotrovimab in patients with mild to moderate COVID-19 Omicron BA.1 and BA.2 subvariant infections using a propensity score matching method. The propensity score-matched cohort study population was derived from patients who received sotrovimab. We derived a comparator group from an age- and sex-matched population who were recuperating in a medical facility after COVID-19 infection or from elderly person entrance facilities during the same period who were eligible for but did not receive sotrovimab treatment. In total, 642 patients in the BA.1 subvariant group and 202 in the BA.2 subvariant group and matched individuals were analyzed. The outcome was the requirement for oxygen therapy. In the treatment group, 26 patients with the BA.1 subvariant and 8 patients with the BA.2 subvariant received oxygen therapy. The administration of oxygen therapy was significantly lower in the treatment group than in the control group (BA.1 subvariant group, 4.0% vs. 8.7%, p = 0.0008; BA.2 subvariant group, 4.0% vs. 9.9%, p = 0.0296). All these patients were admitted to our hospitals and received additional therapy and then recovered. No deaths were observed in either group. Our results demonstrate that the sotrovimab antibody treatment may be associated with a reduction in the requirement for oxygen therapy among high-risk patients with mild to moderate COVID-19 Omicron BA.1 and BA.2 subvariants.

Validation of JRS atypical pneumonia score in patients with community-acquired Chlamydia psittaci pneumonia.

INTRODUCTION: The Japanese Respiratory Society (JRS) atypical pneumonia score is a useful tool for the rapid presumptive diagnosis of atypical pneumonia. We investigated the clinical features of community-acquired pneumonia (CAP) due to Chlamydia psittaci and validated the JRS atypical pneumonia score in patients with C. psittaci CAP. METHODS: This study was conducted at 30 institutions and assessed a total of 72 sporadic cases with C. psittaci CAP, 412 cases with Mycoplasma pneumoniae CAP, and 576 cases with Streptococcus pneumoniae CAP. RESULTS: Sixty-two of 72 patients with C. psittaci CAP had a history of avian exposure. Among the six parameters of the JRS score, matching rates of four parameters were significantly lower in the C. psittaci CAP than the M. pneumoniae CAP in the following parameters: age <60 years, no or minor comorbid illness, stubborn or paroxysmal cough, and absence of chest adventitious sounds. The sensitivity of the diagnosis of atypical pneumonia in patients with C. psittaci CAP was significantly lower than the M. pneumoniae CAP (65.3% and 87.4%, p < 0.0001). When the diagnostic sensitivity was analyzed for different ages, the diagnostic sensitivities for the C. psittaci CAP were 90.5% for non-elderly patients and 30.0% for elderly patients. CONCLUSIONS: The JRS atypical pneumonia score is a useful tool for distinguishing between C. psittaci CAP and bacterial CAP in patients aged <60 years, but not in patients aged ≥60 years. A history of avian exposure in middle-aged patients with normal white blood cell count may be suggestive of C. psittaci pneumonia.

Alectinib in a patient with ALK-positive non-small lung cancer unable to swallow capsules.

INTRODUCTION: The treatment landscape of metastatic non-small-cell lung cancer (NSCLC) has changed dramatically in the last decade. Anaplastic lymphoma kinase (ALK) rearrangement has been a focus of interest since ALK inhibitors produced outstanding clinical results compared with chemotherapy with cytotoxic agents in patients with ALK-positive NSCLC. CASE REPORT: We present the case of a 56-year-old woman with metastatic ALK-positive NSCLC and an inability to swallow capsules or tablets. Unfortunately, all ALK inhibitors are capsule or tablet formulations. MANAGEMENT AND OUTCOME: We, therefore, decided to administer alectinib orally by opening the capsules and suspending the contents in water. Clinical imaging performed 12 months after initiating alectinib therapy indicated a complete response (CR). After 54 months of follow-up, CR has been maintained, and oral alectinib therapy has continued with no recurrence of the swallowing disturbance. DISCUSSION: There are no current guidelines for oral targeted therapy in patients with swallowing disturbance, but alectinib administered orally by opening the capsules and suspending the contents in water can be a treatment option in patients with ALK-positive NSCLC and swallowing difficulty.

Prognosis of activities of daily living function in hospitalized patients with nursing and healthcare-associated pneumonia due to COVID-19.

Nursing and healthcare-associated pneumonia (NHCAP) is associated with decreased physical function. We investigated the functional outcomes at 1 year after hospital discharge in patients with COVID-19 pneumonia. Functional decline rates for calculating the Barthel Index at the time of hospital discharge and at 1 year after hospital discharge were significantly higher in the NHCAP group than the community-acquired pneumonia group (at hospital discharge, 54.0% vs. 31.2%, respectively, p < 0.0001; 1 year follow-up, 37.9% vs. 8.6%, respectively, p < 0.0001). It is necessary to consider early rehabilitation, and treatment depending on the presence or absence of applicable criteria for NHCAP.

Assessment of the pneumonia severity score in community-acquired and nursing and healthcare-associated pneumonia due to COVID-19.

INTRODUCTION: The Japanese Respiratory Society (JRS) pneumonia guidelines recommend simple predictive rules, the A-DROP scoring system, for assessment of the severity of community-acquired pneumonia (CAP) and nursing and healthcare-associated pneumonia (NHCAP). We evaluated whether the A-DROP system can be adapted for assessment of the severity of coronavirus disease 2019 (COVID-19) pneumonia. METHODS: Data from 1141 patients with COVID-19 pneumonia were analyzed, comprising 502 patients observed in the 1st to 3rd wave period, 338 patients in the 4th wave and 301 patients in the 5th wave in Japan. RESULTS: The mortality rate and mechanical ventilation rate were 0% and 1.4% in patients classified with mild disease (A-DROP score, 0 point), 3.2% and 46.7% in those with moderate disease (1 or 2 points), 20.8% and 78.3% with severe disease (3 points), and 55.0% and 100% with extremely severe disease (4 or 5 points), indicating an increase in the mortality and mechanical ventilation rates in accordance with severity (Cochran-Armitage trend test; p = <0.001). This significant relationship between the severity in the A-DROP scoring system and either the mortality rate or mechanical ventilation rate was observed in patients with COVID-19 CAP and NHCAP. In each of the five COVID-19 waves, the same significant relationship was observed. CONCLUSIONS: The mortality rate and mechanical ventilation rate in patients with COVID-19 pneumonia increased depending on severity classified according to the A-DROP scoring system. Our results suggest that the A-DROP scoring system can be adapted for the assessment of severity of COVID-19 CAP and NHCAP.