Effects of sodium-glucose co-transporter 2 inhibitors on ultrafiltration in patients with peritoneal dialysis: a protocol for a randomized, double-blind, placebo-controlled, crossover trial (EMPOWERED).

BACKGROUND: Volume overload is common and associated with high mortality in patients on peritoneal dialysis (PD). Traditional strategies including diuretics, water/salt restriction, and icodextrin-based solutions cannot always fully correct this condition, necessitating novel alternative strategies. Recent studies confirmed the expression of sodium-glucose cotransporter 2 (SGLT2) in the human peritoneum. Experimental data suggest that SGLT2 inhibitors decrease glucose absorption from the PD solution, thereby increasing the ultrafiltration volume. This trial aims to assess whether SGLT2 inhibitors increase the ultrafiltration volume in patients on PD. METHODS: The EMPOWERED trial (trial registration: jRCTs051230081) is a multicenter, randomized, double-blind, placebo-controlled, crossover trial. Patients with clinically diagnosed chronic heart failure are eligible regardless of the presence of diabetes if they use at least 3 L/day glucose-based PD solutions. Participants will be randomly assigned (1:1) to receive empagliflozin 10 mg once daily and then placebo or vice versa. Each treatment period will last 8 weeks with a 4-week washout period. This study will recruit at least 36 randomized participants. The primary endpoint is the change in the daily ultrafiltration volume from baseline to week 8 in each intervention period. The key secondary endpoints include changes in the biomarkers of drained PD solutions, renal residual function, and anemia-related parameters. CONCLUSIONS: This trial aims to assess the benefit of SGLT2 inhibitors in fluid management with a novel mechanism of action in patients on PD. It will also provide insights into the effects of SGLT2 inhibitors on solute transport across the peritoneal membrane and residual renal function.

Coronavirus Disease 19 (COVID-19) Vaccine Effectiveness Against Symptomatic Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection During Delta-Dominant and Omicron-Dominant Periods in Japan: A Multicenter Prospective Case-control Study (Factors Associated with SARS-CoV-2 Infection and the Effectiveness of COVID-19 Vaccines Study).

BACKGROUND: Although several coronavirus disease 2019 (COVID-19) vaccines initially showed high efficacy, there have been concerns because of waning immunity and the emergence of variants with immune escape capacity. METHODS: A test-negative design case-control study was conducted in 16 healthcare facilities in Japan during the Delta-dominant period (August-September 2021) and the Omicron-dominant period (January-March 2022). Vaccine effectiveness (VE) against symptomatic severe acute respiratory syndrome coronavirus 2 infection was calculated for 2 doses for the Delta-dominant period and 2 or 3 doses for the Omicron-dominant period compared with unvaccinated individuals. RESULTS: The analysis included 5795 individuals with 2595 (44.8%) cases. Among vaccinees, 2242 (55.8%) received BNT162b2 and 1624 (40.4%) received messenger RNA (mRNA)-1273 at manufacturer-recommended intervals. During the Delta-dominant period, VE was 88% (95% confidence interval [CI], 82-93) 14 days to 3 months after dose 2 and 87% (95% CI, 38-97) 3 to 6 months after dose 2. During the Omicron-dominant period, VE was 56% (95% CI, 37-70) 14 days to 3 months since dose 2, 52% (95% CI, 40-62) 3 to 6 months after dose 2, 49% (95% CI, 34-61) 6+ months after dose 2, and 74% (95% CI, 62-83) 14+ days after dose 3. Restricting to individuals at high risk of severe COVID-19 and additional adjustment for preventive measures (ie, mask wearing/high-risk behaviors) yielded similar estimates, respectively. CONCLUSIONS: In Japan, where most are infection-naïve, and strict prevention measures are maintained regardless of vaccination status, 2-dose mRNA vaccines provided high protection against symptomatic infection during the Delta-dominant period and moderate protection during the Omicron-dominant period. Among individuals who received an mRNA booster dose, VE recovered to a high level.

Inflammation as an exacerbation marker and target for prophylaxis against Coronavirus Disease 2019-related thrombosis.

Objectives: There are currently no appropriate markers and target for prophylaxis against COVID-19-related thrombosis, especially in the not-severe cases. We tested the hypothesis that inflammation is a suitable marker and target for prophylaxis against COVID-19-related thrombosis. Methods: Data of all 32 COVID-19 patients admitted to Saitama Medical Center between January 1 and March 30, 2021, were analyzed. Patients were divided into severe (requiring oxygen, n=12) and non-severe (no requirement for oxygen, n=20), and also those with high C-reactive protein (CRP) level (cutoff value: 30 mg/L, n=21) and low-CRP (n=11). We also compared the clinical and laboratory data of a 46-year-old post-liver transplant male patient, who was treated with a combination of immunosuppressants (methylprednisolone, fludrocortisone, cyclosporine, and everolimus) with those of other COVID-19 patients, using the Smirnoff-Grubbs and Box plots tests. Results: The levels of CRP, ferritin, lactate dehydrogenase, aspartate aminotransferase, and thrombin-antithrombin complex (TAT) were significantly higher in the high-severity group than the low-severity group; while other coagulation parameters were comparable. The time between onset of illness and blood levels of lactate dehydrogenase, fibrinogen, D-dimer, TAT, and plasmin alpha2-plasmin inhibitor complex (PIC) were significantly higher whereas lymphocyte count was significantly lower in the high-CRP group. Extremely low levels of TAT, PIC, and plasminogen activator inhibitor-1 (PAI-1) were recorded in the liver transplant patient treated with immunosuppressants. The TAT, PIC, and PAI-1 levels were deemed outliers. Conclusions: Inflammation is a potentially suitable marker and target for prophylaxis against COVID-19-related thrombosis.

A case of renal abscess and bacteremia caused by Burkholderia pseudomallei that was first unidentifiable by matrix-assisted laser desorption ionization-time of flight mass spectrometry in a Japanese-man.

Melioidosis, an infectious disease caused by Burkholderia pseudomallei, is endemic in specific regions, including Southeast Asia and Northern Australia. In Japan, where no autochthonous has been reported to date, melioidosis is a rare infectious disease. Herein, we report a case of melioidosis in a 68-year-old Japanese man with renal abscess and bacteremia, but without pneumonia. The patient presented to our hospital and was admitted for fever and chills that have persisted for two months. It was speculated that he was infected in Thailand, where his family lives because he shuttled between Thailand and Japan. Blood cultures on admission identified Burkholderia species; however, the species was unidentifiable by matrix-assisted laser desorption ionization-time of flight mass spectrometry. Further re-examination, including culture, loop-mediated isothermal amplification, and multiplex polymerase chain reaction methods, finally identified Burkholderia pseudomallei. We treated the patient with intravenous ceftazidime for four weeks. In addition to the antibiotics administration, puncture drainage of the renal abscess was performed, and he gradually became afebrile. Intravenous ceftazidime was switched to oral sulfamethoxazole/trimethoprim on post-admission day 32, and he was discharged. After five months of oral sulfamethoxazole/trimethoprim, no recurrence was observed one year after discharge. To diagnose melioidosis, especially in non-endemic areas, a precise and thorough understanding of its epidemiology, presentation, and identification methods is necessary.

Nondestructive High-Sensitivity Detections of Metallic Lithium Deposited on a Battery Anode Using Muonic X-rays.

Metallic Li deposited on the anode is known to induce short circuiting and degradation of the charge capacity of Li-ion batteries. However, no reliable technique is currently available to observe such Li metal without removing the case of the battery. An elemental analysis using muonic X-rays is proposed here because of its unique properties of nondestructive measurement, high sensitivity to light elements, and depth resolution. We demonstrated that this technique can be applied to detection of Li deposited on the surface of an anode containing Li ions, using a fully charged anode with Li deposited due to overcharge in an Al-laminated plastic pouch. The basis for the detection method is the difference in the atomic Coulomb capture ratio of the negative muons between the Li metal and ions. We have found, as a result, that the intensity of the muonic X-rays from metallic Li was approximately 50 times higher than that from Li ions. Consequently, the Li metal on the anode was clearly distinguishable from the intercalated Li ions in the anode. Furthermore, measurements of two overcharged anodes with 1.3 and 2.7 mg of metallic Li deposition, respectively, indicated that this technique is suitable for quantitative analysis. Distribution analysis is also possible, as shown by a preliminary observation on an overcharged anode from the back side. Therefore, this technique offers a new approach to the analysis of Li deposited on the anode of a Li-ion pouch battery.

Recommendations for Maintaining the Cardiovascular Care System Under the Conditions of the COVID-19 Pandemic　- 1st Edition, April 2020.

BACKGROUND: The Japanese Circulation Society proposes recommendations for all healthcare professionals involved in cardiovascular medicine to protect them from infection and ensure that seriously ill patients requiring urgent care receive proper treatment.Methods and Results:Patients are divided into "Positive or suspected coronavirus disease 2019 (COVID-19)" and "All others". Furthermore, tests and treatments are divided into emergency or standby. For each category, we propose recommendations. CONCLUSIONS: To maintain the cardiovascular care system, The Japanese Circulation Society recommends completely preventing nosocomial COVID-19 infections, ensuring adequate PPE necessary for healthcare personnel, and learning and implementing standard precautions.

Infective endocarditis caused by Capnocytophaga canimorsus; a case report.

BACKGROUND: Capnocytophaga canimorsus is a gram-negative bacterium and an oral commensal in dogs and cats, but occasionally causes serious infections in humans. Septicemia is one of the most fulminant forms, but diagnosis of C. canimorsus infection is often difficult mainly because of its very slow growth. C. canimorsus infective endocarditis (IE) is rare and is poorly understood. Since quite a few strains produce ß-lactamase, antimicrobial susceptibility is pivotal information for adequate treatment. We herein report a case with C. canimorsus IE and the results of drug susceptibility test. CASE PRESENTATION: A 46-year-old man had a dog bite in his left hand 3 months previously. The patient was referred to our hospital for fever (body temperature > 38 °C), visual disturbance, and dyspnea. Echocardiography showed aortic valve regurgitation and vegetation on the leaflets. IE was diagnosed, and we initially administered cefazolin and gentamycin assuming frequently encountered microorganisms and the patient underwent aortic valve replacement. C. canimorsus was detected in the aortic valve lesion and blood cultures. It was also identified by 16S ribosome DNA sequencing. Ceftriaxone were started and continued because disk diffusion test revealed the isolate was negative for ß-lactamase and this case had cerebral symptoms. The patient successfully completed antibiotic treatment following surgery. CONCLUSIONS: We diagnosed C. canimorsus sepsis and IE by extended-period blood cultures and 16S ribosome DNA sequencing by polymerase chain reaction, and successfully identified its drug susceptibility.

Early postoperative change in serum creatinine predicts acute kidney injury after cardiothoracic surgery: a retrospective cohort study.

BACKGROUND: Acute kidney injury (AKI) is one of the most severe complications after cardiothoracic surgery (CTS). However, diagnosis of AKI by elevation of serum creatinine (SCr) misses a critical time period for prevention and treatment of AKI. We have observed that patients who develop AKI show a smaller SCr decrease after CTS than those without AKI. Hence, we hypothesized that the magnitude of the SCr change (ΔSCr) measured early after CTS can predict subsequent AKI. METHODS: We conducted a retrospective analysis from January 2014 to December 2016 to examine the association of ΔSCr with AKI. ΔSCr was calculated as follows: (early postoperative SCr on intensive care unit [ICU] admission) - (preoperative SCr). Established risk factors and demographics were included in the multivariate-adjusted logistic regression model. AKI was defined by SCr criteria of the Kidney Disease: Improving Global Outcomes group. RESULTS: Among 252 patients who underwent CTS, 69 developed AKI. The median ΔSCr was - 0.14 mg/dL (range - 0.96-0.45). Patients were divided into three groups based on ΔSCr: Group 1, ≤ - 0.2 mg/dL (n = 84); Group 2, > - 0.2 to < - 0.1 mg/dL (n = 76); and Group 3, ≥ - 0.1 mg/dL (n = 92). In the multivariate analysis, Group 3 had a significantly higher incidence of AKI than Group 1 (odds ratio, 7.34; 95% confidence interval 2.55-23.3). ΔSCr was an independent risk factor for AKI (odds ratio for every 0.1-mg/dL increase in ΔSCr, 1.55; 95% confidence interval 1.23-1.97). CONCLUSIONS: A minor change in the SCr level early after CTS can predict subsequent AKI just after ICU admission.

Hypercalcemia and acute kidney injury induced by eldecalcitol in patients with osteoporosis: a case series of 32 patients at a single facility.

BACKGROUND: Eldecalcitol (ELD) is an active vitamin D3 analog that is widely used in Japan for the treatment of osteoporosis. The most common adverse drug reaction of ELD is hypercalcemia. However, few reports have focused on acute kidney injury (AKI) associated with ELD-induced hypercalcemia. MATERIALS AND METHODS: We retrospectively reviewed the medical records at our hospital for cases of hypercalcemia-induced AKI between April 2013 and February 2018. Among them, we focused on patients who developed AKI secondary to ELD-induced hypercalcemia. RESULTS: Among 69 patients who developed hypercalcemia-induced AKI, 32 patients (46.4%) developed AKI associated with ELD-induced hypercalcemia. Their mean age was 82 ± 5 years, 97% of them were female, mean corrected serum calcium level was 12.2 ± 1.5 mg/dL, serum creatinine level was 2.5 ± 2.2 mg/dL, and estimated glomerular filtration rate was 23.9 ± 14.4 ml/min/1.73 m2 on admission. ELD administration was discontinued in all patients and some of them were treated with hydration with or without calcitonin, which was followed by a normalization of serum calcium level. Corrected serum calcium level on admission was significantly higher (p < .05) in patients treated with magnesium oxide. Although there were no significant differences, serum calcium and creatine levels on admission tended to be higher in patients who were treated with other drugs that affect renal hemodynamics and renal calcium metabolism than those not taking these drugs. CONCLUSIONS: Prescribers of ELD should regularly monitor serum calcium levels and kidney function to prevent hypercalcemia and AKI associated with ELD and pay more attention to concomitant drugs especially magnesium oxide.

[A Case of Legionella Pneumonia Causing Neurological Symptoms Related to a Reversible Corpus Callosum Lesion].

A 51-year-old man presented at the emergency department with a one-day history of fever, altered mental status, slurred speech, worsening gait instability, nausea, vomiting, and diarrhea. The patient did not have a history of alcoholism or drug abuse. On physical examination, crackles were heard over the right lower lobe. Neurological findings revealed ataxic gait, dysarthria and bilateral dysmetria upon finger-nose testing. The results of laboratory tests revealed leukocytosis, renal failure, and hyponatremia. Chest radiography and lung computed tomography (CT) revealed right lower lobe infiltrates with air bronchograms. The result of a urinary Legionella antigen test was positive. The results of brain CT and cerebrospinal fluid (CSF) analyses did not reveal any signs of infection, but brain magnetic resonance imaging (MRI) revealed a corpus callosum lesion upon admission. The patient's symptoms began to resolve after the administration of intravenous levofloxacin. A subsequent brain MRI examination performed 9 days after admission showed the complete resolution of the lesion. He was discharged 11 days after admission without any neurological sequelae. He was finally diagnosed as having clinically mild encephalitis/ encephalopathy with a reversible splenial lesion (MERS).

COVID-19 vaccine effectiveness against severe COVID-19 requiring oxygen therapy, invasive mechanical ventilation, and death in Japan: A multicenter case-control study (MOTIVATE study).

INTRODUCTION: Since the SARS-CoV-2 Omicron variant became dominant, assessing COVID-19 vaccine effectiveness (VE) against severe disease using hospitalization as an outcome became more challenging due to incidental infections via admission screening and variable admission criteria, resulting in a wide range of estimates. To address this, the World Health Organization (WHO) guidance recommends the use of outcomes that are more specific to severe pneumonia such as oxygen use and mechanical ventilation. METHODS: A case-control study was conducted in 24 hospitals in Japan for the Delta-dominant period (August-November 2021; "Delta") and early Omicron (BA.1/BA.2)-dominant period (January-June 2022; "Omicron"). Detailed chart review/interviews were conducted in January-May 2023. VE was measured using various outcomes including disease requiring oxygen therapy, disease requiring invasive mechanical ventilation (IMV), death, outcome restricting to "true" severe COVID-19 (where oxygen requirement is due to COVID-19 rather than another condition(s)), and progression from oxygen use to IMV or death among COVID-19 patients. RESULTS: The analysis included 2125 individuals with respiratory failure (1608 cases [75.7%]; 99.2% of vaccinees received mRNA vaccines). During Delta, 2 doses provided high protection for up to 6 months (oxygen requirement: 95.2% [95% CI:88.7-98.0%] [restricted to "true" severe COVID-19: 95.5% {89.3-98.1%}]; IMV: 99.6% [97.3-99.9%]; fatal: 98.6% [92.3-99.7%]). During Omicron, 3 doses provided high protection for up to 6 months (oxygen requirement: 85.5% [68.8-93.3%] ["true" severe COVID-19: 88.1% {73.6-94.7%}]; IMV: 97.9% [85.9-99.7%]; fatal: 99.6% [95.2-99.97]). There was a trend towards higher VE for more severe and specific outcomes. CONCLUSION: Multiple outcomes pointed towards high protection of 2 doses during Delta and 3 doses during Omicron. These results demonstrate the importance of using severe and specific outcomes to accurately measure VE against severe COVID-19, as recommended in WHO guidance in settings of intense transmission as seen during Omicron.

Atypical clinical and radiological presentations of lumbar spinal tuberculosis mimicking a spinal tumor: A case report.

INTRODUCTION: Tuberculosis (TB) is an important infectious disease worldwide. Classical spinal TB has specific radiological findings involving adjacent vertebral bodies with destruction of the intervertebral disc and involvement of paravertebral soft tissues with cold abscess formation. However, a few cases not exhibiting the radiological characteristics of TB spondylitis have been reported. We report a rare case of lumbar spinal TB with atypical clinical and radiological presentations that was difficult to differentiate from a malignant spinal tumor. PATIENT CONCERNS: A 21-year-old man, who had immigrated to Japan from the Philippines 5 years ago, without a significant medical history, presented with back pain lasting 1 month and progression of gait disturbance 2 weeks prior to presentation. DIAGNOSIS: Laboratory tests showed normal blood cell counts and normal value of C-reactive protein levels. Preoperative imaging studies indicated a possible spinal tumor. However, histopathologic findings of the epidural soft tissues at the first surgery led to the diagnosis of spinal mycobacterial infection. The diagnosis of spinal TB was confirmed by a positive culture of Mycobacterium tuberculosis obtained at the second surgery. INTERVENTIONS: Given the progressive nature of neurologic deterioration, instead of needle biopsy, we proceeded with surgical intervention 8 days after admission; simultaneous neural decompression and open biopsy. Histological findings of the excised epidural soft tissues led to the diagnosis of spinal mycobacterial infection. We performed the second surgery involving additional resection of epidural soft tissues for further dural decompression and to obtain specimens for mycobacterial culture. Immediately after the second surgery, the patient commenced combination therapy with anti-tuberculous drugs. OUTCOMES: The patient demonstrated significant recovery of motor function in the lower extremities, and was able to run at 2 months after the second surgery. The epidural granulomas completely disappeared on magnetic resonance imaging 3 months postoperatively. CONCLUSION: Atypical clinical and radiological presentations of spinal TB present a challenge for appropriate diagnosis and early treatment. Even in developed countries where there are very few spinal TB patients, clinicians should be aware that spinal TB is an important differential diagnosis, especially in elderly patients or patients coming from countries with a middle-high prevalence of TB.

Effectiveness of BA.1- and BA.4/BA. 5-Containing Bivalent COVID-19 mRNA Vaccines Against Symptomatic SARS-CoV-2 Infection During the BA.5-Dominant Period in Japan.

In this multicenter, prospective, test-negative, case-control study in Japan, the effectiveness of both BA.1-containing and BA.4/BA.5-containing bivalent coronavirus disease 2019 mRNA vaccines against symptomatic infection during the BA.5-dominant period was high compared with no vaccination (65% and 76%) and moderate compared with monovalent vaccines administered over half a year earlier (46% combined).

Immune escape and waning immunity of COVID-19 monovalent mRNA vaccines against symptomatic infection with BA.1/BA.2 and BA.5 in Japan.

BACKGROUND: Repeated emergence of variants with immune escape capacity and waning immunity from vaccination are major concerns for COVID-19. We examined whether the surge in Omicron subvariant BA.5 cases was due to immune escape or waning immunity through vaccine effectiveness (VE) evaluation. METHODS: A test-negative case-control study was conducted in 16 clinics/hospitals during the BA.1/BA.2-dominant and BA.5-dominant periods. VE against symptomatic infection was estimated after adjusting for age, sex, comorbidity, occupation, testing frequency, prior infection, close contact history, clinic/hospital, week, and preventive measures. Absolute VE (aVE) was calculated for 2/3/4 doses, compared to the unvaccinated. Relative VE (rVE) was calculated, comparing 3 vs 2 and 4 vs 3 doses. RESULTS: 13,025 individuals were tested during the BA.1/BA.2-dominant and BA.5-dominant periods with similar baseline characteristics. For BA.1/BA.2, aVE was 52 % (95 %CI:34-66) 14 days-3 months post-dose 2, 42 % (29-52) > 6 months post-dose 2, 71 % (64-77) 14 days-3 months post-dose 3, and 68 % (52-79) 3-6 months post-dose 3. rVE was 49 % (38-57) 14 days-3 months post-dose 3 and 45 % (18-63) 3-6 months post-dose 3. For BA.5, aVE was 56 % (27-73) 3-6 months post-dose 2, 32 % (12-47) > 6 months post-dose 2, 70 % (61-78) 14 days-3 months post-dose 3, 59 % (48-68) 3-6 months post-dose 3, 50 % (29-64) > 6 months post-dose 3, and 74 % (61-83) ≥ 14 days post-dose 4. rVE was 56 % (45-65) 14 days-3 months post-dose 3, 39 % (27-48) 3-6 months post-dose 3, 25 % (-2-45) > 6 months post-dose 3, and 30 % (-6-54) ≥ 14 days post-dose 4. CONCLUSIONS: Booster doses initially provided high protection against BA.5 at a level similar to that against BA.1/BA.2. However, the protection seemed shorter-lasting against BA.5, which likely contributed to the surge. Furthermore, rVE post-dose 4 was low even among recent vaccinees. These results support the introduction of variant-containing vaccines and emphasize the need for vaccines with longer duration of protection.

Hospital-acquired pneumonia in Japan may have a better mortality profile than HAP in the United States: a retrospective study.

The characteristics of hospital-acquired pneumonia (HAP) are not well documented. In the present study we investigated the severity and mortality, microbiological profile, and the value of Gram staining in culture-confirmed HAP in a Japanese hospital by retrospective review conducted at a Japanese university hospital. Only culture-confirmed cases with good specimen quality were included in the analysis. The clinical characteristics of HAP, as well as the causative organisms, were investigated. Furthermore, the prognostic ability of existing prediction rules were evaluated for prediction of overall mortality. Forty-two cases were enrolled in this analysis. The majority of patients were admitted to the ICU (61.9 %), and 40.5 % had ventilator-associated pneumonia (VAP). The 30-day mortality was 23.8 %, which is less than that reported in the United States. Factors commonly known to be associated with worse outcome in the USA did not appear to influence the mortality from HAP in Japan. The most frequent causative organisms were methicillin-resistant Staphylococcus aureus (MRSA), followed by Pseudomonas spp. Sensitivity and negative predictive value of Gram staining were 89.4 and 85.7 %, respectively. SMART-COP predicted 30-day mortality with an area under the ROC curve (AUC) >0.7. The characteristics of HAP in Japan differ from HAP reported in the USA. In addition to lower mortality, we found both fewer ICU cases and VAP. Gram staining of good-quality specimens demonstrated promising sensitivity to predict the causative organisms. SMART-COP predicted mortality with appropriate ROC curve (AUC).

SARS-CoV-2 RNA load and detection rate in exhaled breath condensate collected from COVID-19 patients infected with Delta variant.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant is considered responsible for worldwide surges in coronavirus disease 2019 (COVID-19) cases in 2021, with increased infectivity compared to the wild type (Wuhan-1). In a previous study, we identified temporal changes in wild-type SARS-CoV-2 RNA load and detection rate in EBC collected from COVID-19 patients. The primary objective of this study was to clarify temporal changes in Delta-variant SARS-CoV-2 RNA load and detection rates in EBC collected from patients, and to validate the feasibility of Delta-variant SARS-CoV-2 RNA detection from EBC for diagnosing COVID-19. The secondary objective was to compare SARS-CoV-2 RNA loads in EBC between Delta-variant and wild-type. Subjects were 41 COVID-19 patients infected with the Delta-variant. EBC samples were collected from subjects on the day of or the day after admission using R-tube® (Respiratory Research, Austin, Texas, USA), as in our previous study. SARS-CoV-2 RNA in EBC samples was detected and quantified by RT-PCR assay targeting the E gene, using the same settings and reagents as in the previous study. The results indicated that SARS-CoV-2 RNA load in EBC collected from subjects infected with Delta-variant decreased exponentially with the passage of days from symptom onset. Sustained high detection rates support the feasibility of Delta-variant SARS-CoV-2 RNA detection from EBC by RT-PCR assay as a diagnostic test for COVID-19 within 8 d of onset. SARS-CoV-2 RNA load in EBC collected 2-8 d from onset was significantly higher in Delta-variant-infected subjects than in wild-type-infected subjects on a day-to-day basis (p= 0.005-0.029). However, because of the heterogeneity of the study cohort, conclusions cannot be reached regarding differences in viral RNA load between strains, regardless of the timing of EBC collection.

How Fluorine Introduction Solves the Spinel Transition, a Fundamental Problem of Mn-Based Positive Electrodes.

In pursuit of high-capacity Mn-based oxides as positive electrode materials for lithium-ion batteries, the changes in the charge-discharge curve due to the spinel transition still stand in the way of the cycling stability. We found in this study that Li1.12Mn0.74O1.60F0.40 (LMOF05) positive electrodes with a loose-crystalline rock salt structure (LCRS), in which F is placed near Mn, show a stable and high capacity (300 mA h g-1, 952 W h kg-1) with little change in the charge-discharge curve. We demonstrated by F K-edge soft X-ray absorption spectroscopy and X-ray diffraction (XRD) that a part of F in the LCRS positive electrode forms F-Mn bonds. Operando XRD/X-ray absorption fine structure measurements revealed the lattice size and Mn surrounding environment during charge/discharge of F-containing LCRS positive electrodes (LMOF05), LCRS-LiMnO2 (LMO), and a spinel-like Li1.1Al0.1Mn1.8O4 positive electrode (SPINEL). Micro- and macroscopic structural changes indicate how the introduction of F suppresses the local spinel transition in Mn-based positive electrodes. These findings should be an effective tool for applying Co-free positive electrode materials for lithium-ion batteries.

Acute femoral osteomyelitis due to hypermucoviscous Klebsiella pneumoniae.

Hypervirulent hypermucoviscous Klebsiella pneumoniae strains have emerged as clinically important pathogens causing invasive infections. K. pneumoniae osteomyelitis is uncommon in adult patients, and may mimic bone tumors on presentation. We report a patient with left rectus femoris muscle abscess and acute osteomyelitis of the left femur due to hypermucoviscous K. pneumoniae with negative blood culture, who was initially thought to have left thigh tumor. The patient's infection resolved with surgical drainage and debridement and intravenous and antibiotic therapy.