Association between loss of hypercoagulable phenotype, clinical features and complement pathway consumption in COVID-19.

Background: Coronavirus disease 2019 (COVID-19) features a hypercoagulable state, but therapeutic anticoagulation effectiveness varies with disease severity. We aimed to evaluate the dynamics of the coagulation profile and its association with COVID-19 severity, outcomes, and biomarker trajectories. Methods: This multicenter, prospective, observational study included patients with COVID-19 requiring respiratory support. Rotational thromboelastometry findings were evaluated for coagulation and fibrinolysis status. Hypercoagulable status was defined as supranormal range of maximum clot elasticity in an external pathway. Longitudinal laboratory parameters were collected to characterize the coagulation phenotype. Results: Of 166 patients, 90 (54%) were severely ill at inclusion (invasive mechanical ventilation, 84; extracorporeal membrane oxygenation, 6). Higher maximum elasticity (P=0.02) and lower maximum lysis in the external pathway (P=0.03) were observed in severely ill patients compared with the corresponding values in patients on non-invasive oxygen supplementation. Hypercoagulability components correlated with platelet and fibrinogen levels. Hypercoagulable phenotype was associated with favorable outcomes in severely ill patients, while normocoagulable phenotype was not (median time to recovery, 15 days vs. 27 days, P=0.002), but no significant association was observed in moderately ill patients. In patients with severe COVID-19, lower initial C3, minimum C3, CH50, and greater changes in CH50 were associated with the normocoagulable phenotype. Changes in complement components correlated with dynamics of coagulation markers, hematocrit, and alveolar injury markers. Conclusions: While hypercoagulable states become more evident with increasing severity of respiratory disease in patients with COVID-19, normocoagulable phenotype is associated with triggered by alternative pathway activation and poor outcomes.

Effects of acute phase intensive electrical muscle stimulation in COVID-19 patients requiring invasive mechanical ventilation: an observational case-control study.

We investigated the effects of acute-phase intensive electrical muscle stimulation (EMS) on physical function in COVID-19 patients with respiratory failure requiring invasive mechanical ventilation (IMV) in the intensive care unit (ICU). Consecutive COVID-19 patients requiring IMV admitted to a university hospital ICU between January and April 2022 (EMS therapy group) or between March and September 2021 (age-matched historical control group) were included in this retrospective observational case-control study. EMS was applied to both upper and lower limb muscles for up to 2 weeks in the EMS therapy group. The study population consisted of 16 patients undergoing EMS therapy and 16 age-matched historical controls (median age, 71 years; 81.2% male). The mean period until initiation of EMS therapy after ICU admission was 3.2 ± 1.4 days. The EMS therapy group completed a mean of 6.2 ± 3.7 EMS sessions, and no adverse events occurred. There were no significant differences between the two groups in Medical Research Council sum score (51 vs. 53 points, respectively; P = 0.439) or ICU mobility scale at ICU discharge. Addition of upper and lower limb muscle EMS therapy to an early rehabilitation program did not result in improved physical function at ICU discharge in severe COVID-19 patients.

Physical function and mental health trajectories in COVID-19 patients following invasive mechanical ventilation: a prospective observational study.

This prospective observational cohort study was performed to investigate the physical function and mental health trajectories of novel coronavirus disease 2019 (COVID-19) patients requiring invasive mechanical ventilation (IMV) after discharge from the intensive care unit (ICU). The study population consisted of 64 patients (median age, 60 years; 85.9% male; median IMV duration, 9 days). At ICU discharge, 28.1% of the patients had Medical Research Council (MRC) sum score < 48 points, and prolonged IMV was significantly associated with lower MRC sum score and handgrip strength. Symptoms were similar between groups at ICU discharge, and the symptoms most commonly reported as moderate-to-severe were impaired well-being (52%), anxiety (43%), tiredness (41%), and depression (35%). Although muscle strength and mobility status were significantly improved after ICU discharge, Edmonton Symptom Assessment System score did not improve significantly in the prolonged IMV group. EuroQol five-dimension five-level summary index was significantly lower in the prolonged than short IMV group at 6 months after ICU discharge. We found substantial negative physical function and mental health consequences in the majority of surviving COVID-19 patients requiring IMV, with prolonged period of IMV showing greater negative effects not only immediately but also at 6 months after discharge from the ICU.

Lethal ventricular arrhythmia due to entrectinib-induced Brugada syndrome: a case report and literature review.

Entrectinib, a multikinase inhibitor of ROS1 and tropomyosin receptor kinases, is recommended to treat ROS1-positive metastatic non-small cell lung cancer (NSCLC). In a previous study, entrectinib-related cardiotoxicity occurred in 2% of patients; however, lethal arrhythmias remain understudied. We encountered a case of fatal arrhythmia due to drug-induced Brugada syndrome caused by entrectinib. An 81-year-old Japanese male with lung adenocarcinoma harboring ROS1-fusion gene was treated with entrectinib. The patient developed lethal arrhythmias three days after drug initiation, including ventricular tachycardia with Brugada-like electrocardiogram changes. Echocardiography and coronary angiography revealed no evidence of acute coronary syndrome or myocarditis. Following the termination of entrectinib, the electrocardiogram abnormality improved within 12 days. Hence, paying special attention to and monitoring electrocardiogram changes is necessary. In addition, it is also necessary to consider early therapeutic interventions and discontinuation of the drug in cases of drug-induced Brugada syndrome.

Impact of antimicrobial stewardship program-driven educational intervention for vancomycin loading dose on mortality.

BACKGROUND: Although the loading dose (LD) of vancomycin (VCM) contributes to its efficacy, it may not be conducted adequately. Herein, the objective was to evaluate the effect of LD on patient prognosis using therapeutic drug monitoring by pharmacists and elucidate the impact of an antimicrobial stewardship program (ASP)-driven educational intervention on the LD implementation rate and patient prognosis. MATERIALS AND METHODS: First, a retrospective cohort study was conducted involving 121 adult patients administered with VCM and compared with 28-day mortality in LD and non-LD groups. To avoid confounding, the propensity score method was employed. Second, post-training with ASP-driven lectures, a questionnaire survey was conducted for healthcare workers, including physicians, nurses, and pharmacists. The rates of VCM LD implementation and 28-day mortality were compared during a period of one year and 9 months between the pre-ASP (n = 38) and post-ASP (n = 33) groups. RESULTS: After propensity score matching, the 28-day mortality in the LD group was significantly improved, suggesting that the early increase in blood levels of VCM due to an LD is an important factor influencing patient prognosis. After the lecture, a questionnaire survey revealed that the understanding rates of "well" and "slightly well" for educational lectures exceeded 80% of all healthcare workers. The rate of LD implementation significantly increased to 63.6% (21/33) in the post-ASP group compared with 31.6% (12/38) in the pre-ASP group (p = 0.007), and the 28-day mortality declined from 23.7% (9/38) to 6.1% (2/33) (p = 0.041). CONCLUSION: This method of ASP-driven educational intervention would facilitate LD implementation, improving patient prognosis.

Exploratory Study of Pharmacists' Monitoring Methods Based on Left Ventricular Function for Hypermagnesemia by Magnesium Oxide in Heart Failure.

Serum magnesium (Mg) monitoring in patients with heart failure (HF) receiving magnesium oxide (MgO) is not adequately performed. Furthermore, the relationship between left ventricular function (LVF) and hypermagnesemia in HF is unknown. Here, we investigated the efficacy of serum Mg monitoring by protocol-based pharmaceutical management (PBPM) and the effect of LVF on hypermagnesemia. This protocol is for patients with an estimated glomerular filtration rate of <45 mL/min, receiving MgO, and admitted to the cardiology unit. The pharmacist includes the measurement of Mg when a blood test is ordered for a patient by their physician. Rates of serum Mg measurement and hypermagnesemia detection were compared at 2 years pre-PBPM (n = 88) and at 2 years post-PBPM (n = 55). LVF parameters and reported factors for hypermagnesemia were selected as explanatory factors on multivariate logistic regression. The measurement rate of serum Mg concentration significantly increased from 19.3% pre-PBPM to 80.0% post-PBPM (P < .001). The detection rate of hypermagnesemia also increased from 3.4% to 27.3%, respectively (P < .001). Our results suggest that serum Mg monitoring by PBPM may contribute to the early detection of hypermagnesemia and prevent its progression in HF. According to logistic regression, the adjusted odds ratio for hypermagnesemia with an exacerbation of HF was 9.57 (95% confidence interval: 1.594-57.477, P = .014), and the E/e' > 15, an index of reduced left ventricular diastolic capacity, was 6.46 (95% confidence interval: 1.291-32.364, P = .023). We propose that serum Mg monitoring should be performed during exacerbations of HF in patients with left ventricular diastolic dysfunction, with a pharmacist's assistance.

Antiresorptive Drugs and the Risk of Femoral Shaft Fracture in Men and Women With Osteoporosis: A Cohort Study Using the National Database of Health Insurance Claims of Japan.

BACKGROUND: This cohort study aimed to estimate incidence rates of femoral shaft fracture in patients who were treated with antiresorptive drugs. METHODS: We used data from the National Database of Health Insurance Claims of Japan from April 2009 and October 2016. All patients with new use of an antiresorptive drug, prescription-free period of ≥3 months, and no prior femoral fractures were included. Femoral shaft fractures were identified using a validated definition based on International Classification of Diseases, 10th revision (ICD-10) codes. Incidence rate ratios were estimated using Poisson regression, with adjustment for sex, age, and the Charlson Comorbidity Index. RESULTS: We identified 7,958,655 patients (women: 88.4%; age ≥75 years: 51.2%). Femoral shaft fractures were identified in 22,604 patients. Incidence rates per 100,000 person-years were 74.8 for women, 30.1 for men, 30.1 for patients aged ≤64 years, 47.7 for patients aged 65-74 years, and 99.0 for patients aged ≥75 years. Adjusted incidence rate ratios in patients taking versus not taking each type of antiresorptive drug were 1.00 (95% confidence interval [CI], 0.98-1.03) for bisphosphonates, 0.46 (95% CI, 0.44-0.48) for selective estrogen receptor modulators, 0.24 (95% CI, 0.18-0.32) for estrogens, 0.75 (95% CI, 0.71-0.79) for calcitonins, and 0.93 (95% CI, 0.84-1.03) for denosumab. The adjusted incidence rate ratio for alendronate was 1.18 (95% CI, 1.14-1.22). CONCLUSION: The incidence rates of femoral shaft fracture varied across patients treated with different antiresorptive drugs. Further research on a specific antiresorptive drug can increase understanding of the risk of femoral shaft fracture.

Influence of COVID-19 on the 10-year carbon footprint of the Nagoya University Hospital and medical research centre.

BACKGROUND: Amidst the climate crisis, a key goal of the medical sector is to reduce its large carbon footprint. Although the Coronavirus disease 2019 (COVID-19) pandemic greatly impacted the medical sector, its influence on carbon footprints remains unknown. Therefore, the aim of this study was to evaluate changes in the carbon footprint of a university hospital with a medical research centre over the past 10 years. METHODS: Data on electricity, gas, and water usage, pharmaceutical and medical supply costs, and waste amounts were recorded for Nagoya University Hospital from April 2010 to March 2021. The relevant emission factors were obtained from the Japanese government and the overall monthly carbon footprint was reported according to the Greenhouse Gas Protocol. The effect of the COVID-19 pandemic on the carbon footprint was then compared for three types of emission sources. Moreover, a regression model was used to plot quadratic functions as approximate functions using monthly carbon emissions and monthly average external temperatures. Finally, the monthly carbon footprint was calculated per hospital admission. RESULTS: The overall carbon footprint of the hospital was 73,546 tCO2e in 2020, revealing an increase of 26.60% over the last 10 years. Carbon emissions from electricity consumption represented 26% of total emissions. The individual carbon footprints of pharmaceuticals, medical supplies, waste, and water usage also increased from 2010 to 2020. The overall monthly carbon footprint was positively correlated with the average monthly temperature (R2 = 0.7566, p < 0.001). Compared with 2019, the overall carbon footprint decreased by 2.19% in 2020. Moreover, the monthly carbon footprint per hospital admission increased significantly between 2018 (0.24 tCO2e/admission) and 2020 (0.26 tCO2e/admission) (p = 0.002). CONCLUSION: The overall carbon footprint of the hospital generally increased over the last decade. During the COVID-19 epidemic in 2020, the carbon footprint decreased slightly, likely because of the reduced number of patients. However, the carbon footprint per admission increased, which was attributed to more complicated patient backgrounds because of the ageing population. Therefore, evaluation of carbon emissions in the medical sector is urgently required in order to act on the climate crisis as soon as possible.

[Evaluation of Disopyramide Efficacy for Refractory Syncope in Heart Failure with Preserved Ejection Fraction Using Holter Electrocardiography: A Case Report].

The management of syncope is clinically important for heart failure (HF) patients. We herein describe a case on the efficacy of disopyramide for refractory syncope in HF with preserved ejection fraction (HFpEF). An 82-year-old man was hospitalized for respiratory distress and lower limb edema and was subsequently diagnosed with HFpEF. The use of diuretics improved HF symptoms; however, on day 10 after hospitalization, a rapid decrease in blood pressure and transient loss of consciousness developed. After neurologic examination, he was diagnosed with pure autonomic failure. Although he was administered midodrine 8 mg/d, fludrocortisone 0.1 mg/d, and droxidopa 300 mg/d, syncope was observed once a day on average. According to the Holter electrocardiogram, the patient's heart rate and coefficient of variation of R-R intervals (CVRR) during the day were unstable. In addition, high frequency power (parasympathetic nerve activity) was significantly higher than low frequency power (both sympathetic and parasympathetic nerves activity), suggesting that the parasympathetic nerves may have been highly active while the sympathetic nerves would have been blocked. On day 29, a pharmacist proposed disopyramide 300 mg/d, which blocks parasympathetic nerves and improves neural-mediated syncope, to the attending doctor. After the initiation of disopyramide, transient loss of consciousness was not observed. Furthermore, the diurnal variation in the heart rate and CVRR completely disappeared. In conclusion, disopyramide would be effective for refractory syncope in patients with HFpEF, and the Holter electrocardiogram may be a useful tool for the assessment of drug efficacy by pharmacists.

Risk assessment of micafungin-induced liver injury using spontaneous reporting system data and electronic medical records.

INTRODUCTION: There is limited information regarding antifungal-induced liver injuries, which have high mortality rates. Therefore, we used the Japanese Adverse Drug Event Report (JADER) database for signal detection associated with antifungal-induced liver injuries and medical records for risk assessment. METHODS: Reports of antifungal-induced liver injuries from JADER data were analyzed to calculate the reporting odds ratio (ROR) and 95% confidence interval (CI). A medical record-based study involving 109 adult patients treated with micafungin shows liver injury as the primary outcome in patients treated with micafungin. The albumin-bilirubin (ALBI) score was calculated based on albumin and total bilirubin levels. We selected five explanatory factors for multivariable logistic regression: alanine aminotransferase ≥20 IU/L, alkaline phosphatase ≥372 IU/L, aspartate aminotransferase ≥25 IU/L, ALBI score ≥ -1.290, and age ≥65 years. RESULTS: Signal detection for micafungin was observed in both, hepatocellular and cholestatic injuries, as per data from JADER. Univariate analyses performed on medical records suggest that alanine aminotransferase (p = 0.008), aspartate aminotransferase (p = 0.036), alkaline phosphatase (p = 0.045), and ALBI score (p = 0.028) may be factors associated with micafungin-induced liver injury. Based on multivariable logistic regression, the adjusted odds ratio for micafungin-induced liver injury in patients with ALBI score ≥ -1.290 was 2.78 (95% CI: 1.014-7.605, p = 0.047), suggesting that low hepatic functional reserve could be a risk factor for micafungin-induced liver injury. CONCLUSIONS: Careful monitoring of liver function may be necessary for micafungin administration in patients with low hepatic functional reserve.

Evaluation of the Expression Profile of Antibiotic-Induced Thrombocytopenia Using the Japanese Adverse Drug Event Report Database.

Drug-induced thrombocytopenia (DITP) can be triggered by antibiotics; however, the details remain unclear. Here, we evaluated the expression profiles of DITP using the Japanese Adverse Drug Event Report (JADER) database. We analyzed reports of DITP between April 2004 and January 2021 from the JADER database. The reporting odds ratio (ROR) and 95% confidence interval (CI) were used to detect DITP signals. Factors thought to affect DITP, such as male sex and an age of at least 60 years, were added as covariates. We evaluated the time-to-onset profile and hazard type using the Weibull shape parameter. The JADER database contained 1,048,576 reports. Twelve of 60 antibiotics showed signals for DITP; the RORs (95% CIs) for ampicillin/sulbactam, ceftazidime, cefozopran, ciprofloxacin, fluconazole, fos-fluconazole, linezolid, pazufloxacin, piperacillin/tazobactam, teicoplanin, trimethoprim/sulfamethoxazole, and voriconazole were 1.75 (1.41-2.16), 1.77 (1.42-2.18), 1.35 (1.06-1.72), 2.56 (2.19-2.98), 1.93 (1.67-2.23), 2.08 (1.76-2.46), 5.29 (2.73-9.60), 1.92 (1.51-2.41), 1.54 (1.05-2.19), 1.47 (1.16-1.84), 1.92 (1.73-2.14), and 2.32 (1.59-3.30), respectively. In multiple logistic regression analysis, 7 and 6 antibiotics were detected for the factors age and male sex, respectively. The median times-to-onset of DITP for ciprofloxacin (oral treatment), fluconazole, linezolid, piperacillin/tazobactam, and trimethoprim/sulfamethoxazole were 91, 91, 11.5, 10, and 9 days, respectively. Furthermore, the 95% CI of the Weibull shape parameter ß for these antibiotics was above and excluded 1, indicating that the antibiotics were the wear out failure type. We revealed the expression profiles of DITP following treatment with 12 antibiotics.

Assessment of Critical Care Surge Capacity During the COVID-19 Pandemic in Japan.

Japan has the highest proportion of older adults worldwide but has fewer critical care beds than most high-income countries. Although the COVID-19 infection rate in Japan is low compared with Europe and the United States, by the end of 2020, several infected people died in ambulances because they could not find hospitals to accept them. Our study aimed to examine the Japanese healthcare system's capacity to accommodate critically ill COVID-19 patients during the pandemic. We created a model to estimate bed and staff capacity at 3 levels of pandemic response (conventional, contingency, and crisis), as defined by the US National Academy of Medicine, and the function of Japan's healthcare system at each level. We then compared our estimates of the number of COVID-19 patients requiring intensive care at peak times with the national health system capacity using expert panel data. Our findings suggest that Japan's healthcare system currently can accommodate only a limited number of critically ill COVID-19 patients. It could accommodate the surge of pandemic demands by converting nonintensive care unit beds to critical care beds and using nonintensive care unit staff for critical care. However, bed and staff capacity should not be expanded uniformly, so that the limited number of physicians and nurses are allocated efficiently and so staffing does not become the bottleneck of the expansion. Training and deploying physicians and nurses to provide immediate intensive care is essential. The key is to introduce and implement the concept and mechanism of tiered staffing in the Japanese healthcare system. More importantly, most intensive care facilities in Japanese hospitals are small-scaled and thinly distributed in each region. The government needs to introduce an efficient system for smooth dispatching of medical personnel among hospitals regardless of their founding institutions.

The protective effect of tight-fitting powered air-purifying respirators during chest compressions.

BACKGROUND: Airborne personal protective equipment is required for healthcare workers when performing aerosol-generating procedures on patients with infectious diseases. Chest compressions, one of the main components of cardiopulmonary resuscitation, require intense and dynamic movements of the upper body. We aimed to investigate the protective effect of tight-fitting powered air-purifying respirators (PAPRs) during chest compressions. METHODS: This single-center simulation study was performed from February 2021 to March 2021. The simulated workplace protection factor (SWPF) is the concentration ratio of ambient particles and particles inside the PAPR mask; this value indicates the level of protection provided by a respirator when subjected to a simulated work environment. Participants performed continuous chest compressions three times for 2 min each time, with a 4-min break between each session. We measured the SWPF of the tight-fitting PAPR during chest compression in real-time mode. The primary outcome was the ratio of any failure of protection (SWPF <500) during the chest compression sessions. RESULTS: Fifty-four participants completed the simulation. Overall, 78% (n = 42) of the participants failed (the measured SWPF value was less than 500) at least one of the three sessions of chest compressions. The median value and interquartile range of the SWPF was 4304 (685-16,191). There were no reports of slipping down of the respirator or mechanical failure during chest compressions. CONCLUSIONS: Although the median SWPF value was high during chest compressions, the tight-fitting PAPR did not provide adequate protection.

Failure of non-invasive respiratory support after 6 hours from initiation is associated with ICU mortality.

A previous study has shown that late failure (> 48 hours) of high-flow nasal cannula (HFNC) was associated with intensive care unit (ICU) mortality. The aim of this study was to investigate whether failure of non-invasive respiratory support, including HFNC and non-invasive positive pressure ventilation (NPPV), was also associated with the risk of mortality even if it occurs in the earlier phase. We retrospectively analyzed 59 intubated patients for acute respiratory failure due to lung diseases between April 2014 and June 2018. We divided the patients into 2 groups according to the time from starting non-invasive ventilatory support until their intubation: ≤ 6 hours failure and > 6 hours failure group. We evaluated the differences in the ICU mortality between these two groups. The multivariate logistic regression analysis showed the highest mortality in the > 6 hours failure group as compared to the ≤ 6 hours failure group, with a statistically significant difference (p < 0.01). It was also associated with a statistically significant increased 30-day mortality and decreased ventilator weaning rate. The ICU mortality in patients with acute respiratory failure caused by lung diseases was increased if the time until failure of HFNC and NPPV was more than 6 hours.

Combination therapy of midodrine and droxidopa for refractory hypotension in heart failure with preserved ejection fraction per a pharmacist's proposal: a case report.

BACKGROUND: Patients with chronic heart failure (CHF) are often treated using many diuretics for symptom relief; however, diuretic use may have to continue despite hypotension development in these patients. Here, we present a case of heart failure with preserved ejection fraction (HFpEF), which is defined as ejection fraction ≥50% in CHF, and refractory hypotension, which was treated with midodrine and droxidopa to normalize blood pressure. CASE PRESENTATION: The patient was a 62-year-old man with a history of HFpEF due to mitral regurgitation and complaints of dyspnea on exertion. He had been prescribed multiple medications at an outpatient clinic for CHF management, including azosemide 60 mg/day, bisoprolol 2.5 mg/day, enalapril 2.5 mg/day, spironolactone 50 mg/day, and tolvaptan 15 mg/day. The systolic blood pressure (SBP) of the patient remained at 70-80 mmHg because the use of the diuretic could not be reduced or discontinued owing to edema and weight gain. He was hospitalized for the exacerbation of CHF. Although midodrine 8 mg/day was administered to improve hypotension, the SBP of the patient increased only up to 90 mmHg. On the 35th day after hospitalization, the urine volume decreased significantly (< 100 mL/day) due to hypotension. When droxidopa 200 mg/day replaced intravenous noradrenaline on the 47th day, the SBP remained at 100-120 mmHg and the urine volume increased. CONCLUSIONS: Oral combination treatment with midodrine and droxidopa might contribute to the maintenance of blood pressure and diuretic activity in HFpEF patients with refractory hypotension. However, further long-term studies evaluating the safety and efficacy of this combination therapy for patients with HFpEF are needed.

A case of reexpansion pulmonary edema and acute pulmonary thromboembolism associated with diffuse large B-cell lymphoma treated with venovenous extracorporeal membrane oxygenation.

A 37-year-old man diagnosed with diffuse large B-cell lymphoma two weeks previously, visited our emergency department with sudden dyspnea. He had a severe respiratory failure with saturated percutaneous oxygen at 80% (room air). Chest radiography showed a large amount of left pleural effusion. After 1000 mL of the effusion was urgently drained, reexpansion pulmonary edema (RPE) occurred. Despite ventilator management, oxygenation did not improve and venovenous extracorporeal membrane oxygenation (VV-ECMO) was initiated in the intensive care unit. The next day, contrast-enhanced computed tomography showed a massive thrombus in the right pulmonary artery, at this point the presence of pulmonary thromboembolism (PTE) was revealed. Fortunately, the patient's condition gradually improved with anticoagulant therapy and VV-ECMO support. VV-ECMO was successfully discontinued on day 4, and chemotherapy was initiated on day 8. We speculated the following mechanism in this case: blood flow to the right lung significantly reduced due to acute massive PTE, and blood flow to the left lung correspondingly increased, which could have caused RPE in the left lung. Therefore, our observations suggest that drainage of pleural effusion when contralateral blood flow is impaired due to acute PTE may increase the risk of RPE. .

Efficacy of favipiravir for an end stage renal disease patient on maintenance hemodialysis infected with novel coronavirus disease 2019.

BACKGROUND: Novel coronavirus disease 2019 (COVID-19) refers to infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogen, and has spread to pandemic levels since its inception in December 2019. While several risk factors for severe presentation have been identified, the clinical course for end-stage renal disease (ESRD) patients on maintenance hemodialysis with COVID-19 has been unclear. Previous studies have revealed that some antiviral agents may be effective against COVID-19 in the general population, but the pharmacokinetics and pharmacodynamics of these agents in ESRD patients remain under investigation. Favipiravir, an antiviral agent developed for treatment of influenza, is one candidate treatment for COVID-19, but suitable dosages for patients with renal insufficiency are unknown. Here we provide a first report on the efficacy of favipiravir in a patient with ESRD undergoing hemodialysis. CASE PRESENTATION: The case involved a 52-year-old woman with COVID-19 who had been undergoing maintenance hemodialysis three times a week for 3 years due to diabetic nephropathy. She had initially been treated with lopinavir/ritonavir and ciclesonide for 5 days, but developed severe pneumonia requiring invasive positive-pressure ventilation. Those antiviral agents were subsequently switched to favipiravir. She recovered gradually, and after 2 weeks was extubated once the viral load of SARS-CoV-2 fell below the limit of detection. Although concentrations of several biliary enzymes were elevated, no major adverse events were observed. CONCLUSION: Favipiravir may be an effective option for the treatment of COVID-19-infected patients with ESRD.

Surgical strategy and optimal timing of tracheostomy in patients with COVID-19: Early experiences in Japan.

OBJECTIVE: Tracheostomy is an important surgical procedure for coronavirus disease-2019 (COVID-19) patients who underwent prolonged tracheal intubation. Surgical indication of tracheostomy is greatly affected by the general condition of the patient, comorbidity, prognosis, hospital resources, and staff experience. Thus, the optimal timing of tracheostomy remains controversial. METHODS: We reviewed our early experience with COVID-19 patients who underwent tracheostomy at one tertiary hospital in Japan from February to September 2020 and analyzed the timing of tracheostomy, operative results, and occupational infection in healthcare workers (HCWs). RESULTS: Of 16 patients received tracheal intubation with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, five patients (31%) received surgical tracheostomy in our hospital. The average consultation time for surgical tracheostomy was 7.4 days (range, 6 - 9 days) from the COVID-19 team to the otolaryngologist. The duration from tracheal intubation to tracheostomy ranged from 14 to 27 days (average, 20 days). The average time of tracheostomy was 27 min (range, 17 - 39 min), and post-wound bleeding occurred in only one patient. No significant differences in hemoglobin (Hb) levels were found between the pre- and postoperative periods (mean: 10.2 vs. 10.2 g/dl, p = 0.93). Similarly, no difference was found in white blood cell (WBC) count (mean: 12,200 vs. 9,900 cells /µl, p = 0.25). After the tracheostomy, there was no occupational infection among the HCWs who assisted the tracheostomy patients during the perioperative period. CONCLUSION: We proposed a modified weaning protocol and surgical indications of tracheostomy for COVID-19 patients and recommend that an optimal timing for tracheostomy in COVID-19 patients of 2 - 3 weeks after tracheal intubation, from our early experiences in Japan. An experienced multi-disciplinary tracheostomy team is essential to perform a safe tracheostomy in patients with COVID-19 and to minimize the risk of occupational infection in HCWs.

Factors influencing the effectiveness of recombinant human soluble thrombomodulin on disseminated intravascular coagulation: a retrospective study.

BACKGROUND: Although recombinant human soluble thrombomodulin (rTM) has been widely used to treat disseminated intravascular coagulation (DIC) in Japan, there is no consensus regarding rTM efficacy. Therefore, if the factors influencing rTM efficacy is revealed, it may be possible to demonstrate the effectiveness of rTM by limiting the patients who use rTM. This study investigated the factors of rTM treatment which influence DIC status. METHODS: This retrospective case-control study enrolled hospitalized adult patients treated with rTM from October 2010 to May 2020. Among these patients, 227 who were diagnosed with DIC according to the Japanese Association for Acute Medicine DIC scoring system were assessed. The primary endpoint was the 28-day mortality after rTM treatment. For Cox-proportional hazards model, explanatory factors determined using univariate analysis with p <  0.1 were used. In addition, some factors considered to affect DIC-related mortality such as age ≥ 75 years, rTM dose ≥380 U/kg, antithrombin III treatment, and diseases with a poor prognosis (sepsis, solid tumors, and trauma) were added as covariates. RESULTS: Univariate analyses suggested that male sex (p = 0.029), treatment in intensive care unit (p = 0.061), and prothrombin time-international normalized ratio (PT-INR) (p <  0.001) were the factors influencing DIC-related 28-day mortality after rTM treatment. According to Cox-proportional hazard analysis, the adjusted odds ratio for DIC-related 28-day mortality in patients with PT-INR ≥ 1.67 was 2.23 (95% confidence interval: 1.451-3.433, p <  0.001), age ≥ 75 years was 1.57 (95% confidence interval: 1.009-2.439, p = 0.046), and male sex was 1.66 (95% confidence interval: 1.065-2.573, p = 0.025), respectively. As life-threatening bleeding events were not observed, prolonged PT-INR might directly or indirectly affect DIC-related mortality caused by rTM treatment. CONCLUSION: rTM treatment for DIC was less effective in male patients with PT-INR ≥ 1.67 and age ≥ 75 years.