Chronic kidney disease and clinical outcomes in patients with COVID-19 in Japan.

BACKGROUND: Identifying predictive factors for coronavirus disease 2019 (COVID-19) is crucial for risk stratification and intervention. Kidney dysfunction contributes to the severity of various infectious diseases. However, the association between on-admission kidney dysfunction and the clinical outcome in COVID-19 patients is unclear. METHODS: This study was a multicenter retrospective observational cohort study of COVID-19 patients, diagnosed by polymerase chain reaction. We retrospectively analyzed 500 COVID-19 patients (mean age: 51 ± 19 years) admitted to eight hospitals in Japan. Kidney dysfunction was defined as a reduced estimated glomerular filtration rate (< 60 mL/min/1.73 m2) or proteinuria (≥ 1 + dipstick proteinuria) on admission. The primary composite outcome included in-hospital death, extracorporeal membrane oxygenation, mechanical ventilation (invasive and noninvasive methods), and intensive care unit (ICU) admission. RESULTS: Overall, 171 (34.2%) patients presented with on-admission kidney dysfunction, and the primary composite outcome was observed in 60 (12.0%) patients. Patients with kidney dysfunction showed higher rates of in-hospital death (12.3 vs. 1.2%), mechanical ventilation (13.5 vs. 4.0%), and ICU admission (18.1 vs. 5.2%) than those without it. Categorical and multivariate regression analyses revealed that kidney dysfunction was substantially associated with the primary composite outcome. Thus, on-admission kidney dysfunction was common in COVID-19 patients. Furthermore, it correlated significantly and positively with COVID-19 severity and mortality. CONCLUSIONS: On-admission kidney dysfunction was associated with disease severity and poor short-term prognosis in patients with COVID-19. Thus, on-admission kidney dysfunction has the potential to stratify risks in COVID-19 patients.

Therapeutic potential of ciclesonide inahalation for COVID-19 pneumonia: Report of three cases.

No specific and effective anti-viral treatment has been approved for COVID-19 so far. Systemic corticosteroid has been sometimes administered to severe infectious diseases combined with the specific treatment. However, as lack of the specific anti-SARS-CoV-2 drug, systemic steroid treatment has not been recommended for COVID-19. We report here three cases of the COVID-19 pneumonia successfully treated with ciclesonide inhalation. Rationale of the treatment is to mitigate the local inflammation with inhaled steroid that stays in the lung and to inhibit proliferation of the virus by antiviral activity. Larger and further studies are warranted to confirm the result of these cases.

Clinical course of 2019 novel coronavirus disease (COVID-19) in individuals present during the outbreak on the Diamond Princess cruise ship.

We investigated the clinical course of individuals with 2019 novel coronavirus disease (COVID-19) who were transferred from the Diamond Princess cruise ship to 12 local hospitals. The conditions and clinical courses of patients with pneumonia were compared with those of patients without pneumonia. Among 70 patients (median age: 67 years) analyzed, the major symptoms were fever (64.3%), cough (54.3%), and general fatigue (24.3%). Forty-three patients (61.4%) had pneumonia. Higher body temperature, heart rate, and respiratory rate as well as higher of lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and C-reactive protein (CRP) levels and lower serum albumin level and lymphocyte count were associated with the presence of pneumonia. Ground-glass opacity was found in 97.7% of the patients with pneumonia. Patients were administered neuraminidase inhibitors (20%), lopinavir/ritonavir (32.9%), and ciclesonide inhalation (11.4%). Mechanical ventilation and veno-venous extracorporeal membrane oxygenation was performed on 14 (20%) and 2 (2.9%) patients, respectively; two patients died. The median duration of intubation was 12 days. The patients with COVID-19 transferred to local hospitals during the outbreak had severe conditions and needed close monitoring. The severity of COVID-19 depends on the presence of pneumonia. High serum LDH, AST and CRP levels and low serum albumin level and lymphocyte count were found to be predictors of pneumonia. It was challenging for local hospitals to admit and treat these patients during the outbreak of COVID-19. Assessment of severity was crucial to manage a large number of patients.

[Practical Utilization of Home Care Support System and Influence of Home Care on the Regional Core Hospital].

The home care support system, newly established in 2014, is a system that always secures the hospitalization of pre-registered home care patients who need to be hospitalized. Ashigarakami Hospital has operated this system since April 2014. As of May 2018, a total of 215 people registered, and 156 people have died. Among the deceased patients, 77(49.4%)died at home, which was higher than the proportion of home deaths(13.0%)in the Japanese population dynamics survey in 2016. In patients who had malignant diseases, they could spend more than half of the period from their introduction to the system up to death being treated at home. Even in the case of death at a hospital, the duration of the last hospitalization was 18 days on average(median of 12 days). In most cases, patients were treated at home until shortly before death.

Cancer treatment and management for elderly patients 80 years of age or older with malignant solid tumors.

OBJECTIVE: We retrospectively analyzed the backgrounds, treatment and nursing care for 96 patients aged 80 years or more with malignant tumors. Twenty of them were hospitalized on an emergency basis. Sixty patients were male and 36 were female, with a median age of 83 years (range: 80-94 years). Twenty-seven had a PS of 3 or 4, and 41 were rated as not independent based on analysis of autonomy at hospitalization. Forty-seven patients had clinical stage III or IV malignancies. The proportions of patients with disease complications were 33.3% for neurological disease, 21.9% for respiratory disease, 70.8% for cardiovascular disease including hypertension, and 36.5% for metabolic disease. Thirty-nine patients underwent surgical or endoscopic resection of their tumors. Twenty-three patients received chemotherapy: hormonal treatment in 14, local injection of cytotoxic agent(s) in 6 and systemic anti-cancer therapy in 3. Thirty-nine patients received supportive care only. Forty-three patients newly required nursing care or an increased level of care at discharge. The median survival time was 10.9 and 15.3 months for stage III/IV and 0/I/II patients, respectively. In conclusion, most elderly patients with malignant tumors require full supportive care, including social nursing care, from the time of cancer diagnosis.

Comparison of Spinach Sex Chromosomes with Sugar Beet Autosomes Reveals Extensive Synteny and Low Recombination at the Male-Determining Locus.

Spinach (Spinacia oleracea, 2n = 12) and sugar beet (Beta vulgaris, 2n = 18) are important crop members of the family Chenopodiaceae ss Sugar beet has a basic chromosome number of 9 and a cosexual breeding system, as do most members of the Chenopodiaceae ss. family. By contrast, spinach has a basic chromosome number of 6 and, although certain cultivars and genotypes produce monoecious plants, is considered to be a dioecious species. The loci determining male and monoecious sexual expression were mapped to different loci on the spinach sex chromosomes. In this study, a linkage map with 46 mapped protein-coding sequences was constructed for the spinach sex chromosomes. Comparison of the linkage map with a reference genome sequence of sugar beet revealed that the spinach sex chromosomes exhibited extensive synteny with sugar beet chromosomes 4 and 9. Tightly linked protein-coding genes linked to the male-determining locus in spinach corresponded to genes located in or around the putative pericentromeric and centromeric regions of sugar beet chromosomes 4 and 9, supporting the observation that recombination rates were low in the vicinity of the male-determining locus. The locus for monoecism was confined to a chromosomal segment corresponding to a region of approximately 1.7Mb on sugar beet chromosome 9, which may facilitate future positional cloning of the locus.

QTL analysis of femaleness in monoecious spinach and fine mapping of a major QTL using an updated version of chromosome-scale pseudomolecules.

Although spinach is predominantly dioecious, monoecious plants with varying proportions of female and male flowers are also present. Recently, monoecious inbred lines with highly female and male conditions have been preferentially used as parents for F1-hybrids, rather than dioecious lines. Accordingly, identifying the loci for monoecism is an important issue for spinach breeding. We here used long-read sequencing and Hi-C technology to construct SOL_r2.0_pseudomolecule, a set of six pseudomolecules of spinach chromosomes (total length: 879.2 Mb; BUSCO complete 97.0%) that are longer and more genetically complete than our previous version of pseudomolecules (688.0 Mb; 81.5%). Three QTLs, qFem2.1, qFem3.1, and qFem6.1, responsible for monoecism were mapped to SOL_r2.0_pseudomolecule. qFem3.1 had the highest LOD score and corresponded to the M locus, which was previously identified as a determinant of monoecious expression, by genetic analysis of progeny from female and monoecious plants. The other QTLs were shown to modulate the ratio of female to male flowers in monoecious plants harboring a dominant allele of the M gene. Our findings will enable breeders to efficiently produce highly female- and male-monoecious parental lines for F1-hybrids by pyramiding the three QTLs. Through fine-mapping, we narrowed the candidate region for the M locus to a 19.5 kb interval containing three protein-coding genes and one long non-coding RNA gene. Among them, only RADIALIS-like-2a showed a higher expression in the reproductive organs, suggesting that it might play a role in reproductive organogenesis. However, there is no evidence that it is involved in the regulation of stamen and pistil initiation, which are directly related to the floral sex differentiation system in spinach. Given that auxin is involved in reproductive organ formation in many plant species, genes related to auxin transport/response, in addition to floral organ formation, were identified as candidates for regulators of floral sex-differentiation from qFem2.1 and qFem6.1.

Relationship between 2nd-generation angiotensin receptor blockers and the risk of hypotension in COVID-19 patients admitted to hospital.

It has not yet been established whether angiotensin II receptor blockers (ARB), statins, and multiple drugs affect the severity of COVID-19. Therefore, we herein performed an observational study on the effects of 1st- and 2nd-generation ARB, statins, and multiple drugs, on COVID-19 in patients admitted to 15 Japanese medical facilities. The results obtained showed that ARB, statins, and multiple drugs were not associated with the primary outcome (odds ratio: 1.040, 95% confidence interval: 0.688-0.571; 0.696, 0.439-1.103; 1.056, 0.941-1.185, respectively), each component of the primary outcome (in-hospital death, ventilator support, extracorporeal membrane oxygenation support, and admission to the intensive care unit), or the secondary outcomes (oxygen administration, disturbed consciousness, and hypotension, defined as systolic blood pressure ≤90 mmHg). ARB were divided into 1st- and 2nd-generations based on their approval for use (before 2000 and after 2001), with the former consisting of losartan, candesartan, and valsartan, and the latter of telmisartan, olmesartan, irbesartan, and azilsartan. The difference of ARB generation was not associated with the primary outcome (odds ratio with 2nd-generation ARB relative to 1st-generation ARB: 1.257, 95% confidence interval: 0.613-2.574). The odd ratio for a hypotension as one of the secondary outcomes with 2nd-generation ARB was 1.754 (95% confidence interval: 1.745-1.763) relative to 1st-generation ARB. These results suggest that patients taking 2nd-generation ARB may be at a higher risk of hypotension than those taking 1st-generation ARB and also that careful observations are needed. Further studies are continuously needed to support decisions to adjust medications for co-morbidities.

Detection of SARS-CoV-2 RNA Using RT-qPCR in Saliva Samples and Nasopharyngeal, Lingual, and Buccal Mucosal Swabs.

Coronavirus disease 2019 is diagnosed based on the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in nasopharyngeal swabs or saliva samples using reverse-transcription quantitative polymerase chain reaction. Nasopharyngeal swabs should be collected by medical professionals who are covered with full personal protective equipment (PPE), while saliva samples can be collected by patients themselves without any PPE. However, collecting saliva is difficult for people who are unable to follow instructions, including infants or unconscious patients. Owing to the high viscosity of saliva, special attention is required to handle saliva samples in laboratories. To solve these problems, we compared lingual and buccal mucosal swabs (oral swabs) with nasopharyngeal swabs and saliva samples. Among 13 patients who had a positive result for SARS-CoV-2 RNA in their nasopharyngeal swabs, 8 and 10 patients had a positive result for SARS-CoV-2 RNA in their saliva (concordance rate, 61.5%) and oral swabs (76.9%), respectively. Among the eight patients with a positive result for SARS-CoV-2 RNA in saliva, seven (87.5%) had SARS-CoV-2 detected in their oral swabs. We could not obtain saliva samples from four patients, but we found perfect concordance of SARS-CoV-2 positivity between the nasopharyngeal and oral swabs. Therefore, oral swabs can be used for SARS-CoV-2 RNA detection.

A regionally specific drinking custom 'Otori' and its association with alcohol consumption/alcohol use disorders: a cross-sectional study.

OBJECTIVES: The primary objective was to describe the characteristics of Otori, a regionally specific drinking custom in the Miyakojima region of Okinawa, Japan, and its participants. The secondary objective was to clarify the distribution of alcohol consumption/alcohol use disorders as measured by the Alcohol Use Disorders Identification Test (AUDIT) and its association with the frequency of engagement in Otori per month. DESIGN: Cross-sectional study. SETTING: Tarama Island, a remote island in Okinawa, Japan. PARTICIPANTS: Individuals who lived on Tarama Island, participated in a mass general health check or mass influenza vaccination programme, were aged ≥20 years and had decision-making capacity were eligible to participate. PRIMARY OUTCOME MEASURES: Alcohol consumption/alcohol use disorders as measured by the AUDIT, frequency of engagement in Otori per month, settings in which people engage in Otori and attitudes toward Otori. RESULTS: Among 478 eligible participants, 401 answered the questionnaire. Approximately 15% reported attitudes toward Otori of 'like' or 'somewhat like'; around 80% of these participants were middle-aged to older adult men. Compared with the national average, a higher percentage of people (9.2% and 40.9% of women and men, respectively) had AUDIT scores indicating 'hazardous drinking or more', which was associated with 'low or intermediate frequency' and 'high frequency' of engagement in Otori per month (ORs of 7.626 and 20.321, respectively). CONCLUSIONS: Social obligation generated by some community members could pressure most of the population into participating in Otori, possibly leading to a higher percentage of people engaging in hazardous/harmful alcohol consumption and alcohol dependence. However, healthcare professionals should carefully consider the beneficial and detrimental effects of the custom on biomedical and social conditions and avoid advocating to promote or abolish the custom by only highlighting one aspect.

Corticosteroids for hospitalized patients with mild to critically-ill COVID-19: a multicenter, retrospective, propensity score-matched study.

Corticosteroids use in coronavirus disease 2019 (COVID-19) is controversial, especially in mild to severe patients who do not require invasive/noninvasive ventilation. Moreover, many factors remain unclear regarding the appropriate use of corticosteroids for COVID-19. In this context, this multicenter, retrospective, propensity score-matched study was launched to evaluate the efficacy of systemic corticosteroid administration for hospitalized patients with COVID-19 ranging in the degree of severity from mild to critically-ill disease. This multicenter, retrospective study enrolled consecutive hospitalized COVID-19 patients diagnosed January-April 2020 across 30 institutions in Japan. Clinical outcomes were compared for COVID-19 patients who received or did not receive corticosteroids, after adjusting for propensity scores. The primary endpoint was the odds ratio (OR) for improvement on a 7-point ordinal score on Day 15. Of 1092 COVID-19 patients analyzed, 118 patients were assigned to either the corticosteroid and non-corticosteroid group, after propensity score matching. At baseline, most patients did not require invasive/noninvasive ventilation (85.6% corticosteroid group vs. 89.8% non-corticosteroid group). The odds of improvement in a 7-point ordinal score on Day 15 was significantly lower for the corticosteroid versus non-corticosteroid group (OR, 0.611; 95% confidence interval [CI], 0.388-0.962; p = 0.034). The time to improvement in radiological findings was significantly shorter in the corticosteroid versus non-corticosteroid group (hazard ratio [HR], 1.758; 95% CI, 1.323-2.337; p < 0.001), regardless of baseline clinical status. The duration of invasive mechanical ventilation was shorter in corticosteroid versus non-corticosteroid group (HR, 1.466; 95% CI, 0.841-2.554; p = 0.177). Of the 106 patients who received methylprednisolone, the duration of invasive mechanical ventilation was significantly shorter in the pulse/semi-pulse versus standard dose group (HR, 2.831; 95% CI, 1.347-5.950; p = 0.006). In conclusion, corticosteroids for hospitalized patients with COVID-19 did not improve clinical status on Day 15, but reduced the time to improvement in radiological findings for all patients regardless of disease severity and also reduced the duration of invasive mechanical ventilation in patients who required intubation.Trial registration: This study was registered in the University hospital Medical Information Network Clinical Trials Registry on April 21, 2020 (ID: UMIN000040211).

Renin-angiotensin system inhibitors and the severity of coronavirus disease 2019 in Kanagawa, Japan: a retrospective cohort study.

Since the beginning of the coronavirus disease 2019 (COVID-19) outbreak initiated on the Diamond Princess Cruise Ship at Yokohama harbor in February 2020, we have been doing our best to treat COVID-19 patients. In animal experiments, angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II type-1 receptor blockers (ARBs) are reported to suppress the downregulation of angiotensin converting enzyme 2 (ACE2), and they may inhibit the worsening of pathological conditions. We aimed to examine whether preceding use of ACEIs and ARBs affected the clinical manifestations and prognosis of COVID-19 patients. One hundred fifty-one consecutive patients (mean age 60 ± 19 years) with polymerase-chain-reaction proven severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who were admitted to six hospitals in Kanagawa Prefecture, Japan, were analyzed in this multicenter retrospective observational study. Among all COVID-19 patients, in the multiple regression analysis, older age (age ≥ 65 years) was significantly associated with the primary composite outcome (odds ratio (OR) 6.63, 95% confidence interval (CI) 2.28-22.78, P < 0.001), which consisted of (i) in-hospital death, (ii) extracorporeal membrane oxygenation, (iii) mechanical ventilation, including invasive and noninvasive methods, and (iv) admission to the intensive care unit. In COVID-19 patients with hypertension, preceding ACEI/ARB use was significantly associated with a lower occurrence of new-onset or worsening mental confusion (OR 0.06, 95% CI 0.002-0.69, P = 0.02), which was defined by the confusion criterion, which included mild disorientation or hallucination with an estimation of medical history of mental status, after adjustment for age, sex, and diabetes. In conclusion, older age was a significant contributor to a worse prognosis in COVID-19 patients, and ACEIs/ARBs could be beneficial for the prevention of confusion in COVID-19 patients with hypertension.