Successful maintenance treatment of disseminated nocardiosis with cerebral abscess in a severely immunocompromised patient allergic to trimethoprim-sulfamethoxazole using moxifloxacin and high-dose minocycline: A case report.

Nocardiosis in patients after allogeneic hematopoietic stem cell transplantation (HSCT) is rare, but is associated with a significant mortality risk. Although trimethoprim-sulfamethoxazole (TMP/SMX) remains the cornerstone of nocardiosis treatment, optimal alternative therapies for patients intolerant to TMP/SMX are not well-established. Herein, we report a case of disseminated nocardiosis with bacteremia and multiple lesions in the lungs and brain caused by Nocardia farcinica, in a 60-year-old man who had previously undergone allogeneic HSCT and was receiving immunosuppressants for severe chronic graft-versus-host disease. The patient received atovaquone for the prophylaxis of Pneumocystis pneumonia because of a previous serious allergic reaction to TMP/SMX. The patient was initially treated with imipenem/cilastatin and amikacin, which were later switched to ceftriaxone and amikacin based on the results of antimicrobial susceptibility testing. After switching to oral levofloxacin and a standard dose of minocycline, the patient experienced a single recurrence of brain abscesses. However, after switching to oral moxifloxacin and high-dose minocycline, the patient did not experience any relapses during the subsequent two years and seven months of treatment. In treating nocardiosis with brain abscesses, it is crucial to select oral antibiotics based on the antimicrobial susceptibility test results and pharmacokinetics, especially when TMP/SMX is contraindicated. A combination of oral moxifloxacin and high-dose minocycline could be a promising alternative therapy.

Risk stratification and prognosis prediction using cardiac biomarkers in COVID-19: a single-centre retrospective cohort study.

OBJECTIVE: There is a need for a robust tool to stratify the patient's risk with COVID-19. We assessed the prognostic values of cardiac biomarkers for COVID-19 patients. METHODS: This is a single-centre retrospective cohort study. Consecutive laboratory-confirmed COVID-19 patients admitted to the Kobe City Medical Center General Hospital from July 2020 to September 2021 were included. We obtained cardiac biomarker values from electronic health records and institutional blood banks. We stratified patients with cardiac biomarkers as high-sensitive troponin I (hsTnI), N-terminal pro-B-type natriuretic peptide (NT-proBNP), creatine kinase (CK) and CK myocardial band (CK-MB), using the clinically relevant thresholds. Prespecified primary outcome measure was all-cause death. RESULTS: A total of 917 patients were included. hsTnI, NT-proBNP, CK and CK-MB were associated with the significantly higher cumulative 30-day incidence of all-cause death (hsTnI: <5.0 ng/L group; 4.3%, 5.0 ng/L-99%ile upper reference limit (URL) group; 8.8% and ≥99% ile URL group; 25.2%, p<0.001. NT-proBNP: <125 pg/mL group; 5.3%, 125-900 pg/mL group; 10.5% and ≥900 pg/mL group; 31.9%, p<0.001. CK:

Profiling of Unfolded Protein Response Markers and Effect of IRE1α-specific Inhibitor in Pituitary Neuroendocrine Tumor.

CONTEXT: Inositol-requiring enzyme 1α (IRE1α) and PKR-like ER kinase (PERK), which are endoplasmic reticulum (ER) membrane proteins, regulate the unfolded protein response (UPR). These molecules have recently gained attention as a novel therapeutic target in secretory tumors. The roles of the UPR in pituitary neuroendocrine tumors (PitNETs) are unclear. OBJECTIVE: To clarify UPR profiling of PitNETs and to investigate the effect of pharmacological modulation of UPR by KIRA8, a newly developed IRE1α-specific inhibitor. METHODS: In 131 patients with PitNETs, we evaluated RNA expression of UPR markers in PitNETs and their clinical phenotypes. Using GH3 cells, we examined the effects of KIRA8 and its combination with octreotide on UPR profiling, cell growth, and apoptosis. RESULTS: Cytoprotective adaptive-UPR (A-UPR) markers were more increased in functioning PitNETs (FPitNETs, n = 112) than in nonfunctioning PitNETs (NFPitNETs, n = 19), while there was no difference in proapoptotic terminal-UPR (T-UPR) markers. Similarly, overt somatotroph tumors (STs, acromegaly, n = 11) increased A-UPR compared with silent STs (n = 10). In STs, serum IGF-1 levels were inversely correlated with Txnip mRNA expression, a representative T-UPR marker. KIRA8 inhibited cell growth and facilitated apoptosis in GH3 cells with increased expressions of T-UPR markers, which was enhanced by the combination with octreotide. Octreotide increased mRNA expression of Txnip and Chop, but decreased spliced Xbp1 under ER stress. Octreotide is suggested to inhibit activation of IRE1α but to reciprocally induce T-UPR under PERK. CONCLUSION: UPR markers in FPitNETs are implicated as dominant A-UPR but blunted T-UPR. KIRA8, enhanced with octreotide, unbalances the UPR, leading to antitumor effects. Targeting IRE1α may provide a novel strategy to treat PitNETs.

Sequential cellular and humoral responses after repetitive COVID-19 vaccination in patients treated with anti-CD20 antibodies.

Patients treated with anti-CD20 antibodies for haematological disorders have insufficient immune responses to mRNA COVID-19 vaccines; however, relevant sequential data are lacking. We sequentially evaluated the humoral and cellular immune responses in 22 patients who had received anti-CD20 antibodies within 12 months before the first vaccination, before and after the third and fourth vaccinations. Humoral responses improved gradually, along with the resolution of B-cell depletion. A steady increase was noted in cellular responses, regardless of the B-cell status. Our findings suggest the potential benefit of repeated vaccinations in these patients until B-cell recovery is confirmed while enhancing cellular responses.

Thyroid function, glycemic control, and diabetic nephropathy in patients with type 2 diabetes over 24 months: prospective observational study.

BACKGROUND: The higher prevalence of thyroid dysfunction in type 1 diabetes patients has been well established, whereas it is a matter of debate whether that is also observed in type 2 diabetes patients. This study was conducted to reveal whether higher prevalence of thyroid dysfunction is observed in patients with type 2 diabetes. METHODS: We examined thyroid functions and thyroid autoantibodies in 200 patients with type 2 diabetes and 225 controls, with 24 months follow up for those with type 2 diabetes. RESULTS: Serum free triiodothyronine (fT3) levels and fT3/free thyroxine (fT4) ratio were significantly lower, while fT4 levels were significantly higher in patients with type 2 diabetes. The number of patients with thyroid dysfunction or patients positive for thyroid autoantibodies were not different between the two groups. The fT3/fT4 ratio was positively and negatively correlated with serum c-peptide and HbA1c levels, respectively, suggesting that the difference can be attributable to insulin resistance and diabetic control. In the follow-up observation, we found no significant correlation between basal thyrotropin (TSH), fT3, fT4 or fT3/fT4 ratio with the amounts of changes of HbA1c levels at 12 or 24 months after the basal measurements. There was a negative relationship between TSH levels and eGFR at baseline measurements, but TSH levels did not seem to predict future decline of eGFR levels. No relationship was observed between urine albumin/ g‧cre levels and thyroid function. CONCLUSION: Thyroid dysfunction and thyroid autoantibodies were not different in prevalence between patients with type 2 diabetes and controls, although in patients with type 2 diabetes, the fT3/fT4 ratio was decreased. Basal thyroid function did not predict future diabetes control or renal function within 24 months of follow-up.

Predictive factors and clinical impact of ICU-acquired weakness on functional disability in mechanically ventilated patients with COVID-19.

BACKGROUND: Patients with critical COVID-19 often require invasive mechanical ventilation (IMV) and admission to the intensive care unit (ICU), resulting in a higher incidence of ICU-acquired weakness (ICU-AW) and functional decline. OBJECTIVE: This study aimed to examine the causes of ICU-AW and functional outcomes in critically ill patients with COVID-19 who required IMV. METHODS: This prospective, single-center, observational study included COVID-19 patients who required IMV for ≥48 h in the ICU between July 2020 and July 2021. ICU-AW was defined as a Medical Research Council sum score <48 points. The primary outcome was functional independence during hospitalization, defined as an ICU mobility score ≥9 points. RESULTS: A total of 157 patients (age: 68 [59-73] years, men: 72.6%) were divided into two groups (ICU-AW group; n = 80 versus non-ICU-AW; n = 77). Older age (adjusted odds ratio [95% confidence interval]: 1.05 [1.01-1.11], p = 0.036), administration of neuromuscular blocking agents (7.79 [2.87-23.3], p < 0.001), pulse steroid therapy (3.78 [1.49-10.1], p = 0.006), and sepsis (7.79 [2.87-24.0], p < 0.001) were significantly associated with ICU-AW development. In addition, patients with ICU-AW had significantly longer time to functional independence than those without ICU-AW (41 [30-54] vs 19 [17-23] days, p < 0.001). The development of ICU-AW was associated with delayed time to functional independence (adjusted hazard ratio: 6.08; 95% CI: 3.05-12.1; p < 0.001). CONCLUSIONS: Approximately half of the patients with COVID-19 requiring IMV developed ICU-AW, which was associated with delayed functional independence during hospitalization.

Trajectories of the SARS-CoV-2 RNA load in patients with hematological malignancy.

OBJECTIVES: The higher risk of prolonged viral shedding in coronavirus disease (COVID-19) patients with hematological malignancies (HM) necessitates test-based de-isolation strategies. However, evidence to establish their appropriate isolation period is insufficient. This study investigated the factors affecting prolonged viral shedding and the requisite isolation period in these patients. METHODS: We retrospectively reviewed 14 COVID-19 patients with HM between January and April 2022, who were subjected to our test-based de-isolation strategy, followed by analysis of the viral load trajectory. The viral loads of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were evaluated using the cycle threshold (Ct ) of the reverse-transcription quantitative polymerase chain reaction. The trajectories were classified according to the time-interval from COVID-19 onset to the attainment of Ct values >30. RESULTS: The median interval between onset and attainment of a Ct value >30 was 22 days. Five patients with mild or moderate COVID-19 without intense treatment histories achieved Ct values >30 within 20 days. The other nine patients needed more than 20 days, including three patients who did not meet this criterion during the observation period. CONCLUSIONS: The SARS-CoV-2 viral load trajectories in patients with HM can be stratified by treatment history for the underlying HM and severity of COVID-19.

A pseudo-outbreak of COVID-19 associated pulmonary aspergillosis: a microbiological investigation of both the patients and the environment.

Background: We experienced a pseudo-outbreak of aspergillosis in a newly constructed COVID-19 ward. Within the first 3 months from the commencement of the ward, six intubated patients of COVID-19 developed probable or possible pulmonary aspergillosis. We suspected an outbreak of pulmonary aspergillosis associated with ward construction and launched air sampling for the investigation of the relationship between these. Methods: The samples were collected at 13 locations in the prefabricated ward and three in the general wards, not under construction, as a control. Results: The results from samples revealed different species of Aspergillus from those detected by the patients. Aspergillus sp. was detected not only from the air samples in the prefabricated ward but also in the general ward. Discussion: In this investigation, we could not find evidence of the outbreak that links the construction of the prefabricated ward with the occurrence of pulmonary aspergillosis. It might suggest that this series of aspergillosis was more likely occurred from fungi that inherently colonized patients, and was associated with patient factors such as severe COVID-19 rather than environmental factors. Once an outbreak originating from building construction is suspected, it is important to conduct an environmental investigation including an air sampling.

Effect of SARS-CoV-2 BNT162b2 mRNA vaccine on thyroid autoimmunity: A twelve-month follow-up study.

Objectives: Graves' disease (GD) has been highlighted as a possible adverse effect of the respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccine. However, it is unknown if the SARS-CoV-2 vaccine disrupts thyroid autoimmunity. We aimed to present long-term follow-up of thyroid autoimmunity after the SARS-CoV-2 BNT162b2 mRNA vaccine. Methods: Serum samples collected from seventy Japanese healthcare workers at baseline, 32 weeks after the second dose (pre-third dose), and 4 weeks after the third dose of the vaccine were analyzed. The time courses of anti-SARS-CoV-2 spike immunoglobulin G (IgG) antibody, thyroid-stimulating hormone receptor antibody (TRAb), and thyroid function were evaluated. Anti-thyroglobulin antibodies (TgAb) and anti-thyroid peroxidase antibodies (TPOAb) were additionally evaluated in thirty-three participants. Results: The median age was 50 (IQR, 38-54) years and 69% were female. The median anti-spike IgG antibody titer was 17627 (IQR, 10898-24175) U/mL 4 weeks after the third dose. The mean TRAb was significantly increased from 0.81 (SD, 0.05) IU/L at baseline to 0.97 (SD, 0.30) IU/L 4 weeks after the third dose without functional changes. An increase in TRAb was positively associated with female sex (ß = 0.32, P = 0.008) and low basal FT4 (ß = -0.29, P = 0.02) and FT3 (ß = -0.33, P = 0.004). TgAb was increased by the third dose. Increase in TgAb was associated with history of the thyroid diseases (ß = 0.55, P <0.001). Conclusions: SARS-CoV-2 BNT162b2 mRNA vaccine can disrupt thyroid autoimmunity. Clinicians should consider the possibility that the SARS-CoV-2 vaccine may disrupt thyroid autoimmunity.

Humoral response and safety of the BNT162b2 and mRNA-1273 COVID-19 vaccines in allogeneic hematopoietic stem cell transplant recipients: An observational study.

BACKGROUND: The effectiveness of mRNA COVID-19 vaccines and the optimal timing of vaccine administration in allogeneic hematopoietic stem cell transplantation (Allo-HSCT) recipients remains inadequately investigated. We examine the effectiveness and safety of mRNA COVID-19 vaccines in allo-HSCT recipients. METHOD: This prospective observational study included 44 allo-HSCT recipients and 38 healthy volunteers. The proportion of subjects acquiring anti-S1 IgG antibodies were considered as the primary endpoint. The occurrence of adverse events after vaccination and objective deterioration of chronic graft-versus-host disease (GVHD) were defined as secondary endpoints. In addition, we compared the geometric mean titers (GMT) of anti-S1 antibody titers in subgroups based on time interval between transplantation and vaccination. RESULTS: A humoral response to the vaccine was evident in 40 (91%) patients and all 38 healthy controls. The GMT of anti-S1 titers in patients and healthy controls were 277 (95% confidence interval [CI]: 120-643) BAU/mL and 532 (95% CI 400-708) BAU/mL, respectively. (p = 0.603). A short time interval between transplantation and vaccination (≤6 months) was associated with low anti-S1 IgG antibody titers. No serious adverse events and deterioration of chronic GVHD were observed. Only one case of new development of mild chronic GVHD was recorded. CONCLUSION: Messenger RNA COVID-19 vaccines induce humoral responses in allo-HSCT recipients and can be administered safely.

Clinical outcomes of COVID-19 caused by the Alpha variant compared with one by wild type in Kobe, Japan. A multi-center nested case-control study.

OBJECTIVES: The emergence of the Alpha variant of novel coronavirus 2019 (SARS-CoV-2) is a concerning issue but their clinical implications have not been investigated fully. METHODS: We conducted a nested case-control study to compare severity and mortality caused by the Alpha variant (B.1.1.7) with the one caused by the wild type as a control from December 2020 to March 2021, using whole-genome sequencing. 28-day mortality and other clinically important outcomes were evaluated. RESULTS: Infections caused by the Alpha variant were associated with an increase in the use of oxygen (43.4% vs 26.3%. p = 0.017), high flow nasal cannula (21.2% vs 4.0%, p = 0.0007), mechanical ventilation (16.2% vs 6.1%, p = 0.049), ICU care (30.3% vs 14.1%, p = 0.01) and the length of hospital stay (17 vs 10 days, p = 0.031). More patients with the Alpha variant received medications such as dexamethasone. However, the duration of each modality did not differ between the 2 groups. Likewise, there was no difference in 28-day mortality between the 2 groups (12% vs 8%, p = 0.48), even after multiple sensitivity analyses, including propensity score analysis. CONCLUSION: The Alpha variant was associated with a severe form of COVID-19, compared with the non-Alpha wild type, but might not be associated with higher mortality.

Clinical characteristics and risk factors for multidrug-resistant bacterial isolation in patients with international travel history.

BACKGROUND: International travelers are at risk of carrying resistant bacteria. It is critical to identify risk factors associated with multidrug-resistant organism (MDRO) colonization in travelers. METHODS: A retrospective chart review observational study was conducted at two tertiary centers in Japan for inpatients who had been hospitalized or visited an outpatient clinic overseas within the previous 12 months. These patients underwent MDRO screening upon admission. To identify independent predictors for the isolation of MDROs, multivariable analyses were performed using logistic regression. RESULTS: In total, 77 (36%) of the 216 patients were positive for MDROs at admission. The majority of bacteria detected in stool samples were extended-spectrum beta-lactamase-producing Escherichia coli (ESBLEC) (n = 67 [89%]). ESBLEC was detected in nearly 40% of patients who traveled to Asia. Travel to Asia was an independent risk factor for any MDRO and ESBLEC isolation. For non-ESBLEC MDRO isolation, a history of surgery abroad was an independent risk factor for detection. DISCUSSION AND CONCLUSIONS: A history of hospitalization abroad has previously been found to be associated with MDRO colonization in travelers, which was not identified as a risk factor in this study. The risk factors for MDRO colonization were different between ESBLEC and non-ESBLEC MDROs.

Cold agglutinin anti-I antibodies in two patients with COVID-19.

BACKGROUND: Cold agglutinin syndrome (CAS) is associated with various diseases. Several studies of CAS associated with coronavirus disease 2019 (COVID-19) reported hemolytic anemia and thrombosis; however, the clinical significance of cold agglutinins (CA) in patients with COVID-19 is unclear. Here, we present two cases of CA identified in the context of COVID-19 without hemolytic anemia and clotting. CASE REPORT AND DISCUSSION: Two patients with no known risk factors for CA were diagnosed with COVID-19; peripheral blood smears reveal red blood cells (RBCs) agglutination. These patients showed a high CA titer. We confirmed retrospectively that the CA was an anti-I antibody. The two COVID-19 cases with a high CA titer showed no hemolysis or thrombosis. Mycoplasma pneumoniae is known to cause CAS, but not all patients who have a high CA titer show hemolysis. Coagulation abnormalities are documented in severe COVID-19 cases. Although CA increases the risk of thrombosis in those with lymphoproliferative diseases, the role of anti-I antibodies in COVID-19 is unclear. The impact of CAS on clinical presentations in COVID-19 remains a matter of verification. CONCLUSIONS: A high CA titer was identified in COVID-19 patients without hemolytic anemia and clotting. Anti-I antibodies were identified. Further studies are required to clarify the pathophysiology of CA in COVID-19.

Patient-centered outcomes at hospital discharge in mechanically ventilated COVID-19 patients in Kobe, Japan: A single-center retrospective cohort study.

BACKGROUND: Apart from saving the lives of coronavirus disease (COVID-19) patients on mechanical ventilation (MV), recovery from the sequelae of prolonged MV (PMV) is an emerging issue.c METHODS: We conducted a retrospective study among consecutive adult COVID-19 patients admitted to an intensive care unit (ICU) in Kobe, Japan, between March 3, 2020, and January 31, 2021, and received invasive MV. Clinical outcomes included in-hospital mortality and recovery from COVID-19 in survivors regarding organ dysfunction, respiratory symptoms, and functional status at discharge. We compared survivors' outcomes with MV durations of >14 days and ≤14 days. RESULTS: We included 85 patients with a median age of 69 years (interquartile range, 64-75 years); 76 (89%) patients had at least 1 comorbidity, 72 (85%) were non-frail, and 79 (93%) were functionally independent before COVID-19 infection. Eighteen patients (21%) died during hospitalization. At discharge, 59/67 survivors (88%) no longer required respiratory support, 50 (75%) complained of dyspnea, and 40 (60%) were functionally independent. Of the survivors, 23 patients receiving MV for >14 days had a worse recovery from COVID-19 at discharge compared with those on MV for ≤14 days, as observed using the Barthel index (median: 35 [5-65] vs. 100 [85-100]), ICU mobility scale (8 [5-9] vs. 10 [10-10]), and functional oral intake scale (3 [1-7] vs. 7 [7-7]) (P < 0.0001). CONCLUSION: Although four-fifths of the patients survived and >50% of survivors demonstrated clinically important recovery in organ function and functional status during hospitalization, PMV was related to poor recovery from COVID-19 at discharge.

Impact of serum lactate dehydrogenase on the short-term prognosis of COVID-19 with pre-existing cardiovascular diseases.

BACKGROUND: Patients with coronavirus disease 2019 (COVID-19) and underlying cardiovascular comorbidities have poor prognoses. Our aim was to identify the impact of serum lactate dehydrogenase (LDH), which is associated with mortality in acute respiratory distress syndrome, on the prognoses of patients with COVID-19 and underlying cardiovascular comorbidities. METHODS: Among 1518 patients hospitalized with COVID-19 enrolled in the CLAVIS-COVID (Clinical Outcomes of COVID-19 Infection in Hospitalized Patients with Cardiovascular Diseases and/or Risk Factors study), 515 patients with cardiovascular comorbidities were analyzed. Patients were divided into tertiles based on LDH levels at admission [tertile 1 (T1), <235 U/L; tertile 2 (T2), 235-355 U/L; and tertile 3 (T3); ≥356 U/L]. We investigated the impact of LDH levels on the in-hospital mortality. RESULTS: The mean age was 70.4 ± 30.0 years, and 65.3% were male. There were significantly more in-hospital deaths in T3 than in T1 and T2 [n = 50 (29.2%) vs. n = 15 (8.7%), and n = 24 (14.0%), respectively; p < 0.001]. Multivariable analysis adjusted for age, comorbidities, vital signs, and laboratory data including D-dimer and high-sensitivity troponin showed T3 was associated with an increased risk of in-hospital mortality (adjusted hazard ratio, 3.04; 95% confidence interval, 1.50-6.13; p = 0.002). CONCLUSIONS: High serum LDH levels at the time of admission are associated with an increased risk of in-hospital death in patients with COVID-19 and known cardiovascular disease and may aid in triage of these patients.

Estimation of seroprevalence of novel coronavirus disease (COVID-19) using preserved serum at an outpatient setting in Kobe, Japan: A cross-sectional study.

OBJECTIVES: Coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 has been affecting many people on earth and our society. Japan is known to have relatively smaller number of its infections as well as deaths among developed nations. However, accurate prevalence of COVID-19 in Japan remains unknown. Therefore, we conducted a cross-sectional study to estimate seroprevalence of SARS-CoV-2 infection. METHODS: We conducted a cross-sectional serologic testing for SARS-CoV-2 antibody using 1000 samples from patients at outpatient settings who visited the clinic from March 31 to April 7, 2020, stratified by the decade of age and sex. RESULTS: There were 33 positive IgG among 1000 serum samples (3.3%, 95%CI: 2.3-4.6%). By applying this figure to the census of Kobe City (population: 1,518,870), it is estimated that the number of people with positive IgG be 50,123 (95%CI: 34,934-69,868). Age and sex adjusted prevalence of positivity was calculated 2.7% (95%CI: 1.8-3.9%), and the estimated number of people with positive IgG was 40,999 (95%CI: 27,333-59,221). These numbers were 396 to 858-fold more than confirmed cases with PCR testing in Kobe City. CONCLUSIONS: Our cross-sectional serological study suggests that the number of people with seropositive for SARS-CoV-2 infection in Kobe, Japan is far more than the confirmed cases by PCR testing.

Autosomal Dominant Hypocalcemia With Atypical Urine Findings Accompanied by Novel CaSR Gene Mutation and VitD Deficiency.

INTRODUCTION: Autosomal dominant hypocalcemia (ADH) is caused by gain-of-function mutations of the calcium sensing receptor (CaSR). It is characterized by hypercalciuria in spite of hypocalcemia. Vitamin D deficiency increases calcium reabsorption in the distal tubules of the kidneys, resulting in hypocalciuria. MATERIALS AND METHODS: A 38-year-old female proband had hypocalcemia, hypocalciuria, and vitamin D deficiency. Her father and brother also had hypocalcemia, but her mother was normocalcemic. We analyzed the CaSR gene abnormality in this family. Polymerase chain reaction (PCR) and sequence analysis were performed to explore the CaSR gene mutation. Mutagenesis, transfection, and functional analysis were performed on the discovered genetic abnormalities. RESULT: PCR and sequence analysis revealed that the proband, her father, and brother had a novel heterozygous mutation of the CaSR genes that causes threonine to asparagine substitution at codon 186 (T186N). Using HEK293 cells transfected with wild-type or T186N CaSR complementary DNA, we assessed the intracellular Ca2+ concentration in response to changes in the extracellular Ca2+ concentration. The cells transfected mutant CaSR gene had higher activity than that of wild-type. Therefore, we determined our patient had ADH with a novel mutation of the CaSR gene and hypocalciuria resulting from a vitamin D deficiency. We administered vitamin D to the proband, which caused elevation of her urinary calcium level, a typical finding of ADH. CONCLUSION: Vitamin D deficiency was suggested to potentially mask hypercalciuria in ADH. Hypocalcemia with vitamin D deficiency should be diagnosed with care.

Clinical characteristics and outcomes of critically ill patients with COVID-19 in Kobe, Japan: a single-center, retrospective, observational study.

PURPOSE: Coronavirus disease 2019 (COVID-19) has placed a great burden on critical care services worldwide. Data regarding critically ill COVID-19 patients and their demand of critical care services outside of initial COVID-19 epicenters are lacking. This study described clinical characteristics and outcomes of critically ill COVID-19 patients and the capacity of a COVID-19-dedicated intensive care unit (ICU) in Kobe, Japan. METHODS: This retrospective observational study included critically ill COVID-19 patients admitted to a 14-bed COVID-19-dedicated ICU in Kobe between March 3, 2020 and June 21, 2020. Clinical and daily ICU occupancy data were obtained from electrical medical records. The last follow-up day was June 28, 2020. RESULTS: Of 32 patients included, the median hospital follow-up period was 27 (interquartile range 19-50) days. The median age was 68 (57-76) years; 23 (72%) were men and 25 (78%) had at least one comorbidity. Nineteen (59%) patients received invasive mechanical ventilation for a median duration of 14 (8-27) days. Until all patients were discharged from the ICU on June 5, 2020, the median daily ICU occupancy was 50% (36-71%). As of June 28, 2020, six (19%) died during hospitalization. Of 26 (81%) survivors, 23 (72%) were discharged from the hospital and three (9%) remained in the hospital. CONCLUSION: During the first months of the outbreak in Kobe, most critically ill patients were men aged ≥ 60 years with at least one comorbidity and on mechanical ventilation; the ICU capacity was not strained, and the case-fatality rate was 19%.