Impact of diabetes and Krebs von den Lungen-6 on coronavirus disease 2019 severity: A single-center study from Japan.

AIMS/INTRODUCTION: Diabetes mellitus is reported as a risk factor for increased coronavirus disease 2019 (COVID-19) severity and mortality, but there have been few reports from Japan. Associations between diabetes mellitus and COVID-19 severity and mortality were investigated in a single Japanese hospital. MATERIALS AND METHODS: Patients aged ≥20 years admitted to Osaka City General Hospital for COVID-19 treatment between April 2020 and March 2021 were included in this retrospective, observational study. Multivariable logistic regression analysis was carried out to examine whether diabetes mellitus contributes to COVID-19-related death and severity. RESULTS: Of the 262 patients included, 108 (41.2%) required invasive ventilation, and 34 (13.0%) died in hospital. The diabetes group (n = 92) was significantly older, more obese, had longer hospital stays, more severe illness and higher mortality than the non-diabetes group (n = 170). On multivariable logistic regression analysis, age (odds ratio [OR] 1.054, 95% confidence interval [CI] 1.023-1.086), body mass index (OR 1.111, 95% CI 1.028-1.201), history of diabetes mellitus (OR 2.429, 95% CI 1.152-5.123), neutrophil count (OR 1.222, 95% CI 1.077-1.385), C-reactive protein (OR 1.096, 95% CI 1.030-1.166) and Krebs von den Lungen-6 (OR 1.002, 95% CI 1.000-1.003) were predictors for COVID-19 severity (R2 = 0.468). Meanwhile, age (OR 1.104, 95% CI 1.037-1.175) and Krebs von den Lungen-6 (OR 1.003, 95% CI 1.001-1.005) were predictors for COVID-19-related death (R2 = 0.475). CONCLUSIONS: Diabetes mellitus was a definite risk factor for COVID-19 severity in a single Japanese hospital treating moderately-to-severely ill patients.

Analysis of glutathione S-transferase and cytochrome P450 gene polymorphism in recipients of dose-adjusted busulfan-cyclophosphamide conditioning.

Sporadic incidence of veno-occlusive disease (VOD) continues to occur, despite achievement of recommended busulfan (BU) concentrations after real-time BU dose adjustment. To explore the potential influence of glutathione S-transferase (GST) and cytochrome P450 (CYP) genotypes on plasma BU concentration, subsequent VOD, and transplant outcome, we assessed the polymorphisms of multiple GST and CYP genes. Fifty-five patients were included (median age 38 years; range 21-67). Of these, 49 received dose-adjusted BU/CY therapy. Twenty-six patients received transplants from human leukocyte antigen-identical siblings, 26 from unrelated donors. The GSTA1*A/*A genotype was significantly associated with lower BU first-dose area under curve (AUC1st). We found that patients with higher AUC1st showed a significantly higher serum total bilirubin during the first month after transplantation, but this was not necessarily associated with subsequent development of VOD. We further analyzed a possible association of GST and CYP polymorphisms and VOD development, and found none of the polymorphisms investigated was associated with VOD incidence. Regarding transplant outcomes, GSTM1-positive patients showed lower relapse rates and better overall survival in multivariate analyses. These results suggest that a GSTM1-positive genotype in patients receiving BU/CY conditioning protects against relapse of hematological malignancies after allogeneic hematopoietic stem cell transplantation.

Correction to: Analysis of glutathione S-transferase and cytochrome P450 gene polymorphism in recipients of dose-adjusted busulfan-cyclophosphamide conditioning.

In the original article of Terakura et al., the COI disclosure were missing.

Effectiveness of sitagliptin in a patient with late dumping syndrome after total gastrectomy.

An 83-year-old man developed hypoglycemia after undergoing total gastrectomy for gastric cancer in 200X-4. The patient was admitted to our hospital in May 200X and placed on continuous glucose monitoring (CGM). Glycemic excursions were examined while on 3-meal/day (1700kcal) and 6-meal/day (1800kcal) diets. Oxyhyperglycemia followed about 2h later by a sudden drop in glucose levels was seen with both regimens. These findings were consistent with late dumping syndrome. CGM was continued, oral miglitol at 150mg/day or sitagliptin at 50mg/day was started, and glycemic excursions were compared. Results were similar for both drugs, with reductions in postprandial glucose elevations. Meal tolerance testing 3 months after oral sitagliptin, compared to before starting treatment, showed reductions in both early postprandial hyperglycemia and insulin hypersecretion. These findings suggest that DPP-4 inhibitors such as sitagliptin may be effective for treating post-gastrectomy late dumping syndrome.

Sitagliptin reduces the urine albumin-to-creatinine ratio in type 2 diabetes through decreasing both blood pressure and estimated glomerular filtration rate.

BACKGROUND: We investigated the change in the urine albumin-to-creatinine ratio (ACR) to examine the effect of sitagliptin on diabetic nephropathy. METHODS: Sitagliptin at a dose of 50 mg was administered to 247 outpatients with type 2 diabetes. Data were collected on the patients' laboratory results (including the ACR), blood pressure, and body weight. Clinical data were compared before and after 3 months' administration of sitagliptin. RESULTS: The ACR changed from 150.0 ± 538.6 mg/gCre to 148.3 ± 764.6 mg/gCre over 3 months. In the patients with micro- and macro-albuminuria, the ACR after 3 months significantly decreased compared with the baseline (P = 0.04 and P = 0.02, respectively). The subjects whose ACR decreased experienced significantly larger decreases over the 3-month period in blood pressure and estimated glomerular filtration rate (eGFR) than the other subjects. There was no significant correlation between change in ACR (ΔACR) and change in hemoglobin A1c (ΔHbA1c) during 3 months (r = 0.04, P = 0.59), but there was a significant correlation between change in ΔACR and change in systolic blood pressure (r = 0.16, P = 0.03). Multiple regression analysis revealed that the significant predictors for ΔACR were change in systolic blood pressure (ß = 0.21, P = 0.016) and change in eGFR (ß = 0.20, P = 0.024) over 3 months (r = 0.35, P = 0.04). CONCLUSIONS: Sitagliptin reduces the ACR through decreasing both blood pressure and eGFR, with no correlation with a decrease in HbA1c over a 3-month period. These results may reflect the direct action of sitagliptin on the kidneys.

Epithelioid inflammatory myofibroblastic sarcoma responsive to surgery and an ALK inhibitor in a patient with panhypopituitarism.

We encountered a case of epithelioid inflammatory myofibroblastic sarcoma (EIMS) originating from an abdominal organ that rapidly regrew twice. The patient underwent two surgeries. Large tumors grew within three months after the second surgery. The patient subsequently received chemotherapy with an anaplastic lymphoma kinase (ALK) inhibitor. Although EIMS has a poor prognosis, the patient continues to be alive with disease 14 months after surgical treatment and the administration of the ALK inhibitor.

Phase II study of dose-modified busulfan by real-time targeting in allogeneic hematopoietic stem cell transplantation for myeloid malignancy.

We aimed to evaluate the efficacy and safety of allogeneic hematopoietic stem cell transplantation with targeted oral busulfan (BU) and cyclophosphamide (CY) in a phase II study. Busulfan (1.0 mg/kg) was given initially in six doses. Based on the estimated concentration at steady state after the first dose of BU, subsequent (7th-16th) doses were adjusted to obtain a targeted overall concentration at steady state of 700-900 ng/mL. The primary endpoint was 1-year overall survival (OS). Fifty patients were registered and 46 (median age, 53 years; range, 18-62 years) received planned transplant, including 24 with AML, 16 with myelodysplastic syndrome, and six with CML. Fourteen patients were categorized as standard risk. Nineteen patients received transplant from human leukocyte antigen-identical siblings, 27 from unrelated donors. The BU dose required reduction in 32 patients and escalation in six patients. One-year OS was 65% (95% confidence interval, 50-77%). Cumulative incidence of hepatic sinusoidal obstruction syndrome was 11%. One-year transplant-related mortality was 18%. Both OS and transplant-related mortality were favorable in this study, including patients of older age and with high risk diseases. Individual dose adjustment based on BU pharmacokinetics was feasible and effective in the current phase II study. This trial is registered in the University Hospital Medical Information Network Clinical Trial Registry System (UMIN-CTR, ID:C000000156).

[Survey of analytical work done for drugs at the emergency and critical care centers equipped with high-performance instruments provided by the Ministry of Health and Welfare (at present: Ministry of Health, Labour and Welfare) in fiscal 1998].

A questionnaire was sent to 73 emergency and critical care centers where high-performance instruments for analyzing drugs and chemicals were provided by the Ministry of Health and Welfare (currently Ministry of Health, Labour and Welfare) in fiscal 1998. 52 centers (71.2%) responded to the questionnaire. Among these, the instruments have been in operation at 36 centers. This means that analytical work has been performed in at least 49.3% (36/73) of facilities with the instruments. A positive correlation was observed between the annual number of patients tested for drugs and chemicals and analytical work hours at the 36 facilities. The results indicated that 150 cases may be tested for drugs and chemicals in a year on the condition that 100 hours a month of analytical work are secured, and 200 or more cases may be tested if 200 hours a month are secured. As for the running costs required for the operation of the instruments, the instrument maintenance and repair cost was estimated at 2 million yen a year, and it was calculated that 100 cases could be handled with a maximum annual supply expense of 1 million yen and 150 cases could be handled with a maximum annual supply expense of 2 million yen. These results suggest that the instrument running cost would be fully covered at nationwide emergency and critical care centers if the additional 5,000 NHI points (1 point = 10 yen) for hospital admission, which is approved for advanced emergency and critical care centers, were applicable to all facilities. Among the 36 facilities, the implementation of analysis varied for each of the 15 toxic substances recommended for analysis by the Japanese Society for Clinical Toxicology. Further research will be necessary to investigate and assess the frequency of analysis requests and combination of simple qualitative and instrumental analyses for each of the 15 substances, in order to evaluate the approach to the 15 substances in analytical work.

[Analytic role in clinical toxicology--impact on the diagnosis and treatment of a poisoned patient].

The measurement of plasma or urine levels of drugs or toxins at an appropriate time after ingestion and assessment of the clinical status can have a significant impact in the clinical management of a poisoned patient. Qualitative screening of blood and urine is helpful in identifying ingested toxins, whereas quantitative analyses are useful in determining appropriate therapy with selected toxins (e.g., salicylate, paraquat, and acetaminophen). The common analgesic acetaminophen, which is available without prescription, is a potential hepatotoxin on overdose. The most widely accepted approach to determine the risk of hepatotoxicity following acute, single ingestion is to plot the plasma acetaminophen concentration on the Rumack-Matthew nomogram. This nomogram is based on a series of patients with and without hepatotoxicity and their corresponding blood levels. Antidotal treatment should be administered to any patient with a plasma level in the potentially toxic range. As an aid in the diagnosis and treatment of toxic incidents, as well as in monitoring the effectiveness of treatment regimens, an analytical approach is useful to clearly identify the nature of the toxic exposure and measure the amount of the toxic substance which has been absorbed. A cardinal rule in the treatment of poisoning cases is to remove any unabsorbed material, limit the absorption of additional poison, and hasten its elimination. The laboratory serves an additional purpose in the treatment phase by monitoring the amount of toxic agent remaining in circulation or measuring that excreted.