Effect of age and gender on ventricular-arterial coupling estimated using a non-invasive technique.

BACKGROUND: Left ventricular-arterial coupling is assessed as the ratio of left ventricular end-systolic elastance (Ees) to arterial elastance (Ea). Previous studies have introduced non-invasive estimations of Ees/Ea. It requires only four variables, namely pre-ejection period, ejection time, end-systolic pressure and diastolic pressure. The aims of the present study were to clarify the reference values of Ees/Ea estimated using the noninvasive technique, and to investigate the effects of age and gender on Ees/Ea in healthy subjects. METHODS: This retrospective study utilized data from healthy, 30-79-year-old subjects. We recorded electrocardiogram, phonocardiogram, and brachial arterial pulse waves simultaneously using the vascular screening system, and used the observed variables to calculate Ees/Ea. We separated subjects into five groups according to their age and compared Ees/Ea among the different age groups. RESULTS: The study included 2114 males and 2292 females. Ees/Ea ranged from 1.87 to 2.04 in males, and 1.98 to 2.32 in females. We observed no age-related differences in Ees/Ea in males (p = 0.10), and significant differences in females (p < 0.001). Ees/Ea in males was not different compared to those in females in 60-69-year-old group (p = 0.92). Whereas Ees/Ea was higher in females compared to those in males in the other age groups. The differences between medians of Ees/Ea in males and those in females were 0.45 (p < 0.001), 0.24 (p < 0.001), 0.13 (p = 0.01), and 0.13 (p = 0.03) in 30-39, 40-49, 50-59, and 70-79-year-old age groups, respectively. CONCLUSIONS: We clarified the reference values of Ees/Ea in healthy subjects. The effect of age on Ees/Ea is different in males and females, although Ees/Ea is maintained within a relatively narrow range in all subjects.

A case of prolonged COVID-19 treated with tixagevimab/cilgavimab.

A 54-year-old woman presented to our hospital with a fever and cough. The patient had a medical history of follicular lymphoma treated with obinutuzumab. She was infected with an omicron variant of coronavirus disease 2019 and developed viral pneumonia. Antibiotics, molnupiravir, sotrovimab, and prednisolone were administered but were ineffective. The patient's symptoms and pneumonia persisted. She could not produce antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) because she was administered obinutuzumab. Finally, when we administered 300 mg of tixagevimab and cilgavimab, pneumonia immediately improved. However, the infection was prolonged for more than 4 months. Patients treated with anti-CD20 monoclonal antibodies may have a prolonged SARS-CoV-2 infection. In such cases, tixagevimab/cilgavimab may be effective.

[Ultra high-risk refractory multiple myeloma with a complex karyotype including t(14;19)].

A 78-year-old man was hospitalized because of rapid progression of chronic renal failure and diagnosed with multiple myeloma (MM) IgG-λ type ISS-III R-ISS-II with complex karyotype including t(14;19). Even after receiving bortezomib-based regimens, his renal failure progressed. He became dependent on dialysis, which was required three times a week. After introducing the daratumumab (DARA)-based regimen, his renal function improved, the frequency of dialysis decreased to twice a week, and the free light chain (FLC) ratio also improved. However, his myeloma eventually followed a refractory course; therefore, pomalidomide (POM)-dexamethasone (Pd) regimen was administered. Pd regimen had a marked effect and normalized the FLC ratio after three courses of the treatment. However, his myeloma reprogressed with multiple extramedullary masses and he became del(17p) positive; eventually, he died on the 470th day of disease. MM with t(14;19) is rare and has a poor prognosis with a highly aggressive course; however, early introduction of DARA or POM may provide long-term response.

The effects of ipragliflozin on the liver-to-spleen attenuation ratio as assessed by computed tomography and on alanine transaminase levels in Japanese patients with type 2 diabetes mellitus.

We assessed the effects of a 12-week ipragliflozin treatment on the liver-to-spleen attenuation ratio (L/S ratio) using computed tomography and on alanine transaminase (ALT) levels in Japanese patients with type 2 diabetes mellitus (T2DM). Sixty-two patients with T2DM [age, 56 ± 8 years; hemoglobin A1c (HbA1c) levels, 8.1 ± 0.9%; body mass index (BMI), 27.5 ± 3.3 kg/m2] were randomly assigned in a 2:1 ratio to receive ipragliflozin (50 mg/day; ipragliflozin group; n = 40) or continued treatment (control group; n = 22) for 12 weeks. The primary endpoints were changes in ALT levels; the secondary endpoints included changes in the L/S ratio and in the visceral fat area (VFA) and subcutaneous fat area (SFA) before and after 12 weeks of the treatment as assessed by computed tomography. ALT levels (-12.45 vs. +5.82 IU/l, P < 0.001), L/S ratio (+0.07 vs. -0.08, P < 0.001), SFA (-5.8 vs. +13.3 cm2, P < 0.05), and VFA (+1.4 vs. +20.4 cm2, P < 0.05) significantly changed from baseline in the ipragliflozin group compared with the values in the control group. Multiple regression analysis among all subjects revealed that the independent factor contributing to the %ΔALT and %ΔL/C ratio was treatment group alone (ipragliflozin group = 1; control group = 0; ß coefficient = -32.08, P < 0.001 and ß coefficient = 19.98, P < 0.05, respectively). Thus, ipragliflozin may lower ALT levels associated with increased L/S ratios, indicating its potential therapeutic efficacy in T2DM-associated hepatic steatosis.

Non-high-density cholesterol level as a predictor of maximum carotid intima-media thickness in Japanese subjects with type 2 diabetes: a comparison with low-density lipoprotein level.

AIM: To determine whether non-high-density lipoprotein cholesterol (non-HDL-C) level, in comparison with low-density lipoprotein cholesterol (LDL-C) level, is useful for predicting the values of various surrogate atherosclerosis markers in Japanese subjects with type 2 diabetes (T2DM). METHODS: Data were retrieved from medical records of 265 subjects with T2DM who underwent laboratory tests to evaluate for atherosclerosis by using the following parameters: brachial-ankle pulse wave velocity, mean and maximum carotid intima-media thickness (mean CIMT and max-CIMT), and ankle-brachial index, with simultaneous fasting blood sampling for routine lipid parameters. RESULTS: In a multiple stepwise regression analysis, non-HDL-C level, but not LDL-C level, positively correlated with max-CIMT (ß coefficient = 0.14, F = 6.84). Stepwise logistic regression analysis revealed that a 0.26 mmol/L (10 mg/dL) increase in non-HDL-C level, but not LDL-C level, was significantly associated with high risk of max-CIMT (≥1.1 mm; odds ratio, 1.096; 95 % confidence interval, 1.003-1.202; p = 0.046). However, in a receiver operating characteristic curve (ROC) analysis, the addition of non-HDL-C level to the three significant independent variables obtained from the stepwise analyses did not significantly increased the area under the ROC curve (from 0.7789 to 0.7864, p = 0.4343). CONCLUSIONS: Non-HDL-C levels may be non-inferior to LDL-C level for the prediction of high-risk max-CIMT in Japanese subjects with T2DM.

Chronic hyperglycemia may attenuate the serum-uric-acid-lowering effect of low-dose febuxostat in Japanese patients with type 2 diabetes mellitus.

AIMS: This study investigated the independent predictors of the serum uric acid (sUA)-lowering effect of low-dose febuxostat, a novel xanthine oxidase inhibitor, in Japanese patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: Data of 130 T2DM patients who had been taking febuxostat 10 mg once daily for elevated sUA (≥7 mg/dl) for at least 12 weeks were retrieved from medical records. Spearman's rank correlation coefficients were calculated to determine the correlations between sets of two independent continuous variables. Multiple stepwise linear regression analysis was used to determine independent predictors of the percent change of sUA levels after 12 weeks of febuxostat treatment (%ΔsUA). RESULTS: Among all patients, %ΔsUA was significantly correlated with age (ρ = 0.192, P = 0.030) and mean glycated hemoglobin (HbA1c) level (ρ = -0.186, P = 0.036). Multiple stepwise linear regression analysis of all patients revealed that major independent factors contributing to %ΔsUA were mean HbA1c (ß = -3.14, P = 0.022) and mean glycated albumin (ß = -0.743, P = 0.013) levels. CONCLUSIONS: High HbA1c and glycated albumin levels significantly attenuated the sUA-lowering effect of low-dose febuxostat in Japanese patients with T2DM. Further detailed analysis using a larger population is warranted to confirm these findings.

Switching from atorvastatin to rosuvastatin lowers small, dense low-density lipoprotein cholesterol levels in Japanese hypercholesterolemic patients with type 2 diabetes mellitus.

AIMS: This open-label, randomized, parallel-group comparative study compared the efficacy of rosuvastatin (5mg/day) and atorvastatin (10mg/day) for reduction of small dense low-density lipoprotein cholesterol (sd LDL-C) levels in Japanese patients with type 2 diabetes mellitus (T2DM). METHODS: Patients with T2DM and hypercholesterolemia with detectable sd LDL-C after receiving 10mg/day atorvastatin for ≥ 24 weeks were randomly assigned to receive rosuvastatin (5mg/day; switched treatment) or atorvastatin (10mg/day; continued treatment) for 12 weeks. The primary endpoints were changes in sd LDL-C levels and sd LDL-C/total LDL-C ratio evaluated using the LipoPhor AS(®) system. RESULTS: There were no significant percent changes from baseline for LDL-C levels between the switched (n=55) and the continued treatment group (n=56). However, the former group exhibited a statistically significant reduction from baseline of sd LDL-C levels, sd LDL-C/total LDL-C ratio compared with the latter group (-3.8 mg/dL vs. -1.4 mg/dL, p=0.014; -2.3% vs. -0.6%, p=0.004, respectively). Multiple regression analysis among all subjects revealed that independent factors contributing to the reduction in sd LDL-C levels were a change in LDL-C (p=0.003) and triglyceride (TG) levels (p=0.006), treatment group (the switched group=1, the continued group=0; standard coefficient=-1.2, p=0.034) and baseline glycated hemoglobin A1c (HbA1c) (p=0.045), respectively. CONCLUSION: Switching from 10mg atorvastatin to 5mg rosuvastatin may be a useful therapeutic option to reduce sd LDL-C levels in Japanese hypercholesterolemic patients with T2DM.

Ipragliflozin lowers small, dense low-density lipoprotein cholesterol levels in Japanese patients with type 2 diabetes mellitus.

AIMS: This preliminary randomized, parallel-group comparative study evaluated the efficacy of ipragliflozin for reduction of small dense low-density lipoprotein cholesterol (sd LDL-C) levels in Japanese patients with type 2 diabetes mellitus (T2DM). METHODS: Sixty-two patients with T2DM (age, 56 ± 8 years; hemoglobin A1c levels, 8.1 ± 0.9%; BMI, 27.5 ± 3.3 kg/m2) were randomly assigned in a 2:1 ratio to receive ipragliflozin (50 mg/day) (treatment group; n = 40) or continued treatment (control group; n = 22) for 12 weeks. The primary endpoints were changes in sd LDL-C levels detected using the LipoPhor AS® system; the secondary endpoints included changes in the sd LDL-C/large buoyant LDL-C (lb LDL-C) ratio, a surrogate marker for LDL particle size, and percent changes in routine lipid parameters. RESULTS: The treatment group exhibited a statistically significant reduction from baseline for LDL-C levels (-0.37 mg/dL vs. 14.4 mg/dL, p = 0.038), sd LDL-C levels (-1.28 mg/dL vs. 2.81 mg/dL, p = 0.012), and sd LDL-C/lb LDL-C ratio (-3.20% vs. 4.58%, p = 0.040) compared with the control group. Multiple regression analysis among all subjects revealed change in TG levels (p = 0.011) and LDL-C levels (p = 0.024) as well as change in body weight (p = 0.006) as independent factors contributing to the reduction in sd LDL-C. CONCLUSIONS: Ipragliflozin may have a potential for lowering sd LDL-C levels associated with increasing LDL particle size in Japanese patients with T2DM.