Role of arterial stiffness and endothelial dysfunction on lower limb performance in older adults with type 2 diabetes: A cross-sectional study

AimTo verify whether arterial stiffness and endothelial dysfunction influence lower limb muscle strength and gait speed in older adults with type 2 diabetes mellitus (T2DM).MethodsCross-sectional study including seventy-eight older adults with T2DM (aged 67 ± 6 years and 42 % male). Arterial stiffness was assessed using pulse wave velocity (PWV), while endothelial function was measured by flow-mediated dilation (FMD). Lower limb muscle strength and gait speed were assessed using the 30-second chair stand test (30s-CST) and 10-Meter Walk Test, respectively.ResultsBoth PWV (m/s) and FMD (%) were univariately associated with number of repetitions in 30s-CST and gait speed (P < 0.05). After control for age, sex and body mass index, PWV remained associated with repetitions in 30s-CST (95 % CI: ?0.494 to ?0.054; P = 0.015) and gait speed (95 % CI: ?0.039 to ?0.002; P = 0.031). After adjustments for control variables, T2DM duration and glycemic control, FMD was associated with repetitions in 30s-CST (95 % CI: 0.008 to 0.324; P = 0.039) and gait speed (95 % CI: 0.011 to 0.038; P = 0.001).ConclusionIn older adults with T2DM, both arterial stiffness and endothelial dysfunction are associated with decreased leg muscle strength and slower gait speed.     

Effectiveness and safety of bilateral internal iliac artery ligation with pre-peritoneal pelvic packing for life-threatening pelvic trauma

This study analyzed the outcomes of bilateral internal iliac artery (IIA) ligation with preperitoneal pelvic packing (PPP) in hemodynamically unstable patients with major pelvic fractures. All-cause mortality was examined, periprocedural safety for critical circumstances was reviewed, and iliac artery ligation-related complications of the postoperative phase were evaluated. A total of 20 patients who suffered substantially from severe pelvic trauma with hemodynamic instability and subsequently underwent bilateral IIA ligation with PPP between January 1, 2017, and December 31, 2021, were enrolled in the study. The median participant age was 60.5 years, and 65.0% were male. The median systolic blood pressure was 68.5 mmHg on arrival. Increased lactate level (median, 11.05 mmol/L) suggested that the patients were in shock distinctly due to hypovolemia. It took approximately 1 h to complete the ligation of bilateral IIA to accomplish hemostasis (median, 65.5 min). The iliac vein was injured during dissection in three cases. During the ICU stay (median, 17.5 days), acute kidney injury was identified in 13 patients, likely due to volume depletion. The median ventilator-free days was 13.5; six patients were confirmed with ventilator-associated pneumonia. Moreover, 12 patients were diagnosed with acute respiratory distress syndrome. There was one case in which the lower extremity artery was acutely occluded. Anatomic hemostasis was achieved in 18 patients. The two patients for which anatomic hemostasis failed became two mortality cases from preperitoneal hemorrhage. Our analysis showed that bilateral IIA ligation with PPP was effective as a lifesaving procedure in hemodynamically unstable patients with a major pelvic fracture in terms of mortality due to fracture-related exsanguination. Moreover, the incidence of periprocedural complications was considered tolerable, making the procedure worth a try, especially in austere and underdeveloped healthcare settings.     

Standardisierte Kontrastmittelsonographie (CEUS) in der klinischen Akut- und Notfallmedizin sowie Intensivmedizin (CEUS-Akut)

Die Anaesthesiologie -     

Clinical Practice Guideline for the Therapeutic Drug Monitoring of Voriconazole in Non-Asian and Asian Adult Patients: Consensus Review by the Japanese Society of Chemotherapy and the Japanese Society of Therapeutic Drug Monitoring

PurposeVoriconazole, an antifungal drug, is metabolized by a cytochrome P450 isozyme. Increased adverse effects are observed in Asians because of the high rate of poor metabolizers. In this therapeutic drug monitoring (TDM) guideline, recommendations were made according to ethnic group.MethodsFive clinical questions were used. For the preparation of the guideline, the performance of TDM in multicenter studies was surveyed (study 1). We also conducted a systematic review and meta-analysis (study 2) to establish recommendations for non-Asians and Asians.FindingsIn study 1, 401 patients were surveyed. A risk of supratherapeutic concentrations was found in Japanese patients who adhered to the recommended dose. Target trough levels were achieved in 87% of patients with dose reductions. Although the trough level measured at the onset of adverse effects (AEs) was significantly associated with hepatotoxicity, no significant correlation was found between the initial trough level and hepatotoxicity, which indicated that hepatotoxicity was successfully prevented by the trough-guided dosing. In study 2, 22 studies (11 Asian locations and 11 non-Asian locations) were included in meta-analysis for the relationship between trough cutoff level (3, 4, 5, 5.5, and 6 µg/mL) and AEs. Significant differences were found for all cutoff levels, with the highest odds ratio for 4.0 µg/mL in Asian locations. In contrast, in non-Asian locations, no more than 1 study was available for any trough cutoff level, except for 5.5 µg/mL, at which level a significant increase in AEs was found. These findings indicate that TDM is strongly recommended to prevent AEs in Asians, and TDM is generally recommended for non-Asians to address subtherapeutic concentrations. TDM on day 3 is recommended to assess pharmacokinetic properties, including loading and maintenance doses. If the patient condition permits, delaying until day 5 is suggested for Asians because of the prolonged t_½ in poor metabolizers. A trough level ≥1.0 µg/mL is strongly recommended to improve efficacy. Trough levels ≥2.0 µg/mL are suggested for invasive aspergillosis. To decrease adverse effects, trough levels <4.0 µg/mL are strongly recommended in Asians, whereas trough levels <5.5 µg/mL are generally recommended in non-Asians. Maintenance doses of 4 and 3 mg/kg twice daily are recommended in non-Asians and Asians, respectively.ImplicationsDifferent indications, timings, and target trough levels for TDM and different regimens are suggested for Asians and non-Asians.     

Hyperamylasemia grade versus drain fluid amylase: which better predicts pancreatectomy outcomes?

BackgroundThe clinical importance of postoperative hyperamylasemia (POHA) grade is unknown. Our objectives were to evaluate the association of POHA grade with clinically relevant postoperative pancreatic fistula (CR-POPF) and compare its prognostic utility against postoperative day 1 drain fluid amylase (DFA-1).MethodsPatients who underwent pancreatectomy from January 2019 through March 2020 were identified in the ACS NSQIP pancreatectomy-targeted dataset. POHA grade was assigned using post-operative serum amylase and clinical sequelae. The primary outcome was CR-POPF within 30 days. The association of POHA grade with CR-POPF was assessed using multivariable logistic regression, and c-statistics were used to compare POHA grade versus DFA-1.ResultsPOHA occurred in 520 patients at 98 hospitals, including 261 (50.2%) with grade A, 234 (45.0%) with grade B, and 25 (4.8%) with grade C POHA. CR-POPFs were increased among patients with grade B (66.2%, OR 9.28 [5.84–14.73]) and C (68.0%, OR 10.50 [3.77–29.26]) versus grade A POHA (19.2%). POHA-inclusive models better predicted CR-POPF than those with DFA-1 alone (p < 0.002) and models with both predictors outperformed POHA alone (p = 0.039).ConclusionPOHA grade represents a measure of post-pancreatectomy outcomes that predicts CR-POPF and outperforms DFA-1 but must be aligned with new international definitions.     

Clinical effect of early administration of tocilizumab following the initiation of corticosteroid therapy for patients with COVID-19

IntroductionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first broke out in Wuhan in December 2019, and has since caused a global pandemic. The efficacy of several drugs has been evaluated, and it is now evident that tocilizumab has a beneficial effect, especially combined with corticosteroids, in patients with Coronavirus Disease 2019 (COVID-19). However, the optimal timing of tocilizumab administration has not yet been established. The goal of the present study was to determine the optimal timing of tocilizumab administration after starting corticosteroid therapy in patients with COVID-19.MethodsWe retrospectively analyzed the clinical characteristics of patients who were hospitalized for COVID-19 and treated with tocilizumab and corticosteroids in our hospital. The patients were divided into concurrent and sequential groups. The concurrent group received tocilizumab ≤24 h after corticosteroids, and the sequential group received tocilizumab >24 h after corticosteroid administration.ResultsThe baseline clinical characteristics of tocilizumab administration were similar between the two groups. White blood cell counts were significantly lower and C-reactive protein levels were significantly higher in the concurrent group than the sequential group. In the concurrent group, tocilizumab administration led to a significant decrease in maximum body temperature. In addition, there were significantly more oxygen-free days in the concurrent group than in the sequential group. However, survival rate was not significantly different between the concurrent and the sequential groups.ConclusionsIn the combination therapy with tocilizumab and corticosteroids, early administration of tocilizumab after starting corticosteroid treatment is effective when treating COVID-19.