A case of sudden cardiac death due to mitochondrial disease

A 25-year-old, emaciated man without medical treatment was found to have died suddenly at home by his mother. At autopsy, there were no injuries to his body, but significant circulatory insufficiency was observed. Electron microscopy revealed abnormal mitochondria in cells of the cardiac conduction system. The conduction system was filled with mitochondrial size abnormalities and mitochondrial cristae abnormalities. No notable abnormal findings were observed in other organs. Genetic examination of the blood revealed the mitochondrial pathogenetic variant m.3243A>G. Epileptic seizures, diabetic ketoacidosis, and hyperosmolar hyperglycemic state were unlikely to be the cause of sudden death. The cause of death was diagnosed as arrhythmia possibly induced by the failure of the cardiac conduction system due to mitochondrial disease. This is a rare case of sudden death caused by an accumulation of abnormal mitochondria in the cardiac conduction system.     

Prognosis Comparison Between Chronic Hepatitis B Patients Receiving a Finite Course of Tenofovir and Entecavir Treatment: A Nationwide Cohort Study in Taiwan

PurposeEntecavir (ETV) and tenofovir disoproxil fumarate (TDF) are both recommended as first-line treatments for patients with chronic hepatitis B virus (CHB) infection according to international HBV treatment guidelines. However, recent studies reported conflicting results regarding the preferred antiviral in the prevention of hepatocellular carcinoma (HCC). This cohort study aimed to investigate this issue by using Taiwan's National Health Insurance Research Database, wherein a “finite” but not life-long treatment policy was applied.MethodsFrom January 2008 to December 2013, a total of 12,388 consecutive adult patients with CHB who received a finite course of TDF treatment (n = 1250) or ETV treatment (n = 11,138) were analyzed through screening for study eligibility followed by the 1:4 propensity score matching method.FindingsIn the entire cohort, the annual incidence and survival between the ETV and TDF groups were not significantly different regarding HCC occurrence (2.05 vs 2.74 per 100 patient-years [PY]; P = 0.055; hazard ratio [HR], 0.975; log-rank, P = 0.966), cirrhosis-related complications (1.9 vs 2.4 per 100 PY; P = 0.149; HR, 0.869; log-rank, P = 0.388), or all-cause mortality (2.16 vs 1.6 per 100 PY; P = 0.119; HR, 0.831; log-rank, P = 0.342), respectively. Propensity score matching analyses yielded similar results regarding HCC occurrence, cirrhosis-related complications, and all-cause mortality. In addition, these findings were consistently reproduced in the subgroups of patients with chronic hepatitis and cirrhosis that developed before antiviral treatment.ImplicationsETV and TDF did not significantly differ in prevention of HCC occurrence or reduction of cirrhosis-related complications and all-cause mortality in patients with CHB receiving a finite period of treatment.     

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.     

Clinical course of masticatory function recovery following arthrocentesis in patients with unilateral mandibular condyle head fracture

The aim of this study was to investigate the clinical course of masticatory function recovery following arthrocentesis. Patients with a unilateral condylar head fracture who underwent arthrocentesis for therapeutic reasons were evaluated and compared with patients with a unilateral condylar head fracture who did not undergo arthrocentesis. At 3 months after treatment, the occlusal contact area and maximum bite force in patients with a fracture treated with arthrocentesis were greater than in those who did not receive arthrocentesis at the same time points, although the differences were not significant. Moreover, at 1 and 3 months following arthrocentesis, mean (±SD) occlusal contact area (1 month: 1.99 ± 0.55 mm², p = 0.01; 3 months: 2.90 ± 1.36 mm², p = 0.03) and maximum bite force (1 month: 82.45 ± 15.04 N, p = 0.01; 3 months: 101.11 ± 14.53 N, p = 0.01) on the fractured side in patients who underwent that treatment were significantly reduced when compared with those on the non-fractured side. The authors conclude that if the priority is to avoid open reduction and internal fixation, then the arthrocentesis approach might be a less invasive alternative, albeit with the price of a prolonged healing interval.     

Women-Focused Cardiovascular Rehabilitation: An International Council of Cardiovascular Prevention and Rehabilitation Clinical Practice Guideline

Women-focused cardiovascular rehabilitation (CR; phase II) aims to better engage women, and might result in better quality of life than traditional programs. This first clinical practice guideline by the International Council of Cardiovascular Prevention and Rehabilitation (ICCPR) provides guidance on how to deliver women-focused programming. The writing panel comprised experts with diverse geographic representation, including multidisciplinary health care providers, a policy-maker, and patient partners. The guideline was developed in accordance with Appraisal of Guidelines for Research and Evaluation (AGREE) II and the Reporting Items for practice Guidelines in HealTh care (RIGHT). Initial recommendations were on the basis of a meta-analysis. These were circulated to a Delphi panel (comprised of corresponding authors from review articles and of programs delivering women-focused CR identified through ICCPR’s audit; N = 76), who were asked to rate each on a 7-point Likert scale in terms of impact and implementability (higher scores positive). A Web call was convened to achieve consensus; 15 panelists confirmed strength of revised recommendations (Grading of Recommendations Assessment, Development, and Evaluation [GRADE]). The draft underwent external review from CR societies internationally and was posted for public comment. The 14 drafted recommendations related to referral (systematic, encouragement), setting (model choice, privacy, staffing), and delivery (exercise mode, psychosocial, education, self-management empowerment). Nineteen (25.0%) survey responses were received. For all but 1 recommendation, ≥ 75% voted to include; implementability ratings were < 5/7 for 4 recommendations, but only 1 for effect. Ultimately 1 recommendation was excluded, 1 separated into 2 and all revised (2 substantively); 1 recommendation was added. Overall, certainty of evidence for the final recommendations was low to moderate, and strength mostly strong. These recommendations and associated tools can support all programs to feasibly offer some women-focused programming.     

Comparison of retroperitoneal and transperitoneal surgical routes in laparoscopic nodal staging for locally advanced cervical cancers (FIGO IB3-IVA)

BackgroundThis study compares morbidity and mortality associated with retroperitoneal and transperitoneal para-aortic lymphadenectomy (PAAL) for pretherapeutic nodal staging of locally advanced cervical cancers (FIGO IB3–IVA).MethodsPre-, per- and postoperative data of patients treated for locally advanced stage cervical cancer between 1999 and 2018 in 12 French referral centers (FRANCOGYN Study Group) were retrospectively collected.ResultsThe study was conducted using a sample of 448 patients, of whom 223 (49,8%) underwent retroperitoneal (group 1) and 225 (50,2%) had transperitoneal PAAL (group 2). No differences were noted concerning clinical and histological characteristics between the two groups. Among these 448 patients, 23 (5,1%) had an intraoperative complication (9 (2,0%) in group 1 and 14 (3,1%) in group 2, p = 0.28) and 47 (10,5%) had a postoperative complication (22 (4,9%) in group 1 and 25 (5,6%) in group 2, p = 0.44), only one of which required revision surgery but the patient died. The length of hospital stay was significantly shorter in group 1 than in group 2 (3.97 versus 4.88 days, p < 0.001). There was no significant difference in mortality between the two groups; 34 of 223 patients in group 1 (15.3%) and 40 of 225 patients in group 2 (15.6%) died (HR = 0.968, 95% CI [0.591–1.585]). There was no significant difference in recurrence-free or overall survival between the two groups.ConclusionRetroperitoneal PAAL appears as a valuable and safety surgical route for nodal staging in locally advanced cervical cancer compared with standard transperitoneal PAAL.