Innovative immunosuppression in kidney transplantation: A challenge for unmet needs

Due to the optimal results obtained in kidney transplantation and to the lack of interest of the industries, new innovative drugs in kidney transplantation are difficult to be encountered. The best strategy to find the new drugs recently developed or under development is to search in the sections of kidney transplantation still not completely covered by the drugs on the market. These unmet needs are the prevention of delayed graft function (DGF), the protection of the graft over the long time and the desensitization of preformed anti human leukocyte antigen antibodies and the treatment of the acute antibody-mediated rejection. These needs are particularly relevant due to the expansion of some kind of kidney transplantation as transplantation from non-heart beating donor and in the case of antibody-incompatible grafts. The first are particularly exposed to DGF, the latter need a safe desensitization and a safe treatments of the antibody mediated rejections that often occur. Particular caution is needed in treating these drugs. First, they are described in very recent studies and the follow-up of their effect is of course rather short. Second, some of these drugs are still in an early phase of study, even if in well-conducted randomized controlled trials. Particular caution and a careful check need to be used in trials launched 2 or 3 years ago. Indeed, is always necessary to verify whether the study is still going on or whether and why the study itself was abandoned.     

Epidemiology of gout and hyperuricemia in New Caledonia

ObjectivesNew Caledonia is a Pacific island of 270,000 inhabitants with mixed ethnicities, including Polynesians (10.2%), people from European ancestry (27.2%), and Melanesians (39.1%),. This study aimed at determining the prevalence of gout and hyperuricemia in the general population and the various ethnicities of New Caledonia.MethodsA 3-degree random sample of the population aged 18 to 60 years was adjusted according to the 2014 New Caledonia census. Face-to-face planned interviews and physical measurements were performed by trained nurses. All consenting participants underwent capillary measurement of creatinine; all consenting men and only women older than 40 years underwent point-of-care uricemia testing. Gout was defined by a validated algorithm. Two definitions of hyperuricemia were used: capillary level equivalent to plasma uric acid level > 360 μmol/l (6 mg/dl) and > 420 μmol/l (7 mg/dl) and/or urate-lowering drug treatment for both thresholds.ResultsWe included 1144 participants (adjusted mean age 37.7 ± 12.0 years; adjusted sex ratio 50.4% men). The adjusted prevalence of gout was 3.3% (95% confidence interval 2.2–4.9). Prevalence was 6.7% (2.5–16.8), 4.1% (1.8–8.9), and 2.6% (1.4–4.7) for Polynesians, Europeans and Melanesians, respectively, and 1.9% (0.5–6.6) for other ethnicities. Prevalence of hyperuricemia, determined in 658 participants, was 67.0% (61.9–71.6) and 37.0% (32.3–42.0) for the 360- and 420-μmol/l thresholds, respectively, and was significantly greater for Polynesians and Melanesians than Europeans for both thresholds.ConclusionsThe prevalence of gout and hyperuricemia in New Caledonia was high, including in patients of European descent.     

The comparative effects of metabolic surgery,SGLT2i,or GLP-1RA in patients with obesity and type 2 diabetes: a retrospective cohort study

BackgroundNew antidiabetic agents (sodium-glucose cotransporter-2 inhibitor [SGLT2i] and glucagon-like peptide-1 receptor agonist [GLP-1RA]) and metabolic surgery have protective effects on metabolic syndromes.ObjectivesTo compare the changes of metabolic parameters and costs among patients with obesity and type 2 diabetes undergoing metabolic surgery and initiating new antidiabetic agents over 12 months.SettingHong Kong Hospital Authority database from 2006–2017.MethodsThis is a population-wide retrospective cohort study consisting of 2616 patients (1810 SGLT2i, 528 GLP-1RA, 278 metabolic surgery). Inverse probability treatment weighting of propensity score was applied to balance baseline covariates of patients with obesity and type 2 diabetes who underwent metabolic surgery, or initiated SGLT2i or GLP-1RA. Metabolic parameters and direct medical costs were measured and compared from baseline to 12 months in metabolic surgery, SGLT2i, and GLP-1RA groups.ResultsPatients in all 3 groups had improved metabolic parameters over a 12-month period. Patients with metabolic surgery achieved significantly better outcomes in BMI (?5.39, ?.56, ?.40 kg/m², P < .001), % total weight loss (15.16%, 1.34%, 1.63%, P < .001), systolic (?2.21, ?.59, 1.28 mm Hg, P < .001) and diastolic (?1.16, .50, ?.13 mm Hg, P < .001) blood pressure, HbA1c (?1.80%, ?.77%, ?.80%, P < .001), triglycerides (?.64, ?.11, ?.09 mmol/L, P < .001), and estimated glomerular filtration rate (3.08, ?1.37, ?.41 mL/min/1.73m², P < .001) after 12 months compared with patients with SGLT2i and GLP1-RA. Although the metabolic surgery group incurred the greatest direct medical costs (US$33,551, US$10,945, US$10,627, P < .001), largely due to the surgery itself and related hospitalization, the total monthly direct medical expenditure of metabolic surgery group became lower than that of SGLT2i and GLP-1RA groups at 7 months.ConclusionBeneficial weight loss and metabolic outcomes at 12 months were observed in all 3 groups, among which the metabolic surgery group showed the most remarkable effects but incurred the greatest medical costs. However, studies with a longer follow-up period are warranted to show long-term outcomes.     

试论加强国际合作与促进我国医学伦理学教育的发展

原北京医科大学(现为北京大学医学部)从20世纪90年代初开始,积极寻求与美国中华医学基金会的合作以促进医学伦理学的学科发展和国际化水平的提高。十几年来,北京大学医学部作为基地和依托极大地支持和引领了我国医学伦理学的教学改革与发展,增强了相关人员的医学伦理意识以及医学伦理学理论对实践的指导作用,促进了伦理学知识和能力的培训,提升了我国生物医学科研伦理的实力,奠定了医学伦理学继续教育的基础,使医学伦理学实现了系统性和跨越式的发展。     

A new bioabsorbable sleeve for lung staple-line reinforcement (FOREseal™): report of a three-center phase II clinical trial

Objective: To investigate on the feasibility, safety, and effectiveness of a new bioabsorbable material for lung staple-line reinforcement. Methods: This prospective open trial included 66 patients (mean age of 56 ± 17 years) who underwent various types of lung resection using staplers with knitted calcium alginate sleeves for buttressing (FOREseal™, Laboratoires Brothier, Nanterre, France) at three academic centers: 29 lobectomies, 22 emphysema surgeries, 15 wedge resections or lung biopsies. Intraoperative air leakage was assessed at a mean respiratory peak pressure of 30 cmH₂O, and rated as grade 1, 2, or 3. Persistent air leakage in the postoperative course, as well as any relevant event, was assessed daily. The follow-up period was of 6 months. Results: No technical problem linked to the device occurred. Hemostasis of the cutting edges was completed in all patients. Fifty-six percent of the patients had no intraoperative air leak and 27.3% had grade 1 leaks. Mean postoperative air leaks and thoracic drainage times were 1.9 ± 2.3 days and 6 ± 5.3 days, respectively. In-hospital mortality was nil. There was no empyema. Mean hospital stay was 9.1 ± 6.6 days. At follow-up, one patient underwent lung transplantation, and pathology of the explanted specimen showed the absence of device-related foreign-body inflammation. One patient complained from metalloptysis, and another one, with a metastatic invasive aspergillosis, developed an infectious recurrence that required reoperation. Conclusions: FOREseal is an ergonomic, safe, and promising new material instead of nonabsorbable materials and xenomaterials for staple-line reinforcement. A randomized comparative study is now in progress.     

Serum 25-hydroxyvitamin D concentrations of New Zealanders aged 15 years and older

Introduction Vitamin D plays an important role in bone health. Our purpose was to measure serum 25-hydroxyvitamin D concentrations and their determinants in a national sample (n=2,946) of New Zealanders aged 15 years and over.Findings Mean (99% CI) serum 25-hydroxyvitamin D concentrations were 47 (45–50) nmol/l in women and 52 (49–55) nmol/l in men. Mean concentrations in New Zealand European and Others (NZEO, n=2,440), Mori (n=370), and Pacific (n=136) were 51 (49–53), 42 (38–46) and 37 (33–42) nmol/l, respectively. Three percent of New Zealanders had serum 25-hydroxyvitamin D concentrations indicative of deficiency (≤17.5 nmol/l); 48% and 84% were insufficient based on cutoffs of ≤50 and ≤80 nmol/l. Determinants of serum 25-hydroxyvitamin D concentrations in women were age, ethnicity, obesity, latitude and season; determinants in men were ethnicity and season. Serum 25-hydroxyvitamin D in women declined with age; mean concentration was 13 (8–18) nmol/l lower in women 65 years or older and 9 (5–13) nmol/l lower in women 45–64 years compared with women 15–18 years. Spring to summer differences in serum 25-hydroxyvitamin D were 31 (28–34) and 28 (25–31) nmol/l in women and men, respectively. Obese women had lower vitamin status than normal-weight women by 6 (3–10). Women living in the South Island had a mean serum 25-hydroxyvitamin D that was 6 (3–9) nmol/l lower than women living in the North Island. Ethnicity and season are the major determinants of serum 25-hydroxyvitamin D in New Zealanders.Conclusion The high prevalence of vitamin D insufficiency in New Zealanders, particularly in older women, may warrant strategies to improve vitamin D status.     

83例6个月以下婴儿室间隔缺损的外科治疗

目的 总结外科手术治疗小婴儿期室间隔缺损(VSD)的临床经验.方法 对2000-2005年83例＜6月龄VSD患儿,年龄12 d至6(4.3±1.2)个月,体重3～6.5(5.1±0.8)kg.膜周部VSD 74例,干下型VSD 8例,膜周部并肌部VSD1例.术前中、重度肺动脉高压69例(83.1%).所有患儿均在浅低温体外循环下手术.结果 全组手术死亡4例,手术病死率为4.8%.术后主要并发症为肺动脉高压危象、肺部感染和心律失常.结论 随着麻醉、体外循环、手术技术和围术期监护处理措施的进步,在小婴儿期施行VSD的外科手术已成为安全的治疗方式.术后对肺高压的处理是手术成功的关键.     

大鼠皮质神经元的体外培养和纯化

目的：探讨大鼠皮质神经元分离纯化的有效方法。方法：取胎鼠大脑皮质细胞，分别在不同的培养液中进行原代培养，利用相差显微镜对培养的细胞进行动态观察；并以免疫细胞化学技术对神经元进行染色。结果：在相差显微镜下可见加用N2添加剂和胎牛血清培养的神经元生长良好，胞体形态多样，突起数目多，长度长，与邻近神经元的胞体或突起形成接触，而胶质细胞则大量死亡，神经元纯化率达94％以上，未加用N2添加剂培养的神经元胶质细胞大量存在，神经元纯化率达50％左右。结论：N2添加剂和胎牛血清联合应用可使大鼠皮质神经元得到良好的生长和有效纯化。