Biological secondary contributors to osteoporosis in fractured patients,is an early systematic assay relevant?

ObjectiveTo evaluate the prevalence of biological abnormalities leading to secondary osteoporosis in recently fractured patients.MethodsAdults older than 50, hospitalized for a non-vertebral fracture from July 2015 to October 2016, were assessed for bone fragility contributors in the orthopedics department. Bone mineral density (BMD) measurements and vertebral fracture assessment (VFA) were performed within 3 months. We assessed the prevalence of biological abnormalities in all the patients with recent fracture and in subgroups.ResultsAmong 439 hospitalized patients for non-vertebral low trauma fracture, 372 had biological tests (285 women, mean age 77.5 ± 13 years) and 353 (94.6%) had at least ≥ 1 biological abnormality, most frequently vitamin D insufficiency (< 75 nmol/L) (80%). Hypercalcemia was found in 22 (7.7%) patients, explained by possible primary hyperparathyroidism in 6 cases, and by the other causes of hypercalcemia including postoperative low albumin. A high PTH level was observed in 64 (20.8%) patients. We found 3 monoclonal bands. Results were similar in patients with and without vertebral fracture or osteoporosis. Finally, many biological abnormalities can be explained by the postoperative context (low TSH, hypogammaglobulinemia, low albumin, low alkaline phosphatase) and need a control.ConclusionThis study performed in patient with recent low trauma non-vertebral fractures showed that 94.6% of patients had at least one contributor to bone fragility, which was the vitamin D insufficiency in most of cases. We found a high proportion of biological abnormalities which require additional explorations but most of them can be explained by the postoperative context.     

儿童反复上呼吸道感染补充维生素D后LL-37水平的变化研究

背景　流行病学调查显示全球大约有10亿人存在维生素D缺乏或不足，我国维生素D缺乏尤为严重。反复上呼吸道感染作为小儿常见病及多发病，严重影响小儿身心健康，维生素D缺乏是导致抗菌肽LL-37下调的主要原因，因此维生素D缺乏越来越引起人们的重视。目的　探讨反复上呼吸道感染患儿补充维生素D后LL-37水平变化。方法　选取2017年5-11月河北大学附属医院门诊就诊的反复上呼吸道感染并存在维生素D不足或缺乏的患儿54例，采用随机数字表法分为试验组及对照组，每组各27例。试验组给予常规治疗联合补充维生素D，对照组给予常规治疗联合安慰剂，随访12个月，记录治疗前和治疗后12个月时上呼吸道感染次数，检测血浆25-羟维生素D3及痰上清LL-37的变化。结果　45例患儿完成了随访，试验组23例，对照组22例。治疗前，两组患儿上呼吸道感染次数、血浆25-羟维生素D3及痰上清LL-37水平比较，差异均无统计学意义（P>0.05）；治疗后12个月，试验组患儿上呼吸道感染次数少于对照组，血浆25-羟维生素D3、痰上清LL-37水平高于对照组（P<0.05）。对照组患儿治疗前后上呼吸道感染次数、血浆25-羟维生素D3及痰上清LL-37水平比较，差异均无统计学意义（P>0.05）；试验组患儿治疗后12个月上呼吸道感染次数少于治疗前，血浆25-羟维生素D3、痰上清LL-37水平高于治疗前（P<0.05）。Pearson直线相关分析结果显示，试验组治疗后12个月血浆25-羟维生素D3与痰上清LL-37呈正相关（r=0.505，P<0.05）。结论　补充维生素D有助于减少反复上呼吸道感染患儿上呼吸道感染次数，这种作用可能与LL-37产生增加有关。     

The Role of Metastasectomy in Urothelial Carcinoma: Where Are We in 2020?

Systemic therapy is the mainstay of treatment for metastatic urothelial carcinoma (UC). Responses to first-line platinum-based therapy tend to be short-lived with potential toxicity. Despite the approval of checkpoint inhibitors, the long-term prognosis for patients with metastatic UC remains dismal. Herein we report the case of a patient with a solitary pulmonary metastatic lesion of urothelial origin as the only site of metastatic disease who remained free of disease for more than 2 years without systemic therapy after metastasectomy. We review the literature discussing the role of combined surgical and medical management of oligometastatic UC. As our case illustrates, a growing body of evidence suggests a potential role for a multimodal approach in patients with oligometastatic UC.     

Tadalafil for the treatment of benign prostatic hyperplasia

Introduction: In men, lower urinary tract symptoms (LUTS) are primarily attributed to benign prostatic hyperplasia (BPH). Therapeutic options are targeted to relax prostate smooth muscle and/or reduce prostate enlargement.

Areas covered: This article reviews the major preclinical and clinical data on PDE5 inhibitors with a specific focus on tadalafil. It includes details of the role of the nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) – PDE5 pathway in the LUT organs (bladder and prostate) in addition to the available data on tadalafil in patients with LUTS secondary to BPH with or without erectile dysfunction (ED).

Expert opinion: Preclinical and clinical data have clearly demonstrated that PDE5 inhibitors induce bladder and prostate relaxation, which contributes to the improvement seen in storage symptoms in both animal models of bladder and prostate hypercontractility. Tadalafil is effective both as a monotherapy and add-on therapy in patients with LUTS secondary to BPH. Furthermore, as LUTS-BPH and ED are urological disorders that commonly coexist in aging men, tadalafil is more advantageous than α1-adrenoceptors and should be used as the first option. Tadalafil is a safe and tolerable therapy and unlike α1- adrenoceptors and 5-alpha reductase inhibitors, which can cause sexual dysfunctions, tadalafil improves sexual function.     

Efficacy and safety of pembrolizumab for the treatment of advanced biliary cancer: Results from the KEYNOTE-158 and KEYNOTE-028 studies

We present data from patients with advanced biliary tract cancer (BTC) receiving pembrolizumab in the KEYNOTE-158 (NCT02628067; phase 2) and KEYNOTE-028 (NCT02054806; phase 1b) studies. Eligible patients aged ≥18 years from both studies had histologically/cytologically confirmed incurable BTC that progressed after standard treatment regimen(s), measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, Eastern Cooperative Oncology Group performance status 0/1, and no prior immunotherapy. Programmed death ligand 1 (PD-L1)-positive tumors were required for eligibility in KEYNOTE-028 only. Patients received pembrolizumab 200 mg every three weeks (KEYNOTE-158) or 10 mg/kg every two weeks (KEYNOTE-028) for ≤2 years. Primary efficacy endpoint was objective response rate (ORR) by RECIST v1.1. Response assessed by independent central review is reported. KEYNOTE-158 enrolled 104 patients and KEYNOTE-028 enrolled 24 patients. Median (range) follow-up was 7.5 months (0.6-34.3) in KEYNOTE-158 and 5.7 months (0.6-55.4) in KEYNOTE-028. In KEYNOTE-158, ORR was 5.8% (6/104; 95% CI, 2.1%-12.1%); median duration of response (DOR) was not reached (NR) (range, 6.2-26.6+ months). Median (95% CI) OS and PFS were 7.4 (5.5-9.6) and 2.0 (1.9-2.1) months. Among PD-L1-expressers (n = 61) and PD-L1-nonexpressers (n = 34), respectively, ORR was 6.6% (4/61) and 2.9% (1/34). In KEYNOTE-028, ORR was 13.0% (3/23; 95% CI, 2.8%-33.6%); median DOR was NR (range, 21.5-53.2+ months). Median (95% CI) OS and PFS were 5.7 (3.1-9.8) and 1.8 (1.4-3.1) months. Grade 3 to 5 treatment-related adverse events occurred in 13.5% of patients in KEYNOTE-158 (no grade 4; grade 5 renal failure, n = 1) and 16.7% in KEYNOTE-028 (no grade 4/5). In summary, pembrolizumab provides durable antitumor activity in 6% to 13% of patients with advanced BTC, regardless of PD-L1 expression, and has manageable toxicity.