Electrophysiological findings in immune checkpoint inhibitor-related peripheral neuropathy

ObjectiveTo report the electrodiagnostic features of immune checkpoint inhibitor (ICI)-related neuropathy.MethodsWe retrospectively reviewed clinical presentations and electrodiagnostic features of 23 patients studied after receiving immune checkpoint inhibitors (ICIs). The presentations for electrodiagnostic evaluation included an acute neuropathy or neuromuscular junction disorder. We applied established electrodiagnostic criteria for polyneuropathy and acute demyelinating neuropathy.ResultsWe identified acute demyelinating neuropathy (13 cases), axonal sensory motor neuropathy (5), pure sensory neuropathy (4) and mononeuropathy (1). 13 patients had acute demyelinating neuropathy confirmed by demonstrating demyelination in 2 or more nerves; 3 additional patients had demyelination in only one nerve. Analysis of motor nerve conduction parameters revealed demyelination involving median and ulnar nerve distal motor latencies as well as median, ulnar and peroneal nerve conduction velocities. Conduction block was found in median, ulnar and peroneal nerves. The remaining one-third patients without demyelination had acute painful axonal neuropathy. Coexisting myopathic changes (6) and neuromuscular junction dysfunction (4) were also identified.ConclusionsOur findings suggest that, while immune-mediated motor nerve demyelination is the primary underlying mechanism of ICI-related neuropathy, axonal painful neuropathy can also be an important presentation. Early recognition and effective intervention may reduce morbidity and permanent disability.SignificanceElectrophysiological studies might be useful in the evaluation of ICI-related neuropathy.     

Genetics of coronary heart disease: towards causal mechanisms,novel drug targets and more personalized prevention

Coronary heart disease (CHD) is an archetypical multifactorial disorder that is influenced by genetic susceptibility as well as both modifiable and nonmodifiable risk factors, and their interactions. Advances during recent years in the field of multifactorial genetics, in particular genomewide association studies (GWASs) and their meta‐analyses, have provided the statistical power to identify and replicate genetic variants in more than 50 risk loci for CHD and in several hundreds of loci for cardiometabolic risk factors for CHD such as blood lipids and lipoproteins. Although for a great majority of these loci both the causal variants and mechanisms remain unknown, progress in identifying the causal variants and underlying mechanisms has already been made for several genetic loci. Furthermore, identification of rare loss‐of‐function variants in genes such as PCSK9, NPC1L1, APOC3 and APOA5, which cause a markedly decreased risk of CHD and no adverse side effects, illustrates the power of translating genetic findings into novel mechanistic information and provides some optimism for the future of developing novel drugs, given the many genes associated with CHD in GWASs. Finally, Mendelian randomization can be used to reveal or exclude causal relationships between heritable biomarkers and CHD, and such approaches have already provided evidence of causal relationships between CHD and LDL cholesterol, triglycerides/remnant particles and lipoprotein(a), and indicated a lack of causality for HDL cholesterol, C‐reactive protein and lipoprotein‐associated phospholipase A2. Together, these genetic findings are beginning to lead to promising new drug targets and novel interventional strategies and thus have great potential to improve prevention, prediction and therapy of CHD.     

Axin2+ Peribiliary Glands in the Periampullary Region Generate Biliary Epithelial Stem Cells That Give Rise to Ampullary Carcinoma

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Extracorporeal shock-wave lithotripsy for retained common bile duct stones

Retained common bile duct stones (CBDS) become a challenging problem when percutaneous and endoscopic methods fail. Extracorporeal shock-wave lithotripsy (ESWL) is a noninvasive and effective treatment modality, and can be used as an alternative treatment of retained CBDS. We report our experience with 20 patients who had retained CBDS, using a second-generation electromagnetic lithotriptor. Thirteen patients who had cholecystectomy and common bile duct exploration, with stone extraction and T-tube drainage, were in the early postoperative period. Seven patients had undergone previous endoscopic sphincterotomy and nasobiliary drainage. Fourteen patients had only one ESWL session. Stone fragmentation rates were 100% and 57% in patients with T-tube and nasobiliary catheter, respectively. The overall stone fragmentation rate was 85% and complete stone clearance was achieved in all these patients (85%). Complications were mild and relatively infrequent (20%). There was no mortality. We conclude that ESWL for retained CBDS is a safe, effective and minimally-invasive treatment modality. ESWL should be considered as a significant alternative to surgery when endoscopic and percutaneous treatment modalities are not successful.     

Laparoscopic exploration of common bile duct: A solution to difficult choledocholithiasis

Objective: To evaluate the role of laparoscopic exploration of common bile duct (LECBD) in the management of common bile duct stone, particularly for patients with failed endoscopic extraction and patients younger than 60 years old. Method: Prospective data of laparoscopic exploration of common bile duct during 1995–1999 were analysed. Results: During 1995–1999, 27 laparoscopic exploration of common bile duct (LECBD) were performed in patients with concomitant gallstone and common bile duct stone, in which half of these LECBD were performed after unsuccessful endoscopic retrieval (13 patients). LECBD was also indicated in patients younger than 60 years old (14 patients) because there was a concern about the potential long‐term complications of papillotomy‐like papillary stenosis and ascending cholangitis. One transcystic duct exploration and 26 choledochotomies were performed. Mean operating time was 138.7 min (70–300 min) and additional procedures included 19 laparoscopic ultrasounds (LUS), three laparoscopic intraoperative cholangiograms (LIOC) and two laparoscopic choledochoduodenostomies. Stone clearance rate was 96% with only one exception. Complications were encountered in nine patients (33%) and one patient died of sepsis subsequent to major bile leak (3.7%). Complications included bile leak/stent migration/collection (4), wound infection (3), minor wound bleeding (1) and self‐limiting postoperative intestinal obstruction (1). Conclusion: LECBD has a high success rate of ductal clearance in patients with ‘difficult common bile duct stones’ despite unsuccessful attempts at endoscopic extraction.     

继发性胆总管结石两种开腹胆道探查手术方式的临床研究

目的 比较治疗继发性胆总管结石的两种开腹胆道探查手术方式(术中胆道镜经胆囊颈管胆总管探查术与传统胆道切开探查T管引流术)的临床效果.方法 符合入组标准病例113例,传统术式58例,经胆囊颈管胆道探查55例.对手术成功率、手术时间、术后并发症、住院时间、住院费用等指标行对照研究.结果 两组均成功完成手术且无严重术后并发症,手术时间经胆囊管胆道探查术组与传统手术组无显著差异,平均住院时间及住院费用经胆囊管胆道探查组显著低于传统手术组.结论 对于继发性胆总管结石,经胆囊颈管途径胆道探查较传统方式有较明显优势,应作为胆道探查的首选途径.     

Implementing Substance Use Screening in Family Planning

Although substance use has negative health effects on women, especially during the reproductive years, family planning practices in which nurse practitioners are key care providers, generally do not adequately screen and intervene for alcohol and drugs. Screening, brief intervention, and referral to treatment (SBIRT) can limit the effects of substance use on women and families. This study explored barriers and facilitators to SBIRT through qualitative analysis of focus groups with family planning providers. Results suggest family planning providers are favorable to implementation. Barriers include training and organizational support; facilitators include use of electronic health records and setting patient expectations.     

Solution-focused brief therapy for Chilean primary care patients: Exploring a linguistic adaptation

Solution-focused brief therapy (SFBT) is a resource-based, future-oriented therapeutic approach that focuses on finding exceptions to problems and identifying coping strategies to build solutions. SFBT has been efficacious with individuals with alcohol use disorders. Chile experiences high levels of alcohol consumption and alcohol-related health consequences. Despite the international dissemination of SFBT, this is the first study to attempt a linguistic adaptation of SFBT in a Latin American country. We conducted 9 cognitive interviews to examine 13 translated main SFBT tools and 3 focus groups to gather information on cultural aspects of alcohol use in primary care. Results suggest that Chileans understood most SFBT tools, albeit with some linguistic modifications of original translations, and that family, gender, and meaningful issues should be considered when working with individuals with alcohol use disorders.