Correction to: Influence of oral anticoagulation on success rates and risk of bleeding events after iStent inject implantation combined with phacoemulsification

Graefe's Archive for Clinical and Experimental Ophthalmology - The published online version contains mistake as the author's first name and last name have been interchanged as "Hild...     

Coronary Artery Embolism: Two Case Reports and a Review of the Literature

Coronary embolism (CE) is an uncommon and unique cause of acute myocardial infarction. In this report, we review 216 cases of CE including 2 new cases from our institution. The mean patient age was 52.5 years and 62% of the patients were males. Chest pain was the most common presenting symptom followed by dyspnea, and the most commonly affected vessel was the left anterior descending artery. Leading etiologies of the embolus were atrial fibrillation, septic emboli, and iatrogenic causes. Treatment approaches varied with thrombus aspiration being used in 30% of cases. In-hospital mortality rate was 36% and 13% of the cases were complicated by cerebrovascular accident. CE is a unique pathology that leads to acute myocardial infarction. It portends a high mortality rate and requires a high level of suspicion as symptoms may be misleading. Further research is needed in order to improve recognition and management and to lower associated mortality.     

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.     

Modulators of platelet function in aging

Abstract

Platelets are small, anucleated effector cells that play an important role in linking the hemostatic and inflammatory processes in the body. Platelet function is known to be altered under various inflammatory conditions including aging. A gain in platelet function during aging can increase the risk of thrombotic events, such as stroke and acute myocardial infarction. Anti-platelet therapy is designed to reduce risk of serious cerebrovascular and cardiovascular events, but the adverse consequences of therapy, such as risk for bleeding increases with aging as well. Age-associated comorbidities such as obesity, diabetes, and hyperlipidemia also contribute to increased platelet activity and thus can enhance the risk of thrombosis. Therefore, identification of unique mechanisms of platelet dysfunction in aging and in age-associated comorbidities is warranted to design novel antiplatelet drugs. This review outlines some of the current areas of research on aging-related mechanisms of platelet hyperactivity and addresses the clinical urgency for designing anti-platelet therapies toward novel molecular targets in the aging population.     

Loss of mitochondrial ClpP,Lonp1, and Tfam triggers transcriptional induction of Rnf213, a susceptibility factor for moyamoya disease

neurogenetics - Human RNF213, which encodes the protein mysterin, is a known susceptibility gene for moyamoya disease (MMD), a cerebrovascular condition with occlusive lesions and compensatory...     

Differential diagnosis of diarrhoea in patients with neuroendocrine tumours:A systematic review

BACKGROUND Approximately 20% of patients with neuroendocrine tumours(NETs) develop carcinoid syndrome(CS),characterised by flushing and diarrhoea.Somatostatin analogues or telotristat can be used to control symptoms of CS through inhibition of serotonin secretion.Although CS is often the cause of diarrhoea among patients with gastroenteropancreatic NETs(GEP-NETs),other causes to consider include pancreatic enzyme insufficiency(PEI),bile acid malabsorption and small intestinal bacterial overgrowth.If other causes of diarrhoea unrelated to serotonin secretion are mistaken for CS diarrhoea,these treatments may be ineffective against the diarrhoea,risking detrimental effects to patient quality of life.AIM To identify and synthesise qualitative and quantitative evidence relating to the differential diagnosis of diarrhoea in patients with GEP-NETs.METHODS Electronic databases(MEDLINE,Embase and the Cochrane Library) were searched from inception to September 12,2018 using terms for NETs and diarrhoea.Congresses,systematic literature review bibliographies and included articles were also hand-searched.Any study designs and publication types were eligible for inclusion if relevant data on a cause(s) of diarrhoea in patients with GEP-NETs were reported.Studies were screened by two independent reviewers at abstract and full-text stages.Framework synthesis was adapted to synthesise quantitative and qualitative data.The definition of qualitative data was expanded to include all textual data in any section of relevant publications.RESULTS Forty-seven publications(44 studies) were included,comprising a variety of publication types,including observational studies,reviews,guidelines,case reports,interventional studies,and opinion pieces.Most reported on PEI on/after treatment with somatostatin analogs;9.5%-84% of patients with GEP-NETs had experienced steatorrhoea or confirmed PEI.Where reported,14.3%–50.7% of patients received pancreatic enzyme replacement therapy.Other causes of diarrhoea reported in patients with GEP-NETs included bile acid malabsorption(80%),small intestinal bacterial overgrowth(23.6%-62%),colitis(20%) and infection(7.1%).Diagnostic approaches included faecal elastase,breath tests,tauroselcholic(selenium-75) acid(Se HCAT) scan and stool culture,although evidence on the effectiveness or diagnostic accuracy of these approaches was limited.Assessment of patient history or diarrhoea characteristics was also reported as initial approaches for investigation.From the identified evidence,if diarrhoea is assumed to be CS diarrhoea,consequences include uncontrolled diarrhoea,malnutrition,and perceived ineffectiveness of CS treatment.Approaches for facilitating differential diagnosis of diarrhoea include improving patient and clinician awareness of non-CS causes and involvement of a multidisciplinary clinical team,including gastroenterologists.CONCLUSION Diarrhoea in GEP-NETs can be multifactorial with misdiagnosis leading to delayed patient recovery and inefficient resource use.This systematic literature review highlights gaps for further research on prevalence of non-CS diarrhoea and suitability of diagnostic approaches,to determine an effective algorithm for differential diagnosis of GEP-NET diarrhoea.     

Treatment of classical Hodgkin’s lymphoma in children and adolescents

Introduction: The treatment of classical Hodgkin lymphoma (cHL) in children is a story of success. Nowadays, more than 90% of patients are cured and overall survival is nearly 100% at 5 years. Efforts have been made to avoid related effects of therapies; therefore, children are treated using different chemotherapy schemes in comparison with adults.

Areas covered: This review includes a view of the clinical classification and risk assessment in children suffering from HL. The chemotherapy more commonly employed is revisited. The use of PET/CT to evaluate the disease in order to guide therapy is analyzed. New options of chemotherapy and emerging immunotherapy are also included.

Expert opinion: In order to make the right treatment choice, a proper initial assessment of risk is mandatory. The choice of therapy in these kinds of patients must be done according to the experience of the team, and also, the cost and logistics related to the eligible scheme are very important. If possible, efforts must be made to include PET/CT in guiding therapy and avoiding overtreatment and long-term adverse effects in children. New options in immunotherapy are emerging and must be considered with caution in selected patients.