Contribution of different somatosensory afferent input to subcortical somatosensory evoked potentials in humans

ObjectivesTo investigate the subcortical somatosensory evoked potentials (SEPs) to electrical stimulation of either muscle or cutaneous afferents.MethodsSEPs were recorded in 6 patients suffering from Parkinson’s disease (PD) who underwent electrode implantation in the pedunculopontine (PPTg) nucleus area. We compared SEPs recorded from the scalp and from the intracranial electrode contacts to electrical stimuli applied to: 1) median nerve at the wrist, 2) abductor pollicis brevis motor point, and 3) distal phalanx of the thumb. Also the high-frequency oscillations (HFOs) were analysed.ResultsAfter median nerve and pure cutaneous (distant phalanx of the thumb) stimulation, a P1-N1 complex was recorded by the intracranial lead, while the scalp electrodes recorded the short-latency far-field responses (P14 and N18). On the contrary, motor point stimulation did not evoke any low-frequency component in the PPTg traces, nor the N18 potential on the scalp. HFOs were recorded to stimulation of all modalities by the PPTg electrode contacts.ConclusionsStimulus processing within the cuneate nucleus depends on modality, since only the cutaneous input activates the complex intranuclear network possibly generating the scalp N18 potential.SignificanceOur results shed light on the subcortical processing of the somatosensory input of different modalities.     

Atrial fibrillation after cardiac surgery: A systematic review and meta-analysis

ObjectiveNew-onset postoperative atrial fibrillation (POAF) after cardiac surgery is common, with rates up to 60%. POAF has been associated with early and late stroke, but its association with other cardiovascular outcomes is less known. The objective was to perform a meta-analysis of the studies reporting the association of POAF with perioperative and long-term outcomes in patients with cardiac surgery.MethodsWe performed a systematic review and a meta-analysis of studies that presented outcomes for cardiac surgery on the basis of the presence or absence of POAF. MEDLINE, EMBASE, and the Cochrane Library were assessed; 57 studies (246,340 patients) were selected. Perioperative mortality was the primary outcome. Inverse variance method and random model were performed. Leave-one-out analysis, subgroup analyses, and metaregression were conducted.ResultsPOAF was associated with perioperative mortality (odds ratio [OR], 1.92; 95% confidence interval [CI], 1.58-2.33), perioperative stroke (OR, 2.17; 95% CI, 1.90-2.49), perioperative myocardial infarction (OR, 1.28; 95% CI, 1.06-1.54), perioperative acute renal failure (OR, 2.74; 95% CI, 2.42-3.11), hospital (standardized mean difference, 0.80; 95% CI, 0.53-1.07) and intensive care unit stay (standardized mean difference, 0.55; 95% CI, 0.24-0.86), long-term mortality (incidence rate ratio [IRR], 1.54; 95% CI, 1.40-1.69), long-term stroke (IRR, 1.33; 95% CI, 1.21-1.46), and longstanding persistent atrial fibrillation (IRR, 4.73; 95% CI, 3.36-6.66).ConclusionsThe results suggest that POAF after cardiac surgery is associated with an increased occurrence of most short- and long-term cardiovascular adverse events. However, the causality of this association remains to be established.     

Rucaparib in the landscape of PARP inhibition in ovarian cancer

Introduction: The landscape of poly (ADP-ribose) polymerase (PARP) inhibition in ovarian cancer is rapidly evolving and becoming increasingly complex. Ovarian cancer is leading therapeutic innovation by providing the proof of concept for DNA repair as a target. Three different PARP inhibitors have now received approvals in the US and Europe in different indications. Subtle but crucial differences can be found among the licensed indications for each PARP inhibitor in terms of histology, type of BRCA mutation (germline and/or somatic), number of prior lines of chemotherapy and whether the indication is in the treatment or maintenance settings.

Areas covered: We review the latest clinical data regarding the PARP inhibitor rucaparib in ovarian cancer, provide an update on the evolving landscape of PARP inhibition in ovarian cancer, and summarize avenues of ongoing and future research.

Expert opinion: All eligible patients should be offered a PARP inhibitor. SOLO1 trial results demonstrated an unprecedented benefit maintenance with PARP inhibitors in first line. Results from trials evaluating PARP inhibitors as maintenance in first line regardless of BRCA status and from trials evaluating combinatorial strategies are eagerly awaited.     

Recent advances with cyclin-dependent kinase inhibitors: therapeutic agents for breast cancer and their role in immuno-oncology

Introduction: Collaborative interactions between several diverse biological processes govern the onset and progression of breast cancer. These processes include alterations in cellular metabolism, anti-tumor immune responses, DNA damage repair, proliferation, anti-apoptotic signals, autophagy, epithelial-mesenchymal transition, components of the non-coding genome or onco-mIRs, cancer stem cells and cellular invasiveness. The last two decades have revealed that each of these processes are also directly regulated by a component of the cell cycle apparatus, cyclin D1.

Area covered: The current review is provided to update recent developments in the clinical application of cyclin/CDK inhibitors to breast cancer with a focus on the anti-tumor immune response.

Expert opinion: The cyclin D1 gene encodes the regulatory subunit of a proline-directed serine-threonine kinase that phosphorylates several substrates. CDKs possess phosphorylation site selectivity, with the phosphate-acceptor residue preceding a proline. Several important proteins are substrates including all three retinoblastoma proteins, NRF1, GCN5, and FOXM1. Over 280 cyclin D3/CDK6 substrates have b\een identified. Given the diversity of substrates for cyclin/CDKs, and the altered thresholds for substrate phosphorylation that occurs during the cell cycle, it is exciting that small molecular inhibitors targeting cyclin D/CDK activity have encouraging results in specific tumors.     

益气养精法对老年肺癌患者肿瘤标志物、生存期影响研究

目的探究益气养精法对老年肺癌患者肿瘤标志物、生存期影响。方法研究纳入60例老年肺癌患者,均由本院2016年1月-2017年1月收治,采取随机数字表法将患者分为两组,对照组患者(30例)常规化疗治疗,观察组患者(30例)在化疗基础上联合益气养精法治疗,比较两组患者治疗效果、治疗前后癌胚抗原(carcino-embryonic antigen,CEA)及血清癌抗原125(serum oncoantigen 125,CA 125)肿瘤标志物水平、不良反应情况及患者2年生存率。结果观察组患治疗有效率高于对照组,P<0.05;治疗前,两组患者CEA及CA 125水平相当,P>0.05,治疗后均改善,观察组优于对照组,P<0.05;观察组患者不良反应与对照组相当,均较低,P>0.05;观察组患者2年生存率高于对照组,P<0.05。结论益气养精法治疗老年肺癌患者效果患者,患者症状改善,不良反应少,安全可靠,且患者2年生存率较高。     

Sacituzumab govitecan: breakthrough targeted therapy for triple-negative breast cancer

Introduction: Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype associated with an increased risk of recurrence and cancer-related death. Unlike hormone receptor-positive or HER2-positive breast cancers, there are limited targeted therapies available to treat TNBC and cytotoxic chemotherapy remains the mainstay of treatment. Sacituzumab govitecan (IMMU-132) is an antibody-drug conjugate targeting Trop-2 expressing cells and selectively delivering SN-38, an active metabolite of irinotecan.

Areas covered: This review covers the mechanism of action, safety and efficacy of sacituzumab govitecan in patients with previously treated, metastatic TNBC. Additionally, efficacy data in other epithelial malignancies is included based on a PubMed search for ‘sacituzumab govitecan’ and ‘clinical trial’.

Expert opinion: Sacituzumab govitecan has promising anti-cancer activity in patients with metastatic TNBC previously treated with at least two prior lines of systemic therapy based on a single arm Phase I/II clinical trial. A confirmatory Phase III randomized clinical trial is ongoing. Sacituzumab govitecan has a manageable side effect profile, with the most common adverse events being nausea, neutropenia, and diarrhea. The activity of sacituzumab govitecan likely extends beyond TNBC with promising early efficacy data in many other epithelial cancers, including hormone receptor-positive breast cancer.     

原发性骶尾部脊索瘤的CT分型及征象

目的对治疗前原发性骶尾部脊索瘤(PSC)CT图像分型,并分析其CT征象,为诊断和个性化治疗提供依据。方法回顾性分析101例PSC患者治疗前的CT图像,包括肿瘤的部位、范围、大小、密度、肿瘤与邻近结构的关系。按照肿瘤的部位由上及下分为Ⅰ~Ⅳ型,并根据肿瘤侵犯的范围从小到大分为a^d亚型。采用Kruskal-Wallis H检验比较PSC各亚型的占比,并对各亚型之间进行两两比较。采用R×C列联表精确概率检验比较分型和亚型肿瘤钙化的发生率。采用单因素方差分析及LSD-t检验对各分型和亚型肿瘤的大小和密度进行分析、比较。结果101例PSC中,Ⅰ~Ⅳ型的发生率分别为17.8%、30.7%、36.6%、14.9%,a^d亚型的占比分别为9.9%、25.7%、58.4%、5.9%。各亚型的占比差异具有统计学意义(P=0.012)。c亚型明显高于a亚型(P=0.039),d亚型明显低于a亚型(P=0.036),其余各型之间无明显差异。各分型肿瘤内钙化的差异无统计学意义(P=0.233);各亚型肿瘤内钙化的差异有统计学意义(P=0.003),a^d亚型肿瘤钙化的比率逐渐增加。Ⅰ型肿瘤的左右径及上下径明显大于Ⅱ~Ⅳ型(P<0.05)。a亚型与b亚型肿瘤之间前后径的差异无统计学意义(P=0.102),b^d亚型之间前后径的差异均有统计学意义(P<0.05);不同亚型肿瘤之间的左右径、上下径之间的差异均有统计学意义(P<0.05),a亚型径线最小,d亚型径线最大。结论101例PSC中,Ⅱ、Ⅲ型最多见,肿瘤较少累及第一骶骨;各亚型中,a型较少见,c亚型最多见,d亚型最少见。肿瘤的密度与分型无关,肿瘤内钙化与亚型有关。Ⅰ型肿瘤侵犯的范围较Ⅱ~Ⅳ型广泛,a^d亚型肿瘤的径线逐渐增大,CT分型有利于判断肿瘤的范围。PSC诊断延迟现象比较明显,但很少发生远处侵犯和转移。CT图像可对治疗前PSC分型,为诊断和个性化治疗提供依据。     

A case of purulent pneumococcal pericarditis

Background

Purulent bacterial pericarditis is a rare and potentially fatal disease. The course may be fulminant, and the presentation may pose a diagnostic challenge.

Two cases of Klebsiella pneumoniae liver abscess necessitating liver resection for effective treatment

We report two British cases of liver abscess, due to Klebsiella pneumoniae and associated with synchronous infection elsewhere, which required liver resection for definitive treatment. They illustrate the geographic spread of aggressive K pneumoniae liver infection and demonstrate the importance of early aggressive treatment.