A perioperative multidisciplinary care bundle reduces surgical site infections in patients undergoing synchronous colorectal and liver resection

Background

Surgical site infections (SSIs) are a major cause of morbidity, mortality, and healthcare costs, and patients undergoing simultaneous colorectal/liver resections are at an especially high SSI risk.

Pacemaker pseudodysfunction with a coronary sinus pacemaker

A permanent transvenous coronary sinus pacemaker functioned effectively for 22 months both as an atrial and ventricular pacemaker. Slow atrial flutter resulted in failure of the pacemaker to capture the myocardium and thus incorrectly suggested pacemaker dysfunction. Transtelephonic evaluation of this phenomenon was particularly difficult and could have resulted in unnecessary replacement of the pacing unit     

Protein aggregation and prionopathies

Prion protein and prion-like proteins share a number of characteristics. From the molecular point of view, they are constitutive proteins that aggregate following conformational changes into insoluble particles. These particles escape the cellular clearance machinery and amplify by recruiting the soluble for of their constituting proteins. The resulting protein aggregates are responsible for a number of neurodegenerative diseases such as Creutzfeldt-Jacob, Alzheimer, Parkinson and Huntington diseases. In addition, there are increasing evidences supporting the inter-cellular trafficking of these aggregates, meaning that they are “transmissible” between cells. There are also evidences that brain homogenates from individuals developing Alzheimer and Parkinson diseases propagate the disease in recipient model animals in a manner similar to brain extracts of patients developing Creutzfeldt-Jacob's disease. Thus, the propagation of protein aggregates from cell to cell may be a generic phenomenon that contributes to the evolution of neurodegenerative diseases, which has important consequences on human health issues. Moreover, although the distribution of protein aggregates is characteristic for each disease, new evidences indicate the possibility of overlaps and crosstalk between the different disorders. Despite the increasing evidences that support prion or prion-like propagation of protein aggregates, there are many unanswered questions regarding the mechanisms of toxicity and this is a field of intensive research nowadays.     

Tau Accumulation via Reduced Autophagy Mediates GGGGCC Repeat Expansion-Induced Neurodegeneration in Drosophila Model of ALS

Expansions of trinucleotide or hexanucleotide repeats lead to several neurodegenerative disorders, including Huntington disease [caused by expanded CAG repeats (CAGr) in the HTT gene], and amyotrophic lateral sclerosis [ALS, possibly caused by expanded GGGGCC repeats (G4C2r) in the C9ORF72 gene], of which the molecular mechanisms remain unclear. Here, we demonstrated that lowering the Drosophila homologue of tau protein (dtau) significantly rescued in vivo neurodegeneration, motor performance impairments, and the shortened life-span in Drosophila expressing expanded CAGr or expanded G4C2r. Expression of human tau (htau4R) restored the disease-related phenotypes that had been mitigated by the loss of dtau, suggesting an evolutionarily-conserved role of tau in neurodegeneration. We further revealed that G4C2r expression increased tau accumulation by inhibiting autophagosome–lysosome fusion, possibly due to lowering the level of BAG3, a regulator of autophagy and tau. Taken together, our results reveal a novel mechanism by which expanded G4C2r causes neurodegeneration via an evolutionarily-conserved mechanism. Our findings provide novel autophagy-related mechanistic insights into C9ORF72-ALS and possible entry points to disease treatment.Electronic supplementary materialThe online version of this article (10.1007/s12264-020-00518-2) contains supplementary material, which is available to authorized users.     

Nucleus–cytoplasm cross-talk in the aging brain

Aging is a primary risk factor for fatal neurodegenerative disorders, yet the mechanisms underlying physiological healthy aging and pathological aging, and how these mechanisms can divert one scenario to the other, are not completely understood. In recent years, reports indicate that alterations in nucleocytoplasmic transport may be a hallmark of both healthy and pathological aging. In this review, I summarize recent evidence supporting this information, specifically focusing on the association between the nucleocytoplasmic transport and aging of the brain, indicating both common and case-specific mechanisms and their interplay, and pointing out alterations of these mechanisms as regulatory “switches” for the fate of the aging brain. Importantly, some of these alterations are intervenable druggable targets, paving the way to a future pharmacotherapeutic intervention.     

Mandibular rescue: Application of the ALT fascia free flap to arrest osteoradionecrosis of the mandible

ObjectivesTo evaluate the use of the anterolateral thigh fascia free flap for use in neovascularization of mandibular bone in moderate osteoradionecrosis (ORN). All patients had ORN secondary to prior radiation therapy that was not severe enough to warrant segmental resection and reconstruction.Study designCase series.SettingTertiary medical center.MethodsIRB approval was obtained, and a retrospective chart review performed of all mandibular rescue procedures performed from 2011 to 2014. Patients with a minimum of two years of follow-up were included in the study.ResultsAll surgeries were performed by the senior surgeon (MF). Eight patients underwent the mandibular rescue procedure with resolution of pain and return to oral feeding in all patients, and no evidence of ORN progression on follow-up imaging. A total of 9 ALT free flaps were performed (one patient had 2 surgeries). Gender was distributed evenly (4 female/4 male). The average age was 66 (58-78), average length of hospitalization was 2.8 days (1–7), and average follow-up was 46.5 months (25–63).ConclusionsThe mandibular rescue procedure is a novel technique using the ALT fascia lata free flap to provide coverage and nutrient blood flow to mandible devascularized secondary to radiation therapy. The flap provides the advantages of low morbidity, ease of harvest, two-team approach to ablation and reconstruction, and quick recovery resulting in ‘short-stay’ free flap surgery. Although conclusions must be tempered in this small case series, our early clinical experience shows the ALT fascia lata flap holds promise in halting the destructive progression of ORN that is not yet advanced enough to require a segmental resection and reconstruction.     

武汉地区CAG扩增突变致青少年发病的亨廷顿舞蹈病的家系分析

目的对青少年发病的亨廷顿舞蹈病（Huntington disease）家系进行致病IT15基因早期诊断分析,为家系成员提供遗传咨询, 并为后续的HD发病机制及实验治疗研究提供依据。方法按照知情同意原则抽取家系成员外周血,提取基因组DNA,采用改良的降落PCR方法扩增IT15基因致病区域,DNA测序检测异常等位基因（CAG） n 三核苷酸重复次数。结果在该家系三代25名成员中,共发现8名致病IT15基因携带者,其中,III10、III12、III14、IV3和V2 CAG三核苷酸的拷贝数均为48,IV11和IV12均为（CAG） 67, IV14为（CAG） 63,而对照组35名正常人的CAG三核苷酸的拷贝数为8-25,两者之间没有重叠。结论家系中第四代致病基因携带者IV14与第三代患者III10比较,CAG三核苷酸重复次数增加15次,即本家系IT15基因在传递过程中发生了扩增突变。同时,扩增突变导致该家系出现青少年发病及遗传早现现象。