A molecular perspective for the use of type IV tyrosine kinase inhibitors as anticancer therapeutics

Tyrosine kinases are enzymes that can transfer a phosphate group from ATP to a specific protein tyrosine, serine or threonine residue within a cell, operating as a switch that can turn ‘on’ and ‘off’ causing different physiological alterations in the body. Mutated kinases have been shown to display an equilibrium shift toward the activated state. Types I–III have been studied intensively leading to drugs like imatinib (type II), cobimetinib (type III), among others. It is the same scenario for types V–VII; however, there is a lacuna in information regarding type IV inhibitors, although recently some advances have surfaced. This review aims to accumulate the knowledge gained so far about type IV inhibitors.     

A Pre-Protocol/Post-Protocol Quality Improvement Initiative Specific to One Hospital for Security of Pathologic Specimen

ObjectiveThe objective of this study was to reduce errors in a pathologic specimen with the help of a protocol systematizing the pathology specimen management process in the operating room.Materials and methodThis quasi-experimental study was carried out in the operating room unit of a research and training hospital. A protocol systematizing the process of specimen management in secure surgical pathology and prepared in light of the current literature was used as an intervention, and the effectiveness of the protocol was tested.ResultsIt was determined that the rate of adverse events decreased from .3226% (68 of 21,078) to .032% (6 of 18,706) after the protocol systematizing the surgical pathology specimen management process prepared by the researchers, and the protocol was found to be effective by 90% (P = .03).ConclusionBased on the data obtained in this study, we recommend the use of a pathologic specimen management protocol in the operating room.     

Future directions in managing aniridia-associated keratopathy

Congenital aniridia is a panocular disorder that is typically characterized by iris hypoplasia and aniridia-associated keratopathy (AAK). AAK results in the progressive loss of corneal transparency and thereby loss of vision. Currently, there is no approved therapy to delay or prevent its progression, and clinical management is challenging because of phenotypic variability and high risk of complications after interventions; however, new insights into the molecular pathogenesis of AAK may help improve its management. Here, we review the current understanding about the pathogenesis and management of AAK. We highlight the biological mechanisms involved in AAK development with the aim to develop future treatment options, including surgical, pharmacological, cell therapies, and gene therapies.     

Hirschsprung-associated inflammatory bowel disease: A multicenter study from the APSA Hirschsprung disease interest group

Background/PurposeA small number of Hirschsprung disease (HD) patients develop inflammatory bowel disease (IBD)-like symptoms after pullthrough surgery. The etiology and pathophysiology of Hirschsprung-associated IBD (HD-IBD) remains unknown. This study aims to further characterize HD-IBD, to identify potential risk factors and to evaluate response to treatment in a large group of patients.MethodsRetrospective study of patients diagnosed with IBD after pullthrough surgery between 2000 and 2021 at 17 institutions. Data regarding clinical presentation and course of HD and IBD were reviewed. Effectiveness of medical therapy for IBD was recorded using a Likert scale.ResultsThere were 55 patients (78% male). 50% (n = 28) had long segment disease. Hirschsprung-associated enterocolitis (HAEC) was reported in 68% (n = 36). Ten patients (18%) had Trisomy 21. IBD was diagnosed after age 5 in 63% (n = 34). IBD presentation consisted of colonic or small bowel inflammation resembling IBD in 69% (n = 38), unexplained or persistent fistula in 18% (n = 10) and unexplained HAEC >5 years old or unresponsive to standard treatment in 13% (n = 7). Biological agents were the most effective (80%) medications. A third of patients required a surgical procedure for IBD.ConclusionMore than half of the patients were diagnosed with HD-IBD after 5 years old. Long segment disease, HAEC after pull through operation and trisomy 21 may represent risk factors for this condition. Investigation for possible IBD should be considered in children with unexplained fistulae, HAEC beyond the age of 5 or unresponsive to standard therapy, and symptoms suggestive of IBD. Biological agents were the most effective medical treatment.Level of EvidenceLevel 4     

What is the impact of zinc deficiency for pancreatectomies in patients with pancreatic ductal adenocarcinoma?

Backgroundand purpose: Zinc is an essential element for human health and plays an important role in metabolic, immunological and other biological processes. The present study was conducted to investigate the association between zinc deficiency (ZD) and the perioperative clinical course in patients with pancreatic ductal adenocarcinoma (PDAC).MethodsOf 216 patients with PDAC who underwent elective pancreatectomy between 2013 and 2017 at our institution, 206 patients with sufficient clinical data were retrospectively reviewed. The perioperative variables were compared and the risk factors associated with infectious complications were identified.ResultsZD was preoperatively present in 36 (17.5%) of 206 patients with PDAC. In the patients of the ZD group, a higher proportion of males, higher preoperative modified Glasgow prognostic scores, a higher neutrophil-to-lymphocyte ratio, and a higher occurrence of postoperative infectious complications after pancreatectomy were observed, compared to the non-ZD group. By a univariate analysis, three risk factors were significantly associated with infectious complications after pancreatectomy: ZD (vs non-ZD: p = 0.002), serum albumin <3.5 g/dl (vs ≥ 3.5 g/dl: p = 0.005), and the procedure of pancreaticoduodenectomy (vs others: p = 0.013). By multivariate logistic regression analysis, the occurrence of infectious complications was significantly associated with ZD (OR 3.430, 95%CI 1.570 to 7.490, p = 0.002) and the procedure of pancreaticoduodenectomy (OR 2.030, 95%CI 1.090 to 3.770, p = 0.025).ConclusionsThe current study newly demonstrated that ZD could serve as a preoperative predictor of infectious complications after pancreatectomies in the patients with PDAC.     

微创和传统开放后路腰椎椎间融合术治疗腰椎退行性疾病的远期预后

目的探讨微创后路腰椎椎间融合术(MIS-PLIF)和传统开放PLIF对腰椎退行性疾病(LDD)远期疗效及安全性的影响。方法 2011年1月-2014年12月收治LDD患者182例,其中96例采用传统开放PLIF治疗(PLIF组),86例采用MIS-PLIF治疗(MIS-PLIF组)。比较2组腰椎矢状位参数、多裂肌横截面积及萎缩率、融合率、疼痛视觉模拟量表(VAS)评分、日本骨科学会(JOA)评分、Oswestry功能障碍指数(ODI)及术后并发症发生情况,分析多裂肌萎缩率与顽固性腰背痛的相关性。结果 2组术后各随访时间点椎间隙高度恢复值和节段性前凸角恢复值差异均无统计学意义(P > 0.05)。2组术后1年腰椎前凸角恢复值差异无统计学意义(P > 0.05);但术后5年和末次随访时,MIS-PLIF组腰椎前凸角恢复值显著高于PLIF组,差异均有统计学意义(P < 0.05)。MIS-PLIF组术后各随访时间点多裂肌横截面积大于PLIF组,多裂肌萎缩率低于PLIF组,差异均有统计学意义(P < 0.05)。2组术后随访6个月融合率差异无统计学意义(P > 0.05)。2组术后各随访时间点下肢痛VAS评分差异无统计学意义(P > 0.05);MIS-PLIF组术后各随访时间点腰痛VAS评分、JOA评分及ODI均优于PLIF组,差异有统计学意义(P < 0.05)。MIS-PLIF组顽固性腰背痛发生率显著低于PLIF组,差异有统计学意义(P < 0.05)。合并顽固性腰背痛患者多裂肌萎缩率高于未合并顽固性腰背痛的患者,差异有统计学意义(P < 0.05)。结论术后多裂肌萎缩可能是导致顽固性腰背痛的重要原因,相较于传统开放PLIF,MIS-PLIF治疗LDD能够更有效地保持腰椎生理曲度,改善肢体活动功能,降低多裂肌萎缩程度,有助于避免顽固性腰背痛的发生。