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.     

林兰教授运用柴胡芍药枳实甘草汤临证探析

林兰教授对柴胡芍药枳实甘草汤有独特的理论见解。柴胡芍药枳实甘草汤证的病机，在经为邪郁少阳、气机壅滞，主气郁；在腑为经隧挛急、胆气不降。柴胡芍药枳实甘草汤和解少阳，理气开滞，舒挛止痛，为临床舒畅气血、治疗气郁之名方，临证可用于甲状腺疾病、肝胆疾病、乳腺疾病、妇科疾病及多种疑难杂症。     

Adherence to a Mediterranean Lifestyle and Changes in Frequency,Severity, and Localization of Pain in Older Adults

ObjectiveTo assess the association between adherence to a Mediterranean lifestyle and changes in pain, and its characteristics over time in older adults.Patients and MethodsWe analyzed data from 864 and 862 community-dwelling individuals aged 65+ years from the Study on Cardiovascular Health, Nutrition and Frailty in Older Adults in Spain (Seniors-ENRICA) Seniors-ENRICA-1 (2008–2010 to 2012) and Seniors-ENRICA-2 (2015–2017 to 2019) cohorts, with a median follow-up of 2.8 and 2.4 years, respectively. Adherence to a Mediterranean lifestyle was assessed at baseline with the 27-item Mediterranean lifestyle (MEDLIFE) index. Pain changes over time were calculated with a pain scale that assessed the frequency, severity, and the number of pain locations both at baseline and follow-up. Multivariable-adjusted relative risk ratios (RRRs) were obtained using multinomial logistic regression.ResultsIn the pooled cohorts, after a median follow-up of 2.6 years, pain worsened for 697 participants, improved for 734, and did not change for 295. Compared with the lowest category of MEDLIFE adherence, those in the highest category showed an RRR of improvement vs worsening of overall pain of 1.85 (95% CI, 1.28 to 2.67; P-trend<.001). MEDLIFE adherence was also linked to improvement in pain frequency (RRR, 1.98; 95% CI, 1.31 to 3.01; P-trend=.001), pain severity (RRR, 2.00; 95% CI, 1.33 to 3.00; P-trend=.001), and a reduction in the number of pain locations (RRR, 1.68; 95% CI, 1.13 to 2.50; P-trend=.004). Limitations of this study are the use of self-reported lifestyle data.ConclusionA Mediterranean lifestyle was associated with improvement of pain characteristics in older adults. Experimental studies should assess the efficacy of an integral lifestyle approach for the management of pain in older adults.     

Contemporary Epidemiology of and Risk Factors Associated with Removal of a Pathologically Normal Appendix in Children with Suspected Appendicitis

BackgroundThe goal of this study was to characterize contemporary performance benchmarks and risk factors associated with negative appendectomy (NA) in children with suspected appendicitis.MethodsA multicenter retrospective cohort analysis of children undergoing appendectomy for suspected appendicitis was performed using data from the 2016–2021 NSQIP-Pediatric Appendectomy Targeted Public Use Files. Multivariable regression was used to evaluate the influence of year, age, sex, and WBC count on NA rate, and to generate rate estimates for NA based on different combinations of demographic characteristics and WBC profiles.Results100,322 patients were included from 140 hospitals. The overall NA rate was 2.4%, and rates decreased significantly during the study period (2016: 3.1% vs. 2021: 2.3%, p < 0.001). In adjusted analyses, the highest risk for NA was associated with a normal WBC (<9000/mm³; OR 5.31 [95% CI: 4.87–5.80]), followed by female sex (OR 1.55 [95% CI: 1.42–1.68]) and age <5 years (OR 1.64 [95% CI 1.39, 1.94]). Model-estimated risk for NA varied significantly across demographic and WBC strata, with a 14.4-fold range in rates between subgroups with the lowest and highest predicted risk (males 13–17 years with elevated WBC [1.1%] vs. females 3–4 years with normal WBC [15.8%]).ConclusionsContemporary NA rates have decreased over time, however NA risk remains high in children without a leukocytosis, particularly for girls and children <5 years of age. These data provide contemporary performance benchmarks for NA in children with suspected appendicitis and identify high-risk populations where further efforts to mitigate NA risk should be targeted.Level of EvidenceIII.     

Collar Badge Lens Dose Equivalent Values among United States Physicians Performing Fluoroscopically Guided Interventional Procedures

PurposeTo describe the range of occupational badge dose readings and annualized dose records among physicians performing fluoroscopically guided interventional (FGI) procedures using job title information provided by the same 3 major medical institutions in 2009, 2012, and 2015.Materials and MethodsThe Radiation Safety Office of selected hospitals was contacted to request assistance with identifying physicians in a large commercial dosimetry database. All entries judged to be uninformative of occupational doses to FGI procedure staff were excluded. Monthly and annualized doses were described with univariate statistics and box-and-whisker plots.ResultsThe dosimetry data set of interventional radiology staff contained 169 annual dose records from 77 different physicians and 698 annual dose records from 455 nonphysicians. The median annualized lens dose equivalent values among physicians (11.9 mSv; interquartile range [IQR], 6.9–20.0 mSv) was nearly 3-fold higher than those among nonphysician medical staff assisting with FGI procedures (4.0 mSv; IQR, 1.8–6.7 mSv) (P < .001). During the study period, without eye protection, 25% (23 of 93) of the physician annualized lens dose equivalent values may have exceeded 20 mSv; for nonphysician medical staff, this value may have been exceeded 3.5% (6 of 173) of the time. However, these values did not account for eye protection.ConclusionsThe findings from this study highlight the importance of mitigating occupational dose to the eyes of medical staff, particularly physicians, performing or assisting with FGI procedures. Training on radiation protection principles, the use of personal protective equipment, and patient radiation dose management can all help ensure that the occupational radiation dose is adequately controlled.     

Novel pathogenic variants in an Indian cohort with epidermolysis bullosa: Expanding the genotypic spectrum

BackgroundEpidermolysis bullosa (EB) is a genodermatosis characterized by skin fragility and blisters with variable severity. Patients with Dystrophic EB (DEB) or Junctional EB (JEB) mainly present to clinic due to greater functional impairment. Pathogenic sequence variations in COL7A1 are implicated in DEB.ObjectiveWe have tried to decipher the molecular spectrum and genotype phenotype correlation of 21 Indian patients with EB.MethodsNext generation sequencing (NGS) was performed to determine the pathogenic variants. Sanger sequencing was also done for validation of the variants in eleven individuals.ResultsPathogenic variants were detected in 20 individuals (diagnostic yield of 95%). Majority of them (90%) had sequence variation in COL7A1 while two had pathogenic variants in ITGB4 and KRT14 respectively. Out of the 18 patients confirmed to have DEB, 3 had Dominant DEB (DDEB) whereas 15 patients had Recessive DEB (RDEB). Amongst 23 sequence variations identified, 12 were found to be novel (3 were missense, 5 were premature termination codon variants while 4 were splice-site changes).ConclusionGenotype phenotype correlation was noted with milder manifestations in those with dominant inheritance types. Exact molecular diagnosis can be ascertained by NGS in majority of cases.     

Cold‐inducible RNA‐binding protein (CIRP) in inflammatory diseases: Molecular insights of its associated signalling pathways

Cold‐inducible RNA‐binding protein (CIRP) was previously identified as an intracellular stress‐response protein, which can respond to a variety of stress conditions by changing its expression and regulating mRNA stability through its binding site on the 3′‐UTR of its targeted mRNAs. Recently, extracellular CIRP (eCIRP) was discovered to be present in various inflammatory conditions and could act as a pro‐inflammatory factor. Genetic studies have demonstrated a key role for eCIRP in inflammatory conditions that led to the importance of targeting eCIRP in these diseases. Currently, the underlying mechanism of eCIRP‐induced inflammation is under intensive investigation and several signalling pathways are being explored. Here, we epitomized various signalling pathways that mediate the pro‐inflammatory effects of CIRP and also recapitulated all the CIRP‐derived peptides that can block the interaction between CIRP and its receptors in inflammatory setting.     

Identification of two pathogenic mutations in SORL1 in early-onset Alzheimer’s disease

The sortilin-related receptor 1 (SORL1) gene has been the subject of many studies focusing on frequent polymorphisms, which is associated with increased risk for Alzheimer’s Disease (AD). By whole-exome sequencing (WES), we identified two pathogenic missense mutations c.579C > G (p.F193L) and c.1397A > G (p.N466S) in SORL1. The two mutations were located in the same protein domain, and the two unrelated probands both had an onset of memory problems at less than 65 years of age, but their clinical manifestations and cranial imaging are different. The protein structure and function affected by these mutations were predicted using bioinformatics analysis, which suggested they were pathogenic. 3D protein structural analysis revealed that these amino acid substitutions might result in instability of protein structure and adverse intramolecular interactions. These findings suggest that both F193L and N466S should be thought as potential causative mutations in early-onset Alzheimer’s disease (EOAD) patients. Further functional studies are warranted to evaluate their roles in the pathogenesis of AD.