The social vulnerability metric (SVM) as a new tool for public health

Objective

To derive and validate a new ecological measure of the social determinants of health (SDoH), calculable at the zip code or county level.

Data Sources and Study Setting

The most recent releases of secondary, publicly available data were collected from national U.S. health agencies as well as state and city public health departments.

Study Design

The Social Vulnerability Metric (SVM) was constructed from U.S. zip-code level measures (2018) from survey data using multidimensional Item Response Theory and validated using outcomes including all-cause mortality (2016), COVID-19 vaccination (2021), and emergency department visits for asthma (2018). The SVM was also compared with the existing Centers for Disease Control and Prevention's Social Vulnerability Index (SVI) to determine convergent validity and differential predictive validity.

Data Collection/Extraction Methods

The data were collected directly from published files available to the public online from national U.S. health agencies as well as state and city public health departments.

Principal Findings

The correlation between SVM scores and national age-adjusted county all-cause mortality was r = 0.68. This correlation demonstrated the SVM's robust validity and outperformed the SVI with an almost four-fold increase in explained variance (46% vs. 12%). The SVM was also highly correlated (r ≥ 0.60) to zip-code level health outcomes for the state of California and city of Chicago.

Conclusions

The SVM offers a measurement tool improving upon the performance of existing SDoH composite measures and has broad applicability to public health that may help in directing future policies and interventions. The SVM provides a single measure of SDoH that better quantifies associations with health outcomes.     

Methodological advances in the design of peptide-based vaccines

The tremendous advances in genomics, recombinant DNA technology, bioengineering and nanotechnology, in conjunction with the development of high-end computations, have been instrumental in the process of rational design of peptide-based vaccines. The use of peptide vaccines was limited owing to their inherent instability when systemically administered; however, advanced formulation techniques have been developed for their systemic delivery, thereby overcoming their degradation, clearance, cellular uptake and off-target effects. With the rise of sophisticated immunological predictors and experimental techniques, several methodological advances have occurred in this field. This review examines contemporary methods to identify and optimize epitopes, engineer their immunogenic properties and develop their safe and efficient delivery into the host.     

Recent progress in molecular mechanisms of postoperative recurrence and metastasis of hepatocellular carcinoma

Hepatectomy is currently considered the most effective option for treating patients with early and intermediate hepatocellular carcinoma (HCC). Unfortunately, the postoperative prognosis of patients with HCC remains unsatisfactory, predominantly because of high postoperative metastasis and recurrence rates. Therefore, research on the molecular mechanisms of postoperative HCC metastasis and recurrence will help develop effective intervention measures to prevent or delay HCC metastasis and recurrence and to improve the long-term survival of HCC patients. Herein, we review the latest research progress on the molecular mechanisms underlying postoperative HCC metastasis and recurrence to lay a foundation for improving the understanding of HCC metastasis and recurrence and for developing more precise prevention and intervention strategies.     

Maternal influenza vaccination and child mortality: Longitudinal,population-based linked cohort study

Influenza vaccination is recommended to protect mothers and their infants from influenza. Few studies have evaluated the association between maternal influenza vaccination and child mortality. We aimed to evaluate the association between in utero exposure to seasonal inactivated influenza vaccine (IIV) and mortality among young children. This longitudinal, population-based cohort study included 191,247 maternal-child pairs in Western Australia between April 2012 and December 2017. Maternal vaccine information was obtained from a state-wide antenatal vaccination database. Mortality was defined as a record of a death registration. We used Cox proportional hazard models, weighted by the inverse-probability of treatment (vaccination), to estimate the hazard ratio of child mortality associated with in utero exposure to seasonal IIV. This study found no association between in utero exposure to seasonal IIV and mortality through age five years.     

Quantitative assessment of bony orbital volume symmetry: CT analysis in the uninjured caucasian population

There is a surprising lack of evidence documenting the volumetric symmetry of the bony orbit. This paper establishes reference values for orbital volume (OV) and symmetry in the 25 - 40 year old caucasian population. Secondarily, this paper sets a landmark for the tolerances in OV that can be expected when reconstructing the bony defects which may occur from trauma. A standardised method of quantitative OV measurement was developed using CT sinus examinations acquired for indications unrelated to orbital trauma. Sex, ethnicity, age, right and left OV were recorded. Data for 100 patients was obtained (50 male, 50 female). Mean left OV was 23.1cm³ and mean right OV was 23.3cm³. Left and right OV were strongly positively correlated (correlation coefficient: 0.96). Mean female OV was 21.6cm³ and mean male OV was 24.8cm³. On average, male OV is 3.2cm³ larger than female OV. The mean difference between left and right OV was 0.5cm³ in females and 0.6cm³ in males. The intra-class coefficient score between the two assessors was 0.973 (excellent). There is strong positive correlation between left and right OV in this study population. Previous work suggests that orbital volume loss less than 1cm³ would not lead to significant clinical symptoms of orbital fracture. When orbital reconstruction is undertaken, this study suggests that a volume symmetry difference of <0.5cm³ in females and <0.6cm³ in males would be consistent with the variation seen in the study population of uninjured caucasian 25-40 year olds and is therefore a reasonable goal of surgical management.     

肾素-血管紧张素系统在儿童膀胱尿道功能障碍中的作用研究进展

膀胱尿道功能障碍临床表现各异,部分患者治疗效果不佳(尤其是神经源性膀胱患者),后期可引起各种严重的并发症,甚至可引起致死性肾功能衰竭。肾素-血管紧张素系统(renin-angiotensin system,RAS)尤其是局部RAS在炎症及器官重塑等方面的作用已被证实,相关研究表明,RAS抑制剂(包括ACEI和ARBs)和新近发现的拮抗轴ACE2-Ang(1-7)-Mas轴具有改善下尿路功能和组织保护等功能。本文主要就ACE-AngⅡ-AT1轴和ACE2-Ang(1-7)-Mas轴在膀胱尿道功能障碍及其相关并发症的作用进行综述,探讨泌尿系统局部RAS作为儿童膀胱尿道功能障碍及其相关并发症药物治疗新靶点的可行性。     

Limited clinical activity of palbociclib and ribociclib monotherapy in advanced cancers with cyclin D-CDK4/6 pathway alterations in the Dutch DRUP and Australian MoST trials

The Dutch Drug Rediscovery Protocol (DRUP) and the Australian Cancer Molecular Screening and Therapeutic (MoST) Program are similar nonrandomized, multidrug, pan-cancer trial platforms that aim to identify signals of clinical activity of molecularly matched targeted therapies or immunotherapies outside their approved indications. Here, we report results for advanced or metastatic cancer patients with tumors harboring cyclin D-CDK4/6 pathway alterations treated with CDK4/6 inhibitors palbociclib or ribociclib. We included adult patients that had therapy-refractory solid malignancies with the following alterations: amplifications of CDK4, CDK6, CCND1, CCND2 or CCND3, or complete loss of CDKN2A or SMARCA4. Within MoST, all patients were treated with palbociclib, whereas in DRUP, palbociclib and ribociclib were assigned to different cohorts (defined by tumor type and alteration). The primary endpoint for this combined analysis was clinical benefit, defined as confirmed objective response or stable disease ≥16 weeks. We treated 139 patients with a broad variety of tumor types; 116 with palbociclib and 23 with ribociclib. In 112 evaluable patients, the objective response rate was 0% and clinical benefit rate at 16 weeks was 15%. Median progression-free survival was 4 months (95% CI: 3-5 months), and median overall survival 5 months (95% CI: 4-6 months). In conclusion, only limited clinical activity of palbociclib and ribociclib monotherapy in patients with pretreated cancers harboring cyclin D-CDK4/6 pathway alterations was observed. Our findings indicate that monotherapy use of palbociclib or ribociclib is not recommended and that merging data of two similar precision oncology trials is feasible.     

Diagnosis of pituitary abscess and treatment via transsphenoidal surgery: experience from 15 cases

ObjectivePituitary abscess is an often misdiagnosed, rare clinical disorder. To improve diagnostic accuracy and the efficacy of surgical and antibiotic therapy for patients with pituitary abscess, herein, we retrospectively reviewed 15 patients who presented with pituitary abscesses from 2005 to 2022.DesignRetrospective study.PatientsFifteen patients underwent transsphenoidal surgery and received antibiotic treatment.MeasurementsComplete details regarding medical history, clinical manifestations, laboratory examinations, imaging studies, and treatment strategies were obtained for all patients.ResultsMost patients presented with hypopituitarism and headaches, while some presented with fever, visual disturbances, and diabetes insipidus (DI). Abscesses showed significant annular enhancement post gadolinium injection. In most patients, pituitary abscess can be cured via microscopic or endoscopic drainage of the abscess followed by antibiotic treatment. Complete cure of pituitary abscess was observed in nine patients, with six cases of prolonged hypopituitarism and only one case of recurrence. Long-term hormone replacement therapy was effective in the postoperative management of hypopituitarism.ConclusionsThe typical manifestations of pituitary abscess include hypopituitarism and headaches; the presence of an enhanced ring at the edge of the mass on contrast-enhanced magnetic resonance images (MRI) is highly suggestive of pituitary abscess. We recommend antibiotic treatment for 4–6 weeks postoperatively, based on the results of bacterial cultures or metagenomic next-generation sequencing (mNGS).     

Effect of Preclinical Simulation on Family Nurse Practitioner Student’s Readiness for Practice

This project aimed to enhance clinical education preparation in a family nurse practitioner graduate program in rural central Appalachian by providing a psychomotor skills-based simulation with the use of the defusing, discovering, and deepening (3D) debriefing method. The students were surveyed after graduation to determine effectiveness. Program outcomes to measure readiness to practice were graduation, employment, and certification rates. The postgraduation surveys indicated the simulation contributed to an increase in psychomotor skill performance, practicing safe patient care, and making independent decisions in practice. Common themes emerged of feeling “prepared for practice” and being “more marketable” with the procedural skills learned in the simulation.     

ω-3多不饱和脂肪酸对慢性移植物抗宿主病狼疮小鼠的免疫调控作用

目的探讨ω-3多不饱和脂肪酸(ω-3 poly unsaturated fatty acids,ω-3 PUFAs)对慢性移植物抗宿主病(chronic graft versus host disease,cGVH)狼疮模型小鼠的免疫调节功能影响。方法单次腹腔注射bm12小鼠淋巴细胞建立cGVH小鼠模型,造模当天分别给予90%ω-3 PUFAs和97%EPA灌胃治疗,持续14 d。通过流式细胞术检测小鼠脾脏淋巴细胞中各免疫指标,ELISA检测小鼠血清中总IgG水平。结果与正常对照组相比,cGVH组明显下调Treg亚群,明显上调T_FH细胞、生发中心B细胞和浆细胞亚群;与模型对照组相比,90%ω-3和97%EPA均明显上调Treg亚群,并明显下调T_FH细胞、生发中心B细胞和浆细胞亚群;且97%EPA组小鼠血清中总IgG水平明显下降。结论在cGVH狼疮小鼠模型中,ω-3 PUFAs通过增加Treg细胞,减少T_FH细胞、生发中心B细胞和浆细胞,抑制IgG的分泌,从而发挥免疫抑制作用,且其免疫抑制作用可能与ω-3 PUFAs含量相关。