Outcomes of surgical versus nonsurgical treatment for multiple rib fractures: A US hospital matched cohort database analysis.

BACKGROUND: Treatment for multiple rib fractures includes surgical stabilization of rib fractures (SSRF) or nonoperative management (NOM). Meta-analyses have demonstrated that SSRF results in faster recovery and lower long-term complication rates versus NOM. Our study evaluated postoperative outcomes for multiple rib fracture patients following SSRF versus NOM in a real-world, all-comer study design. METHODS: Multiple rib fracture patients with inpatient admissions in the PREMIER hospital database from October 1, 2015, to September 30, 2020, were identified. Outcomes included discharge disposition, and 3- and 12-month lung-related readmissions. Demographics, comorbidities, concurrent injuries at index, Abbreviated Injury Scale and Injury Severity Scores, and provider characteristics were determined for all patients. Patients were excluded from the cohort if they had a thorax Abbreviated Injury Scale score of <2 (low severity patient) or a Glasgow Coma Scale score of ≤8 (extreme high severity patient). Stratum matching between SSRF and NOM patients was performed using fine stratification and weighting so that all patient data were kept in the final analysis. Outcomes were analyzed using generalized linear models with quasinormal distribution and logit links. RESULTS: A total of 203,450 patients were included, of which 200,580 were treated with NOM and 2,870 with SSRF. Compared to NOM, patients with SSRF had higher rates of home discharge (62% SSRF vs. 58% NOM) and lower rates of lung-related readmissions (3 months, 3.1% SSRF vs. 4.0% NOM; 12 months, 6.2% SSRF vs. 7.6% NOM). The odds ratio (OR) for home or home health discharge in patients with SSRF versus NOM was 1.166 (95% confidence interval [CI], 1.073-1.266; p = 0.0002). Similarly, ORs for lung-related readmission at 3- and 12-month were statistically lower in the patients treated with SSRF versus NOM (OR [3 months], 0.764 [95% CI, 0.606-0.963]; p = 0.0227 and OR [12 months], 0.799 [95% CI, 0.657-0.971]; p = 0.0245). CONCLUSION: Surgical stabilization of rib fractures results in greater odds of home discharge and lower rates of lung-related readmissions compared with NOM at 12 months of follow-up. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

ADAR1 averts fatal type I interferon induction by ZBP1.

Mutations of the ADAR1 gene encoding an RNA deaminase cause severe diseases associated with chronic activation of type I interferon (IFN) responses, including Aicardi-Goutières syndrome and bilateral striatal necrosis1-3. The IFN-inducible p150 isoform of ADAR1 contains a Zα domain that recognizes RNA with an alternative left-handed double-helix structure, termed Z-RNA4,5. Hemizygous ADAR1 mutations in the Zα domain cause type I IFN-mediated pathologies in humans2,3 and mice6-8; however, it remains unclear how the interaction of ADAR1 with Z-RNA prevents IFN activation. Here we show that Z-DNA-binding protein 1 (ZBP1), the only other protein in mammals known to harbour Zα domains9, promotes type I IFN activation and fatal pathology in mice with impaired ADAR1 function. ZBP1 deficiency or mutation of its Zα domains reduced the expression of IFN-stimulated genes and largely prevented early postnatal lethality in mice with hemizygous expression of ADAR1 with mutated Zα domain (Adar1mZα/- mice). Adar1mZα/- mice showed upregulation and impaired editing of endogenous retroelement-derived complementary RNA reads, which represent a likely source of Z-RNAs activating ZBP1. Notably, ZBP1 promoted IFN activation and severe pathology in Adar1mZα/- mice in a manner independent of RIPK1, RIPK3, MLKL-mediated necroptosis and caspase-8-dependent apoptosis, suggesting a novel mechanism of action. Thus, ADAR1 prevents endogenous Z-RNA-dependent activation of pathogenic type I IFN responses by ZBP1, suggesting that ZBP1 could contribute to type I interferonopathies caused by ADAR1 mutations.

Surgical treatment, complications, reoperations, and healthcare costs among patients with clavicle fracture in England.

INTRODUCTION: The clinical and economic burden of clavicle fractures in England is not well documented. This study evaluated rates of surgical treatment, post-surgical complications, reoperations and costs in patients with clavicle fractures using the Clinical Practice Research Datalink (CPRD) database. METHODS: CPRD data were linked to National Health Service Hospital Episode Statistics data. Patients with a diagnosis of clavicle fracture between 2010-2018 were selected in CPRD (date of fracture = index date). Of those, patients with surgical intervention within 180 days from index fracture were identified. Rates of post-surgical complications (i.e., infection, non-union, and mal-union), reoperations (for device removal or for postoperative complications), post-operative costs and median time to reoperations were evaluated up to 2 years after surgery. RESULTS: 21,340 patients with clavicle fractures were identified (mean age 35.0 years(standard deviation (SD): 26.5), 66.7% male). Surgery was performed on 672 patients (3.2% of total cohort) at an average 17.1 (SD: 25.2) days post-fracture. Complications (i.e., infection, non-union, or malunion) affected 8.1% of surgically treated clavicle fracture patients; the rate of infection was 3.5% (95% CI, 1.7%- 5.2%), non-union 4.4% (95% CI, 2.4%-6.5%), and mal-union 0.3% (95% CI, 0%-0.7%). Adjusting for age, gender, comorbidities and time to surgery, the all-cause reoperation rate was 20.2% (13.2%-30.0%) and the adjusted rate of reoperation for implant removal was 17.0% (10.7%-25.9%)-84% of all-cause reoperations were thus performed for implant removal. Median time to implant removal was 254 days. The mean cost of reoperations for all causes was £5,000. The most expensive reoperations were for cases that involved infection (mean £6,156). CONCLUSIONS: Complication rates following surgical clavicle fracture care averaged 8.1%. However, reoperation rates exceed 20%, the vast majority of reoperations being performed for device removal. Technologies to alleviate secondary device removal surgeries would address a significant clinical unmet need.

Dynamics of human monocytes and airway macrophages during healthy aging and after transplant.

The ontogeny of airway macrophages (AMs) in human lung and their contribution to disease are poorly mapped out. In mice, aging is associated with an increasing proportion of peripherally, as opposed to perinatally derived AMs. We sought to understand AM ontogeny in human lung during healthy aging and after transplant. We characterized monocyte/macrophage populations from the peripheral blood and airways of healthy volunteers across infancy/childhood (2-12 yr), maturity (20-50 yr), and older adulthood (>50 yr). Single-cell RNA sequencing (scRNA-seq) was performed on airway inflammatory cells isolated from sex-mismatched lung transplant recipients. During healthy aging, the proportions of blood bronchoalveolar lavage (BAL) classical monocytes peak in adulthood and decline in older adults. scRNA-seq of BAL cells from lung transplant recipients indicates that after transplant, the majority of AMs are recipient derived. These data show that during aging, the peripheral monocyte phenotype is consistent with that found in the airways and, furthermore, that the majority of human AMs after transplant are derived from circulating monocytes.

A commonly used rumen-protected conjugated linoleic acid supplement marginally affects fatty acid distribution of body tissues and gene expression of mammary gland in heifers during early lactation.

BACKGROUND: Conjugated linoleic acids (CLA) in general, and in particular the trans-10,cis-12 (t10,c12-CLA) isomer are potent modulators of milk fat synthesis in dairy cows. Studies in rodents, such as mice, have revealed that t10,c12-CLA is responsible for hepatic lipodystrophy and decreased adipose tissue with subsequent changes in the fatty acid distribution. The present study aimed to investigate the fatty acid distribution of lipids in several body tissues compared to their distribution in milk fat in early lactating cows in response to CLA treatment. Effects in mammary gland are further analyzed at gene expression level. METHODS: Twenty-five Holstein heifers were fed a diet supplemented with (CLA groups) or without (CON groups) a rumen-protected CLA supplement that provided 6 g/d of c9,t11- and t10,c12-CLA. Five groups of randomly assigned cows were analyzed according to experimental design based on feeding and time of slaughter. Cows in the first group received no CLA supplement and were slaughtered one day postpartum (CON0). Milk samples were taken from the remaining cows in CON and CLA groups until slaughter at 42 (period 1) and 105 (period 2) days in milk (DIM). Immediately after slaughter, tissue samples from liver, retroperitoneal fat, mammary gland and M. longissimus (13th rib) were obtained and analyzed for fatty acid distribution. Relevant genes involved in lipid metabolism of the mammary gland were analyzed using a custom-made microarray platform. RESULTS: Both supplemented CLA isomers increased significantly in milk fat. Furthermore, preformed fatty acids increased at the expense of de novo-synthesized fatty acids. Total and single trans-octadecenoic acids (e.g., t10-18:1 and t11-18:1) also significantly increased. Fatty acid distribution of the mammary gland showed similar changes to those in milk fat, due mainly to residual milk but without affecting gene expression. Liver fatty acids were not altered except for trans-octadecenoic acids, which were increased. Adipose tissue and M. longissimus were only marginally affected by CLA supplementation. CONCLUSIONS: Daily supplementation with CLA led to typical alterations usually observed in milk fat depression (reduction of de novo-synthesized fatty acids) but only marginally affected tissue lipids. Gene expression of the mammary gland was not influenced by CLA supplementation.

Phenome-transcriptome correlation unravels anxiety and depression related pathways.

The identification of pathways pertinent to human diseases is critical for gaining a better understanding of their pathophysiology. Pathway knowledge in turn can provide disease marker information required for diagnosis, drug development and improved patient treatment. Psychiatric disorders including anxiety and depression are complex diseases and are caused by a combination of multiple genetic and environmental factors affecting certain brain circuits. Here we used a systems biology approach to identify molecular pathways that affect anxiety- and depression-like phenotypes. For this purpose we screened pathways for stable enrichment in a great number of publicly available transcriptome data from the Gene Expression Omnibus related to anxiety- and depression-like phenotypes. In case of anxiety our analysis implicate a dysregulation of carbohydrate metabolism, tight junction and the phosphatidylinositol signaling system, whereas for depression gap junction, gonadotropin-releasing hormone signaling and ubiquitin-mediated proteolysis pathways are affected. Furthermore, both anxiety and depression show a dysregulation of VEGF signaling, long term potentiation and the glycolysis pathway. Molecular entities that are part of the identified pathways can serve as biomarkers and potential therapeutic targets for diagnosis and treatment of depression and anxiety disorders.

Extensive necrosis of the bladder with hypostatic abscess: a late complication after radiotherapy.

BACKGROUND: Late urological complications after radiotherapy of a primary tumor in the pelvis are rare but challenging. We report a case of extensive bladder necrosis with hydronephrosis and sepsis nearly 45 years after radiotherapy. CASE REPORT: An 80-year-old woman with infected hydronephrosis and with a history of radiotherapy due to cervical carcinoma was treated with JJ stenting. Due to the absence of any improvement, we performed a computed tomography which showed bilateral hypostatic abscesses in both thighs that were not apparent at first look. The initiated series of diagnostics and therapies finally led to complete healing. The patient was discharged after 6 months with completely healed wounds and nearly normal renal parameters. CONCLUSION: Special emphasis should be put here on the extremely long latency period, the utmost importance of the past history, the individualized surgical management, and the notion about late complications after radiotherapy.

Nonverbal Medical Symptom Validity Test performance of elderly healthy adults and clinical neurology patients.

The study aimed to provide independent data on the specificity of the Nonverbal Medical Symptom Validity Test (NV-MSVT; Green, 2008 ), a new test that combines conventional decision making based on cutoffs with profile analyses in order to identify invalid test performance and to reduce false positive classifications. The results of 65 bona fide neurological patients (with 21 of them meeting Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition, DSM-IV, core criteria for dementia) were compared to 50 healthy volunteers. One patient was wrongly classified as malingering, resulting in a specificity of 98.5% for neurological patients and 100% for controls. A total of 13 patients with dementia (62%), 6 patients without dementia (14%), and 1 healthy participant exhibited a dementia profile in the NV-MSVT. While these results confirm the high specificity of the NV-MSVT for the classification insufficient effort, its sensitivity has to be verified by independent research data.