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e change of sputum eosinophil rather than neutrophil counts is an independent predictor for the longitudinal change in FEV1, forced expiratory flow at 25% to 75% of forced vital capacity, specific effective airway resistance, residual lung volume, and lung clearance index.

In asthma, airway eosinophilic inflammation is the main driver of lung function impairment and poor disease outcomes, which might also be aggravated by the coexistence of airway neutrophilia to confer a severe mixed granulocytic asthma phenotype. Persistent airway eosinophilia might be associated with dynamic SAD even in patients with stable FEV1.

In asthma, airway eosinophilic inflammation is the main driver of lung function impairment and poor disease outcomes, which might also be aggravated by the coexistence of airway neutrophilia to confer a severe mixed granulocytic asthma phenotype. Persistent airway eosinophilia might be associated with dynamic SAD even in patients with stable FEV1.

The optimal treatment modality for saccular aneurysms of the posterior inferior cerebellar artery (PICA) remains unclear. A previous meta-analysis on the topic included a heterogenous study population, limiting the conclusions that can be drawn from its results. The aim of this study was to perform a systematic review and meta-analysis to compare outcomes of microsurgical and endovascular treatment (EVT) of these aneurysms.

A search of 4 online databases was performed for studies describing the management of saccular PICA aneurysms. The primary outcome was complete aneurysm occlusion. Data were also collected on neurologic outcomes, cranial nerve palsies, and requirement for re-treatment. A random effects model was used for calculation of pooled proportions. Our protocol was registered with PROSPERO (CRD42021232784).

A total of 17 studies were included in the final analysis, reporting the treatment outcomes of 455 aneurysms, with a mean follow-up of 20 months. The pooled occlusion rates were 94.8% (95% quired to assess the duration and severity of cranial nerve palsies following surgical treatment, and long-term aneurysm occlusion and the requirement for re-intervention following EVT.

Stage 3 acute kidney injury (AKI) has been observed to develop after serious traumatic brain injury (TBI) and is associated with worse outcomes, though its incidence is not consistently established. This study aims to report the incidence of stage 3 AKI in serious isolated TBI in a large, national trauma database and explore associated predictive factors.

This was a retrospective cohort study using 2015-2018 data from the American College of Surgeons Trauma Quality Improvement Program, a national database of trauma patients. Adult trauma patients admitted to the hospital with isolated serious TBI were included. Variables relating to demographics, comorbidities, vitals, hospital presentation, and course of stay were assessed. Imputed multivariable logistic regression assessed factors predictive of stage 3 AKI development.

A total of 342,675 patients with isolated serious TBI were included, 1585 (0.5%) of whom developed stage 3 AKI. Variables associated with stage 3 AKI in multivariable analysis were older age, male sex, Black race, higher body mass index, history of hypertension, diabetes, peripheral artery disease, chronic kidney disease, higher injury severity score, higher heart rate on arrival, lower oxygen saturation and motor Glasgow Coma Scale, admission to the intensive care unit or operating room, development of catheter-associated urinary tract infections or acute respiratory distress syndrome, longer intensive care unit stay, and ventilation duration.

Stage 3 AKI occurred in 0.5% of serious TBI cases. Complications of acute respiratory distress syndrome and catheter-associated urinary tract infections are more likely to co-occur with stage 3 AKI in patients with serious TBI.

Stage 3 AKI occurred in 0.5% of serious TBI cases. Complications of acute respiratory distress syndrome and catheter-associated urinary tract infections are more likely to co-occur with stage 3 AKI in patients with serious TBI.

Mucormycosis infection of the maxillofacial region and brain has been associated with coronavirus disease 2019 (COVID-19) infection. Mucormycosis was relatively a rare infection before COVID-19, and imaging findings are not very well described.

A retrospective imaging study of 101 patients diagnosed with COVID-19-associated mucormycosis by histopathology and/or culture was performed. All patients underwent computed tomography and/or magnetic resonance imaging based on the clinical condition of the patient and on consensus decision by the team of treating physicians. A simple 3-stage classification system based on imaging findings was adopted.

One hundred one cases were included in the final analysis (mean age= 55.1 years; male/female ratio= 6734). The affected patients had diabetes in 94% of the instances (n= 95), 80.1% (n= 81) received steroids), whereas 59.4% (n= 60) patients received supplemental oxygen. The majority underwent surgical intervention, whereas in 6 cases, patients were treated with antiion.The emergence of antibiotic-resistant bacteria is a critical worldwide healthcare problem. In the specific case of wound care, new and effective alternatives to currently available solutions are urgently needed. Cellulose-based dressings, for example, could be made more attractive if rendered antimicrobial. This work proposes a new strategy to modify cellulose-based materials with the short antimicrobial hexapeptide MP196 (RWRWRW-NH2) that relies on a biomolecular recognition approach based on carbohydrate binding modules (CBMs). Specifically, we focused on the modification of hydrogels, paper, and microfibrillated cellulose (MFC) with fusions of the CBM3 from Clostridium thermocellum (C. thermocellum) with derivatives of MP196. MEDICA16 The fusions are prepared by promoting the formation of a disulfide bond between Cys-terminated derivatives of MP196 and a CBM3 that is pre-anchored in the materials. The CBM3-MP196-modified materials displayed antibacterial activity against Escherichia coli (E. coli), Pseudomonas aeruexapeptide that relies on a biomolecular recognition approach based on carbohydrate binding modules. The modified materials displayed antibacterial activity against both Gram-negative and Gram-positive bacteria. The biomolecular strategy provides a favorable orientation, exposure, and distancing of the peptide from the matrix. This versatile concept offers a toolbox for the functionalization of different cellulose materials with a broad choice in peptides. Functionalization under mild biological conditions avoids further purification steps, allowing for translational research and multiple applications.Atherosclerosis progression is a result of chronic and non-resolving inflammation, effective treatments for which still remain to be developed. We designed and developed branched poly(ß-amino ester) nanoparticles (NPs) containing plasmid DNA encoding IL-10, a potent anti-inflammatory cytokine to atherosclerosis. The NPs (NP-VHPK) are functionalized with a targeting peptide (VHPK) specific for VCAM-1, which is overexpressed by endothelial cells at sites of atherosclerotic plaque. The anionic coating affords NP-VHPK with significantly lower toxicity than uncoated NPs in both endothelial cells and red blood cells (RBCs). Following injection of NP-VHPK in ApoE-/- mice, Cy5-labelled IL-10 significantly accumulates in both whole aortas and aortic sinus sections containing plaque compared to injection with a non-targeted control. Furthermore, IL-10 gene delivery results in an attenuation of inflammation locally at the plaque site. NP-VHPK may thus have the potential to reduce the inflammatory component of atherosclerosis in a safe and effective manner. STATEMENT OF SIGNIFICANCE Atherosclerosis is a chronic inflammatory disease that results in the formation of lipid-laden plaques within vascular walls. Although treatments using drugs and antibodies are now beginning to address the inflammation in atherosclerosis, neither is sufficient for long-term therapy. In this paper, we introduce a strategy to deliver genes encoding the anti-inflammatory protein interleukin-10 (IL-10) in vivo. We showed that Branched Poly(ß-aminoester) carrying the IL-10 gene are able to localize specifically at the plaque via surface-functionalized targeting moieties against inflamed VCAM-1 and/or ICAM-1 and to facilitate gene transcription by ECs to increase the local concentration of the IL-10 within the plaque. To date, there is no report involving non-viral nanotechnology to provide gene-based therapies for atherosclerosis.

Afatinib and pembrolizumab have separately shown survival benefit in patients with squamous cell carcinoma (SqCC) of the lung, and there is biological rationale for concurrent inhibition of the programmed death ligand-1 and epidermal growth factor receptor (EGFR) pathways in this patient population.

This open-label, single-arm study enrolled patients with SqCC of the lung who had progressed during/after first-line chemotherapy and comprised two parts a safety run-in to establish the recommended phase II dose (RP2D; afatinib 40mg or 30mg once daily with pembrolizumab 200mg every 3weeks); and the main part assessing efficacy and safety of the RP2D. The primary endpoint was objective response rate (ORR); secondary endpoints included the RP2D, progression-free survival (PFS) and overall survival (OS).

Twenty-four patients were treated in the safety run-in (afatinib 40mg/30mg cohorts n=12/12). Median age was 63.5years; 79.2% of patients were male. All patients discontinued afatinib and pembrolizumab, most commonly due to disease progression (58.3% and 75.0%, respectively) or adverse events (AEs; 37.5% and 25.0%, respectively). The study was discontinued early after completion of the safety run-in, and no patients entered the main part. ORR was 12.5%; median PFS and OS were 13.1 and 29.3weeks, respectively. All patients had≥1 drug-related AE (grade≥3 45.8%).

While there were no new or unexpected safety findings, exploratory analysis of antitumor activity indicated limited efficacy with afatinib plus pembrolizumab in patients with SqCC of the lung who had progressed during/after first-line chemotherapy.

NCT03157089.

NCT03157089.

Rotator cuff disease is a common cause of shoulder pain. Comorbidities such as diabetes, hypertension, and hyperlipidemia may be associated with rotator cuff disease, likely because of mechanisms related to vascular insufficiency.

We performed a systematic review of the association of diabetes, hypertension, and hyperlipidemia with the diagnosis of rotator cuff disease.

Following systematic queries of PubMed, Embase, Cochrane, CINAHL, and Science Direct, articles meeting eligibility criteria and reporting on the association of one or more risk factors (diabetes, hypertension, and hyperlipidemia) and rotator cuff disease were considered. Meta-analysis was performed to quantitatively summarize the associations between each risk factor and rotator cuff disease. We assessed study quality with the Newcastle-Ottawa Scale (NOS) and performed a qualitative assessment of risk of bias.

After a full-text review of 212 articles, 12 articles assessing diabetes, 5 assessing hypertension and 8 assessing hyperlipidemia were eligible.

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