The Determinants of Eosinophilia in Patients With Severe Asthma.

Background: Asthma is defined by the Global Initiative for Asthma (GINA) as a heterogeneous disease characterized by chronic airway inflammation. The pathogenesis of the disease is better understood with the comprehension of immunological pathways. These pathways differ by the type of recruited cells and released interleukin (IL). Thus, asthma can be classified into subtypes based on the underlying immune mechanism: eosinophilic asthma (EA) and non-eosinophilic asthma (NEA). Patients with EA tend to respond better to inhaled corticosteroid as compared to those with NEA. The distinction of EA is very important in the light of emergent type 2 inflammation targeted therapies. Methods: We performed a 1-year (2018) retrospective cohort analysis of the Nationwide Inpatient Database (NIS). We included all adult patients presenting with severe asthma. Patients were stratified into two groups: eosinophilic severe asthma and non-eosinophilic severe asthma. The primary outcomes measures were the prevalence of chronic steroid use, status asthmaticus, family history of asthma, food, drug and environmental allergies, presence of nasal polyps, allergic rhinitis, allergic dermatitis, need for mechanical ventilation, need for oxygen supplementation, gastroesophageal reflux disease, in-hospital mortality, and length of stay. We performed descriptive statistics. Continuous parametric variables were reported using a mean and standard deviation. Continuous nonparametric variables were reported using a median and interquartile range. To compare the characteristics of the two groups, we used the independent t-test for continuous parametric variables and the Mann-Whitney U test for continuous nonparametric variables. The Chi-square test was used to assess differences in categorical variables. Results: A total of 2,646 patients were included, out of which 882 belonged to the eosinophilic group and 1,764 were in the non-eosinophilic group. Comparing EA versus NEA, we have found that eosinophilic group was characterized by higher percentage of steroid use (18.3% vs. 9.5%, P < 0.001). This group also had higher rates of status asthmaticus and positive family history (P = 0.009 and 0.004, respectively). The presence of allergies, allergic rhinitis, nasal polyps, and allergic dermatitis was higher among patients with eosinophilia. The need for mechanical ventilation and supplemental oxygen was also higher among this group (P < 0.001 for both); however, there was no significant difference in mortality rate (P = 0.347) and the length of hospital stay was similar in both groups (P < 0.001). Conclusion: We showed herein that the eosinophilic subtype of asthma differs widely from the non-eosinophilic phenotype. Clinically, patients with eosinophilia might exhibit different symptomatology, more atopy, and concomitant comorbidities. However, this group might have better response to steroid therapy and might benefit from the new emergent T2 immune targeted therapy. The identification of EA is crucial for better disease control.

Toll-like receptor-2 induced inflammation causes local bone formation and activates canonical Wnt signaling.

It is well established that inflammatory processes in the vicinity of bone often induce osteoclast formation and bone resorption. Effects of inflammatory processes on bone formation are less studied. Therefore, we investigated the effect of locally induced inflammation on bone formation. Toll-like receptor (TLR) 2 agonists LPS from Porphyromonas gingivalis and PAM2 were injected once subcutaneously above mouse calvarial bones. After five days, both agonists induced bone formation mainly at endocranial surfaces. The injection resulted in progressively increased calvarial thickness during 21 days. Excessive new bone formation was mainly observed separated from bone resorption cavities. Anti-RANKL did not affect the increase of bone formation. Inflammation caused increased bone formation rate due to increased mineralizing surfaces as assessed by dynamic histomorphometry. In areas close to new bone formation, an abundance of proliferating cells was observed as well as cells robustly stained for Runx2 and alkaline phosphatase. PAM2 increased the mRNA expression of Lrp5, Lrp6 and Wnt7b, and decreased the expression of Sost and Dkk1. In situ hybridization demonstrated decreased Sost mRNA expression in osteocytes present in old bone. An abundance of cells expressed Wnt7b in Runx2-positive osteoblasts and ß-catenin in areas with new bone formation. These data demonstrate that inflammation, not only induces osteoclastogenesis, but also locally activates canonical WNT signaling and stimulates new bone formation independent on bone resorption.

A Comprehensive Analysis of Litigation in Organ Transplantation for Allegations of Insufficient Policy Coverage, Discrimination and Malpractice.

Introduction: Transplantation is a field with unique medical and administrative challenges that involve an equally diverse array of stakeholders. Expectantly, the litigation stemming from this field should be similarly nuanced. There is a paucity of comprehensive reviews characterizing this medicolegal landscape. Design: The Caselaw Access Project Database was used to collect official court briefs of 2053 lawsuits related to kidney, liver, heart, lung, and pancreas transplantation. A thematic analysis was undertaken to characterize grounds for litigation, defendant type, and outcomes. Cases were grouped into policy, discrimination, poor or unsuccessful outcome, or other categories. Results: One hundred sixty-four court cases were included for analysis. Cases involving disputes over policy coverage were the most common across all organ types (N = 55, 33.5%). This was followed by poor outcomes (N = 51, 31.1%), allegations of discrimination against prison systems and employers (N = 37, 22.6%) and other (N = 21, 12.8%). Defendants involved in discrimination trials won with the greatest frequency (N = 29, 90.62%). Defendants implicated in policy suits won 65.3% (N = 32), poor outcomes 62.2% (N = 28), and other 70% (N = 14). Of the 51 cases involving poor outcomes, plaintiffs indicated lack of informed consent in 23 (45.1%). Conclusion: Reconsidering the informed consent process may be a viable means of mitigating future legal action. Most discrimination suits favoring defendants suggested previous concerns of structural injustices in transplantation may not be founded. The prevalence of policy-related cases could be an indication of financial burden on patients. Future work and advocacy will need to substantiate these concerns and address change where legal recourse falls short.

Threshold collision induced dissociation of protonated water clusters.

We report threshold collision induced dissociation experiments on protonated water clusters thermalized at low temperature for sizes n = 19-23. Fragmentation cross sections are recorded as a function of the collision energy and analyzed with a statistical model. This model allows us to account for dissociation cascades and provides values for the dissociation energies of each cluster. These values, averaging around 0.47 eV, are in good agreement with theoretical predictions at various levels of theory. Furthermore, the dissociation energies show a trend for the n = 21 magic and n = 22 anti-magic numbers relative to their neighbours, which is also in agreement with theory. These results provide further evidence to resolve the disagreement between previously published experimental values. A careful quantitative treatment of cascade dissociation in this model introduces interdependence between the dissociation energies of neighboring sizes, which reduces the number of free fitting parameters and improves both reliability and uncertainties on absolute dissociation energies deduced from experiments.

Metastatic melanoma to the lung cured with lobectomy: A case report.

We herein present the case of a 79-year-old female patient who presents with a single asymptomatic pulmonary nodule, melanocytic in nature, later identified as a remote secondary lesion of a primary cutaneous melanoma that was resected 22 years before presentation. Although quite atypical, the patient underwent resection of the affected pulmonary lobe; follow-up imaging did not reveal any local or distant recurrences.

Ultrasonography for the Busy Orthopaedic Surgeon: The Upper Extremity.

Ultrasonography is increasingly used in the diagnosis and treatment of musculoskeletal conditions and injuries. Ultrasonography possesses multiple advantages compared with other methods of imaging, including low cost, lack of radiation exposure, speed, and means for dynamic examination. Because of these advantages, many orthopaedic surgeons are routinely using ultrasonography to diagnose musculoskeletal conditions of the upper extremity. Musculoskeletal ultrasonography is technically challenging, but with proper guidance and practice, every orthopaedic surgeon can confidently integrate ultrasonography into their clinical practice.

Ultrasonography for the Busy Orthopaedic Surgeon: The Lower Extremity.

Ultrasonography has the potential to become a fundamental component of the diagnosis and management of musculoskeletal conditions and injuries. Moreover, in the context of modern healthcare systems that are focused on optimizing value, ultrasonography has the advantage of minimizing costs when compared with other advanced imaging modalities. Because of its low cost, lack of radiation exposure, speed, and capability to diagnose dynamic conditions, more orthopaedic surgeons are routinely integrating musculoskeletal ultrasonography into their daily practice. It is important to provide a comprehensive review of and approach to common musculoskeletal conditions of the lower extremity for the busy orthopaedic surgeon.

The Conundrum of Patients With Compensated Cirrhosis Requiring Kidney Transplantation; Kidney Alone or Simultaneous Liver Kidney Transplantation.

BACKGROUND: Patients with compensated cirrhosis and chronic kidney disease are increasing along with demand for simultaneous liver kidney transplant (SLKT) and shortages of organs for transplantation. Although these well-compensated patients may not need a liver organ, the alternative of kidney transplant alone (KTA) poses the risk of liver decompensation. Therefore, we aim to characterize outcomes among patients with compensated cirrhosis and chronic kidney disease listed for SLKT or receiving KTA to inform clinical decisions. METHODS: The 2-part retrospective study included a national cohort of patients listed for SLKT in United Network for Organ Sharing from January 2003 to June 2019 with Child A cirrhosis, with model for end-stage liver disease <25, and receiving dialysis; and a cohort of patients who underwent KTA from 2004 to 2019 with Child A cirrhosis identified through a 4-center chart review. Waitlist outcomes (SLKT, death, and clinical improvement) and post-KTA liver decompensation and survival were evaluated in the cohorts, respectively. RESULTS: In the national SLKT cohort (N = 705, median age 56 y, 68.8% male), 5-y cumulative incidence of SLKT was 43.1%, death 32.1%, and clinical improvement 9.1%. Among SLKT recipients, 36.3% remained Child A without ascites or encephalopathy at transplant. In the local KTA cohort (N = 34, median age 54 y, 79.4% male), none had ascites or hepatic encephalopathy before KTA, but 15 had clinical portal hypertension. Five-y post-KTA incidence of liver decompensation was 36.8%, and survival was 89.2%. CONCLUSIONS: SLKT may not be necessary for some patients with compensated cirrhosis needing kidney transplant. KTA is safe for selected patients with intact liver biochemical function, even with portal hypertension but without hepatic encephalopathy or ascites.

Gemella endocarditis.

We herein present the case presenting to our facility complaining of a fever of two months duration, who underwent dental procedure. Patient was diagnosed with infective endocarditis secondary to an uncommon bacteria: Gemella haemolysans. Patient was found to have concomitant severe mitral valve regurgitation. Our patient did not have any comorbidity or risk factor beside his dental procedure. Our patient received intravenous antibiotic therapy for six weeks and was scheduled for mitral valve replacement.

The Role and Efficacy of Vitamin C in Sepsis: A Systematic Review and Meta-Analysis.

Clinical rationale for study: Despite advancements in critical care, the mortality rate of sepsis remains high, with an overall poor prognosis. There is a complex pathophysiology of a lethal cascade of cytokines and inflammatory proteins underlying sepsis. The use of vitamin C can theoretically suppress the inflammatory cascade but remains a questionable practice due to a lack of conclusive evidence. Aims of the study: To appraise the therapeutic role of vitamin C in sepsis. Materials and methods: A systematic review was conducted on PubMed, Embase, and the Central Cochrane Registry. The study included randomized clinical trials (RCTs) with vitamin C as an intervention arm in the septic patient population. For continuous variables, the difference in means (MD) and for discrete variables, the odds ratio (OR) was used. For effect sizes, a confidence interval of 95% was used. A p-value of less than 0.05 was used for statistical significance. The analysis was performed using a random-effects model irrespective of heterogeneity. Heterogeneity was evaluated using the I2 statistic. Results: 23 studies were included with the total sample size of 2712 patients. In patients treated with vitamin C, there was a statistically significant reduction in the mortality: OR = 0.778 (0.635 to 0.954), p = 0.016; the sequential organ failure assessment score (SOFA): MD = −0.749 (−1.115 to −0.383), p < 0.001; and the duration of vasopressor requirement: MD = −1.034 days (−1.622 to −0.445), p = 0.001. No significant difference was found in the hospital or ICU length of stay. Conclusions and clinical implications: Vitamin C treatment regimens were associated with reduced mortality, SOFA score, and vasopressor requirement compared to the control in sepsis. Given its low cost and minimal adverse effects, we strongly encourage further large, randomized trials to establish vitamin C as a standard of care in sepsis management.