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.

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.

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.

Association Between Sarcoidosis and Risk of Venous Thromboembolism: A Retrospective Chart Review.

Introduction Sarcoidosis is a multisystemic disorder of an unclear etiology. It has been postulated that sarcoidosis is a chronic autoimmune inflammation, which may predispose to venous thromboembolism (VTE). Recent studies showed increased VTE events in patients with sarcoidosis and other autoimmune disorders. This multicenter retrospective study aims at determining a possible correlation between VTE and sarcoidosis. Subjects and Method We reviewed charts from a commercial database (Explorys Inc, Cleveland, OH, USA), which is an aggregate of electronic health records from 26 major health care systems. We included patients between 30 and 69 of age. Patients with a condition known to cause a hypercoagulable state were excluded. We calculated the prevalence of VTE in patients with and without a diagnosis of sarcoidosis and compared the results. A multivariate analysis was performed to adjust for gender, race, age, tobacco use, and obesity. Results The overall prevalence of the VTE in patients without sarcoidosis was 1.4% compared to 4.9% in patients with sarcoidosis. Patients with sarcoidosis were more likely to develop VTE (OR: 2.96; 95% CI: 2.84-3.08; p < 0.001). Predictors of VTE in patients with sarcoidosis were gender, age, race, and obesity. Conclusion Our study indicates that sarcoidosis poses a risk of developing VTE. Further prospective studies are needed to shed light on this association and explain the prothrombotic phenotype of sarcoidosis.

Utility of hematological and inflammatory biomarkers in predicting recovery in critical Covid-19 patients: Our experience in the largest Covid-19 treating center in Lebanon.

BACKGROUND: COVID-19 pandemic has led to a catastrophic shortage of ICU beds. This has resulted in the need to identify patients that can be discharged early before full clinical recovery. We designed this study to determine if in changes routine tests like CBCD and CRP can be a useful complement to clinical status when deciding to discharge patients from ICU. METHODS: This retrospective study was conducted in Rafic Hariri University Hospital. Levels of biomarkers measured at admission (T1) and within 3 days of outcome (T2) were collected and ratios (T2/T1) were calculated. The Odds Ratios of association between the changes in these biomarkers and outcome were estimated. Multivariate analysis and AUC for the performance of these biomarkers were also conducted. RESULTS: We found on multivariate analysis that reduction in counts of lymphocyte and platelets and elevation in counts of neutrophils and level of CRP (T2/T1 ratio > 1) are strongly associated with mortality with respective ORs estimated at 6.74, 3.26, 5.65 and 4.34 [p-values < 0.001]. AUCs were found to lie in a range of 0.68 to 0.81 indicating fair to good performance. Other factors found to impact survival were AKI, AF and ACS [p-values < 0.01]. In contrast to other studies, risk factors didn't show an association with survival when adjusted for effects of complications and changes in biomarker levels. CONCLUSIONS: Our results confirm that inexpensive tests like lymphocyte count and CRP can be reliably used to follow COVID-19 patients in ICU and to support the decision to discharge patients.

Insulin use in type II diabetic patients: a predictive of mortality in covid-19 infection.

INTRODUCTION: Starting December 2019, the world has been devastated by the rapid spread of coronavirus disease 2019 (Covid-19). Many risk factors have been associated with worse outcomes and death from Covid-19 pneumonia including having diabetes mellitus. To date, it is not clear if all group of diabetics share the same risk of complications with COVID-19 infection. This study aims to compare disease severity and mortality rate in insulin users versus non-insulin users. METHODS: In this retrospective case-control study conducted at the largest health care network in New York state, we included adult, diabetic patients admitted from March 2020 to October 2020 with Covid-19 pneumonia. We compared the baseline characteristics in addition to outcomes of diabetic patients on home insulin (cases) and non-insulin user diabetics (controls). In addition, to determine if home insulin use is associated with an increased mortality, we conducted a cox regression analysis. RESULTS: We included 696 patients in the study period with a median age of 57 years, interquartile range [IQR] 51-62, and median body mass index 29.9 (IQR: 26-34.7). The majority (476 [68%]) were males. We identified 227 cases (33%) and 469 controls (67%). More cases than controls were hypertensive (74% vs 67%, p = 0.03), on ACE/ARB (50% vs 42%, p = 0.05), and had a hemoglobin A1c > 8.1 (71% vs 44%, p < 0.001). More cases had AKI (52% vs 38%, p < 0.001), however no significant differences were found in intubation rates (26% vs 24%, p = 0.54), detection of pulmonary embolism (4% vs 6%, p = 0.19) or death rate (15% vs 11%, p = 0.22) comparing cases and controls. In a multivariate analysis, we found that home insulin use was independently associated with increased risk of death: Hazard ratio: 1.92, 95% confidence interval (1.13-3.23). CONCLUSION: We showed herein that diabetic patients on home insulin with COVID-19 pneumonia, have worse outcomes and increased mortality compared to diabetics on oral antihyperglycemic agents. Close monitoring of insulin-dependent type II diabetic patients is needed in the current pandemic.

The Impact of Month on Joint Arthroplasty In-Hospital Outcomes: The December Effect.

Background: The purpose of this study was to assess the impact of month of the year on postsurgical outcomes after primary total hip arthroplasty (THA) and total knee arthroplasty (TKA) and to specifically analyze for a December effect. Material and methods: The National Inpatient Sample was used to identify all patients older than 40 years undergoing primary TKA and THA between 2006 and 2015. Patients were stratified based on the month of the year of surgery. In-hospital complication, disposition, and economic outcomes were comparatively analyzed. Results: There were statistically significant differences in outcomes based on month of the year. When comparing December to the other months, both TKA and THA patients had significantly lower rates of any complication, postoperative anemia, and genitourinary complications, while there were significantly higher rates of home than rehab discharge and shorter average length of stay in December. THA patients additionally had significantly lower rates of cardiac and respiratory complications during December. Conclusion: Postoperative outcomes are significantly associated with the month in which arthroplasty is performed. This study provides evidence of a positive "December effect" of improved in-hospital complications and economic outcomes for surgeries performed in December. Future research should direct attention to the impact that social factors may have on outcomes after elective surgical procedures and how these factors may be translated to other months.

Water Attachment onto Size-Selected Cationic Pyrene Clusters.

We report measurements of the attachment rates of water molecules onto mass-selected cationic pyrene clusters for size from n = 4 to 13 pyrene units and for different collision energies. Comparison of the attachment rates with the collision rates measured in collision-induced dissociation experiments provides access to the values of the sticking coefficient. The strong dependence of the attachment rates on size and collision energy is rationalized through a model in which we use a Langevin-type collision rate and adjust on experimental data the statistical dissociation rate of the water molecule from the cluster after attachment. This allows us to extrapolate our results to the conditions of isolation and long time scales encountered in astrophysical environments.

Endobronchial Chondroma: A Rare Case of Benign Tumor With Atypical High Standardized Uptake Value.

Chondroma is a rare benign tumor of the cartilage and occurs in the tracheobronchial tree, either isolated or as part of the Carney triad. It has been sparsely described in the literature, and some were mislabeled as hamartomas. We herein report a case of a 63-year-old female who was initially treated for community-acquired right middle lobe pneumonia. However, the patient's symptoms persisted warranting further workup, which confirmed the diagnosis of post-obstructive pneumonia. Whole-body positron emission tomography (PET) scan showed a hypermetabolic soft tissue lesion within the middle lobe bronchus, with a standardized uptake value (SUV) of 5.4, which is highly concerning for a primary or a secondary lesion. Since no distant lesions were identified, the patient underwent bronchial sleeve lobectomy of the right middle lobe under the assumption of localized disease. Pathology revealed chondroma, which had an unexpectedly high SUV on the PET scan; follow-up imaging denied any recurrence. Our case presents a rare entity of bronchial tumors with high SUV that presented with post-obstructive pneumonia. The patient's consent for writing this report was obtained.

Challenges and perspective of cancer patients during the COVID-19 pandemic and the Lebanese financial crisis: a multicentric cross-sectional study.

Lebanese cancer patients are facing a war on two fronts, between the COVID-19 pandemic and one of the most severe financial crises globally in recent times. This multicentric cross-sectional study was conducted, aiming to analyse challenges and perspective of this particularly vulnerable population. A questionnaire was prepared to assess socio-demographic data, challenges faced during the pandemic, perspectives concerning cancer and COVID-19, a scale was also validated to assess knowledge level regarding COVID-19 in this population. Patients were interviewed in chemotherapy units from four different private and public hospitals in Lebanon during December 2020 and March-June 2021. In total, 272 patients were interviewed (median age, 57 years, range, 22-90 years). Concerning salary during the pandemic, it changed negatively (45.6%), or did not change (7.7%), while 46.7% of participants did not work. Some challenges such as transportation problems (39%), inability to reach their physician by phone (16.9%), deferral of chemotherapy dates (31.6%), difficulty finding chemotherapy medications (49.6%) were more likely to be reported by patients receiving chemotherapy in public compared to private hospitals (p < 0.01 for each). Other challenges include not being able to find non-cancer-related medications (71.3%), this challenge being increased when comparing December 2020 with March-June 2021 (p < 0.02). Using a multivariate analysis, the best predictor for increased knowledge about COVID-19 was higher levels of education (p < 0.001). In conclusion, this study shows that cancer patients in Lebanon are facing many challenges that complicate different aspects of health. Perspective and challenges of these patients must be taken into consideration in order to deliver better care to our patients in these unprecedented times.

Spontaneous Pneumothorax: A Tale of Two Unique Cases.

We herein present two cases of spontaneous pneumothorax. The first one is occurring in an elderly female who has an extensive history of smoking and an underlying chronic obstructive lung disease, whereas the second case represents a congenital bleb in a male patient who has no other underlying pulmonary disorder. Both cases presented to our facility with a spontaneous pneumothorax following pulmonary bleb rupture. Both patients underwent thoracoscopic surgery with subsequent partial pleurectomy and pleurodesis.

Unexpected Gastric Ectopic Pancreas During Sleeve Gastrectomy: A Case Report.

BACKGROUND Ectopic or heterotopic pancreas is relatively rare pathology described as pancreatic tissue lacking communication with the normal pancreas. Ectopic pancreatic tissue can be found along the gastrointestinal tract, with the most common location the stomach along the greater curvature. This congenital condition could be identified incidentally, or present with symptoms that range from pain and bleeding to obstruction and malignant transformation. CASE REPORT We report a case of a 30-year-old female, who underwent laparoscopic sleeve gastrectomy for morbid obesity of body mass index (BMI) of 46 kg/m², and who was found to have a 3 cm submucosal mass at the lesser curvature while dividing the stomach. The sleeved stomach tube's intraoperative gastroscopy showed a submucosal mass at the posterior stomach wall towards the lesser curvature, increasing the suspicion of gastrointestinal stromal tumor (GIST) tumor. The choice was to continue with a secure margin and conversion to roux-en-y gastric bypass with gastric tumor resection. It turned out that the final pathology was submucosal ectopic pancreas. Despite being a rare pathology, for any submucosal gastric mass, ectopic pancreas should be on the differential diagnosis list. During the sleeve surgery, the mass was found, and the approach was changed to intraoperatively subtotal gastrectomy and roux-en-y gastric bypass. CONCLUSIONS Before any bariatric operation, even in asymptomatic young patients, it is worth doing routine upper endoscopy to prevent surprising intraoperative pathology.