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.

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.

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.

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.

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.

Chest Wall Reconstruction with a Bilayered Wound Matrix Mesh Following Toilet Mastectomy.

BACKGROUND Breast cancer is still the most common malignancy in women. Though management of local disease has been thoroughly studied, management of metastatic breast cancer (MBC) is still under much debate. Modern diagnostic tools allow the detection of early metastatic disease, which may be more responsive to treatment than late metastatic disease. Source control of MBC by "toilet mastectomy" is being studied in many case reports and studies. CASE REPORT We present the case of a 43-year-old woman presenting with MBC and complaining of a recurrent breast fungating disease, aiming to highlight the importance of palliative surgical treatment in systemic breast malignancy and to report our experience with the effectiveness of the 'Integra" mesh. CONCLUSIONS Chest wall reconstruction using bilayered wound matrix mesh following "toilet mastectomy" offers excellent reconstructive results and local control of disease, and is a low-morbidity procedure.

Inhibition of lipopolysaccharide-induced osteoclast formation and bone resorption in vitro and in vivo by cysteine proteinase inhibitors.

Inflammation-induced bone destruction is a major treatment target in many inflammatory skeletal diseases. The aim of this study was to investigate if the cysteine proteinase inhibitors cystatin C, fungal cysteine proteinase inhibitor (E-64), and N-benzyloxycarbonyl-arginyl-leucyl-valyl-glycyl-diazomethane acetate (Z-RLVG-CHN2) can inhibit LPS-induced osteoclast formation. Mouse bone marrow macrophages (BMMs) were isolated and primed with receptor activator of NF-κB ligand (RANKL) for 24 h, followed by stimulation with LPS, with and without inhibitors. Adult mice were injected locally with LPS and then treated with E-64 and osteoclast formation assessed by the number of cathepsin K+ multinucleated cells. Cystatin C inhibited LPS-induced osteoclast formation time and concentration dependently (IC50 = 0.3 µM). The effect was associated with decreased mRNA and protein expression of tartrate-resistant acid phosphatase (TRAP) and cathepsin K and of the osteoclastogenic transcription factors c-Fos and NFATc1. LPS-induced osteoclast formation on bone slices was also inhibited by cystatin C, resulting in decreased pit formation and release of bone matrix proteins. Similar data were obtained with E-64 and Z-RLVG-CHN2 Cystatin C was internalized in BMMs stimulated by LPS but not in unstimulated BMMs. Osteoclast formation induced by LPS was dependent on TNF-α, and the 3 inhibitors abolished LPS-induced TNF superfamily 2 (gene encoding TNF-α; Tnfsf2) mRNA expression without affecting Il1b, Il6, or oncostatin M (Osm) expression. Formation of osteoclasts in the skull bones after local LPS stimulation was inhibited by E-64. It is concluded that cysteine proteinase inhibitors effectively inhibit LPS-induced osteoclast formation in vivo and in vitro by inhibition of TNF-α expression. The targeting of cysteine proteinases might represent a novel treatment modality for prevention of inflammatory bone loss.

Toll-Like Receptor 2 Stimulation of Osteoblasts Mediates Staphylococcus Aureus Induced Bone Resorption and Osteoclastogenesis through Enhanced RANKL.

Severe Staphylococcus aureus (S. aureus) infections pose an immense threat to population health and constitute a great burden for the health care worldwide. Inter alia, S. aureus septic arthritis is a disease with high mortality and morbidity caused by destruction of the infected joints and systemic bone loss, osteoporosis. Toll-Like receptors (TLRs) are innate immune cell receptors recognizing a variety of microbial molecules and structures. S. aureus recognition via TLR2 initiates a signaling cascade resulting in production of various cytokines, but the mechanisms by which S. aureus causes rapid and excessive bone loss are still unclear. We, therefore, investigated how S. aureus regulates periosteal/endosteal osteoclast formation and bone resorption. S. aureus stimulation of neonatal mouse parietal bone induced ex vivo bone resorption and osteoclastic gene expression. This effect was associated with increased mRNA and protein expression of receptor activator of NF-kB ligand (RANKL) without significant change in osteoprotegerin (OPG) expression. Bone resorption induced by S. aureus was abolished by OPG. S. aureus increased the expression of osteoclastogenic cytokines and prostaglandins in the parietal bones but the stimulatory effect of S. aureus on bone resorption and Tnfsf11 mRNA expression was independent of these cytokines and prostaglandins. Stimulation of isolated periosteal osteoblasts with S. aureus also resulted in increased expression of Tnfsf11 mRNA, an effect lost in osteoblasts from Tlr2 knockout mice. S. aureus stimulated osteoclastogenesis in isolated periosteal cells without affecting RANKL-stimulated resorption. In contrast, S. aureus inhibited RANKL-induced osteoclast formation in bone marrow macrophages. These data show that S. aureus enhances bone resorption and periosteal osteoclast formation by increasing osteoblast RANKL production through TLR2. Our study indicates the importance of using different in vitro approaches for studies of how S. aureus regulates osteoclastogenesis to obtain better understanding of the complex mechanisms of S. aureus induced bone destruction in vivo.

Effects of Oral L-Carnitine on Liver Functions after Transarterial Chemoembolization in Intermediate-Stage HCC Patients.

Transarterial chemoembolization (TACE) is usually followed by hepatic dysfunction. We evaluated the effects of L-carnitine on post-TACE impaired liver functions. Methods. 53 cirrhotic hepatocellular carcinoma patients at Osaka Medical College were enrolled in this study and assigned into either L-carnitine group receiving 600 mg oral L-carnitine daily or control group. Liver functions were evaluated at pre-TACE and 1, 4, and 12 weeks after TACE. Results. The L-carnitine group maintained Child-Pugh (CP) score at 1 week after TACE and exhibited significant improvement at 4 weeks after TACE (P < 0.01). Conversely, the control group reported a significant CP score deterioration at 1 week (P < 0.05) and 12 weeks after TACE (P < 0.05). L-carnitine suppressed serum albumin deterioration at 1 week after TACE. There were significant differences between L-carnitine and control groups regarding mean serum albumin changes from baseline to 1 week (P < 0.05) and 4 weeks after TACE (P < 0.05). L-carnitine caused prothrombin time improvement from baseline to 1, 4 (P < 0.05), and 12 weeks after TACE. Total bilirubin mean changes from baseline to 1 week after TACE exhibited significant differences between L-carnitine and control groups (P < 0.05). The hepatoprotective effects of L-carnitine were enhanced by branched chain amino acids combination. Conclusion. L-carnitine maintained and improved liver functions after TACE.

TLR5, a novel mediator of innate immunity-induced osteoclastogenesis and bone loss.

Accumulating evidence points to the importance of the innate immune system in inflammation-induced bone loss in infectious and autoimmune diseases. TLRs are well known for being activated by ligands expressed by bacteria, viruses, and fungi. Recent findings indicate that also endogenous ligands in inflammatory processes are important, one being a TLR5 agonist present in synovial fluid from patients with rheumatoid arthritis (RA). We found that activation of TLR5 by its specific ligand, flagellin, caused robust osteoclast formation and bone loss in cultured mouse neonatal parietal bones dependent on increased receptor activator of NF-κB ligand (RANKL):osteoprotegerin ratio, with half-maximal stimulation at 0.01 µg/ml. Flagellin enhanced Rankl mRNA in isolated osteoblasts by a myeloid differentiation primary response gene 88 and NF-κB-dependent mechanism. Injection of flagellin locally over skull bones in 5-wk-old mice resulted in increased mRNA expression of Rankl and osteoclastic genes, robust osteoclast formation, and bone loss. The effects in vitro and in vivo were absent in Tlr5(-/-) mice. These data show that TLR5 is a novel activator of RANKL and osteoclast formation and, therefore, a potential key factor in inflammation-induced bone erosions in diseases like RA, reactive arthritis, and periodontitis. TLR5 might be a promising novel treatment target for prevention of inflammatory bone loss.

Porphyromonas gingivalis Stimulates Bone Resorption by Enhancing RANKL (Receptor Activator of NF-κB Ligand) through Activation of Toll-like Receptor 2 in Osteoblasts.

Periodontitis has been associated with rheumatoid arthritis. In experimental arthritis, concomitant periodontitis caused by oral infection with Porphyromonas gingivalis enhances articular bone loss. The aim of this study was to investigate how lipopolysaccharide (LPS) from P. gingivalis stimulates bone resorption. The effects by LPS P. gingivalis and four other TLR2 ligands on bone resorption, osteoclast formation, and gene expression in wild type and Tlr2-deficient mice were assessed in ex vivo cultures of mouse parietal bones and in an in vivo model in which TLR2 agonists were injected subcutaneously over the skull bones. LPS P. gingivalis stimulated mineral release and matrix degradation in the parietal bone organ cultures by increasing differentiation and formation of mature osteoclasts, a response dependent on increased RANKL (receptor activator of NF-κB ligand). LPS P. gingivalis stimulated RANKL in parietal osteoblasts dependent on the presence of TLR2 and through a MyD88 and NF-κB-mediated mechanism. Similarly, the TLR2 agonists HKLM, FSL1, Pam2, and Pam3 stimulated RANKL in osteoblasts and parietal bone resorption. LPS P. gingivalis and Pam2 robustly enhanced osteoclast formation in periosteal/endosteal cell cultures by increasing RANKL. LPS P. gingivalis and Pam2 also up-regulated RANKL and osteoclastic genes in vivo, resulting in an increased number of periosteal osteoclasts and immense bone loss in wild type mice but not in Tlr2-deficient mice. These data demonstrate that LPS P. gingivalis stimulates periosteal osteoclast formation and bone resorption by stimulating RANKL in osteoblasts via TLR2. This effect might be important for periodontal bone loss and for the enhanced bone loss seen in rheumatoid arthritis patients with concomitant periodontal disease.

Osteoblast-derived WNT16 represses osteoclastogenesis and prevents cortical bone fragility fractures.

The WNT16 locus is a major determinant of cortical bone thickness and nonvertebral fracture risk in humans. The disability, mortality and costs caused by osteoporosis-induced nonvertebral fractures are enormous. We demonstrate here that Wnt16-deficient mice develop spontaneous fractures as a result of low cortical thickness and high cortical porosity. In contrast, trabecular bone volume is not altered in these mice. Mechanistic studies revealed that WNT16 is osteoblast derived and inhibits human and mouse osteoclastogenesis both directly by acting on osteoclast progenitors and indirectly by increasing expression of osteoprotegerin (Opg) in osteoblasts. The signaling pathway activated by WNT16 in osteoclast progenitors is noncanonical, whereas the pathway activated in osteoblasts is both canonical and noncanonical. Conditional Wnt16 inactivation revealed that osteoblast-lineage cells are the principal source of WNT16, and its targeted deletion in osteoblasts increases fracture susceptibility. Thus, osteoblast-derived WNT16 is a previously unreported key regulator of osteoclastogenesis and fracture susceptibility. These findings open new avenues for the specific prevention or treatment of nonvertebral fractures, a substantial unmet medical need.