Unexpectedly high prevalence of sarcoidosis in a representative U.S. Metropolitan population

SummaryThe prevalence of sarcoidosis in the United States is unknown, with estimates ranging widely from 1 to 40 per 100,000. We sought to determine the prevalence of sarcoidosis in our health system compared to other rare lung diseases and to further establish if the prevalence was changing over time. We interrogated the electronic medical records of all patients treated in our health system from 1995 to 2010 (1.48 million patients) using the common ICD9 codes for sarcoidosis (135), lung cancer (162), and several other lung diseases characterized, like sarcoidosis, as “rare lung diseases”. The patient demographic information (race, gender, age) was further analyzed to identify signature data patterns. The prevalence of sarcoidosis in our health system increased steadily from 164/100,000 in 1995 to 330/100,000 in 2010, and this trend could not be ascribed simply to changes in patient demographics or patient referral patterns. We further estimate that the prevalence of sarcoidosis exceeds 48 per 100,000 in Franklin County, Ohio, the demographic profile of which is nearly identical to that of the U.S. Sarcoidosis prevalence increased over time relative to lung cancer, a benchmark disease with stable disease prevalence, and exceeded that of other rare lung diseases. We postulate that the observed 2-fold increase in sarcoidosis disease prevalence in our health system is primarily related to improved detection and diagnostic approaches, and we conclude that the actual prevalence of sarcoidosis in central Ohio greatly exceeds current U.S. estimates

CD44v6 Regulates Growth of Brain Tumor Stem Cells Partially through the AKT-Mediated Pathway

Identification of stem cell-like brain tumor cells (brain tumor stem-like cells; BTSC) has gained substantial attention by scientists and physicians. However, the mechanism of tumor initiation and proliferation is still poorly understood. CD44 is a cell surface protein linked to tumorigenesis in various cancers. In particular, one of its variant isoforms, CD44v6, is associated with several cancer types. To date its expression and function in BTSC is yet to be identified. Here, we demonstrate the presence and function of the variant form 6 of CD44 (CD44v6) in BTSC of a subset of glioblastoma multiforme (GBM). Patients with CD44high GBM exhibited significantly poorer prognoses. Among various variant forms, CD44v6 was the only isoform that was detected in BTSC and its knockdown inhibited in vitro growth of BTSC from CD44high GBM but not from CD44low GBM. In contrast, this siRNA-mediated growth inhibition was not apparent in the matched GBM sample that does not possess stem-like properties. Stimulation with a CD44v6 ligand, osteopontin (OPN), increased expression of phosphorylated AKT in CD44high GBM, but not in CD44low GBM. Lastly, in a mouse spontaneous intracranial tumor model, CD44v6 was abundantly expressed by tumor precursors, in contrast to no detectable CD44v6 expression in normal neural precursors. Furthermore, overexpression of mouse CD44v6 or OPN, but not its dominant negative form, resulted in enhanced growth of the mouse tumor stem-like cells in vitro. Collectively, these data indicate that a subset of GBM expresses high CD44 in BTSC, and its growth may depend on CD44v6/AKTpathway

Complementary and Alternative Medicine Use in Pediatric Functional Abdominal Pain Disorders at a Large Academic Center

To describe the use of complementary and alternative medicine (CAM) in pediatric functional abdominal pain disorders at a large Midwestern pediatric gastroenterology center. A survey of patients attending a follow-up visit for functional abdominal pain disorders was completed. Data were collected on demographics, quality of life, use of conventional therapies, patient's opinions, and perception of provider's knowledge of CAM. Of 100 respondents (mean age, 13.3 ± 3.5 years), 47 (60% female) had irritable bowel syndrome, 29 (83% female) had functional dyspepsia, 18 (67% female) had functional abdominal pain, and 6 (83% female) had abdominal migraine (Rome III criteria). Ninety-six percent reported using at least 1 CAM modality. Dietary changes were undertaken by 69%. Multivitamins and probiotics were the most common supplements used by 48% and 33% of respondents, respectively. One-quarter had seen a psychologist. Children with self-reported severe disease were more likely to use exercise (P < .05); those with active symptoms (P < .01) or in a high-income group (P < .05) were more likely to make dietary changes; and those without private insurance (P < .05), or who felt poorly informed regarding CAM (P < .05), were more likely to use vitamins and supplements. Seventy-seven percent of patients described their quality of life as very good or excellent. The use of CAM in children with functional abdominal pain disorders is common, with a majority reporting a high quality of life. Our study underscores the importance of asking about CAM use and patient/family knowledge of these treatments

Gingival Perfusion and Tissue Biomarkers During Early Healing of Postextraction Regenerative Procedures: A Prospective Case Series

Background—Post-extraction alveolar bone loss, mostly affecting the buccal plate, occurs despite regenerative procedures. To better understand possible determinants, this prospective case series assessed gingival blood perfusion and tissue molecular responses in relation to postextraction regenerative outcomes. Methods—Adults scheduled to receive bone grafting in maxillary, non-molar, single tooth extraction site were recruited. Clinical documentation included probing pocket depth (PD), keratinized tissue width (KT), tissue biotype (TB), plaque (P) and bleeding. Wound closure was clinically evaluated. Gingival blood perfusion was measured by Laser Doppler Flowmetry (LDF). Wound fluid (WF) and gingival biopsies were analyzed for protein levels and gene expression, respectively, of relevant molecular markers. Bone healing outcomes were determined radiographically (Cone Beam Computerized Tomography; CBCT). Healing was followed for 4 months. Results—Data from 15 patients (50 ± 5 years, 8 males) are reported. Postoperatively, neither complications nor changes in PD, KT or TB were observed. Postoperatively, LDF revealed decreased perfusion followed by hyperemia that persisted 1 month (p≤0.05). WF levels of angiopoietin-2, interleukin-8, tumor necrosis factor-α, and vascular endothelial growth factor peaked on day 6 (p≤0.05) and decreased thereafter. Only interleukin-8 and tumor necrosis factor-α exhibited increased gene expression. Linear bone changes were negligible. Volumetric bone changes were minimal but statistically significant, with more bone loss when membrane was used (p=0.05). Conclusion—Gingival blood perfusion following post-extraction bone regenerative procedures follows an ischemia-reperfusion model. Transient increases in angiogenic factor levels and prolonged hyperemia characterize the soft tissue response. These soft tissue responses do not determine radiographic bone changes

The Effect of a Combination Treatment Using Palonosetron, Promethazine, and Dexamethasone on the Prophylaxis of Postoperative Nausea and Vomiting and QTC interval duration in Patients Undergoing Craniotomy Under General Anesthesia: A pilot Study

Introduction: Postoperative nausea and vomiting (PONV) is a displeasing experience that distresses surgical patients during the first 24 hours after a surgical procedure. The incidence of postoperative nausea occurs in about 50%, the incidence of postoperative vomiting is about 30%, and in high-risk patients, the PONV rate could be as high as 80%. Therefore, the study design of this single arm, non-randomized, pilot study assessed the efficacy and safety profile of a triple therapy combination with palonosetron, dexamethasone and promethazine to prevent PONV in patients undergoing craniotomies under general anesthesia.Methods: The research protocol was approved by the institutional review board and 40 subjects were provided written informed. At induction of anesthesia, a triple therapy of palonosetron 0.075 mg IV, dexamethasone 10 mg IV and promethazine 25 mg IV was given as PONV prophylaxis. After surgery, subjects were transferred to the surgical intensive care unit (SICU) or post anesthesia care unit as clinically indicated. Ondansetron 4 mg IV was administered as primary rescue medication to subjects with PONV symptoms. PONV was assessed and collected every 24 hours for 5 days via direct interview and/or medical charts review.Results: The overall incidence of PONV during the first 24 hours after surgery was 30% (n=12). The incidence of nausea and emesis 24 hours after surgery was 30% (n=12) and 7.5% (n=3) respectively. The mean time to first emetic episode, first rescue, and first significant nausea was 31.3 (±33.6) 15.1 (±25.8) and 21.1 (±25.4) hours, respectively . The overall incidence of nausea and vomiting after 24-120 hours period after surgery was 30% (n=12). The percentage of subjects without emesis episodes over 24-120 h postoperatively was 70% (n=28). No subjects presented a prolonged QTC interval ≥500 msec before and/or after surgery.Conclusion: Our data demonstrated that this triple therapy regimen may be an adequate alternative regimen for the treatment of postoperative nausea and vomiting in patients undergoing neurological surgery under general anesthesia. More studies with a control group should be performed to demonstrate the efficacy of this regimen and that palonosetron is a low risk for QTc prolongation

Bone Grafting History Affects Soft Tissue Healing Following Implant Placement

Background This study aimed to determine and compare soft tissue healing outcomes following implant placement in grafted (GG) and non-grafted bone (NGG). Methods Patients receiving single implant in a tooth-bound maxillary non-molar site were recruited. Clinical healing was documented. Volume and content of wound fluid (WF; at 3, 6, and 9 days) were compared with adjacent gingival crevicular fluid (GCF; at baseline, 1, and 4 months). Buccal flap blood perfusion recovery and changes in bone thickness were recorded. Linear mixed model regression analysis and generalized estimating equations with Bonferroni adjustments were conducted for repeated measures. Results Twenty-five patients (49 ± 4 years; 13 males; nine NGG) completed the study. Soft tissue closure was slower in GG (P \u3c 0.01). Differential response in WF/GCF protein concentrations was detected for ACTH (increased in GG only) and insulin, leptin, osteocalcin (decreased in NGG only) at day 6 (P ≤0.04), with no inter-group differences at any time(P \u3e 0.05). Blood perfusion rate decreased immediately postoperatively (P \u3c 0.01, GG) followed by 3-day hyperemia (P \u3e 0.05 both groups). The recovery to baseline values was almost complete for NGG whereas GG stayed ischemic even at 4 months (P = 0.05). Buccal bone thickness changes were significant in GG sites (P ≤ 0.05). Conclusion History of bone grafting alters the clinical, physiological, and molecular healing response of overlying soft tissues after implant placement surgery

Factors Associated with Total Laryngectomy Utilization in Patients with cT4a Laryngeal Cancer

Background: Despite recommendations for upfront total laryngectomy (TL), many patients with cT4a laryngeal cancer (LC) instead undergo definitive chemoradiation, which is associated with inferior survival. Sociodemographic and oncologic characteristics associated with TL utilization in this population are understudied. Methods: This retrospective cohort study utilized hospital registry data from the National Cancer Database to analyze patients diagnosed with cT4a LC from 2004 to 2017. Patients were stratified by receipt of TL, and patient and facility characteristics were compared between the two groups. Logistic regression analyses and Cox proportional hazards methodology were performed to determine variables associated with receipt of TL and with overall survival (OS), respectively. OS was estimated using the Kaplan–Meier method and compared between treatment groups using log-rank testing. TL usage over time was assessed. Results: There were 11,149 patients identified. TL utilization increased from 36% in 2004 to 55% in 2017. Treatment at an academic/research program (OR 3.06) or integrated network cancer program (OR 1.50), male sex (OR 1.19), and Medicaid insurance (OR 1.31) were associated with increased likelihood of undergoing TL on multivariate analysis (MVA), whereas age > 61 (OR 0.81), Charlson–Deyo comorbidity score ≥ 3 (OR 0.74), and clinically positive regional nodes (OR 0.78 [cN1], OR 0.67 [cN2], OR 0.21 [cN3]) were associated with decreased likelihood. Those undergoing TL with post-operative radiotherapy (+/− chemotherapy) had better survival than those receiving chemoradiation (median OS 121 vs. 97 months; p = 0.003), and TL + PORT was associated with lower risk of death compared to chemoradiation on MVA (HR 0.72; p = 0.024). Conclusions: Usage of TL for cT4a LC is increasing over time but remains below 60%. Patients seeking care at academic/research centers are significantly more likely to undergo TL, highlighting the importance of decreasing barriers to accessing these centers. Increased focus should be placed on understanding and addressing the additional patient-, physician-, and system-level factors that lead to decreased utilization of surgery