Black and White Patients with Staphylococcus aureus Bacteremia have Similar Outcomes but Different Risk Factors

alexandrossfakianakis shared this article with you from Inoreader Black and White Patients with Staphylococcus aureus Bacteremia have Similar Outcomes but Different Risk Factors via Clinical Infectious Diseases Advance Access Abstract BACKGROUND Staphylococcus aureus bacteremia (SAB) disproportionately affects Black patients. The reasons for this disparity are unclear. METHODS We evaluated a prospectively ascertained cohort of patients with SAB from 1995 to 2020. Clinical characteristics, bacterial genotypes, and outcome were compared among Black and White patients with SAB. Multivariable logistic regression models were used to determine factor s independently associated with the outcomes. RESULTS Among 3068 patients with SAB, 1107 (36%) were Black. Black patients were younger (Median: 56 years vs. 63 years; p < 0.001), had higher rates of diabetes (47.5% vs. 34.5%; p < 0.001), hemodialysis dependence (40.0% vs. 7.3%; p < 0.001), and HIV (6.4% vs. 0.6%; p < 0.001). Black patients had higher rates of methicillin-resistant S. aureus (49.3% vs 44.9%; p = 0.020), including the USA300 hypervirulent clone (11.5% vs. 8.4%; p = 0.007). White patients had higher rates of corticosteroid use (22.4% vs. 15.8%; p < 0.0001), and surgery in the preceding 30 days (28.1% vs. 18.7%; p < 0.001). Although median Acute Physiology Score (APS) at the time of initial SAB diagnosis was significantly higher in Black patients (Median APS 9, Interquartile Range [IQR] 5-14; vs. Median APS 7, IQR: 4-12; p < 0.001), race was not associated with 90-d ay mortality (risk ratio (RR): 1.02; 95% CI: 0.93–1.12, and rates of metastatic infection were lower among Black patients (37.2% vs. 41.3% White; p = 0.029). CONCLUSIONS Despite differences in Black patients' higher APS on presentation and more risk factors, including a 5 times higher risk of hemodialysis dependence, 90-day mortality among Black and White patients with SAB was similar. View on Web

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Diagnostic Criteria for Temporomandibular Disorders − INfORM recommendations: Comprehensive and short‐form adaptations for children

alexandrossfakianakis shared this article with you from Inoreader Diagnostic Criteria for Temporomandibular Disorders − INfORM recommendations: Comprehensive and short‐form adaptations for children via Journal of Oral Rehabilitation Abstract Background The Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) are used worldwide in adults. Until now, no adaptation for use in children has been proposed. Objective To present comprehensive and short-form adaptations of Axis I and II of the DC/TMD for adults that are appropriate for use with children in clinical and research settings. Methods Global Delphi studies with experts in TMDs and in pain psychology identified ways of adapting the DC/TMD for children. Results The proposed adaptation is suitable for children aged 6−9 years. Proposed changes in Axis I include (i) adapting the language of the Demographics and the Symptom Questionnaires to be developmentally appropriate for children, (ii) adding a general health questionnaire for children and one for their parents, (iii) replacing the TMD Pain Screener with the 3Q/TMD questionnaire, and (iv) modifying the clinical examination protocol. Proposed changes in Axis II include (i) for the Graded Chronic Pain Scale, to be developmentally appropriate for children, and (ii) adding anxiety and depression assessments that have been validated in children, and (iii) adding three constructs (stress, catastrophizing, and sleep disorders) to assess psychosocial functioning in children. Conclusion The recommended DC/TMD, including Axis I and Axis II, for children aged 6−9 years, is appropriate for use in clinical and research settings. This adapted first version for children includes changes in Axis I and Axis II changes requiring reliability and validity testing in international settings. Official translations to different languages according to INfORM requirements will enable a worldwide dissemination and implementation. View on Web

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Full arch immediate occlusal loading using site specific implants: a clinical series of 10 patients (13 arches)

alexandrossfakianakis shared this article with you from Inoreader Full arch immediate occlusal loading using site specific implants: a clinical series of 10 patients (13 arches) via Journal of Prosthodontics Abstract Purpose Osseointegration of dental endosseous implants has proven to be effective, predictable, and clinically successful. Unloaded healing protocols were originally used in treating edentulous patients. Full arch immediate occlusal loading protocols have been shown to be as effective as unloaded healing protocols. This paper reports on the results, benefits, and limitations of one specific immediate loading protocol using site specific implants for fresh extraction and healed extraction sites. Materials and Methods Ten consecutive patients [{13 arches} (age range: 64–81 years; average: 70.1) (4 males/6 females) were treated by the first 2 authors in private practice settings. Hopeless teeth were scheduled for extraction with immediate implant placement and immediate loading with insertion of full arch, screw-retained, acrylic resin interim prostheses within 24 hours. Implants were also placed into healed edentulous ridges. Insertion torque values for each implant were recorded. Interim prostheses were removed after at least 3 months of healing. Implants were reverse torque tested (35Ncm) and evaluated for macroscopic mobility. Definitive full arch prostheses were made. Patients were followed for 21- 48 months post implant surgery. Panoramic radiographs were taken immediately post implant placement and one year post operative. Results Thirteen arches were treated; 11 ultrawide diameter implants were placed into molar sockets, 26 inverted body-shift implants were placed into anterior sockets; 25 standard diameter, tapered implants were placed into edentulous sites; 2 zygomatic implants were placed in one patient. The total number of implants placed was 64 (4 pre-existing implants were also used and not included in this study). The minimum implant insertion torque value was 20Ncm. After 12–18 months of function (average 14 months), the implant and prosthetic survival rates were 100%. Eight patients were restored with definitive zirconia or acrylic resin hybrid fixed prostheses. Two patients were restored with bar titanium frameworks and removable overdenture prostheses. No prosthetic complications were reported for the definitive prostheses. Conclusions The results of this clinical series with site specific implants and immediate full arch occlusal loading in treating edentulous patients resulted in 100% clinical implant and prosthetic survival rates. According to this study, this protocol can be used with high levels of anticipated success. This article is protected by copyright. All rights reserved View on Web

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Gastrectomy Versus Esophagectomy for Gastroesophageal Junction Tumors: Short- and Long-Term Outcomes From the Dutch Upper Gastrointestinal Cancer Audit

alexandrossfakianakis shared this article with you from Inoreader Gastrectomy Versus Esophagectomy for Gastroesophageal Junction Tumors: Short- and Long-Term Outcomes From the Dutch Upper Gastrointestinal Cancer Audit via Annals of Surgery - Most Popular Articles Objective: Investigate long-term survival, morbidity, mortality, and pathology results in patients following esophagectomy or total gastrectomy for gastroesophageal junction (GEJ) cancer. Background: Both a total gastrectomy and an esophagectomy may be valid treatment options in patients with GEJ cancer. Which procedure results in the most optimal patient outcome is not well studied. The aim of this study was to investigate the long-term survival, morbidity, mortality, and pathology results in patients following esophagectomy or total gastrectomy for GEJ cancer. Methods: A retrospective comparative cohort study of prospectively collected data from the Dutch Upper GI Cancer Audit combined with survival data of the Dutch medical insurance database was performed. Patients with GEJ cancer in whom a total gastrectomy or an esophagectomy was performed between 2011 and 2016 were compared. The primary outcome was 3-year overall survival. Postoperative morbidity, mortality, 3-year conditional survival, radicality of resection, and lymph node yield were secondary endpoints. Results: A total of 871 patients were included: 790 following esophagectomy and 81 following gastrectomy. The 3-year overall survival was 35.8% after esophagectomy and 28.4% after gastrectomy (hazard ratio 1.2, 95% confidence interval 0.721–1.836, P = 0.557). Postoperative morbidity, mortality, radicality of resection, lymph node yield, and 3-year conditional survival did not differ significantly between groups. Conclusion: A total gastrectomy and an esophagectomy for GEJ cancer show largely comparable results with regard to long-term survival, postoperative morbidity, mortality, and pathology results. If both procedures are feasible, other parameters such as surgeon's experience and quality of life should be considered when planning for surgery. View on Web

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CTIM-32. FIRST-IN-CHILDREN PHASE 1 TRIAL OF INDOXIMOD-BASED CHEMO-IMMUNOTHERAPY FOR PATIENTS WITH PEDIATRIC BRAIN TUMORS: ANALYSIS OF SAFETY, TOLERABILITY, AND 5-YEAR OUTCOME

alexandrossfakianakis shared this article with you from Inoreader CTIM-32. FIRST-IN-CHILDREN PHASE 1 TRIAL OF INDOXIMOD-BASED CHEMO-IMMUNOTHERAPY FOR PATIENTS WITH PEDIATRIC BRAIN TUMORS: ANALYSIS OF SAFETY, TOLERABILITY, AND 5-YEAR OUTCOME via # Neuro-Oncology Current Issue Abstract BACKGROUND Recurrent brain tumors are the leading cause of cancer death in children. We conducted a first-in-children, two-institution, Phase 1 open-label dose-confirmation study using a 3 + 3 design, with expansion cohorts, to determine the recommended pediatric dose of the IDO pathway-inhibitor indoximod (NCT02502708). DESIGN/ METHODS Eligible patients were 3-22 years old with either recurrent malignant brain tumor or newly-diagnosed diffuse intrinsic pontine glioma (DIPG). Palliative radiation, surgery or dexamethasone were allowed as needed for patient management. Separate dose-finding arms were performed for indoximod plus temozolomide (200 mg/m2/day orally for 5 days of each 28-day cycle) and for indoximod plus conformal radiation (in patients for whom re-irradiation was planned as standard-of-care). At progression, patients who were otherwise clinically stable were offered crossover to indoximod plus a second-line chemot herapy regimen (cyclophosphamide 2.5 mg/kg/day orally and etoposide 50 mg/m2/day orally for 21 days of each 28-day cycle). RESULTS Between December 2015 and January 2019, the study enrolled 81 brain tumor patients, including newly-diagnosed DIPG (n = 13) or recurrent ependymoma (n = 27), glioblastoma/high-grade glioma (n = 19), medulloblastoma (n = 13), or other CNS tumors ( n= 9). Median follow-up was 52 months (range 39-77 months). No dose-limiting toxicities were observed, and the pediatric indoximod dose was determined (19.2 mg/kg/dose, given twice daily). Indoximod was well tolerated and did not affect the ability to deliver chemotherapy or radiation as planned. Median overall survival was 13.6 months (n = 81). Median overall survival was 34.7 months for the subset of patients who continued indoximod with second-line chemotherapy after progression on indoximod plus temozolomide (n = 18). CONCLUSIONS Indoximod was well tolerated and could be combined with a var iety of standard treatments for pediatric brain tumors. Preliminary anti-tumor activity and overall survival suggest that indoximod with standard therapy should be further evaluated in pediatric brain tumors, and potentially other pediatric solid tumors. View on Web

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CTIM-13. LOCAL ADOPTIVE CELLULAR IMMUNOTHERAPY WITH CYTOKINE-INDUCED KILLER (CIK) CELLS FOR HIGH GRADE GLIOMAS: A PILOT STUDY WITH LONG-TERM FOLLOW-UP AND POTENTIAL FACTORS FOR SURVIVAL BENEFITS

alexandrossfakianakis shared this article with you from Inoreader CTIM-13. LOCAL ADOPTIVE CELLULAR IMMUNOTHERAPY WITH CYTOKINE-INDUCED KILLER (CIK) CELLS FOR HIGH GRADE GLIOMAS: A PILOT STUDY WITH LONG-TERM FOLLOW-UP AND POTENTIAL FACTORS FOR SURVIVAL BENEFITS via # Neuro-Oncology Current Issue Abstract BACKGROUND Immunotherapy is emerging as a promising approach for the treatment of high grade gliomas (HGGs). We reported the long-term follow-up of 6 HGG patients treated by local administration of autologous cytokine-induced killer (CIK) cells through Ommaya reservoirs implanted into the tumor cavity following operation. Meanwhile, Gene expression profiles and immune microenvironments of tumors were further compared between the long-term and short -term survivors. METHODS Clinicopathological characteristics and outcomes of patients were reviewed and updated. Gene expression profiles, expressions of cytokines and infiltrations of immune cells in tumors were investigated by RNA sequencing, an electrochemiluminescence assay and immunohistochemistry staining, respectively RESULTS Fever and symptoms of encephaledema occurred in 5 patients after local administration of CIK cells, and could be efficiently relieved by mannito l and dexamethasone. Four patients died from progressive disease during follow-up, and their overall survival ranged from 6 to 26 months. Remarkably, 2 patients have survived more than 200 months without evidence of recurrence. Comparing with the tumors of the short-term survivors, 353 genes which were highly associated with tumor microenvironment immune were differentially expressed (false discovery rate (FDR) < 0.05 and log2 fold change (FC) ≥ 1) in the tumor of the long-term survivor. Higher expressions of cytokines, especially IL-8 and IL-10, were observed in the tumor of the long-term survivor, while the infiltrations of M2 polarized macrophages were significantly higher in the tumors of short-term survivors. CONCLUSION Long-term survival of HGG patients could achieve after local administration of CIK cells into tumor cavity postoperatively. High expressions of cytokines and low infiltrations of M2 polarized macrophages in the tumors potentially benefited the CIK cell therapy. View on Web

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TMIC-78. CIRCADIAN REGULATOR CLOCK DRIVES IMMUNOSUPPRESSION IN GLIOBLASTOMA

alexandrossfakianakis shared this article with you from Inoreader TMIC-78. CIRCADIAN REGULATOR CLOCK DRIVES IMMUNOSUPPRESSION IN GLIOBLASTOMA via # Neuro-Oncology Current Issue Abstract The symbiotic interactions between cancer stem cells and the tumor microenvironment (TME) are critical for tumor progression. However, the molecular mechanism underlying this symbiosis in glioblastoma (GBM) remains enigmatic. Here, we show that circadian locomotor output cycles kaput (CLOCK) and its heterodimeric partner brain and muscle ARNT-like 1 (BMAL1) in glioma stem cells (GSCs) drive immunosuppression in GBM. Integrated analyses of the data from transcriptome profiling, single-cell RNA sequencing, and TCGA datasets, coupled with functional studies, identified legumain (LGMN) as a direct transcriptional target of the CLOCK–BMAL1 complex in GSCs. Moreover, CLOCK-directed olfactomedin-like 3 (OLFML3) upregulates LGMN in GSCs via the hypoxia-inducible factor 1-alpha (HIF1A) signaling. Consequently, LGMN promotes microglial infiltration into the GBM TME via upregulating CD162, and polarizes infiltrating microglia towards an immune-suppressive phenotype. In GBM mouse models, inhibition of the CLOCK–OLFML3–HIF1A–LGMN–CD162 axis reduces intratumoral immune-suppressive microglia, increases CD8+ T cell infiltration, activation and cytotoxicity, and synergizes with anti-PD1 therapy. In human GBM, the CLOCK-regulated LGMN signaling correlates positively with microglial level and poor prognosis. Together, these findings uncover the CLOCK–OLFML3–HIF1A–LGMN axis as a molecular switch that controls microglial biology and immunosuppression, thus revealing potential new therapeutic targets for GBM patients. View on Web

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