Racial implications of time to surgery in disparities in thyroid cancer survival.

INTRODUCTION: The influence of time to surgery on racial/ethnic disparities in papillary thyroid carcinoma (PTC) survival remains unstudied. MATERIALS AND METHODS: The National Cancer Database (2004-2017) was queried for patients with localized PTC. Survival data was compared by time to surgery, patient demographics, and multivariable Cox regression was performed. RESULTS: Of 126,708 patients included, 5% were Black, 10% Hispanic. Of all patients, 85% had no comorbidities. Non-Hispanic White (NHW) patients had a shorter median time to surgery than Black and Hispanic patients (36 vs. 43 vs. 42 days, respectively p â€‹< â€‹0.001). In multivariable analysis, longer time to surgery (>90 days vs â€‹< â€‹30 days) and Black race vs NHW, were associated with worse survival (HR: 1.56, (95%CI, 1.43-1.70), p â€‹< â€‹0.001 and HR: 1.21, (1.08-1.36), p â€‹= â€‹0.001), respectively. CONCLUSION: Delaying surgery for thyroid cancer is associated with worse survival. However, independent of time to surgery and other confounders, there remains a disparity as black patients have poorer outcomes.

Hub and spoke framework for study of surgical centralization within United States health systems.

BACKGROUND: Hospital consolidation into health systems has mixed effects on surgical quality, potentially related to degree of surgical centralization at high-volume (hub) sites. We developed a novel measure of centralization and evaluated a hub and spoke framework. METHODS: Surgical centralization within health systems was measured using hospital surgical volumes (American Hospital Association) and health system data (Agency for Healthcare Research and Quality). Hub and spoke hospitals were compared using mixed effects logistic regression and system characteristics associated with surgical centralization were identified using a linear model. RESULTS: Within 382 health systems containing 3022 hospitals, system hubs perform 63% of cases (IQR 40-84%). Hubs are larger, in metropolitan and urban areas, and more often academically affiliated. Degree of surgical centralization varies ten-fold. Larger, multistate, and investor-owned systems are less centralized. Adjusting for these factors, there is less centralization among teaching systems (p â€‹< â€‹0.001). CONCLUSIONS: A hub-spoke framework applies to most health systems but centralization varies significantly. Future studies of health system surgical care should assess the contributions of surgical centralization and teaching status on differential quality.

A case-controlled investigation of risk factors associated with molar incisor hypomineralization (MIH) in 8-12 year-old children living in Chandigarh, India.

PURPOSE: Despite mounting evidence in favour of various perinatal risk factors for occurrence of MIH, verification of these remains doubtful because of lack of documented proof. The present study was aimed at examining the putative risk factors for MIH based on hospital-maintained records assessment. METHODS: A total of 3176, 8-12 year-old children were screened for MIH using EAPD criteria (2003). Of these, risk factor analysis was carried out for 104 MIH affected and 211 non-MIH affected children with complete peri-natal medical records maintained up to 3 year post-birth. Chi-square test was used for risk factor comparison, while significance was assessed using logistic regression. RESULTS: Prevalence of MIH in study population was 11.72% (372/3176). Various pre-natal, natal and post-natal risk factors including intra-uterine growth retardation (6.7 vs. 1.4%); maternal anaemia (10.6 vs. 3.8%) and neonatal jaundice (29.8 vs. 14.2%) were significantly higher in the MIH group. Furthermore, pre-term birth (OR 3.01), low birth weight (OR 2.37), more than three pyrogenic episodes (OR 7.61) and consumption of Amoxicillin Clavulanate (OR 3.01) were significantly associated with higher risk of developing MIH. CONCLUSIONS: Pre and post-natal risk factors showed a moderate to high association for occurrence of MIH although social and nutritional factors had a lesser association.

Avelumab in patients with previously treated metastatic Merkel cell carcinoma (JAVELIN Merkel 200): updated overall survival data after >5 years of follow-up.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer that has a poor prognosis in patients with advanced disease. Avelumab [anti-programmed death-ligand 1 (PD-L1)] became the first approved treatment for patients with metastatic MCC (mMCC), based on efficacy and safety data observed in the JAVELIN Merkel 200 trial. We report long-term overall survival (OS) data after >5 years of follow-up from the cohort of patients with mMCC whose disease had progressed after one or more prior lines of chemotherapy. PATIENTS AND METHODS: In Part A of the single-arm, open-label, phase II JAVELIN Merkel 200 trial, patients with mMCC that had progressed following one or more prior lines of chemotherapy received avelumab 10 mg/kg by intravenous infusion every 2 weeks until confirmed disease progression, unacceptable toxicity, or withdrawal. In this analysis, long-term OS was analyzed. RESULTS: In total, 88 patients were treated with avelumab. At data cut-off (25 September 2020), median follow-up was 65.1 months (range 60.8-74.1 months). One patient (1.1%) remained on treatment, and an additional patient (1.1%) had reinitiated avelumab after previously discontinuing treatment. Median OS was 12.6 months [95% confidence interval (CI) 7.5-17.1 months], with a 5-year OS rate of 26% (95% CI 17% to 36%). In patients with PD-L1+ versus PD-L1- tumors, median OS was 12.9 months (95% CI 8.7-29.6 months) versus 7.3 months (95% CI 3.4-14.0 months), and the 5-year OS rate was 28% (95% CI 17% to 40%) versus 19% (95% CI 5% to 40%), respectively (HR 0.67; 95% CI 0.36-1.25). CONCLUSION: Avelumab monotherapy resulted in meaningful long-term OS in patients with mMCC whose disease had progressed following chemotherapy. These results further support the role of avelumab as a standard of care for patients with mMCC.

Odderon Exchange from Elastic Scattering Differences between pp and pp[over ¯] Data at 1.96 TeV and from pp Forward Scattering Measurements.

We describe an analysis comparing the pp[over ¯] elastic cross section as measured by the D0 Collaboration at a center-of-mass energy of 1.96 TeV to that in pp collisions as measured by the TOTEM Collaboration at 2.76, 7, 8, and 13 TeV using a model-independent approach. The TOTEM cross sections, extrapolated to a center-of-mass energy of sqrt[s]=1.96 TeV, are compared with the D0 measurement in the region of the diffractive minimum and the second maximum of the pp cross section. The two data sets disagree at the 3.4σ level and thus provide evidence for the t-channel exchange of a colorless, C-odd gluonic compound, also known as the odderon. We combine these results with a TOTEM analysis of the same C-odd exchange based on the total cross section and the ratio of the real to imaginary parts of the forward elastic strong interaction scattering amplitude in pp scattering for which the significance is between 3.4σ and 4.6σ. The combined significance is larger than 5σ and is interpreted as the first observation of the exchange of a colorless, C-odd gluonic compound.

A pre-registered short-term forecasting study of COVID-19 in Germany and Poland during the second wave.

Disease modelling has had considerable policy impact during the ongoing COVID-19 pandemic, and it is increasingly acknowledged that combining multiple models can improve the reliability of outputs. Here we report insights from ten weeks of collaborative short-term forecasting of COVID-19 in Germany and Poland (12 October-19 December 2020). The study period covers the onset of the second wave in both countries, with tightening non-pharmaceutical interventions (NPIs) and subsequently a decay (Poland) or plateau and renewed increase (Germany) in reported cases. Thirteen independent teams provided probabilistic real-time forecasts of COVID-19 cases and deaths. These were reported for lead times of one to four weeks, with evaluation focused on one- and two-week horizons, which are less affected by changing NPIs. Heterogeneity between forecasts was considerable both in terms of point predictions and forecast spread. Ensemble forecasts showed good relative performance, in particular in terms of coverage, but did not clearly dominate single-model predictions. The study was preregistered and will be followed up in future phases of the pandemic.

Identification of other Cellular Receptors for Edema Factor of Bacillus anthracis by Independent Inhibition of Protective Antigen Evidenced by Inhibition of Embryo Growth and Angiogenesis.

Edema factor (EF) is one of the major secretory proteins of anthrax bacteria along with protective antigen (PA) and lethal factor (LF). Edema factor is a calmodulin-and calcium-dependent adenylate cyclase that increases intracellular levels of cAMP. Intracellular trafficking of EF occurs through PA by binding to ATR/CMG2 receptors, which are also involved in other physiological functions of cells. cAMP is a secondary messenger which activates multiple signaling cascades involved in the cytokinetics of actin molecules and cell junction formation. The present study evaluated the effect of EF on growth and angiogenesis patterns in chicken embryos in the in ovo model. Angiogenesis in the chorioallantoic membrane (CAM) of an embryonated chicken egg was decreased and embryo growth was delayed by EF despite the absence of trafficking moiety PA, which is required for transferring the EF molecule inside the cell. Angiogenesis inhibition and embryo growth retardation indicate the use of an alternative receptor by EF to modulate these cellular functions. Additionally, docking was performed between EF as a ligand and hepatocyte growth factor receptor (cMET) and vascular endothelial growth factor (VEGF) receptors, which are mainly involved in growth and angiogenesis. The analysis revealed a very strong binding of EF to cMET receptor (in terms of the number of hydrogen bonds and energy) compared to its ligand hepatocyte growth factor (HGF), which indicates the use of cMET receptor by EF and induction of angiogenesis and embryo growth retardation possibly by competitive inhibition of HGF ligand or receptor-mediated endocytosis.

Introduction of Laparoscopic Donor Nephrectomy: Challenges, Outcomes and Success Strategies.

BACKGROUND: Laparoscopic live donor nephrectomy (LLDN) has become the standard of care and is popular among most of the transplant centers across the globe. Despite proven advantages of LLDN, some transplantation centers hesitate to start the program because of issues concerning donor safety and allograft function. OBJECTIVE: To discusses the main barriers for creating a successful LLDN program, strategies that allowed us to start a successful LLDN program along with the study results. METHODS: The donors undergoing LLDN from December 2016 to February 2018 were enrolled in the study and prospectively evaluated. LLDN were performed by two senior surgeons alternately with assistance by the laparoscopic urologist in all cases. Also, in the present study, two technical alterations were done in the standard surgical technique of transperitoneal LDN. The first important modification made was the use of two additional ports for use by laparoscopic urologists. The second modification involved dissection on both poles of the kidney before hilar dissection. RESULTS: A total of 112 transperitoneal LLDN were performed during the study period. The mean (range) of operation time was 117.5 (81-158) min; the ischemia time was 194 (171-553) sec. Only one patient needed conversion to open surgery. No other major peri-operative or posto-perative complications occurred. All kidney grafts were functioning well. CONCLUSION: With proper planning, team approach, and few technical modifications, introduction of LLDN is safe and effective.

Developing a child patient satisfaction survey: a quality improvement project.

AIM: To develop a child-centred patient satisfaction questionnaire for use in an Outpatient Paediatric Dental Department. METHOD: Data from patient satisfaction interviews was used to develop a child satisfaction questionnaire, which was used in two different centres after piloting. RESULTS: The final questionnaire contained 7 questions and a comments section, using writing and facial images used to record children views. The questionnaire was distributed to 203 children; 95% were happy or okay with the waiting area, 69% were happy about seeing the dentist and 77% children were happy overall. CONCLUSION: Measures of satisfaction of children with regard to dental treatment were very different from those commonly used for adults. Further development and implementation of child satisfaction surveys should be considered.

High somatostatin receptor expression and efficacy of somatostatin analogues in patients with metastatic Merkel cell carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive, high-grade, cutaneous neuroendocrine tumour (NET). Agents blocking programmed death 1/programmed death ligand 1 have efficacy in metastatic MCC (mMCC), but half of patients do not derive durable benefit. Somatostatin analogues (SSAs) are commonly used to treat low- and moderate-grade NETs that express somatostatin receptors (SSTRs). OBJECTIVES: To assess SSTR expression and the efficacy of SSAs in mMCC, a high-grade NET. Methods In this retrospective study of 40 patients with mMCC, SSTR expression was assessed radiologically by somatostatin receptor scintigraphy (SRS; n = 39) and/or immunohistochemically when feasible (n = 9). Nineteen patients (18 had SRS uptake in MCC tumours) were treated with SSA. Disease control was defined as progression-free survival (PFS) of ≥ 120 days after initiation of SSA. RESULTS: Thirty-three of 39 patients (85%) had some degree (low 52%, moderate 23%, high 10%) of SRS uptake. Of 19 patients treated with SSA, seven had a response-evaluable target lesion; three of these seven patients (43%) experienced disease control, with a median PFS of 237 days (range 152-358). Twelve of 19 patients did not have a response-evaluable lesion due to antecedent radiation; five of these 12 (42%) experienced disease control (median PFS of 429 days, range 143-1757). The degree of SSTR expression (determined by SRS and/or immunohistochemistry) did not correlate significantly with the efficacy endpoints. CONCLUSIONS: In contrast to other high-grade NETs, mMCC tumours appear frequently to express SSTRs. SSAs can lead to clinically meaningful disease control with minimal side-effects. Targeting of SSTRs using SSA or other novel approaches should be explored further for mMCC.

Oral and maxillofacial surgery patient satisfaction with telephone consultations during the COVID-19 pandemic.

Due to the COVID-19 pandemic most oral and maxillofacial surgical (OMFS) units have moved to conducting patient consultations over the telephone. The aim of this study was to assess patients' satisfaction with telephone consultations during the COVID-19 pandemic. A retrospective survey was conducted of OMFS patients at our hospital who had telephone consultations between 1 April - 8 June 2020. The survey was conducted by independent interviewers and used the Generic Medical Interview Satisfaction Scale (G-MISS) along with a previously published additional questionnaire. Variables recorded included age, gender, theme of consultation, grade of clinician, and type of consultation. Statistical analysis was performed to assess for any differences between patient groups. The records of 150 consecutive patients were reviewed and 135 met inclusion criteria. A total of 109 patients completed the survey giving a response rate of 80.74%. The total G-MISS score for satisfaction was high, which indicates a high level of satisfaction among all patients. We found no statistical difference in satisfaction when comparing patients in terms of gender, age, theme of consultation, or level of clinician. A significant difference was found in compliance levels between review and new patients, with review patients demonstrating higher compliance levels (p=0.004). Overall, 83.48% of patients said they would be willing to have a telephone consultation in future. The majority of patients in this study reported high levels of satisfaction with telephone consultations. New patients reported lower levels of compliance which may suggest this type of consultation is less suited to telephone consultation.

Pathological and immunological protection induced by inactivated reverse genetics-based H3N8 equine influenza vaccine candidate in murine model.

Equine influenza (EI) is an important viral respiratory disease of equines caused by influenza A virus (IAV). The antigenic drift in IAVs necessitates regular updating and harmonization of vaccine strain with the circulating virus. The reverse genetics-based recombinant viruses could be easy instrument in generating vaccine against circulating virus in a quick and effective manner. Present study has been envisaged to evaluate the immunogenicity and protective efficacy of inactivated recombinant equine influenza virus (rgEIV) vaccine candidate having six segments from H1N1 virus (A/WSN/33/H1N1) and HA (hemaglutinin) and NA (neuraminidase) segments from H3N8 equine influenza virus [(A/eq/Jammu-Katra/06/08) of clade 2 of Florida sublineage] generated through reverse genetic engineering. BALB/c mice were immunized with inactivated rgEIV adjuvanted with aluminium hydroxide gel and challenged with H3N8 virus (A/eq/Jammu-Katra/06/08). The protective efficacy was evaluated through serology, cytokine profiling, clinical signs, gross and histopathological changes, immunohistochemistry and residual virus quantification. Immunizations induced robust humoral immune response as estimated through hemagglutination inhibition assay (HAI). The antibodies were isotyped and the predominant subclass was IgG1. The vaccine candidate produced mixed Th1 and Th2 responses through stimulation of IFN-γ, IL-2, IL-4 and IL-6 expression. Immunization protected mice against challenge as reflected through reduction in clinical signs and body weight loss, early recovery, mild pathological changes (gross and histopathological lesions) as evident through scoring of lesions, low residual virus in nasopharynx and lungs quantified through egg titration and quantitative reverse transcriptase PCR (qRT-PCR). The study demonstrates that inactivated recombinant EIV generated through reverse genetic approach provides equivalent protection to that observed with inactivated whole H3N8 EIV vaccine. Keywords: equine influenza; reverse genetics; vaccine; pathology; murine model.

Intratumoral delivery of tavokinogene telseplasmid yields systemic immune responses in metastatic melanoma patients.

BACKGROUND: Interleukin 12 (IL-12) is a pivotal regulator of innate and adaptive immunity. We conducted a prospective open-label, phase II clinical trial of electroporated plasmid IL-12 in advanced melanoma patients (NCT01502293). PATIENTS AND METHODS: Patients with stage III/IV melanoma were treated intratumorally with plasmid encoding IL-12 (tavokinogene telseplasmid; tavo), 0.5 mg/ml followed by electroporation (six pulses, 1500 V/cm) on days 1, 5, and 8 every 90 days in the main study and additional patients were treated in two alternative schedule exploration cohorts. Correlative analyses for programmed death-ligand 1 (PD-L1), flow cytometry to assess changes in immune cell subsets, and analysis of immune-related gene expression were carried out on pre- and post-treatment samples from study patients, as well as from additional patients treated during exploration of additional dosing schedules beyond the pre-specified protocol dosing schedule. Response was measured by study-specific criteria to maximize detection of latent and potentially transient immune responses in patients with multiple skin lesions and toxicities were graded by the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0). RESULTS: The objective overall response rate was 35.7% in the main study (29.8% in all cohorts), with a complete response rate of 17.9% (10.6% in all cohorts). The median progression-free survival in the main study was 3.7 months while the median overall survival was not reached at a median follow up of 29.7 months. A total of 46% of patients in all cohorts with uninjected lesions experienced regression of at least one of these lesions and 25% had a net regression of all untreated lesions. Transcriptomic and immunohistochemistry analysis showed that immune activation and co-stimulatory transcripts were up-regulated but there was also increased adaptive immune resistance. CONCLUSIONS: Intratumoral Tavo was well tolerated and led to systemic immune responses in advanced melanoma patients. While tumor regression and increased immune infiltration were observed in treated as well as untreated/distal lesions, adaptive immune resistance limited the response.