Τετάρτη, 24 Ιουλίου 2019

Urogynecology

Commentary to: Prospective comparative study on the effects of lidocaine on urodynamic and sensory parameters in bladder-pain syndrome


Commentary on: "Does spinal anesthesia lead to postoperative urinary retention in same day urogynecology surgery: a retrospective review"


Treatment of subacute rectosigmoid obstruction secondary to uterosacral ligament suspension


The transition from resident to consultant


A live porcine model for robotic sacrocolpopexy training

Abstract

Introduction and hypothesis

Robotic sacrocolpopexy is an effective and durable technique for pelvic organ prolapse repair. However, the learning curve for this procedure has underscored the need for an effective surgical training module. Given the cost, infection risk, poor tissue compliance, and scarcity of human cadavers, the live porcine model represents a realistic, available, and cost-effective alternative. This article describes a live porcine model for teaching robotic sacrocolpopexy to determine whether it teaches key aspects of live human robotic sacrocolpopexy to the learner.

Methods

This robotic sacrocolpopexy model was created using the Da Vinci Xi or Si robotic system on domestic pigs under general anesthesia. The main steps of the model include: (1) creating the porcine "cervix" and (2) performing robotic sacrocolpopexy. The model was evaluated with a survey given to 18 board-certified surgeons who attended the training course between December 2016 and April 2018.

Results

All of the participants reported improvements in their economy of motion, tissue handling ability, suturing efficiency, and overall performance of robotic sacrocolpopexy. Furthermore, a majority of participants were likely to incorporate aspects of the model into their practice (88.8%) and recommend the model to colleagues (94.2%).

Conclusions

The porcine model provides a feasible tool for teaching robotic sacrocolpopexy to physicians.



Impairment of urethral coitus due to mid-urethral sling in a woman with vaginal agenesis


Resident simulation training improves operative time of the retropubic midurethral sling procedure for stress incontinence

Abstract

Introduction and hypothesis

Our aim was to assess whether immediate preoperative resident simulation training decreases operative time and improves resident proficiency when performing a retropubic midurethral sling (MUS) procedure.

Methods

This prospective cohort study took place over 8 months at the Icahn School of Medicine, New York, USA. During the first 4 months, all retropubic MUS procedures were performed by residents who underwent immediate preoperative simulation training. The cases completed during the following 4 months were performed by residents who had not received preoperative simulation training. During the 8-month period, residents completed self-assessment questionnaires upon completion of the surgery and attendings evaluated the residents using the Objective Structured Assessment of Technical Skills (OSATS) global rating scale. Operative time between the two periods were compared using two-sample Student's t test. Comparative analysis between groups was performed based on the OSATS scores using the Wilcoxon rank-sum nonparametric test.

Results

There were 22 cases in the simulation group (SG) and 20 in the no simulation group (NSG). SG mean operative time was 12.6 min and NSG mean operative time was 14.6 min (p = 0.12). The SG mean OSATS score was 30.4 versus NSG of 27.8 (p < 0.001).

Conclusions

This study demonstrates that preoperative simulation significantly improves operative performance of the retropubic MUS procedure among residents and also improves their confidence in the operating room. There was a decrease in mean operative time of 2 min in the SG, but the difference was not statistically significant. This data is consistent in demonstrating improved surgical performance and resident confidence with simulation training.



Total vaginal length: Does it matter for assessing uterine prolapse?

Abstract

Introduction and hypothesis

Using the International Continence Society Pelvic Organ Prolapse Quantification (ICS POP-Q) system, uterine prolapse staging requires measurement of total vaginal length (TVL). The aim of this study was to determine whether TVT is a confounder of the relationship between uterine descent and POP symptoms.

Methods

This is a retrospective study on 721 patients seen in a tertiary urogynaecological unit. All patients had undergone a standardised, in-house, physician-led questionnaire and digital POP-Q examination. Patients with a history of hysterectomy or with a dominant prolapse in the anterior ± posterior compartment were excluded from analysis, leaving 393 complete data sets for analysis. Association between prolapse symptoms (lump/drag) and station of cervix (i.e. C) were tested. Age, body mass index (BMI), menospausal status and vaginal parity were tested as potential confounders. Variables that were significant on binary logistic regression (P < 0.05) were included in a model for receiver operting characteristic (ROC) statistical analysis. This was repeated after adding TVL to the model. Likelihood ratio test was performed to compare models.

Results

On binary logistic regression, prolapse symptoms were significantly associated with C, menopausal status and TVL (all P < 0.03). ROC analysis yielded an area under the curve (AUC) of 0.75 with menopausal status and C in the model. Adding TVL yielded an AUC of 0.773. The difference is statistically significant on the likelihood ratio test (P < 0.001).

Conclusions

Adding TVL improved the performance of cervical station in predicting prolapse symptoms, validating the practice of using TVL in staging uterine prolapse.



A multipurpose uterine/vaginal manipulator for laparoscopic urogynecologic procedures

Abstract

Introduction and hypothesis

The use of an appropriate uterine manipulator is key to various laparoscopic gynecologic procedures. Adequate uterine manipulation is important for total or supracervical laparoscopic hysterectomies, laparoscopic sacrocolpopexy as well as laparoscopic repair of vaginal vault prolapse. While several uterine manipulators are available to choose from, their use may be specific to certain procedures and their cost may vary as well.

Methods

This video aims to provide an introduction to a multipurpose, reusable uterine/vaginal manipulator that can be used for laparoscopic supracervical hysterectomy, laparoscopic sacrocolpopexy, laparoscopic hysteropexy as well as laparoscopic repair of vaginal vault prolapse.

Results

The video highlights the user-friendly, easy-to-clean, reusable, multipurpose uterine/vaginal manipulator.

Conclusions

The manipulator is designed for an efficient combination of laparoscopic urogynecologic procedures and supracervical hysterectomy.



National BSUG audit of stress urinary incontinence surgery in England

Abstract

Introduction and hypothesis

The aim of the British Society of Urogynaecology (BSUG) 2013 audit for stress urinary incontinence (SUI) surgery was to conduct a national clinical audit looking at the intra- and postoperative complications and provide outcomes for these procedures. This audit was supported by the Healthcare Quality Improvement Partnership (HQIP) and National Health Service (NHS) England.

Methods

Data were collected for all continence procedures performed in 2013 through the BSUG database. All clinicians in England performing SUI surgery were invited to submit data to a central database. Outcomes data for the different continence procedures were collected and included intraoperative and postoperative complications and the change in continence scores at postoperative follow-up Changing trends in stress incontinence surgery were also assessed.

Results

We recorded 4993 urinary incontinence procedures from 177 consultants at 110 centres in England: 94.6% were midurethral slings; 86.7% (4331) were submitted by BSUG members with the remaining 13.3% submitted by non-BSUG members. Postoperative follow-up data were available for 3983 (80%) patients: 92.3% (3676) were very much better/much better postoperatively, and 4806 (96.3%) proceeded with no reported complications. There were 187 cases (3.7%) in which a perioperative complication was recorded. Pain persisting >30 days was reported in 1.9% of all patients.

Conclusions

Surgery for SUI has good outcomes in the short term. Midurethral synthetic slings have been shown to be safe and effective as a treatment option, with >90% being very much/much better at their postoperative follow-up.



Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480

Clinical Oncology,Pediatric Hematology/Oncology

Maintenance Therapy in Metastatic Solid Tumors: Innovative Strategy or Simple Second-line Treatment?
imageManaging metastatic diseases involves defining the best strategy that is supposed to take into account both efficacy and quality of life. To this end, clinicians use stop and go or maintenance strategies. As a matter of fact, 2 maintenance strategies can be distinguished: continuation maintenance using a drug already present in induction treatment and switch maintenance with a newly introduced drug. Several drugs have been approved as maintenance therapy with several current indications in solid tumors. Questions remain concerning such strategies, notably duration, cost, tolerability, and shortcut between switch maintenance and early second line. If the concept of maintenance strategy remains trendy with numerous trials ongoing, several issues are still pending. The aims of this review were to accurately define and describe the various facets of maintenance therapy through its several indications in real life and then to discuss the future challenges of maintenance therapy in oncology.

Exceptional Responders in Oncology: A Systematic Review and Meta-Analysis of Patient Level Data
imagePurpose: We aim to systematically review and analyze the available literature on "exceptional responders" in oncology. We hypothesize that survival or patients with an exceptional response may be predicted based on clinical factors. Materials and Methods: A PICOS/PRISMA/MOOSE selection protocol was used to find studies that reported oncology patients with an exceptional response. A total of 333 initial articles were screened, and 76 articles were included, accounting for 85 patients. The primary outcome was survival after exceptional response therapy (ERT). The secondary outcome was survival since diagnosis. Univariate and multivariate analyses were conducted for both outcomes with 17 covariates. Results: The median age was 52 years (interquartile range, 35-66 y), 51.8% were male individuals, 18 (21.2%) had lung cancer, and 1 patient (1%) met all National Cancer Institute criteria for exceptional response. The most common treatment resulting in exceptional response was a form of chemotherapy (49.2%) followed by targeted therapy (26.8%) and radiation therapy (7.7%). The median time from diagnosis to initiation of ERT was 7.92 months (interquartile range, 0-24.72 mo). On multivariate analysis of survival after initiation of ERT, there were no predictors of exceptional response. On multivariate analysis of survival since diagnosis, predictors of prolonged survival included time between diagnosis and ERT initiation (hazard ratio, 0.52; 95% confidence interval, 0.32-0.87; P=0.0124) and single prior surgery versus none (0.08; 95% confidence interval, 0.01-0.98; P=0.04853). Conclusions: There were no clinically apparent patient or treatment factors that predicted favorable survival following ERT; instead, reporting of exceptional response appears to be biased.

The Effect of Time to Postoperative Radiation Therapy on Survival in Resected Merkel Cell Carcinoma
imageObjectives: Delays from surgery to adjuvant radiation therapy (aRT) are associated with poorer prognosis in multiple neoplasms. Presently, no data exist for Merkel cell carcinoma (MCC). The authors sought to assess the time interval from surgery to aRT and effect on outcomes in MCC. Materials and Methods: The National Cancer Database was queried for histologically confirmed nonmetastatic MCC status post resection and aRT diagnosed between 2004 and 2015 who received aRT within 24 weeks of surgery. Kaplan-Meier analysis assessed univariate overall survival (OS); multivariable Cox proportional hazards modeling assessed multivariate OS; χ2 and logistic regression assessed differences in baseline characteristics and predictors of delayed aRT. Results: Of 5952 patients meeting criteria, 13% commenced aRT within 4 weeks, 48% between 4 and 7 weeks, 23% between 8 and 11 weeks, 11% between 12 and 15 weeks, and 6% between 16 and 24 weeks. There were no differences in OS on the basis of the surgery-aRT interval (P=0.99). Predictors of worse OS on the multivariate analysis included advanced age, greater comorbidities, male sex, lower regional income, earlier year of diagnosis, more advanced tumor and nodal staging, positive margins, head and neck location, and treatment at community facilities (P<0.05 for all). Factors predictive of delayed aRT were identified. Subset analyses on these factors, such as receipt of chemotherapy or positive lymph nodes, did not demonstrate that the timing of aRT affected survival (P≥0.37). Conclusion: This study of a contemporary national database revealed that delays from resection to aRT were not associated with survival in MCC, somewhat discordant from other malignancies such as squamous cell carcinoma.

Artificial Intelligence Estimates the Importance of Baseline Factors in Predicting Response to Anti-PD1 in Metastatic Melanoma
imageObjective: Prognosis of patients with metastatic melanoma has dramatically improved over recent years because of the advent of antibodies targeting programmed cell death protein-1 (PD1). However, the response rate is ~40% and baseline biomarkers for the outcome are yet to be identified. Here, we aimed to determine whether artificial intelligence might be useful in weighting the importance of baseline variables in predicting response to anti-PD1. Methods: This is a retrospective study evaluating 173 patients receiving anti-PD1 for melanoma. Using an artificial neuronal network analysis, the importance of different variables was estimated and used in predicting response rate and overall survival. Results: After a mean follow-up of 12.8 (±11.9) months, disease control rate was 51%. Using artificial neuronal network, we observed that 3 factors predicted response to anti-PD1: neutrophil-to-lymphocyte ratio (NLR) (importance: 0.195), presence of ≥3 metastatic sites (importance: 0.156), and baseline lactate dehydrogenase (LDH) > upper limit of normal (importance: 0.154). Looking at connections between different covariates and overall survival, the most important variables influencing survival were: presence of ≥3 metastatic sites (importance: 0.202), age (importance: 0.189), NLR (importance: 0.164), site of primary melanoma (cutaneous vs. noncutaneous) (importance: 0.112), and LDH > upper limit of normal (importance: 0.108). Conclusions: NLR, presence of ≥3 metastatic sites, LDH levels, age, and site of primary melanoma are important baseline factors influencing response and survival. Further studies are warranted to estimate a model to drive the choice to administered anti-PD1 treatments in patients with melanoma.

Phase I Study of Sorafenib and Vorinostat in Advanced Hepatocellular Carcinoma
imageObjectives: Preclinical data suggest histone deacetylase inhibitors improve the therapeutic index of sorafenib. A phase I study was initiated to establish the recommended phase 2 dose of sorafenib combined with vorinostat in patients with unresectable hepatocellular carcinoma. Materials and Methods: Patients received vorinostat (200 to 400 mg by mouth once daily, 5 of 7 d) and sorafenib at standard or reduced doses (400 mg [cohort A] or 200 mg [cohort B] by mouth twice daily). Patients who received 14 days of vorinostat in cycle 1 were evaluable for dose-limiting toxicity (DLT). Results: Sixteen patients were treated. Thirteen patients were evaluable for response. Three patients experienced DLTs, 2 in cohort A (grade [gr] 3 hypokalemia; gr 3 maculopapular rash) and 1 in cohort B (gr 3 hepatic failure; gr 3 hypophosphatemia; gr 4 thrombocytopenia). Eleven patients required dose reductions or omissions for non-DLTtoxicity. Ten patients (77%) had stable disease (SD). The median treatment duration was 4.7 months for response-evaluable patients. One patient with SD was on treatment for 29.9 months, and another patient, also with SD, was on treatment for 18.7 months. Another patient electively stopped therapy after 15 months and remains without evidence of progression 3 years later. Conclusions: Although some patients had durable disease control, the addition of vorinostat to sorafenib led to toxicities in most patients, requiring dose modifications that prevented determination of the recommended phase 2 dose. The combination is not recommended for further exploration with this vorinostat schedule in this patient population.

ENvironmental Dynamics Underlying Responsive Extreme Survivors (ENDURES) of Glioblastoma: A Multidisciplinary Team-based, Multifactorial Analytical Approach
imageAlthough glioblastoma (GBM) is a fatal primary brain cancer with short median survival of 15 months, a small number of patients survive >5 years after diagnosis; they are known as extreme survivors (ES). Because of their rarity, very little is known about what differentiates these outliers from other patients with GBM. For the purpose of identifying unknown drivers of extreme survivorship in GBM, the ENDURES consortium (ENvironmental Dynamics Underlying Responsive Extreme Survivors of GBM) was developed. This consortium is a multicenter collaborative network of investigators focused on the integration of multiple types of clinical data and the creation of patient-specific models of tumor growth informed by radiographic and histologic parameters. Leveraging our combined resources, the goals of the ENDURES consortium are 2-fold: (1) to build a curated, searchable, multilayered repository housing clinical and outcome data on a large cohort of ES patients with GBM; and (2) to leverage the ENDURES repository for new insights into tumor behavior and novel targets for prolonging survival for all patients with GBM. In this article, the authors review the available literature and discuss what is already known about ES. The authors then describe the creation of their consortium and some preliminary results.

Cardiac Toxicity in Operable Esophageal Cancer Patients Treated With or Without Chemoradiation
imagePurpose: The purpose of this study was to evaluate predictors of cardiac events in esophageal cancer patients treated with neoadjuvant chemoradiotherapy (NA CRT) followed by surgery compared with surgery alone. Materials and Methods: We retrospectively identified patients treated for esophageal cancer between 2006 and 2016. A total of 123 patients were identified; 70 were treated with surgery alone, and 53 were treated with NA CRT. Cardiac events were scored based on Common Terminology Criteria for Adverse Events (version 4.03), and dosimetric data was compiled for all patients who received radiation. Univariate analysis and multivariable analysis (MVA) were performed to identify predictors of cardiac events. Competing risk of death regression was performed to a model the cumulative incidence of cardiac events. Results: The overall rates of grade ≥3 cardiac events were 24.5% in the NA CRT group versus 10% in the surgery group (P=0.04). On MVA, use of NA CRT (P<0.01, hazard ratio [HR]: 3.45, 95% confidence interval [CI]: 1.35-9.09) predicted for grade ≥3 cardiac events, though no dosimetric variable predicted for grade ≥3 cardiac events or overall survival. On MVA, NA CRT predicted for pericardial effusions of any grade (P<0.01, HR: 3.70, 95% CI: 1.67-8.33). The V45 Gy was the most significant predictor of pericardial effusions (P=0.012, HR: 1.03, 95% CI: 1.01-1.06) Conclusions: NA CRT significantly increased the rate of grade ≥3 cardiac events compared with patients treated with surgery alone. Although no dosimetric parameter predicted for grade ≥3 cardiac events or survival, the V45 Gy predicted for pericardial effusions.

Competing Mortality in Patients With Neuroendocrine Tumors
imageObjectives: Patients with neuroendocrine tumors (NETs) are at increased risk of mortality from competing causes in light of the improvement in overall survival over recent decades. The purpose of this study was to explore the competing causes of deaths and the risk factors associated with competing mortality. Materials and Methods: The Surveillance, Epidemiology, and End Results database was used to identify patients diagnosed with NETs between 1973 and 2015. Risk of competing mortality was estimated by the standardized mortality ratios (SMRs) and by using the Fine and Gray multivariate regression model. Results: Of the 29,981 NET patients, 42.5% of the deaths that occurred during follow-up were attributed to competing causes (83.9% from noncancer causes and 16.1% from second primary neoplasms). Overall SMR of competing mortality was 2.50 (95% confidence interval [CI]: 2.43-2.56). The SMR of noncancer causes was 2.65 (95% CI: 2.58-2.73), with the highest risk present within the first year of diagnosis. The SMR of second primary neoplasms was 1.91 (95% CI: 1.79-2.04), with the highest risk observed after 10-year postdiagnosis. A drastic rise in competing mortality was observed in the last decade between 2005 and 2015. Advanced age, black race, small intestinal and gastric NETs, and surgery were significantly associated with competing mortality. Female, pancreatic and recto-anal NETs, distant and regional spread, chemotherapy and radiotherapy were significantly associated with lower competing mortality. Conclusions: Competing mortality plays an increasingly significant role over the years and may hamper efforts made to improve survival outcomes in NET patients.

Patterns of Postdiagnosis Depression Among Late-Stage Cancer Patients: Do Racial/Ethnic and Sex Disparities Exist?
imageObjectives: The incidence of depression after a late-stage cancer diagnosis is poorly understood and has not been the subject of intense investigation. We used population-based data to examine trends in postdiagnosis depression incidence among racial/ethnic and sexual groups. Methods: We identified 123,066 patients diagnosed with late-stage breast, prostate, lung, or colorectal cancer from 2001 to 2013 in the Surveillance Epidemiology and End Results Medicare-linked database. The primary outcome was the incidence of postdiagnosis depression after a late-stage cancer diagnosis. Trend analysis was performed using the Cochran-Armitage test. Stratified incidence rates were calculated for the racial/ethnic and sexual groups. Results: The incidence of depression after cancer diagnosis increased from 15.3% in 2001 to 24.1% in 2013, Ptrend<0.0001. About 50% of depression was reported in the first 3 months of stage IV cancer diagnosis. A total of 19,775 (20.0%) non-Hispanic whites, 1937 (15.9%) non-Hispanic blacks, and 657 (12.7%) Hispanics were diagnosed with depression during a mean follow-up of 2.7 months (interquartile range: 0.9 to 10.2 mo). The incidence of depression is significantly higher among females than males, 22.7% versus 16.3%, P<0.0001. In the multivariable logistic regression, non-Hispanic whites and females were still independent predictors of higher risk of postdiagnosis depression. Conclusions: There are significant differences in the incidence of postdiagnosis depression among racial/ethnic and sexual groups in the United States. The consideration of racial/ethnic in depression prevention and diagnosis among cancer patients should be discussed as a matter of importance to ensure that there is no diagnosis bias among non-Hispanic blacks and Hispanics.

Surveillance Mammography After Breast Conservation Therapy: Is Tomosynthesis Worth It?
imageIntroduction: We investigated the downstream workup and costs associated with digital breast tomosynthesis (DBT) compared with 2-dimensional full field digital mammogram (FFDM) when employed as initial follow-up imaging in breast conservation therapy. Methods: Between the years 2015 and 2017, 450 consecutive breast conservation therapy patients, ages 32 to 89, with a follow-up DBT (n=162) or FFDM (n=288) were retrospectively reviewed. The primary endpoints were further workup after follow-up mammogram and associated health care costs at 1 year. A single DBT costs an estimated $149 compared with $111 for FFDM, based on Centers for Medicare claims data from the Oncology Care Model. Results: The first posttreatment mammogram was received within 3 (20%), 3 to 6 (32%), or after 6 months (48%) following radiation. Younger patients and those undergoing hypofractionated radiation were more likely to get DBT. There were no differences in stage, receptor status, or mammogram timing between those in the FFDM and DBT groups. The following downstream workup ensued for DBT compared with FFDM imaging: 18% versus 29% short-interval (6-mo) mammogram (odds ratio=1.83, P=0.01), 6% versus 11% breast magnetic resonance imaging (odds ratio=1.90, P=0.08), 4% ultrasound for each, and 3% biopsy for each (1 positive in the FFDM group). Including downstream workup, the estimated cost per patient in the DBT group was $216.14 compared with $237.83 in the FFDM group. Independent predictors for reduced downstream workup per multivariable analysis were the use of DBT and first follow-up mammogram at least 6 months after radiation (P<0.05). Discussion: Excess workup was reduced with DBT compared with FFDM in the posttreatment setting, which translated to an improvement in cost efficiency in this study.


Impact of IgG Monitoring and IVIG Supplementation on the Frequency of Febrile Illnesses in Pediatric Acute Lymphoblastic Leukemia Patients Undergoing Maintenance Chemotherapy
imageMonitoring serum immunoglobulin G (IgG) levels in pediatric oncology patients and treating subtherapeutic levels with intravenous immunoglobulin (IVIG) may prevent infections; however, evidence is limited. This retrospective study assessed pediatric acute lymphoblastic leukemia patients diagnosed 2006 to 2011 to evaluate if monitoring/supplementing IgG would reduce febrile illnesses during maintenance chemotherapy. A subject was categorized as "ever IgG monitored" if they had ≥1 IgG levels checked and their risk days were stratified into not IgG monitored days and IgG monitored days. IgG monitored days were further stratified into IgG monitored with IVIG supplementation, monitored with no IVIG supplementation (IgG level >500 mg/dL) and monitored with no IVIG supplementation days (IgG level <500 mg/dL). Generalized linear mixed effects poisson models were used to compare events (febrile episode, positive blood culture, and febrile upper respiratory infection rates among these groups. In 136 patients, the febrile episode rate was higher in the ever IgG monitored cohort than the never monitored cohort (5.26 vs. 3.78 episodes/1000 d). Among monitored patients, IVIG monitoring and supplementation did not significantly impact the febrile episode, febrile upper respiratory infection, or the positive blood culture rates. These data suggest that monitoring/supplementing low IgG is not indicated for infection prophylaxis in acute lymphoblastic leukemia patients during maintenance chemotherapy.

Methotrexate Polyglutamate Values in Children and Adolescents With Acute Lymphoblastic Leukemia During Maintenance Therapy
imageInadequate adherence to maintenance therapy is a major cause of relapse in patients with acute lymphoblastic leukemia (ALL). Therapeutic monitoring of mercaptopurine (thiopurine) red cell metabolites to assess adherence has been available for many years. Recently a clinical laboratory improvement amendments of 1988-approved test for methotrexate with three polyglutamate residues (MTXPG3) measured in peripheral blood red cells was approved. MTXPG3 is the primary intracellular metabolite of methotrexate, and like thiopurine metabolites, is retained for the life of the red cell giving an estimate of drug exposure over time. Normative values for MTXPG3 are available for adults and children with rheumatoid arthritis on methotrexate monotherapy, which are not applicable for patients with ALL on maintenance. Older literature on the MTXPG3 fraction in children with ALL is limited. We examined the MTXPG3 levels from 123 samples in 76 patients with ALL on maintenance oral methotrexate and mercaptopurine that were collected for clinical care. Male individuals had significantly higher MTXPG3 levels than female individuals which was unrelated to absolute neutrophil count, age, serum creatinine, and average doses of methotrexate or mercaptopurine. The MTXPG3 5th, 10th, 90th, and 95th percentile values are 0, 8.4, 53, and 64, respectively with a median of 24.7 nmol/L. The low 5th percentile MTXPG3 reflects 6 samples from 3 patients, age 16 to 21 years that were considered poorly adherent before collecting the specimen. As with red cell thiopurine (mercaptopurine) metabolites, MTXPG3 normative values may provide useful information to monitor for poor patient adherence or methotrexate toxicity during maintenance chemotherapy in ALL.

Impact of Race and Socioeconomic Status on Psychologic Outcomes in Childhood Cancer Patients and Caregivers
imageComplex relationships between race and socioeconomic status have a poorly understood influence on psychologic outcomes in pediatric oncology. The Family Symptom Inventory was used to assess symptoms of depression and anxiety in pediatric patients with cancer and their caregivers. Separate hierarchical linear regression models examined the relationship between demographic variables, cancer characteristics, socioeconomic status, and access to care and patient or caregiver depression/anxiety. Participants included 196 pediatric patients with cancer (mean age, 11.21 y; 49% African American) and their caregivers. On average, caregivers reported low levels of depression/anxiety. Symptoms of depression and anxiety in patients were correlated with poorer mental health in caregivers (r=0.62; P<0.01). Self-reported financial difficulty (β=0.49; P<0.001) and brain cancer diagnosis for their child (β=0.42; P=0.008) were significantly associated with depression and anxiety in caregivers. Analysis did not reveal significant associations between race, household income, or access to care and patient or caregiver depression/anxiety. Perception of financial hardship can adversely impact mental health in caregivers of children with cancer. Psychosocial assessment and interventions may be especially important for caregivers of patients with brain tumors and caregivers who report feeling financial difficulty.

The Value of 18F-FDG PET/CT in Detecting Bone Marrow Involvement in Childhood Cancers
imageBackground: The aim of this study was to assess the utility of 18F-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in assessing bone marrow involvement (BMI) compared with bone marrow biopsy (BMB) in the initial staging of pediatric patients with non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), Ewing sarcoma (ES), and neuroblastoma (NB). Procedure: A total of 94 patients (57 boys, 37 girls, median age 7 y, range 1 to 18 y) with newly diagnosed NHL, HL, ES, and NB between July 2014 and December 2017, who underwent BMB and 18F-FDG PET/CT before chemotherapy were included in this study. There were 36 patients with NHL, 27 HL, 16 ES, and 15 NB. 18F-FDG PET/CT and BMB results were reviewed and compared retrospectively. Findings: Retrospective analysis of data from 94 pediatric patients (57 boys, 37 girls, median age 7 y, range 1 to 18 y) was performed. Of the 94 patients, 29 had BMI on 18F-FDG PET/CT. BMB was positive in 14, negative in 13, and insufficient in 2 of these 29 patients. In 65 patients negative on 18F-FDG PET/CT, BMB was also negative in 54 and insufficient in 7. For the whole group, sensitivity, specificity, and positive and negative predictive values of 18F-FDG PET/CT in detecting bone marrow metastasis at the time of diagnosis were 90.6%, 100%, 100%, and 95.4% and those of BMB were 53.1%, 87.1%, 94.4%, and 80.6%, respectively. Conclusion: Our study demonstrates that 18F-FDG PET/CT predicts BMI better than BMB. 18F-FDG PET/CT may be used at initial staging of pediatric patients with NHL, HL, ES, and NB.

Intensity of Therapy for Malignancy and Risk for Recurrent and Complicated Clostridium difficile Infection in Children
imageClostridium difficile infection (CDI) is common in pediatric oncology patients and is often associated with recurrences and complications. We hypothesized that higher intensity of chemotherapy would be associated with these outcomes. We conducted a retrospective cohort study including all cases of primary CDI in children with malignancy in our institution for over 7 years. Intensity of chemotherapy was measured by the Intensity of Treatment Rating Scale, third edition, ranging from level 1 (minimal) to 4 (highest). Outcomes included recurrence within both 56 and 180 days, CDI-associated complications, and primary treatment failure (PTF). Risk of recurrence was compared using Cox proportional hazards regression. Among 192 patients with CDI and malignancy, 122 met inclusion criteria. CDI recurred in 27% (31/115) of patients followed for 56 days and 46% (48/104) of patients followed for 180 days. Fourteen patients (11.4%) had a CDI-associated complication, including 4 intensive care unit admissions and 3 surgical procedures, but no deaths. Ten patients (8.2%) had PTF. Although PTF and severe complications were infrequent, recurrence was common in our cohort. None of these outcomes were associated with level of treatment intensity. More research is required to assess oncologic and nononcologic risk factors for CDI recurrence, PTF, and severe CDI-associated complications.

Metabolic Changes in Children that Received Chemotherapy
imageCancer treatments are associated with short and long-effects. Epidemiological reports have revealed clinical features of metabolic syndrome (MS), obesity or overweight in young cancer survivors. The aim of the study was to examine the prevalence of unhealthy weight status and risk factors associated with MS related to chemotherapy. We study 52 pediatric cancer patients and analyze cholesterol, triglycerides, glycosylated hemoglobin, body mass index, waist circumference (WC), FINDRISC test. All the parameters were analyzed according to the percentile corresponding to sex and age of each child. The data show an important modification in weight, body mass index, and WC as in triglycerides, and cholesterol that could be associated with the development of MS. The variance analysis showed that the WC, triglycerides, and cholesterol are statistically correlated in our population. A follow-up for MS in children cancer survivor should be considered necessary.

Characteristics and Survival Outcomes of Children With Hodgkin Lymphoma Treated Primarily With Chemotherapy
imageBackground: Hodgkin disease is a malignant tumor of the lymphatic system that comprises ∼6% of childhood cancers. In developing countries, efforts are made to ensure adherence to standard protocol/regimens, study patients' outcomes, and compare with that in developed world. Materials and Methods: We conducted a retrospective medical records' review of 212 children younger than 20 years presenting to The Indus Hospital in Pakistan with previously untreated Hodgkin lymphoma between August 2000 and December 2012. We collected demographic and other epidemiologic variables such as age, sex, stage, subtype of disease, and survival outcomes. Results: The mean±SD age of patients at time of diagnosis was 9.0±3.8 years with a male to female ratio of ∼4.7:1. In total, 44 (20.8%) patients were 5 years of age or above at presentation. Overall, 131 (61.8%) patients presented with B-symptoms and mixed cellularity was the most frequently diagnosed subtype in 65.1% of cases. In total, 170 (80.2%) achieved full remission after completion of chemotherapy. Patients were treated with alternating cycles of ABVD (Adriamycin, Bleomycin, Vincristine, and Dacarbazine) and COPDAC (Cyclophosphamide, Vincristine, Prednisolone, and Dacarbazine). The majority (n=114, 59.1%) received 6 cycles of chemotherapy, 44 (22.8%) received ≤4 cycles followed by 24 (12.4%) receiving 8 cycles. Radiotherapy was administered only to those patients with significant residual disease at the end of chemotherapy (n=20, 10%). The 5-year overall survival and event-free survival in our cohort was 89.6% and 82.1%, respectively. Conclusion: Our findings suggest that treatment with 4 to 8 alternating cycles of ABVD/COPDAC has an excellent outcome in childhood Hodgkin disease.

Switching to Bortezomib may Improve Recovery From Severe Vincristine Neuropathy in Pediatric Acute Lymphoblastic Leukemia
imagePurpose: The purpose of this study was to evaluate the impact of switching patients being treated for acute lymphoblastic leukemia (ALL) from vincristine to bortezomib. Patients and Methods: A total of 20 patients with ALL were switched from vincristine to bortezomib (1.3 mg/m2/dose) because of worsening neuropathy despite physical therapy interventions (n=18) or at increased risk of neuropathy (n=2). Relapse rates were compared with 56 vincristine-only patients matched by prognostic factors. Maintenance blood counts in bortezomib patients were compared with cooperative group data using vincristine during maintenance. In addition, 6 evaluable patients were assessed for neuropathy using the pediatric-modified total neuropathy score. Neuropathy scores were collected during treatment with vincristine and after switching to bortezomib. Results: After a median follow-up of 3.5 years the relapse rate in patients switched to bortezomib was nonsignificantly different than those remaining on vincristine. Patients on monthly bortezomib had statistically significantly lower platelet counts that did not require transfusions or dose adjustment. Total neuropathy for all 6 cases decreased significantly when switched to bortezomib from vincristine (P=0.015), with motor neuropathy declines in 5 of 6 subjects. Conclusions: Bortezomib substitution for vincristine in ALL treatment is a potential strategy to mitigate severe vincristine neuropathy. These findings should be confirmed in a randomized clinical trial to further assess benefits and risks of this approach.

Investigation of Dynamic Thiol/Disulfide Homeostasis in Children With Acute Immune Thrombocytopenia
imageOxidative stress may play a role in the pathogenesis of immune thrombocytopenia (ITP), but the role of dynamic thiol/disulfide homeostasis has not been studied. The objective of this study was to assess whether there is a change in thiol/disulfide homeostasis in children with acute ITP. A total of 40 children with acute ITP and 50 healthy age-matched and sex-matched controls were included in this study. Serum total thiol and native thiol levels have been measured with a novel automatic spectrophotometric method. The amount of dynamic disulfide bonds and related ratios were calculated from these values. The average total thiol and native thiol levels of the patient group were found to be significantly lower than those levels of controls (P<0.01). However, intravenous immunoglobulin (IVIG) treatment with 1 g/kg/d prevented these reductions. disulfide level was slightly, but not significantly, depressed in ITP patients, but it recovered following IVIG treatment. We detected no marked changes in disulfide/total thiol, disulfide/native thiol, and native thiol/total thiol ratios between groups. These results are the first to demonstrate that thiol/disulfide homeostasis plays a role in ITP pathogenesis, and IVIG treatment can prevent the reduced thiol levels in children.

Probiotic Supplementation Decreases Chemotherapy-induced Gastrointestinal Side Effects in Patients With Acute Leukemia
imageIntroduction: In children with acute leukemia, gut microbiota is modified secondary to chemotherapy administration, leading to gastrointestinal side effects. Probiotics are microorganisms that can restore gut microbiota and may help alleviate gastrointestinal symptoms. The aim of this pilot study was to assess the effects of probiotic supplementation on chemotherapy-induced gastrointestinal side effects in children with acute leukemia (AL). Methods: In this randomized pilot study, patients under 17 years of age diagnosed with AL who were on remission induction or remission reinduction chemotherapy were randomly assigned to receive probiotic supplementation (a concentration of 5×109 CFU per sachet was administered at a standard dose twice daily, by mouth) or no probiotic supplementation. The primary endpoint was the prevalence of gastrointestinal side effects. Vomiting, nausea, flatulence, dyspepsia, diarrhea, constipation, abdominal pain, and abdominal distention were assessed in both groups. Results: Gastrointestinal side effects were less prevalent in the probiotic group, and 3 of the 8 gastrointestinal side effects (nausea, vomiting, and abdominal distension) significantly decreased in the probiotic group (P<0.05). We found for diarrhea a relative risk of 0.5 (95% confidence interval [CI], 0.2-1.2; P=0.04); for nausea an RR of 0.5 (95% CI, 0.4-0.8; P=0.04) and for vomiting an RR of 0.4 (95% CI, 0.2-0.9; P=0.04). Conclusions: Daily supplementation with Lactobacillus rhamnosus reduced chemotherapy-induced gastrointestinal side effects in children with AL.


Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480

Clinical Rheumatology

Folate Supplementation for Methotrexate Therapy in Patients With Rheumatoid Arthritis: A Systematic Review
imageObjective To review the evidence for benefits and harms of folate (folic acid or folinic acid) supplementation on methotrexate (MTX) treatment for rheumatoid arthritis (RA), to assess whether or not folate supplementation would reduce MTX toxicity or reduce MTX benefits, and to decide whether a higher MTX dosage is essential. Methods We performed a sensitive search strategy and searched systematically the Medline, Embase, Web of Science and Cochrane Library databases from inception to 2 June 2016. Abstracts from major rheumatology meetings and major trial registers were also searched to retrieve all randomized controlled trials that interested us. Results Seven studies with 709 patients were included. No significant heterogeneity was found between these trials. For RA patients treated with MTX, those supplied with folate were less likely to have elevated transaminase (odds ratio [OR] 0.15; 95% confidence interval [95% CI] 0.10, 0.23 [p < 0.00001]) and gastrointestinal side-effects such as nausea and vomiting (OR 0.71; 95% CI 0.51, 0.99 [p = 0.04]). Folate appeared to promote compliance to MTX as it reduced patient withdrawal compared to placebo (OR 0.29; 95% CI 0.21, 0.42 [p < 0.00001]). There was no statistical difference for mouth sores between folate and placebo (OR 0.83; 95% CI 0.57, 1.22 [p = 0.35]). As the markers of disease activity in those trials were not consistent, it was impossible to decide whether folate supplementation reduced MTX efficacy. Besides, we compared high-dose folate (≥25 mg per week) and low-dose folate (≤10 mg per week) on MTX efficacy, finding no statistical difference (OR 2.07; 95% CI 0.81, 5.30 [p = 0.13]), nor on MTX toxicity (OR 1.56; 95% CI 0.80,3.04 [p = 0.19]). Conclusion Folate supplementation can reduce the incidence of hepatotoxicity and gastrointestinal side-effects of MTX in patients with RA. It can also reduce patient withdrawal from MTX treatment. Although it tended to reduce mouth sores, it had no statistical significance. No significant difference was found between high-dose folate and low-dose folate on MTX efficacy or toxicity.

Ultrasound as a Useful Tool in the Diagnosis of Rheumatoid Arthritis in Patients With Undifferentiated Arthritis
imageBackground Nowadays, rheumatologists face challenges in finding an effective method to classify and treat patients with undifferentiated arthritis (UA). There is a need for new tools that could ensure accurate characterization of inflammatory processes in these patients. Objective The aim of this study was to investigate if a characterization of UA patients using ultrasound (US) may help to fulfill the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) rheumatoid arthritis (RA) classification criteria in a real-life cohort. Methods We conducted a cross-sectional study in 2 rheumatology care clinics. Patients not fulfilling the 2010 ACR/EULAR RA criteria were included. On the examination day, all patients underwent a physical examination, radiography, and US. The 7-joint US score was adopted to scan all patients. The US was performed according to EULAR criteria and interpreted by Outcome Measures in Rheumatology definitions. Gray-scale and power Doppler synovitis and tenosynovitis were scored. Bone erosions were also evaluated during the US examination. Results A total of 204 patients were included. The diagnosis was modified from UA to RA in 86 patients (42.1%). Also, the final score of the 2010 ACR/EULAR RA classification criteria changed from a mean of 4.6 to 6.5 after the US examination. In addition to synovitis, a wide range of tenosynovitis and bone erosions were detected by US. Synovitis was more frequently detected in second metacarpophalangeal joint followed by second metatarsophalangeal joint (MTPj) and fifth MTPj. The tendons of the wrist and second and third fingers were the most affected. In relation to bone erosions, second metacarpophalangeal joint and fifth MTPj were the joints with more proportion of anatomical damage. Conclusions The US demonstrated to be useful to help accurately classify as RA patients previously diagnosed with UA.

Physician's Experience and Disease Activity Affect the Impact of Ultrasound on the Treatment Decision in Rheumatoid Arthritis
imageBackground/Objective The aim of this cross-sectional study was to explore which factors affect the impact of musculoskeletal ultrasound (MUS) on the treatment proposal among rheumatologists with different degree of experience. Methods Sixteen clinical vignettes summarized data from rheumatoid arthritis (RA) outpatients; vignettes included clinical evaluation and a blank section for a first treatment proposal; MUS information was then added, based on German Ultrasound score, followed by a blank section for treatment re-consideration, if applicable. During a 6 months period, each vignette was concomitantly presented to six trainees and six senior rheumatologists (SR); three SR had ≥15 years of experience. Participants were blinded to colleagues' responses. Appropriated statistics were used. Results Vignettes included data from female patients, who had a mean ± SD age of 43.3 ± 9 years, 7.6 ± 3.5 years of disease duration and comorbidities (68.8%). MUS induced treatment modification in 24% of evaluations, with similar percentage among SR and trainees. Within SR, more experienced rheumatologists (≥15 years) never translated MUS findings in a different treatment proposal, compared to 34% of those with lesser experience, p ≤ 0.0001. There were 60 clinical scenarios each, with remission and moderate disease activity, and 36 clinical scenarios each, with low and high disease activity. MUS-induced treatment modifications were more frequent in scenarios with low and moderate disease activity, compared to remission and high disease activity, p = 0.008. Conclusions Physician's experience and disease activity level affect the impact of MUS on the treatment decision in RA outpatients. RA patients with intermediate disease activity may benefit from MUS incorporation to standard assessments.

Evaluation of PR3-ANCA Status After Rituximab for ANCA-Associated Vasculitis
imageIntroduction The value of antineutrophil cytoplasmic antibody (ANCA) measurements among patients with an established diagnosis of ANCA-associated vasculitis (AAV) to assess disease activity or predict relapse remains controversial, but recent evidence suggests a possible role for rituximab-treated patients. Patients and Methods All patients with active vasculitis and positive proteinase 3 (PR3)–ANCA who were starting a 2-year treatment course of rituximab for induction of remission at Addenbrooke's Hospital between January 2011 and January 2016 were included in this study. Common department practice consists of 6 g of rituximab given over 2 years, concomitant corticosteroids (0.5–1.0 mg/kg) with rapid taper over 3 months, and cessation of oral maintenance immunosuppressive agents at time of first rituximab dose. Clinical and laboratory data were collected retrospectively using electronic patient records. Results Fifty-seven patients with current PR3-ANCA positivity were included in the analysis. Median follow-up was 59 months. PR3-ANCA negativity was achieved in 25 patients (44%) with a median time of 14 months. Clinical remission was achieved in 53 patients (93%) with a median time of 3 months. Among the 53 patients who achieved remission during follow-up, 24 (45%) relapsed with a median time to relapse of 36 months from remission. Both PR3-ANCA–negative status and 50% reduction in PR3-ANCA from baseline (as time-varying covariates) were significantly associated with a longer time to relapse (PR3-ANCA–negative status: hazards ratio, 0.08 [95% confidence interval, 0.01–0.63, p = 0.016]; 50% reduction in PR3-ANCA: hazards ratio, 0.25 [95% confidence interval, 0.18–0.99, p = 0.046]). Conclusions Achieving and maintaining PR3-ANCA negativity after rituximab was associated with longer-lasting remission.

Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis–Like Lupus Erythematosus
imageBackground/Objective Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN)–like lupus erythematosus is a hyperacute and life-threatening form of cutaneous lupus erythematosus. Because of its rarity, little is known about this entity. We aimed to evaluate the clinical characteristics, laboratory findings, systemic manifestations, treatments, and outcome of SJS/ TEN-like lupus erythematosus. Methods We conducted a chart review study from July 2002 to September 2016 of all patients diagnosed with SJS/TEN-like lupus erythematosus who presented with gradual epidermal necrolysis without clear drug or infectious culprit. We evaluate for clinical features, extracutaneous involvement, Systemic Lupus Erythematosus Disease Activity Index, histologic findings, immunofluorescence pattern, serologic abnormalities, treatment, outcome, and recurrence of SJS/TEN-like lupus erythematosus. Results Of 9074 patients diagnosed with cutaneous lupus erythematosus and/or systemic lupus erythematosus, 6 patients justified the diagnosis of SJS/TEN-like lupus erythematosus (5 SJS/TEN-like acute cutaneous lupus erythematosus, 1 TEN-like subacute cutaneous lupus erythematosus), accounting for 0.07%. Fifty percent had epidermal necrolysis as the initial presentation of lupus with a median time from onset of 1.5 months (0–48 months). The median duration between initial rash and epidermal detachment was 4.5 days (3–14 days). All had internal organ involvement (hematologic and renal) and high Systemic Lupus Erythematosus Disease Activity Index score (median, 19.5 [16–24]). Most recovered with systemic corticosteroids, antimalarial drugs, and/or immunosuppressants. None had disease recurrence. Conclusions This is the largest single series of patients with SJS/TEN-like lupus erythematosus. Skin damage is an indicator of disease activity, and careful search for extracutaneous involvement to prevent further complications is mandatory.

Pain and Catastrophizing in Patients With Rheumatoid Arthritis: An Observational Cohort Study
imageBackground The aims of this study were to define changes in catastrophizing that occur with initiation of a new disease-modifying antirheumatic drug (DMARD) and to examine the relationship between changes in Clinical Disease Activity Index (CDAI) and changes in catastrophizing. Methods Participants in an ongoing multisite, observational study completed the Pain Catastrophizing Scale (PCS) before and 12 weeks after DMARD initiation. We used multivariable linear regression models to examine the association between changes in CDAI as the exposure and change in pain catastrophizing as the outcome. We also assessed the relationship between changes in each component of CDAI and change in PCS, using multivariable linear regression models. Results Among the 165 rheumatoid arthritis patients with data on CDAI at both time points, CDAI decreased from 22 to 11.5 on a 76-point scale (p < 0.0001) after 12 weeks. Pain intensity decreased from a median of 5 to 3 on a 10-point numeric rating scale (p < 0.0001), and catastrophizing decreased, from 16.0 to 12.0 on the 52-point PCS (p = 0.0005). Among the 163 with complete data for the regression analysis, changes in CDAI were positively correlated with changes in catastrophizing (standardized β = 0.19, p = 0.01). Of the components of the CDAI, change in assessor global score was most strongly associated with changes in catastrophizing (standardized β = 0.24, p = 0.003). Conclusions Pain catastrophizing decreases, in conjunction with disease activity, after initiation of a new DMARD. These findings provide support for catastrophizing as a dynamic construct that can be altered with treatment directed at decreasing inflammatory disease activity and pain.

ARF, ARF!
imageNo abstract available

Anti-TNF and Physiologic Measures of Metabolic Disease in Rheumatoid Arthritis
imageNo abstract available

Characteristic Radiographic Appearance of Chronic Recurrent Multifocal Osteomyelitis
imageNo abstract available

Cardiac Magnetic Resonance Imaging of Cardiac Amyloidosis
imageNo abstract available

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480

Clinical Obstetrics and Gynecology

Contributors: Burnout and Resilience in Obstetrics and Gynecology
No abstract available

Foreword: Burnout and Resilience in Obstetrics and Gynecology
No abstract available

Burnout in Obstetricians and Gynecologists
imageProfessional burnout threatens all high-functioning professionals and affects not only the individual, but, by extension, the patients they serve. The characteristics that make someone competitive for medical school, residency, or successful in academics or practice, make us particularly vulnerable to burnout: compulsive dedication to goals (and patients), motivation to succeed, self-reliance, leadership experience, delayed gratification, and others. Estimates of the prevalence of burnout in medicine vary widely but are consistently >40% and often as high as 75%. Obstetricians and gynecologists are not unique in suffering from burnout but do rank among the top medical specialties for the rate of professional burnout reported. When burnout is present, there is reduced job satisfaction, lower productivity, increased medical errors (and morbidity), degraded interpersonal interactions, and higher physician dropout rates. Career dissatisfaction, early retirement, and even regret surrounding the original choice of career are all common when burnout is present. There is a growing body of individual actions that can be taken to reduce or reverse the impact of burnout, but the first steps are to understand the causes and identify the symptoms.

Burnout in OB/GYN Students and Residents
imageIn this article we address the concept of burnout, first in the medical student setting, and then in the residency setting. We will review the prevalence followed by a discussion of risk factors, consequences, and finally thoughts on prevention and intervention.

Interventions to Reduce Burnout and Improve Resilience: Impact on a Health System's Outcomes
imageWith the continuously changing health care environment and dramatic shift in patient demographics, institutions have the responsibility of identifying and dedicating resources for maintaining and improving wellness and resilience among front line providers to assure the quality of patient care. Our institution, the Ohio State University Wexner Medical Center (OSUWMC), has addressed the goal to decrease burnout for providers in a multistep, multiprofessional, and multiyear program starting firstly with institutional cultural change then focused provider interventions, and lastly, proactive resilience engagement. We describe herein our approach and outcomes as measured by provider wellness and health system outcomes. In addition, we address the overall feasibility and effectiveness of these programs in promoting provider compassion and mindfulness while reducing burnout and improving resilience. Institutional culture change and readiness were initiated in 2010 with the introduction of Crew Resource Management training for all providers across the OSUWMC. This multiyear program was implemented and has been sustained to the current day. Focused interventions to improve mindfulness were undertaken in the form of both Mindfulness in Motion (MIM) training for intensive care unit personnel and a "flipped classroom" mindfulness training for faculty and residents. Lastly, sustainable changes were introduced in the form of the Gabbe Health and Wellness program which consists of interprofessional MIM training and other wellness offerings for staff, faculty, and residents embedded across the entire medical center. The introduction of Crew Resource Management in 2010 continues to be endorsed and supported throughout OSUWMC for all providers, including residents and students. The improvements seen have not only improved patient satisfaction but also reduced patient safety events and improved national reputation for the institution as a whole. Subsequently, MIM training for intensive care unit providers has resulted in improved resilience as well as decreased patient safety events. In addition, the "flipped classroom" mindfulness training for residents and faculty has resulted in improvements in providing calm and compassionate care, improvements in physician wellbeing, and reductions in emotional exhaustion and depersonalization. Lastly, implementing the Gabbe Health and Wellness program inclusive of interprofessional MIM training for staff, faculty, and residents has resulted in significant reductions in burnout while significantly increasing resilience postintervention. The engagement from staff and enthusiasm to continue this program have escalated and been positively accepted across OSUWMC. To reduce the incidence of burnout, improve resilience, and ultimately improve patient outcomes, a health system must identify and prioritize a commitment and dedication of resources to develop and sustain a multimodal and interprofessional approach to change. These initiatives at OSU originated with cultural transformation allowing the acceptance of change in the form of mindfulness training, resilience building, and the engagement of organizational science, so as to demonstrate the outcomes and impact to the health system and academic peers. Herein we describe the work that has been done thus far, both published and in progress, to understand our journey.

The Impact of Burnout on the Obstetrics and Gynecology Workforce
imageAlthough there has been discussion of a shortage of surgical specialties including OB/GYN, consensus is difficult because of the multiple variables involved in estimating both supply and demand. In addition, burnout has become more recognized as a variable that has not been taken into account in estimating a shortage of OB/GYNs. We estimate OB/GYN physician shortages of 17%, 24%, and 31% by 2030, 2040, and 2050, respectively. Here, we examine the impact of burnout on the OB/GYN workforce. Specifically, we address the associations of burnout, reduction in clinical productivity as well as early retirement. We also discuss the implications of the substantial increase of female OB/GYNs to ∼66% of workforce over the next 10 years and how this may impact the impending OB/GYN shortage. Finally, we briefly consider possible solutions to workforce issues causing burnout.

Physician Work-Life Integration: Challenges and Strategies for Improvement
imageIncreasing evidence shows that physician well-being is linked to patient outcomes, patient and physician satisfaction, and workforce retention. Physician well-being is a broad construct that includes various dimensions of distress (stress, anxiety, fatigue, burnout) and professional fulfillment (meaning in work, engagement). Work-life integration (WLI) is one important component of physician well-being. We will review the current state of WLI among physicians as well as some strategies to improve this aspect of physician well-being. We address this topic through the lens of obstetrics and gynecology, including a discussion of specialty-specific characteristics that present unique challenges and opportunities to improve WLI.

Burnout Woman-Style: The Female Face of Burnout in Obstetrics and Gynecology
imageThis summary will address important information on women physicians, focusing on those practicing OG. We will review traits more commonly found in women, societal influences that make women physicians more susceptible to burnout, as well as the unique features of the medical profession that affect women differently. We conclude with a discussion of the shared responsibilities of both individuals and institutions for implementing interventions that will effectively improve women's resilience, identification of and recovery from burnout.

Moving From Physician Burnout to Resilience
imageWe contend that work ambivalence is a key building block in fostering physician burnout and its sequalae, while engagement in meaningful work and receiving family support for that work enhances resilience. No singular approach to curbing burnout in OBGYN physicians has received empirical support. Clinical experience suggests that curbing physician burnout requires a combination of workplace redesigns, positive leadership behaviors, and resilience training that teaches practical applications from the fields of resilience, emotional intelligence, positive psychology, and relationship systems. This paper highlights organizational and leadership interventions that foster physician engagement, and describes how physicians can foster personal and family resilience.

Organizational Strategies to Create a Burnout-resistant Environment
imageBurnout afflicts a significant number of academic faculty and clinicians. There are many efforts the individual can undertake to prevent or lessen burnout. However, it not likely these will be successful without the institutional environment that promotes and atmosphere that assures self-efficacy, a sense of value and meaning and clear communication between leaders and members of the organization. This review discusses the factors that organizations and their leaders can leverage to create such an environment. Such measures are critically important not only for the health of the individual but to the organization as well.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480

Implant Dentistry

Device Legislation...... Now Tread Cautiously
imageNo abstract available

The Sinus Bone Graft— Third Edition 2019
imageNo abstract available

Ridge Architecture Preservation Following Minimally Traumatic Exodontia Techniques and Guided Tissue Regeneration
imageObjective: To compare hard-tissue healing after 3 exodontia approaches. Materials and Methods: Premolars of dogs were extracted: (1) flapless, (2) flap, and (3) flap + socket coverage with polytetrafluoroethylene (dPTFE) nonresorbable membrane (flap + dPTFE). Animals were euthanized at 1 and 4 weeks. Amount of bone formation within socket and socket total area were measured. Results: Amount of bone formation revealed significant difference between 1 and 4 weeks; however, there was no differences among groups. Socket total area decreased after 4 weeks, and the flap + dPTFE group showed significantly higher socket total area. As a function of time and group, flap + dPTFE 4 weeks presented similar socket total area values relative to flap + dPTFE at 1 week, and significantly higher socket total area than flapless and flap. The histological sections revealed almost no bone formation within socket after 1 week, which increased for all groups at 4 weeks. Conclusion: Socket coverage with polytetrafluoroethylene (dPTFE) membrane showed to effectively preserve bone architecture. Bone formation within sockets was not influenced by tooth extraction technique.

Cone-Beam Computed Tomography Evaluation of the Submandibular Fossa in a Group of Dental Implant Patients
imageObjective: In the mandibular posterior region, presurgical imaging can provide valuable information of anatomical variants. The aim of this study is to evaluate submandibular fossa anatomy in the posterior mandible using cone-beam computed tomography (CBCT) scans. Study Design: One hundred thirty-two preimplant CBCT examinations were used. Several morphometric measurements were performed in the submandibular fossa. Moreover, each patient was classified according to the Kennedy classification. Statistical analysis was used to test the relationship among measurements, sex, side, and each tooth. Results: A total of 2412 measurements were performed from all patients. The deepest concavity at the submandibular fossa in all Kennedy Class groups was in the 1st and 2nd molars. The concavity depth was statistically higher in class I group for 1st and 2nd molars than the other Kennedy Class groups. Class IV group showed less depth than the other groups. When compared with female patients, all measurements in male patients were statistically higher. The patients older than 35 years showed higher measurements than the patients younger than 35 years. Conclusions: Mandibles with any lingual concavity pose a potential increased risk of lingual cortical perforation during surgery. This study revealed that the alveolar bone resorption occurs both vertically and horizontally, and the preservation of teeth can limit the bone resorption.

Distribution of Trabecular Bone Density in the Maxilla and Mandible
imageIntroduction: Implant osseointegration is strongly influenced by the bone quality at the implant insertion site. The present work aims to create distribution diagrams showing the average bone density at each position within the jaws. Materials and Methods: Data were retrospectively collected from 4 oral surgeons who sought bone-density measurements during implant placement using a torque-measuring implant micromotor. Statistical analyses were performed to investigate whether bone density correlated with the patients' sex and age and whether the bone-density values at different positions within each arch correlated to each other. Results: Records of 2408 patients and 6060 bone-density readings were retrieved, and density distribution diagrams were created. Density values showed a significant variation within subjects. Within the same jaw, density between adjacent positions showed significant differences. Density at a given position correlated significantly with that at the other positions in most cases. Bone density was significantly lower in women than in men; no significant correlation was found between bone density and the patient age. Conclusions: Bone density of patients displays significant interindividual variation, thus meaningful assessment must be conducted on a patient-by-patient basis.

Alveolar Ridge Expansion by Osseodensification-Mediated Plastic Deformation and Compaction Autografting: A Multicenter Retrospective Study
imageIntroduction: Osseodensification preserves bone bulk, facilitates compaction autografting, and deforms trabecular bone in an outward strain, which result in alveolar ridge plastic expansion. The aim of this retrospective study was to evaluate ridge expansion after osseodensification. Materials and Methods: Patients treated with implant placement through osseodensification were evaluated. The alveolar ridge width was measured at the level of the crest and 10 mm apical to the crest before and after osseodensification. Insertion torque and implant stability quotient (ISQ) values were recorded at implant placements. Expansion values were grouped into the following 3 groups according to the initial alveolar ridge width: group 1: 3 to 4 mm (n = 9), group 2: 5 to 6 mm (n = 12), and group 3: 7 to 8 mm (n = 7). Results: Twenty-one patients who received 28 implants were included. Twenty-six implants were integrated, resulting in a survival rate of 92.8%. There was a significant difference in the mean expansion value at the coronal aspect of the ridge between group 1, group 2, and group 3 (2.83 ± 0.66 mm, 1.5 ± 0.97 mm, 1.14 ± 0.89 mm, P < 0.05). The mean torque and ISQ values were 61.2 ± 13.9 Ncm and 77 ± 3.74. Conclusion: Osseodensification can alter ridge dimensions and allow for ridge expansion. Greater expansion can be expected at the crest in narrow ridges with adequate trabecular bone volume.

Prevalence of Maxillary Sinus Pathology Based on Cone-Beam Computed Tomography Evaluation of Multiethnicity Dental School Population
imageObjective: The goal of the study was to evaluate prevalence of maxillary sinus pathology among populations considered for possible sinus augmentation procedures for dental implants. Study Design: Eight hundred twenty-one cone-beam computed tomography (CBCT) scans were retrospectively evaluated for prevalence of maxillary sinus pathology. Scans were classified based on the type of sinus pathology detected. Categories of sinus findings were healthy, mucosal thickening larger than 3 mm, polypoidal mucosal thickening, partial opacification, complete opacification, and others. Age, sex, ethnicity, and dentition status were evaluated to determine associated relationships with the incidence of pathology. Results: Sixty-two percent (62.79%) of scans presented with bilateral healthy sinuses and 37.21% of scans exhibited pathology. 73.38% of sinuses were classified as clinical healthy, 14.93% presented with mucosal thickening, 8.53% with polypoidal mucosal thickening, 2.13% with partial opacification, 0.66% with complete opacification, and 0.37% with a foreign body. Sex is found to be a significant factor with higher pathology incidence rates in male patients. Age is a significant factor with higher pathology incidence rates in older subjects. Dentition status and ethnicity did not have a significant association with pathology incidence rates. Conclusions: The prevalence of maxillary sinus pathologies and associations with age, sex, ethnicity, and dentition status were obtained. Thirty-seven percent of scans would require further medical consultation before proceeding with maxillary sinus augmentation surgery for dental implants.

Feasibility of Assessing Maxillary and Mandibular Bone Mineral Density for Dental Implantation by Using Multidetector Computed Tomography
imagePurpose: The purpose of this study was to evaluate the feasibility of measuring bone mineral density (BMD) of the maxillary and mandibular bones for dental implantation by using multidetector computed tomography (MDCT). Materials and Methods: We performed MDCT in 141 patients (78 women and 63 men) at the lumbar vertebrae and at the maxillary and mandibular bones, with a view to dental implantation, from July 2015 to June 2017. Quantitative CT (QCT) using MDCT was performed to obtain Hounsfield unit (HU) values for the maxillary and mandibular bones and to obtain T scores for the lumbar vertebrae. We statistically analyzed the relationships among HU values, and the correlations of QCT values with T scores and of T scores with HU values. Results: There were statistically significant correlations among all these parameters. Conclusions: QCT using MDCT of the maxillary and mandibular bones seems to be a feasible method for measuring BMD before dental implantation.

Effect of Steam Heat Sterilization on the Accuracy of 3D Printed Surgical Guides
imageIntroduction: Steam heat sterilization could be one of the factors that affects the dimensional accuracy of surgical guides, leading to an error during guided implant surgery. Objective: The purpose of this study was to investigate the effect of steam heat sterilization on the dimensional changes of surgical guides. Materials and Methods: A total of 27 surgical guides, which were made by either Formlabs printer (Formlabs Inc., Somerville, MA) or Simplant (DENTSPLY Implants NV, Hasselt, Belgium), were scanned using an intraoral scanner before and after sterilization. The dimensional changes at the center of the implant sleeves were analyzed using the computer-aided design interactive software for 65 implant sites before and after steam heat sterilization at 121°C for 20 minutes. Results: There was no significant difference between the mean x, y, and z axes of the center of the sleeves when measured before and after sterilization (P values were 0.37, 0.24, and 0.29, respectively). Nonparametric analysis showed no significant difference between the mean deviations of either surgical guide (P = 0.908). Conclusion: Steam heat sterilization has a nonsignificant effect on the dimensional changes of the tested surgical guides.

Fracture of Zirconia Abutments in Implant Treatments: A Systematic Review
imagePurpose: The purpose of this systematic review was to identify and summarize clinical studies related to the fracture of zirconia abutments in implant treatments. Material and Methods: Medline, Embase, and Cochrane library searches were performed and complemented by manual searches from database inception to February 11, 2018, for title and abstract analysis. Results: Initially, 645 articles were obtained through database searches. Fifty-three articles were selected for full-text analysis, and 15 studies met the inclusion criteria. The selected studies were analyzed regarding fracture rate, abutment-implant connection, time point of fracture, location of critical crack, causes, managements, and preventive measures with respect to zirconia abutment fracture. Conclusions: Lower fracture rates were reported for internal connection with metal component (2-piece) zirconia abutments compared with external and internal full-zirconia connection (one-piece) zirconia abutments. Overpreparation and overload should be avoided in case of zirconia abutments.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480

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