Factors influencing hospital charges for tonsillectomy to treat obstructive sleep apnea in children.

PURPOSE: This study investigates the impact of patient characteristics and demographics on hospital charges for tonsillectomy as a treatment for pediatric obstructive sleep apnea (OSA). The aim is to identify potential disparities in hospital charges and contribute to efforts for equitable access to care. METHODS: Data from the 2016 Healthcare Cost and Utilization Project (HCUP) Kid Inpatient Database (KID) was analyzed. The sample included 3,304 pediatric patients undergoing tonsillectomy ± adenoidectomy for OSA. Variables such as age, race, length of stay, hospital region, residential location, payer information, and median household income were collected. The primary outcome variable was hospital charge. Statistical analyses, including t-tests, ANOVA, and multiple linear regression, were conducted. RESULTS: Among 3,304 pediatric patients undergoing tonsillectomy for OSA. The average total charges for tonsillectomy were $26,400, with a mean length of stay of 1.70 days. Significant differences in charges were observed based on patient race, hospital region, and payer information. No significant differences were found based on gender, discharge quarter, residential location, or median household income. Multiple linear regression showed race, hospital region, and residential location were significant predictors of total hospital charges. CONCLUSION: This study highlights the influence of patient demographics and regional factors on hospital charges for pediatric tonsillectomy in OSA cases. These findings underscore the importance of addressing potential disparities in healthcare access and resource allocation to ensure equitable care for children with OSA. Efforts should be made to promote fair and affordable treatment for all pediatric OSA patients, regardless of their demographic backgrounds.

How to be a GREAT mentor.

Formal training in how to mentor is not generally available to students, postdoctoral fellows, or junior faculty. We provide here a framework to develop as a mentor, using the GREAT model. This includes giving opportunities and opening doors; reaching out to help students identify their strengths and reach their goals; encouraging them by serving as a positive example; advising each mentee as an individual; and training them for independent thinking. In this personal view, we expand on each of these steps to illustrate how to develop a personalized mentoring style of your own. By combining these approaches, you as a mentor can work with your mentees to develop an effective and productive mentoring relationship.NEW & NOTEWORTHY We provide here a framework to develop as a mentor, using the GREAT model. This includes giving opportunities and opening doors; reaching out to help students identify their strengths and reach their goals; encouraging them by serving as a positive example; advising each mentee as an individual; and training them for independent thinking.

Rate and Risk Factors for Carbapenem Resistant Acinetobacter baumannii Clinical Infections in Colonized Patients.

BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAB) is an important cause of nosocomial infections. Active surveillance for CRAB carriage to identify and isolate colonized patients is used to reduce transmission. OBJECTIVES: To assess the rate and risks of clinical infection among CRAB-carrier and non-carrier patients. METHODS: Hospitalized patients from whom CRAB screening-cultures were obtained between January and June 2018 were identified retrospectively. All CRAB-carriers were compared to a convenient sample of non-carriers and were followed to detect development of CRAB clinical infection during admission. RESULTS: We compared 115 CRAB carriers to 166 non-carriers. The median age in the study group was 76 years (IQR 71-87) vs. 65 years (55-79) in the non-carriers group (P < 0.001). Residence in a nursing facility, debilitated state, and admission to medical wards vs. intensive care units were more frequent among CRAB-carriers (P < 0.001). Mechanically ventilated patients included 51 CRAB carriers (44%) and 102 non-carriers (61%). Clinical infection developed in 49 patients (17%), primarily CRAB pneumonia. Of the CRAB-carriers and non-carriers, 26/115 (23%) and 23/166 (14%), respectively, developed a clinical infection (P = 0.05). One-third of the ventilated patients were infected. Debilitated state and antibiotic treatment during hospitalization were linked to higher infection rates (P = 0.01). Adjusted analysis showed that mechanical ventilation and CRAB colonization were strongly associated with clinical infection (P < 0.05). CONCLUSIONS: The rate of CRAB infection among carriers was high. Mechanical ventilation and CRAB colonization were associated with CRAB clinical infection, primarily pneumonia.

Fetuin-A Promotes 3-Dimensional Growth in LNCaP Prostate Cancer Cells by Sequestering Extracellular Vesicles to Their Surfaces to Act as Signaling Platforms.

The present studies were conducted to evaluate key serum proteins and other components that mediate anchorage-independent growth (3-D growth) of LNCaP prostate cancer cells as spheroids. The cells were cultured on ultra-low attachment plates in the absence and presence of fetuin-A and with or without extracellular vesicles. The data show that fetuin-A (alpha 2HS glycoprotein) is the serum protein that mediates 3-D growth in these cells. It does so by sequestering extracellular vesicles of various sizes on the surfaces of rounded cells that grow as spheroids. These vesicles in turn transmit growth signals such as the activation of AKT and MAP kinases in a pattern that differs from the activation of these key growth signaling pathways in adherent and spread cells growing in 2-D. In the process of orchestrating the movement and disposition of extracellular vesicles on these cells, fetuin-A is readily internalized in adhered and spread cells but remains on the surfaces of non-adherent cells. Taken together, our studies suggest the presence of distinct signaling domains or scaffolding platforms on the surfaces of prostate tumor cells growing in 3-D compared to 2-D.

The Timing of Limb Amputation in Nontraumatic Patients: Impact on Mortality and Postoperative Complication Rates.

Diabetes and peripheral vascular diseases are accompanied frequently by lower limb ischemia and in minority, need for amputation, as a treatment of last resort. Even after a decision has been made regarding amputation, the procedures are often repeatedly postponed due to more urgent surgeries and lack of operating room availability. This study assessed the possible relationship between the duration of time inpatients wait for semiurgent amputations and the incidence of postamputation complications. A retrospective cohort, including all 360 adult patients who underwent nontraumatic limb amputation due to an ischemic/gangrenous/infected foot in a single center during an 11-year period (2007-2017). Most (96%) of the procedures were major amputations. The mean waiting time until amputation was 3 ± 5 days. Mortality during hospitalization occurred in 101 (28%) patients and re-amputation in 38 (11%). The duration of antibiotic treatment was 11 ± 14 days. The rate of sepsis was 30% (107/360). There was no significant difference between the duration of time until amputation and mortality during hospitalization: among those who waited ≤48 hours, the mortality rate was 27% (60/224) and among those who waited >48 hours 30% (41/136) (p = .5). Patients waiting ≤48 hours had higher re-amputation rates than those waiting >48 (31/223 (14%) vs 7/136 (5%), p = .009). Mortality was associated significantly to patients' age and renal function. Correlation was found between the waiting time until amputation (≤48 or >48 hours) and the rates of in-hospital mortality, sepsis, duration of antibiotic treatment and overall duration of hospitalization. Re-amputation rate was higher in group with the shorter waiting time. This correlation may be explained by the fact that patients who needed urgent amputation had a more extensive and severe disease, and thus tended to require more re-amputation operations.

Annona muricata silver nanoparticles exhibit strong anticancer activities against cervical and prostate adenocarcinomas through regulation of CASP9 and the CXCL1/CXCR2 genes axis.

BACKGROUND: Green synthesized nanoparticles have been earmarked for use in nanomedicine including for the development of better anticancer drugs. OBJECTIVE: The aim of this study was to undertake biochemical evaluation of anticancer activities of green synthesized silver nanoparticles (AgNPs) from ethanolic extracts of fruits (AgNPs-F) and leaves (AgNPs-L) of Annona muricata. METHODS: Previously synthesized silver nanoparticles were used for the study. The effects of the AgNPs and 5-Fluorouracil were studied on PC3, HeLa and PNT1A cells. The resazurin, migration and colonogenic assays as well as qRT-PCR were employed. RESULTS: The AgNPs-F displayed significant antiproliferative effects against HeLa cells with an IC50 of 38.58µg/ml and PC3 cells with an IC50 of 48.17µg/ml but selectively spared normal PNT1A cells (selectivity index of 7.8), in comparison with first line drug 5FU and AgNPs-L whose selectivity index were 3.56 and 2.26 respectively. The migration assay revealed potential inhibition of the metastatic activity of the cells by the AgNPs-F while the colonogenic assay indicated the permanent effect of the AgNPs-F on the cancer cells yet being reversible on the normal cells in contrast with 5FU and AgNPs-L. CASP9 was significantly over expressed in all HeLa cells treated with the AgNPs-F (1.53-fold), AgNPs-L (1.52-fold) and 5FU (4.30-fold). CXCL1 was under expressed in HeLa cells treated with AgNPs-F (0.69-fold) and AgNPs-L (0.58-fold) and over expressed in cells treated with 5FU (4.95-fold), but the difference was not statistically significant. CXCR2 was significantly over expressed in HeLa cells treated with 5FU (8.66-fold) and AgNPs-F (1.12-fold) but under expressed in cells treated with AgNPs-L (0.76-fold). CONCLUSIONS: Here we show that biosynthesized AgNPs especially AgNPs-F can be used in the development of novel and better anticancer drugs. The mechanism of action of the AgNPs involves activation of the intrinsic apoptosis pathway through upregulation of CASP9 and concerted down regulation of the CXCL1/ CXCR2 gene axis.

Lenalidomide maintenance for diffuse large B-cell lymphoma patients responding to R-CHOP: quality of life, dosing, and safety results from the randomised controlled REMARC study.

Lenalidomide maintenance therapy prolonged progression-free survival (PFS) versus placebo in elderly patients with diffuse large B-cell lymphoma (DLBCL) responding to induction chemotherapy in the phase 3 REMARC study. This subpopulation analysis assessed the impact of lenalidomide maintenance and treatment-emergent adverse events (TEAEs) on health-related quality of life (HRQOL). Global health status (GHS), and physical functioning and fatigue subscales were evaluated in patients who completed the European Organisation for Research and Treatment of Cancer quality-of-life questionnaire-C30 v3.0. The impact of TEAEs classified post hoc as subjective (patients can feel) or observable (only measurable by physicians) on dose reductions and discontinuations was assessed. Among 457 patients (lenalidomide, n = 229; placebo, n = 228), mean (standard deviation) GHS was similar between treatment arms [68·2 (20·7) Versus 72·0 (17·8)] at randomisation and remained similar during maintenance. Patients receiving lenalidomide experienced no meaningful changes in GHS, physical functioning, or fatigue. Observable TEAEs were more common (81·1% Versus 66·3%) and more likely to lead to dose reductions, than subjective TEAEs in both arms. PFS was superior in the lenalidomide arm regardless of dose reduction. Lenalidomide maintenance prolonged PFS and did not negatively impact HRQOL in patients with DLBCL despite TEAEs being more common, when compared with placebo.

Functional and radiological outcome of anterior retroperitoneal versus posterior transforaminal interbody fusion in the management of single-level lumbar degenerative disease.

OBJECTIVE: In this study the authors compared the anterior lumbar interbody fusion (ALIF) and posterior transforaminal lumbar interbody fusion (TLIF) techniques in a homogeneous group of patients affected by single-level L5-S1 degenerative disc disease (DDD) and postdiscectomy syndrome (PDS). The purpose of the study was to analyze perioperative, functional, and radiological data between the two techniques. METHODS: A retrospective analysis of patient data was performed between 2015 and 2018. Patients were clustered into two homogeneous groups (group 1 = ALIF, group 2 = TLIF) according to surgical procedure. A statistical analysis of clinical perioperative and radiological findings was performed to compare the two groups. A senior musculoskeletal radiologist retrospectively revised all radiological images. RESULTS: Seventy-two patients were comparable in terms of demographic features and surgical diagnosis and included in the study, involving 32 (44.4%) male and 40 (55.6%) female patients with an average age of 47.7 years. The mean follow-up duration was 49.7 months. Thirty-six patients (50%) were clustered in group 1, including 31 (86%) with DDD and 5 (14%) with PDS. Thirty-six patients (50%) were clustered in group 2, including 28 (78%) with DDD and 8 (22%) with PDS. A significant reduction in surgical time (107.4 vs 181.1 minutes) and blood loss (188.9 vs 387.1 ml) in group 1 (p < 0.0001) was observed. No significant differences in complications and reoperation rates between the two groups (p = 0.561) was observed. A significant improvement in functional outcome was observed in both groups (p < 0.001), but no significant difference between the two groups was found at the last follow-up. In group 1, a faster median time of return to work (2.4 vs 3.2 months) was recorded. A significant improvement in L5-S1 postoperative lordosis restoration was registered in the ALIF group (9.0 vs 5.0, p = 0.023). CONCLUSIONS: According to these results, interbody fusion is effective in the surgical management of discogenic pain. Even if clinical benefits were achieved earlier in the ALIF group (better scores and faster return to work), both procedures improved functional outcomes at last follow-up. The ALIF group showed significant reduction of blood loss, shorter surgical time, and better segmental lordosis restoration when compared to the TLIF group. No significant differences in postoperative complications were observed between the groups. Based on these results, the ALIF technique enhances radiological outcome improvement in spinopelvic parameters when compared to TLIF in the management of adult patients with L5-S1 DDD.

Prospective Audit of Empirical Antibiotic Therapy for Septic Patients.

BACKGROUND: Antibiotic stewardship programs are necessary to test the appropriateness of local guidelines for empirical antibiotic treatment by audits. OBJECTIVES: To assess whether compliance to local guidelines achieved a higher rate of appropriate antibiotic treatment and reduced morbidity and mortality, and whether infectious disease counseling improved the rate of appropriate treatment. METHODS: Our cohort comprised 294 patients with proven bacteremia. Data were retrieved from medical records including diagnosis, empiric antibiotic treatment, and outcomes. RESULTS: The empirical treatment was consistent with bacterial susceptibility in 227 patients (77%), and matched in 64% of the time to the first line, and another 24% to the second line of institutional guidelines. A strong correlation was found between appropriate empiric treatment according to bacterial susceptibility and reduced mortality (odds ratio [OR] 0.403, P = 0.007). A similar correlation was found with the choice of appropriate antibiotics according to local guidelines (OR 0.392, P = 0.005). Infectious disease consultation was related to an increase in the rate of appropriateness of treatment according to guidelines (85% vs.76%, P = 0.005). A tendency to increased appropriateness was related to microbial susceptibility (87% vs. 74%, P = 0.07). CONCLUSIONS: In this study, initiation of appropriate empiric antibiotic therapy, according to the hospital's guidelines, was found associated with reduced mortality in patients with bacteremia.

Lapatinib-induced annexin A6 upregulation as an adaptive response of triple-negative breast cancer cells to EGFR tyrosine kinase inhibitors.

The epidermal growth factor receptor (EGFR) is a major oncogene in triple-negative breast cancer (TNBC), but the use of EGFR-targeted tyrosine kinase inhibitors (TKI) and therapeutic monoclonal antibodies is associated with poor response and acquired resistance. Understanding the basis for the acquired resistance to these drugs and identifying biomarkers to monitor the ensuing resistance remain a major challenge. We previously showed that reduced expression of annexin A6 (AnxA6), a calcium-dependent membrane-binding tumor suppressor, not only promoted the internalization and degradation of activated EGFR but also sensitized TNBC cells to EGFR-TKIs. Here, we demonstrate that prolong (>3 days) treatment of AnxA6-low TNBC cells with lapatinib led to AnxA6 upregulation and accumulation of cholesterol in late endosomes. Basal extracellular signal-regulated kinase 1 and 2 (ERK1/2) activation was EGFR independent and significantly higher in lapatinib-resistant MDA-MB-468 (LAP-R) cells. These cells were more sensitive to cholesterol depletion than untreated control cells. Inhibition of lapatinib-induced upregulation of AnxA6 by RNA interference (A6sh) or withdrawal lapatinib from LAP-R cells not only reversed the accumulation of cholesterol in late endosomes but also led to enrichment of plasma membranes with cholesterol, restored EGFR-dependent activation of ERK1/2 and sensitized the cells to lapatinib. These data suggest that lapatinib-induced AnxA6 expression and accumulation of cholesterol in late endosomes constitute an adaptive mechanism for EGFR-expressing TNBC cells to overcome prolong treatment with EGFR-targeted TKIs and can be exploited as an option to inhibit and/or monitor the frequently observed acquired resistance to these drugs.

[PRINCIPLES OF APPROPRIATE ANTIBIOTIC USAGE IN ISRAELBY THE ISRAELI SOCIETY FOR INFECTIOUS DISEASES: TO WHOM ARE THEY DIRECTED?]

INTRODUCTION: In this issue of Harefuah Nesher and Strahilevitz discuss the principles of appropriate antibiotic guidelines based on a position paper by the Israeli Society for Infectious Diseases (ISID). This editiorial discusses for whom this position paper was intended. The first and most obvious target would be the Infectious Disease (ID) physicians themselves. Since the setup of ID units in Israeli hospitals in the 1970s and 1980s, all have engaged in antibiotic control and infection control. Antibiotic control in Israel has always consisted of antibiotic restriction, development of guidelines for the most commonly encountered infections, and oversight of adherence to guidelines (including computer applications). In comparison, antibiotic control was not an ID priority in US hospitals until the concept of antibiotic stewardship emerged in the last decade. Second, the position paper could have been intended for hospital managements, in order to provide the resources necessary to make appropriate antibiotic use an attainable goal, in particular: allocation of highly skilled manpower (physicians, clinical microbiologists, pharmacists) and development of relevant computer applications. Third, the position paper could have been intended as a response to the initiatives by Ministry of Health National Center for Infection Control and Antibiotic Use. The latter was set up more than a decade ago to deal with emerging multi-drug resistant pathogens and to provide professional leadership. Unfortunately, a professional conflict has emerged between the ISID and the National Center, when the latter was trying to impose professional guidelines regarding antibiotic stewardship unilaterally. While Nesher and Strahilevitz outline the ISID view on antibiotic stewardship in Israeli hospitals, they also call for cooperation and joining forces to combat the huge problem of antibiotic resistance in Israel. Forth, the position paper was probably also intended for all physicians who prescribe antimicrobials, to engage them in the responsibility of guarding antibiotics for us and the next generations.

[INTERVENTIONS TO IMPROVE THE QUALITY OF THE INTERNSHIP YEAR].

AIMS: To describe three interventions that have improved the quality of the internship. BACKGROUND: All medical school graduates are required to take a one year internship, rotating through various hospital departments. By various objective and subjective measures, the quality, benefit and efficacy of the internship varies significantly between departments and hospitals and also depends on where the interns studied. METHODS: The interventions were: First, all graduates of foreign medical schools (FMG) were required to interview and present a patient, demonstrating practical knowledge of spoken and written Hebrew and basic medical terminology prior to the start of the internship. Second, on the first day of their internship in internal medicine the new interns participate in an orientation day, addressing multiple clinical, administrative and other components. Third, upon the completion of their rotation in internal medicine, the interns participate in an interactive session to help them prepare for their future career. RESULTS: First, during the first 3 years after introducing the Hebrew test, 101 FMGs took the test, 89 (88%) passed the first time, the remainder passed the 2nd or 3rd test after another 1-3 months of studying Hebrew. Of 31 women, 30 (97%) passed the first time, compared to 59/70 (84%) of the men (p=0.065); 27/28 (96%) of Jewish interns passed the first time compared to 62/73 (85%) non-Jewish interns (p=0.99). Physicians report on the significantly increased ability of FMGs to participate in all activities from the onset of their internship. Second, upon completion of the orientation, 137 interns provided feedback of its 12 components; satisfaction was marked on a Likert scale (ranging from 1 [low] to 5 [high]) and ranged from 4.2±0.1 to 4.7±0.6; high/very high satisfaction with the various components ranged from 79% to 96%. Third, feedback was provided by 96 interns after participating in the interactive session helping to prepare for the future; satisfaction with the 5 components of the session ranged from 3.8±0.8 (on the acquired insight into the possibilities, scope and limitations regarding their future career) to 4.5±0.7 (regarding the relevance of such sessions). Sub-analysis revealed several statistically significant differences between male and female interns (male interns indicated these sessions to be more important to them than females, p<0.01), and FMG (as compared to graduates from Israeli medical schools) indicated that they had acquired relevant information more often (p<0.001). CONCLUSIONS: Various interventions positively impact the quality, benefit and efficacy of the internship as observed by physicians working with the residents, as well as perceived by the interns themselves.

PML-Nuclear Bodies Regulate the Stability of the Fusion Protein Dendra2-Nrf2 in the Nucleus.

BACKGROUND/AIMS: Nuclear factor erythroid 2-related factor 2 (Nrf2) is a basic leucine-zipper transcription factor essential for cellular responses to oxidative stress. Degradation of Nrf2 in the cytoplasm, mediated by Keap1-Cullin3/RING box1 (Cul3-Rbx1) E3 ubiquitin ligase and the proteasome, is considered the primary pathway controlling the cellular abundance of Nrf2. Although the nucleus has been implicated in the degradation of Nrf2, little information is available on how this compartment participates in degrading Nrf2. METHODS: Here, we fused the photoconvertible fluorescent protein Dendra2 to Nrf2 and capitalized on the irreversible change in color (green to red) that occurs when Dendra2 undergoes photoconversion to study degradation of Dendra2-Nrf2 in single live cells. RESULTS: Using this approach, we show that the half-life (t1/2) of Dendra2-Nrf2 in the whole cell, under homeostatic conditions, is 35 min. Inhibition of the proteasome with MG-132 or induction of oxidative stress with tert-butylhydroquinone (tBHQ) extended the half-life of Dendra2-Nrf2 by 6- and 28-fold, respectively. By inhibiting nuclear export using Leptomycin B, we provide direct evidence that degradation of Nrf2 also occurs in the nucleus and involves PML-NBs (Promyelocytic Leukemia-nuclear bodies). We further demonstrate that co-expression of Dendra2-Nrf2 and Crimson-PML-I lacking two PML-I sumoylation sites (K65R and K490R) changed the decay rate of Dendra2-Nrf2 in the nucleus and stabilized the nuclear derived Nrf2 levels in whole cells. CONCLUSION: Altogether, our findings provide direct evidence for degradation of Nrf2 in the nucleus and suggest that modification of Nrf2 in PML nuclear bodies contributes to its degradation in intact cells.

Influence of biochar aged in acidic soil on ecosystem engineers and two tropical agricultural plants.

Biochar amendment to soil is predicted globally as a means to enhance soil health. Alongside the beneficial result on soil nutrient availability and retention, biochar is presumed to increase soil macro / microbiota composition and improve plant growth. However, evidence for such an effect remains elusive in many tropical agricultural soils. The influence of biochar aged in soil was assessed on soil microbiota, macrobiota (Eudrilus eugeniae), seedling emergence and early plant growth of Oryza sativa and Solanum lycopersicum in tropical agricultural soil, over a 90 d biochar-soil contact time. Results showed negative impacts of increased loading of biochar on the survival and growth of E. eugeniae. LC50 and EC50 values ranged from 34.8% to 86.8% and 0.9-23.7% dry biochar kg-1 soil, over time. The growth of the exposed earthworms was strongly reduced (R2 = -0.866, p < 0.05). Biochar significantly increased microbiota abundance relative to the control soil (p < 0.001). However, fungal population was reduced by biochar addition. Biochar application threshold of 10% and 5% was observed for (O. sativa) and (S. lycopersicum), respectively. Furthermore, the addition of biochar to soil resulted in increased aboveground (shoot) biomass (p < 0.01). However, the data revealed that biochar did not increase the belowground (root) biomass of the plant species during the 90 d biochar-soil contact time. The shoot-to-root-biomass increase indicates a direct toxic influence of biochar on plant roots. This reveals that nutrient availability is not the only mechanism involved in biota-biochar interactions. Detailed studies on specific biota-plant-responses to biochars between tropical, temperate and boreal environments are needed to resolve the large variations and mechanisms behind these effects.

[SELECTING A SPECIALTY BY INTERNS IN A CHANGING PERIOD: A MULTI-YEAR AND SINGLE-CENTER EXPERIENCE].

AIMS: To collect data on the expectations of interns at the onset of their internship regarding their professional future and the actual realization of these expectations of medical graduates who completed their internship in one medical center during the years 2010-2015. BACKGROUND: The internship year may have great importance in the decision-making process regarding selection of future residency. Previous research conducted 10-20 years ago involved graduates of Israeli medical schools. In the current era up to 50% of interns are foreign medical graduates (FMG), and it is not clear whether all of these professionals find a residency or employment according to their wishes. METHODS: Our hospital's database includes demographic details of all 237 graduates of the aforementioned years, according to gender (64% male); medical school (Israeli 50%); and ethnicity (Jewish, 66%). The aim of the study was to call all graduates according to the telephone numbers in the database and obtain relevant information on the basis of a pre-arranged script and with a standardized questionnaire to achieve uniform collection of data. RESULTS: Of 237 graduates, 151 (64%) responded, of whom 101 (64%) were male, 90 (60%) were Jewish, and 80 (54%) were FMG. Most interns had decided on a future career at the onset of their internship (114, 75%), but at its completion this rate had decreased to 88 (59%). Their preferences included surgical specialties 40 (36%), pediatrics 34 (30%), internal medicine 22 (19%), family practice 9 (8%), and other specialties 8 (7%). At the conclusion of the internship 108 (75%) immediately started a residency program; the remainder started employment in the community not within the context of a residency. A high degree of satisfaction was examined for three factors: personal relations and ethics - 114 (76%), professional learning - 108 (72%) and counseling regarding their professional future - 46 (31%). At the onset of their internship,) 75 77%( of the men and 46 )75%( of the women had decided upon their future career, without major change by the year's end. In reality, 43 (84%) of the women started a residency, but only 63 (65%) of the men (p=0.013). At the start of the year 67 (77%) of the Jewish interns and 46 (75%) of the Arab interns had decided on a future career; at the end of the year, the rate for Jewish interns had increased to 74 (85%) and it had decreased to 31 (67%) for Arab interns (p=0.026). Of the Jewish sector 74 (85%) had actually started a residency, as compared to 33 (54%) of the Arab sector (p<0.001) and 26 (43%) Arab graduates started work in the community not within the context of a residency. The rate of Israeli graduates who at onset of their internship had decided on their future choice was similar to that of FMG, 55 (82%) as compared to, respectively, 58 (73%) (Non significant), but at the end of the year a significant gap had opened up, 47 (86%) vs. 40 (52%), respectively (p=0.04). In addition, and not surprisingly, there were significant differences in the three measures of satisfaction between the Israeli and foreign graduates. CONCLUSIONS: During the internship year significant differences emerge between the interns, according to gender, ethnic background or the country they had studied medicine. Improved counseling could possibly help interns to secure optimal employment, especially for foreign medical graduates.

[PREVALENCE OF AND POSSIBLE RISK FACTORS FOR PROLONGED HOSPITAL STAY IN DEPARTMENTS OF INTERNAL MEDICINE].

BACKGROUND: Prolonged hospitalization (PH) is associated with increasing rates of complications and cost. OBJECTIVES: To detect and quantify causes and predictors for PH in current practice. METHODS: PH was defined as higher than the 70th percentile of the mean hospitalization duration for each department (two medical departments and one acute geriatric ward). Demographic and clinical data were collected on admission in order to determine predictive factors for PH. Actual causes for PH were tested on the 4th day of hospitalization for all patients by: (1) questioning the patients' attending physicians using a structured questionnaire; (2) assessing the patients' charts using a validated tool. RESULTS: Data were collected during a 5-month study period for all 1092 consecutively admitted patients hospitalized in the three departments in the study of whom 337 (30%) had a PH. In the multivariate analysis we detected the following independent predictors for PH: (1) unmarried patients; (2) dependent-patients; (3) hospitalization in the geriatric versus medical department; (4) an expected high mortality rate according to a validated prediction score; (5) renal failure on admission; (6) prior admission in the previous 6 months. The disease leading to the current admissions was the reason for continued admission on day 4 in the patients with eventual PH in 85% of the cases, as compared to 93% in the control group with regular-duration of hospitalization (p=0.014). On day 4, non-medical reasons for prolonged duration were detected in 7% of those with eventual PH as compared to 1% in the control group (p=0.018). CONCLUSIONS: We already detected demographic and clinical predictors for PH on admission, some of which may be amenable to intervention.

[AN EDUCATIONAL INTERVENTION TO REDUCE THE RATE OF CONTAMINANTS IN BLOOD CULTURES AND IMPROVE APPROPRIATE ANTIBIOTIC TREATMENT].

INTRODUCTION: Blood cultures' contamination (BCC) is associated with unnecessary processing of cultures, higher cost, and occasionally, unjustified antibiotic treatment. We aimed to reduce the rate of BCC by educational intervention. In parallel, we also strove to expand the use of aminoglycosides (AMG) and reduce the utilization of beta-lactam antibiotics. The rate of BCC was assessed prospectively in the study department - the Emergency Department (ED) and in control departments - Medical Departments A, B and Geriatrics. Data was collected continuously during the study period and educational interventions were performed in the ED but not in the control departments. The intervention included meetings with ED staff, emphasizing proper blood culture collection technique, and post-intervention result updates. The utilization of AMG was encouraged in cases of suspected gram-negative bacteremia. The empirical and definitive antibiotic regimen was assessed. During the study period, a 30% decrease in BCC rate [33/564 (5.9%) to 30/734 (4.1%), p=0.143] was noted in the study department whereas a small increase in BCC rate was noted in the control departments. Logistic regression analysis revealed significantly different trends in BCC rate between the study and control departments (p<0.001). Additionally, an increase in AMG utilization was observed (7% to 40%) in patients with suspected gram-negative bacteremia with normal renal function (p=0.16). Educational intervention was successful in reducing the rate of BCC and in parallel, increasing the utilization of AMG. Repeat and frequent interventions are required to maintain such achievements.

Association of calcium sensing receptor polymorphisms at rs1801725 with circulating calcium in breast cancer patients.

BACKGROUND: Breast cancer (BC) patients with late-stage and/or rapidly growing tumors are prone to develop high serum calcium levels which have been shown to be associated with larger and aggressive breast tumors in post and premenopausal women respectively. Given the pivotal role of the calcium sensing receptor (CaSR) in calcium homeostasis, we evaluated whether polymorphisms of the CASR gene at rs1801725 and rs1801726 SNPs in exon 7, are associated with circulating calcium levels in African American and Caucasian control subjects and BC cases. METHODS: In this retrospective case-control study, we assessed the mean circulating calcium levels, the distribution of two inactivating CaSR SNPs at rs1801725 and rs1801726 in 199 cases and 384 age-matched controls, and used multivariable regression analysis to determine whether these SNPs are associated with circulating calcium in control subjects and BC cases. RESULTS: We found that the mean circulating calcium levels in African American subjects were higher than those in Caucasian subjects (p < 0.001). As expected, the mean calcium levels were higher in BC cases compared to control subjects (p < 0.001), but the calcium levels in BC patients were independent of race. We also show that in BC cases and control subjects, the major alleles at rs1801725 (G/T, A986S) and at rs1801726 (C/G, Q1011E) were common among Caucasians and African Americans respectively. Compared to the wild type alleles, polymorphisms at the rs1801725 SNP were associated with higher calcium levels (p = 0.006) while those at rs1801726 were not. Using multivariable linear mixed-effects models and adjusting for age and race, we show that circulating calcium levels in BC cases were associated with tumor grade (p = 0.009), clinical stage (p = 0.003) and more importantly, with inactivating mutations of the CASR at the rs1801725 SNP (p = 0.038). CONCLUSIONS: These data suggest that decreased sensitivity of the CaSR to calcium due to inactivating polymorphisms at rs1801725, may predispose up to 20% of BC cases to high circulating calcium-associated larger and/or aggressive breast tumors.

Spondylodiskitis and endocarditis due to Streptococcus gordonii.

BACKGROUND: Streptococcus gordonii is an infrequent cause of infective endocarditis (IE); associated spondylodiskitis has not yet been described in the literature. PURPOSE: We describe 2 patients who presented with new-onset, severe back pain; blood cultures revealed S. gordonii bacteremia, which led to the diagnosis of spondylodiskitis and IE. We review our 2-decade experience with S. gordonii bacteremia to describe the clinical and epidemiological characteristics of these patients. RESULTS: In our hospital over the last 20 years (1998-2017), a total of 15 patients with S. gordonii bacteremia were diagnosed, including 11 men and 4 women, and the mean age was 65 ± 22 (range 23-95). The most common diagnosis was IE (9 patients), spondylodiskitis (the presented 2 patients, who in addition were diagnosed with endocarditis), necrotizing fasciitis (1), sternitis (1), septic arthritis (1) and pneumonia (1). The 11 patients with IE were treated with penicillin ± gentamicin, or ceftriaxone for 6 weeks, 5 required valve surgery and 10/11 (91%) attained complete cure. The 2 patients with diskitis required 2-3 months of intravenous antibiotics to achieve complete cure. CONCLUSION: Spondylodiskitis was the presenting symptom of 2/11 (18%) patients with S. gordonii endocarditis. Spondylodiskitis should probably be looked for in patients diagnosed with S. gordonii endocarditis and back pain as duration of antibiotic treatment to achieve complete cure may be considerably longer.

Can Procalcitonin Contribute to the Diagnosis of Clostridium difficile Colitis?

BACKGROUND: It is a challenge to diagnosis Clostridium difficile colitis. OBJECTIVES: To determine, among patients who developed nosocomial diarrhea, whether serum procalcitonin (PCT) can distinguish between C. difficile toxin (CDT)-positive and CDT-negative patients. METHODS: This prospective study included 50 adults (>18 years) who developed diarrhea during hospitalization, 25 with a positive fecal test for CDT (study group) and 25 CDT negative (control group). RESULTS: Baseline demographic and underlying illnesses were similar in both groups. Duration of diarrhea was 6 ± 4 days and 3 ± 1 in the study and control groups, respectively (P = 0.001). Mean blood count was 20 ± 15 and 9.9 ± 4, respectively (P = 0.04). CRP level was higher in the study than in the control group (10.9 ± 7.4 and 6.6 ± 4.8, P = 0.028). PCT level was higher in the study group (4.4 ± 4.9) than the control group (0.3 ± 0.5, P = 0.102). A PCT level > 2 ng/ml was found in 7/25 patients (28%) and 1/25 (4%), respectively [odds ratio 9.33, 95% confidence interval (0.98 to 220), P = 0.049]. Multivariate analysis showed that only duration of diarrhea and left shift of peripheral leucocytes were significant indicators of CDT (P = 0.014 and P = 0.019, respectively). The mortality rate was 12/25 (48%) vs. 5/25 (20%), respectively (P = 0.04). CONCLUSIONS: We found a non-significant tendency to higher PCT levels in patients with CDT-positive vs. CDT-negative nosocomial diarrhea. However, a PCT level > 2 ng/ml may help distinguish between these patients.