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Malignant primary spinal tumors are rare making it difficult to perform large studies comparing epidemiologic, survival, and treatment trends. We investigated the largest registry of primary bone tumors, the National Cancer Database (NCDB), to compare epidemiologic and survival trends among these tumors.To use the NCDB to describe current epidemiologic trends, treatment modalities, and overall survival rates in patients with chordomas, osteosarcomas, chondrosarcomas, and Ewing sarcomas of the mobile spine. The secondary objective was to determine prognostic factors that impact overall survival rates.Retrospective study.A total of 1,011 patients with primary bone tumors of the spine (377 chordomas, 223 chondrosarcomas, 278 Ewing sarcomas, and 133 osteosarcomas).Five-year survival.We reviewed the records of 1,011 patients in the NCDB from 2004 through 2015 with histologically confirmed primary osteosarcoma, chondrosarcoma, Ewing sarcoma, or chordoma of the spine. Demographic, clinical, and outcomes data were compiled and compared using chi-squared tests and ANOVA. Long-term survival was compared using the Kaplan-Meier method with statistical comparisons based on the log-rank test. Multivariate analysis was performed to determine survival determinants.Surgical resection was the primary mode of treatment for chondrosarcoma (90%), chordoma (84%), and osteosarcoma (80%). The treatment for Ewing sarcoma was multimodal involving chemotherapy, radiation therapy, and surgical resection. Five-year survival rates varied significantly with chordomas and chondrosarcomas having the greatest survival (70% and 69%), osteosarcomas having the worse survival (38%), and Ewing having intermediate 5-year survival at 62% (overall log-rank p.0001). Multivariate analysis demonstrated significantly improved 5-year survival rates with younger age at diagnosis, private insurance status, lower comorbidity score, lower tumor grade, smaller tumor size, surgical resection, and negative surgical margin. Radiation therapy only improved survival for Ewing sarcoma.This study provides the most comprehensive description of the epidemiologic, treatment, and survival trends of primary bone tumors of the mobile spine. Second, patient and tumor characteristics associated with improved 5-year survival were identified using a multivariate model.

Purpose: To compare the effectiveness of starting the ovarian stimulation on the early follicular phase (“Conventional”) with the newer range of non-conventional approaches starting in the luteal phase (“Luteal”), random-start, and studies implementing them in DuoStim (“Conventional”+“Luteal”). Methods: Systematic review. We searched CENTRAL, PubMed, and Embase, on March 2020. We included randomized and non-randomized controlled trials that compared “Luteal,” random-start ovarian stimulation or DuoStim with “Conventional”; we analyzed them by subgroups: oocyte freezing and patients undergoing ART treatments, both, in the general infertile population and among poor responders. Results: The following results come from a sensitivity analysis that included only the low/moderate risk of bias studies. When comparing “Luteal” to “Conventional,” clinically relevant differences in MII oocytes were ruled out in all subgroups. We found that “Luteal” probably increases the COH length both, in the general infertile population (OR 2.00 days, 95% CI 0.81 to 3.19, moderate-quality evidence) and in oocyte freezing cycles (MD 0.85 days, 95% CI 0.53 to 1.18, moderate-quality evidence). When analyzing DuoStim among poor responders, we found that it appears to generate a higher number of MII oocytes in comparison with a single “Conventional” (MD 3.35, 95%CI 2.54–4.15, moderate-quality evidence). Conclusion: Overall, this systematic review of the available data demonstrates that in poor responders, general infertile population and oocyte freezing for cancer stimulation in the late follicular and luteal phases can be utilized in non-conventional approaches such as random-start and DuoStim cycles, offering similar outcomes to the conventional cycles but potentially with increased flexibility, within a reduced time frame. However, more well-designed trials are required to establish certainty. Fil: Glujovsky, Demian. Centro de Estudios en Ginecología y Reproducción; Argentina. Instituto de Efectividad Clínica y Sanitaria; Argentina Fil: Pesce, Romina. Hospital Italiano; Argentina Fil: Miguens, Mariana. Centro de Estudios en Ginecología y Reproducción; Argentina Fil: Sueldo, Carlos E.. Centro de Estudios en Ginecología y Reproducción; Argentina. University Of California, San Francisco; Estados Unidos Fil: Lattes, Karinna. No especifíca; Fil: Ciapponi, Agustín. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentina

RESEARCH QUESTION: Does a freeze-all strategy improve live birth rates in women of different age groups? DESIGN: Retrospective cohort study of 1882 first embryo transfer cycles, performed between January 2013 and December 2015. Reproductive outcomes between fresh (FRESH) or frozen (FROZEN) embryo transfers were compared in patients stratified by age: 38 years. Student’s t test for independent samples and χ(2) analyses were used as needed. A multivariable logistic regression analysis was performed adjusting for age, triggering drug, number of retrieved oocytes, number of transferred embryos, and percentage of top-quality embryos. MAIN RESULTS AND THE ROLE OF CHANCE: Live birth rates (LBR) were significantly higher for FROZEN in the 38 years groups, LBR for FROZEN vs FRESH were not statistically different (30.9% in the FROZEN group vs 29.3% in the FRESH group, p = 0.70, and 19.8% in the FROZEN group vs 12.7% in the FRESH group, p = 0.07, respectively). The multivariate analysis found a significantly positive effect of performing FROZEN on LBR in the younger group (OR 2.46, 95% CI 1.31–4.62; p = 0.005) but had no impact in women between 35 and 38 years (OR 1.01, 95% CI 0.55–1.83; p = 0.98) or older (OR 0.96, 95% CI 0.43–2.13; p = 0.92). CONCLUSIONS: Performing a freeze-all strategy seems to result in better reproductive outcomes when compared with a fresh ET in women under 35 years, with no significant impact on older women.

STUDY DESIGN: Retrospective review OBJECTIVE: To determine if adjuvant radiation therapy (RT) improves overall survival (OS) following surgical resection of chordomas. SUMMARY OF BACKGROUND DATA: The role of RT for the treatment of chordomas remains incompletely described. Previous studies have not found adjuvant RT to improve OS, but these studies did not group patients based on surgical margin status or radiation dose or modality. We used the National Cancer Database to investigate the role of RT in chordomas following surgical resection. METHODS: Patients were stratified based on surgical margin status (positive vs negative). Utilizing the Kaplan Meier method, OS was compared between treatment modalities (surgical resection alone, therapeutic RT alone, and surgical resection plus therapeutic RT). OS was subsequently compared between patients treated with palliative dose (65Gy) RT. Similarly, OS was compared between advanced RT modalities including proton beam therapy (PBT) and intensity-modulated radiation therapy (IMRT), stereotactic radiosurgery (SRS), and external beam radiation therapy (EBRT). A multivariable model was used to determine adjusted variables predictive of mortality. RESULTS: 1,478 chordoma patients were identified; skull base (n=567), sacral (n=551), and mobile spine (n=360). Surgical resection and therapeutic adjuvant RT improved 5-year survival in patients with positive surgical margins (82% vs 71%, p=0·03). No clear survival benefit was observed with the addition of adjuvant RT in patients with negative surgical margins. High dose RT was associated with improved OS compared to palliative and low dose RT (p65Gy) was superior to EBRT. CONCLUSION: Patients with positive surgical margins benefit from adjuvant RT. Optimal OS is associated with adjuvant RT administered with advanced techniques and cumulative dose >65 Gy.

Facility volume has been correlated with survival in many cancers. This relationship has not been established in primary malignant bone tumors of the vertebral column (BTVC).To investigate whether facility patient volume is associated with overall survival in patients with primary malignant BTVCs.Retrospective comparative cohort.Adult patients with chordomas, chondrosarcomas, or osteosarcomas of the mobile spine.Five-year survival.We retrospectively analyzed 733 patients with primary malignant BTVCs in the national cancer database from 2004 through 2015. Univariate and multivariate analyses were used to correlate specific outcome measures with facility volume. Volume was stratified based on cumulative martingale residuals to determine the inflection point of negative to positive impact on survival based on the patient cohort. Long-term survival was compared between patients treated at high and low volume using the Kaplan-Meier method. Only patients with malignant primary tumors were considered eligible for inclusion; patients with incomplete treatment data or benign tumors were excluded.Patients treated at high-volume centers (HVCs) were younger (p=.0003) and more likely to be insured (p.0001). There were no significant differences in tumor characteristics. Patients treated at high-volume facilities had improved 5-year survival of 71% versus 58% at low-volume centers (p.0001). Patients treated at HVCs were more likely to receive surgical treatment (91% vs. 80%, p.0001); if surgery was performed, they were more likely to undergo an en bloc resection (48% vs. 30%, p.0001). However, there were no differences in margin status or utilization of radiotherapy or chemotherapy between HVCs and low-volume centers. In a multivariate analysis, facility volume was independently associated with improved survival overall (HR 0.75 [0.58-0.97], p=.03).Primary malignant BTVCs are rare, even for HVCs. Despite this, patient survival was significantly improved when treatment was performed at HVCs.

STUDY QUESTION Does the time from ovum pick-up (OPU) to frozen embryo transfer (FET) affect reproductive outcomes in a freeze-all strategy? SUMMARY ANSWER Our study did not detect statistically significant differences between first and subsequent cycles, clinically relevant differences are not ruled out and further and larger studies are required. WHAT IS KNOWN ALREADY Following controlled ovarian hyperstimulation (COH) delaying FET until the endometrium has returned to an optimal pre-stimulation state may have a significant emotional impact on patients, which adds to the stress and anxiety accompanying a standard IVF cycle. Currently there is no agreement on the best time to perform a FET after a freeze-all cycle in order to maximize reproductive outcomes for the patient. STUDY DESIGN, SIZE, DURATION: Retrospective cohort study of 512 freeze-all cycles, performed between January 2012 and December 2014. COH was performed by either a GnRH antagonist (n = 397) or a long GnRH agonist protocol (n = 115). Ovulation was triggered using either a GnRH agonist (n = 258) or hCG (n = 254). Endometrial preparation was performed in an artificial cycle by either oral (n = 238) or transdermal (n = 274) oestrogen. Differences were considered significant if P < 0.05. PARTICIPANTS/MATERIALS, SETTING, METHODS Reproductive outcomes between FETs which took place either within the first menstrual cycle following OPU (Cycle 1; n = 263) or afterwards (Cycle ≥2; n = 249) were compared. Student's t-test for independent samples, Mann-Whitney U-test and Chi-square analysis were used where appropriate. A multivariable logistic regression analysis was performed adjusting for maternal age, drug used for ovulation trigger, number of retrieved oocytes, number of embryos obtained, day of embryonic development at transfer, number of embryos transferred and type of endometrial preparation. Differences were considered significant if P < 0.05. MAIN RESULTS AND THE ROLE OF CHANCE Live birth rate (LBR) was significantly higher in FET performed during Cycle 1 vs Cycle ≥2 (37.6% vs 27.3%, respectively; P = 0.01) before adjusting for confounding factors. We found no difference for biochemical pregnancy (49.8% vs 43.8%; P = 0.17), clinical pregnancy (44.1% vs 36.1%; P = 0.07) or pregnancy loss (11.8% vs 16.1%; P = 0.16). A multivariable analysis found no impact of timing of elective FET on LBR (odds ratio, OR 0.73; 95% CI 0.49-1.08). The impact remained not significant after adjusting for number of retrieved oocytes, drug used for ovulation trigger (hCG vs GnRH agonist) and reason for cryopreservation. The factors that significantly affected LBR were: maternal age in both age categories (women between 35 and 40 years vs women below 35 years, OR 0.63, 95% CI 0.4-0.95; and women over 40 years vs women below 35 years, OR 0.34, 95% CI 0.2-0.7), day of embryonic development at transfer (day +4 vs +3; OR 1.7, 95% CI 1.1-2.8) and number of transferred embryos (OR 2.2, 95% CI 1.4-3.3) and oestrogen used for endometrial preparation (transdermal vs oral; OR 0.62, 95% CI 0.4-0.9). LIMITATIONS REASONS FOR CAUTION The main limitation of our study is its retrospective nature. Although we adjusted our statistical analysis for a number of known and suspected confounders, we cannot exclude the possibility of residual confounding factors. WIDER IMPLICATIONS OF THE FINDINGS According to our results, clinicians might not need to wait more than one menstrual cycle before performing FET. This allows us to reduce unnecessary delays in FET, without compromising reproductive outcomes. STUDY FUNDING/COMPETING INTERESTS No funding was sought for this study. Authors declare no competing interests. TRIAL REGISTRATION NUMBER NA.

STUDY DESIGN Literature review and retrospective case-control study (level 3 evidence) examining 50 adolescent idiopathic scoliosis (AIS) (Lenke I or II curve) cases with 32 healthy controls of the same age. The sagittal profiles were measured preoperatively, 6 months, and 2 years after surgery and compared with those of age-matched controls at baseline. OBJECTIVE The purpose of this study is to compare baseline sagittal profiles of AIS Lenke I and II curves with age-matched healthy controls and at 6 months and 2 years after surgery, as well as with previously published reports. SUMMARY OF BACKGROUND DATA Sagittal alignment and profiles have gained significant attention in spinal deformity outcomes. The sagittal profile of patients with AIS has been previously reported, as well as the effects of surgical correction, with inconsistent results and no clear references to nonscoliotic controls. METHODS Baseline sagittal profiles of 50 patients presenting with Lenke I or II AIS curves treated with selective thoracic fusion were compared with 32 age-matched controls without spinal pathology. These values were also measured at 6 months and 2 years postoperatively to examine effects of selective thoracic fusion over time. Sagittal parameters examined include pelvic incidence, pelvic tilt, C7 plumb line (sagittal vertical alignment), thoracic kyphosis, and lumbar lordosis. A literature review was performed comparing previously published data. Data are presented as mean (95% confidence interval). P value of less than 0.05 was considered significant. RESULTS Interobserver reliability (Cohen κ= 0.49-0.95). All demographic and preoperative sagittal alignment parameters were comparable between controls and patients with AIS prior to surgery. After selective thoracic fusion, thoracic kyphosis decreased significantly from baseline (25.4o [21.6-29.2] vs. 15.3o [12.8-17.8]; P < 0.001) at 6 months and at 2 years (10.3o [7.5-13.1]; P < 0.001). The lumbar lordosis significantly decreased at 6 months from baseline (54.5o [28.6-80.5] vs. 61.8o (33.4-90.1); P < 0.001) and at 2 years (55.4o [29.0-81.9]; P < 0.001). Sagittal vertical alignment, pelvic tilt, and pelvic incidence were comparable between controls and patients with AIS at baseline and did not change with surgery. CONCLUSIONS Adolescents with Lenke I or II curves have comparable sagittal profiles with those of healthy controls of the same age. This suggests that Lenke I and II curves may not be hypokyphotic as previously thought. After selective thoracic fusion, patients with AIS have a significantly decreased thoracic kyphosis, which is accompanied by reciprocal changes in the noninstrumented lumbar curve. Sagittal vertical alignment and pelvic tilt are not significantly affected. These results agree with previous reports, which suggest that constructs with pedicle screws have a higher impact on sagittal curves but do not affect sagittal or spinopelvic alignment. The long-term effects of abnormal sagittal profiles need further clarification. LEVEL OF EVIDENCE 3.

Retrospective cohort study.To demonstrate a correlation between radiculopathy symptoms, foraminal morphology, and curve types.Patients with degenerative scoliosis frequently present with foraminal stenosis and radiculopathy, the origin of which is not well understood.A total of 48 patients (384 foraminas) were included: 14 with low back pain (B); 16 with femoral nerve pain (F); and 18 with sciatic nerve pain (S). The symptomatic foramen of groups F and S were compared with asymptomatic foramina. Alignment was measured from standardized radiographs; 3D-CT reconstructions were used to measure foraminal height and area. Data are presented as mean±SD. The χ, t test, and Pearson coefficients were calculated; as well as interobserver and intraobserver reproducibility (Cohen κ).Seventeen of the 18 patients with sciatic nerve pain (S) presented foraminal stenosis (40 mm) at the concavity of the fractional curve distal to the main lumbar structural curve. The symptomatic foramina were significantly smaller in height (7.8±2.5 vs. 12.1±3.1 mm, P0.0001) and area (30.1±14.3 vs. 57.6±28.7 mm, P0.0001) compared with asymptomatic foramen; 7/7 patients with femoral nerve pain (F) and lumbar structural curves (apex L3 or lower) had foraminal stenosis at the concavity of the fractional curve. Eight of the 9 patients with femoral nerve pain (F) and thoracic, thoracolumbar, or lumbar (apex L2 or higher) curves, presented foraminal stenosis in the concavity of the caudal fractional curve. The symptomatic foraminal spaces were significantly smaller in height (9.2±3.2 vs. 12.1±3.1 mm, P0.0001) and area (30.1±15.2 vs. 57.6±28.7 mm, P0.0001). Foraminal height correlated with foraminal area (r=0.68-0.85; P0.0001). Interobserver agreement was between 0.6092 and 0.8679.A correlation between curve types and symptomatic foraminal stenosis exists. Adult scoliosis patients with sciatic nerve pain typically present with foraminal stenosis at the concavity of the caudal fractional curve. Similarly, patients with femoral nerve pain present with foraminal stenosis at the concavity of the caudal fractional curve when the main structural curve is thoracic, thoracolumbar, or lumbar (apex L2 or higher).

STUDY DESIGN Retrospective review of a prospective cohort. OBJECTIVE To determine the incidence, causes, and risk factors for 30-day unplanned readmissions after lumbar spine surgery. SUMMARY OF BACKGROUND DATA The rising costs associated with lumbar spinal surgery have received national attention. Recently, the government has chosen to target 30-day readmissions as a quality measure. Few studies have specifically analyzed the incidence, causes, and risk factors for readmission in a multicenter patient cohort. METHODS A large, multicenter clinical registry was queried for all patients undergoing lumbar spine surgery in 2012. Current Procedural Terminology codes were used to select patients undergoing lumbar discectomy, laminectomy, anterior and posterior fusions, and multilevel deformity surgery. Thirty-day readmissions rates and causes were identified and analyzed. Univariate and multivariate logistic regression analyses were used to identify patient characteristics, comorbidities, and operative variables predictive of readmission. RESULTS Overall, 695 of 15,668 patients undergoing lumbar spine surgery had unplanned 30-day hospital readmissions (4.4%). When separated by procedure type, readmissions were lowest after discectomy, 3.3%, and highest after deformity surgery, 9.0% (P < 0.001). The top causes for readmission were wound-related (38.6%), pain-related (22.4%), thromboembolic (9.4%), and systemic infections (8.0%). Predictors of readmission included advanced patient age more than 80 years (P = 0.03), African American race (P = 0.03), recent weight loss (P = 0.04), chronic obstructive pulmonary disorder (P < 0.01), history of cancer (P = 0.04), creatinine more than 1.2 (P < 0.01), elevated ASA class (P = 0.01), operative time more than 4 hours (P = 0.01), and prolonged hospital length of stay more than 4 days (P < 0.01). CONCLUSION Thirty-day unplanned readmission rates increased with procedure invasiveness. Both medical and surgical reasons contributed to readmission, many unavoidable. Surgeons should explore optimization measures for those at risk of early, unplanned readmission. LEVEL OF EVIDENCE 3.

Paolo A. Grossi, Alessandro Nanni Costa, Deirdre Fehily, Emily A. Blumberg, Matthew J. Kuehnert, Jay A. Fishman, Michael G. Ison, Roberta Lattes, Camille N. Kotton, Daniele Lilleri, Anne Kabanova, Antonio Lanzavecchia, Giuseppi Gerna, Raymund R. Razonable, Patrizia Comoli, Marco Zecca, Sabrina Basso, Fabrizio Ginevri, Alessandra Grossi, Francesco P. Schena, Antoni Rimola, Patrizia Burra, Elenora De Martin, Kryssia Isabel Rodriguez-Castro, Stefano Fagiuoli, Luisa Pasulo, Raffaele Bruno, Pietro Andreone, Elisabetta Loggi, Fabio Arena, Gian Maria Rossolini, Gabriele Sganga, and Valerio Cozza

Organ transplantation (TX) is a novel transmission modality of Chagas disease. The results of molecular diagnosis and characterization of Trypanosoma cruzi acute infection in naïve TX recipients transplanted with organs from infected deceased donors are reported. Peripheral blood and cerebrospinal fluid samples from the TX recipients of organs from infected donors were prospectively and sequentially studied for detection of T. cruzi by means of kinetoplastid DNA polymerase chain reaction (kDNA-PCR). In positive blood samples, a PCR algorithm for identification of T. cruzi Discrete Typing Units (DTUs) and quantitative real-time PCR (qPCR) to quantify parasitic loads were performed. Minicircle signatures of T. cruzi infecting populations were also analyzed using restriction fragment length polymorphism (RFLP)-PCR. Eight seronegative TX recipients from four infected donors were studied. In five, the infection was detected at 68.4 days post-TX (36–98 days). In one case, it was transmitted to two of three TX recipients. The comparison of the minicircle signatures revealed nearly identical RFLP-PCR profiles, confirming a common source of infection. The five cases were infected by DTU TcV. This report reveals the relevance of systematic monitoring of TX recipients using PCR strategies in order to provide an early diagnosis allowing timely anti-trypanosomal treatment. Fil: Cura, Carolina Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; Argentina Fil: Lattes, R.. Instituto de Nefrologia de Buenos Aires; Argentina Fil: Nagel, C.. Universidad Favaloro; Argentina Fil: Gimenez, M. J.. Hospital Universitario y Politécnico LA FE. Servicio de Microbiología; España Fil: Blanes, M.. Hospital Universitario y Politécnico LA FE. Area Médica. Unidad de Enfermedades Infecciosas; España Fil: Calabuig, E.. Hospital Universitario y Politécnico LA FE. Area Médica. Unidad de Enfermedades Infecciosas; España Fil: Iranzo, A.. Hospital Universitario y Politécnico LA FE. Servicio de Microbiología; España Fil: Barcan, L. A.. Hospital Italiano de Buenos Aires; Argentina Fil: Anders, M.. Hospital Alemán; Argentina Fil: Schijman, Alejandro Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; Argentina

Skin deep: A bioactive formulation for dermal delivery of antihistamines is obtained by using the original properties of catanionic associations towards self-assembly in water. The drug, which participates in its own transport, is preserved from photodegradation when solubilised in the bioactive formulation. The drug release through the skin is also delayed.

STUDY DESIGN Propensity score-adjusted prospective cohort study. OBJECTIVE To compare the incidence of complications in patients undergoing single-level lumbar discectomy between the inpatient and outpatient settings, to determine baseline 30-day complication rates for lumbar discectomy, and to identify independent risk factors for complications. SUMMARY OF BACKGROUND DATA Lumbar discectomy is the most common spinal procedure performed and can be done on an outpatient basis. Lower costs, greater patient satisfaction, and equivalent safety have been reported with outpatient surgery. METHODS Patients undergoing lumbar discectomy between 2005 and 2010 were selected from The American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database. Patient selection was based on a single primary current procedural terminology code. To ensure comparable inpatient and outpatient cohorts, patients with multilevel procedures were excluded. Thirty-day postoperative complications and preoperative patient characteristics were identified and compared. Propensity score matching and multivariate logistic regression analysis were used to adjust for selection bias and identify predictors of 30-day morbidity. RESULTS Of the 4310 lumbar discectomy cases, 2658 (61.7%) underwent an inpatient hospital stay after surgery, whereas 1652 (38.3%) patients had outpatient surgery. Unadjusted overall complication rates (6.5% vs. 3.5%, P < 0. 0001) were higher in those undergoing inpatient surgery. After propensity score matching, overall complication rate was still higher with the inpatient cohort (5.4% vs. 3.5%, P = 0.0068). Adjusted comparison using multivariate logistic regression also demonstrated a significantly higher rate of complication for inpatients (odds ratio, 1.521; 95% confidence interval, 1.048-2.206). Age, diabetes, presence of preoperative wound infection, blood transfusion, operative time, and an inpatient hospital stay were all independent risk factors of short-term complication after lumbar discectomy. CONCLUSION After adjusting for confounders using propensity score matching and multivariate logistic regression analysis, patients undergoing outpatient lumbar discectomy had lower overall complication rates than those treated as inpatients. Surgeons should consider outpatient surgery for lumbar discectomy in appropriate candidates.

Objective To examine the available evidence to assess if cryopreservation of all embryos and subsequent frozen embryo transfer (FET) results in better outcomes compared with fresh transfer. Design Systematic review and meta-analysis. Setting Centers for reproductive care. Patient(s) Infertility patient(s). Intervention(s) An exhaustive electronic literature search in MEDLINE, EMBASE, and the Cochrane Library was performed through December 2011. We included randomized clinical trials comparing outcomes of IVF cycles between fresh and frozen embryo transfers. Main Outcome Measure(s) The outcomes of interest were ongoing pregnancy rate, clinical pregnancy rate, and miscarriage. Result(s) We included three trials accounting for 633 cycles in women aged 27–33 years. Data analysis showed that FET resulted in significantly higher ongoing pregnancy rates and clinical pregnancy rates. Conclusion(s) Our results suggest that there is evidence that IVF outcomes may be improved by performing FET compared with fresh embryo transfer. This could be explained by a better embryo-endometrium synchrony achieved with endometrium preparation cycles.

There exists a lack of comparison between large national healthcare databases reporting surgical morbidity and mortality. Prior authors have expressed concern that the Scoliosis Research Society (SRS) membership may have underreported complications in spinal surgery. Thus, the purpose of the present study was to compare the incidence of morbidity between the SRS and National Surgical Quality Improvement Program (NSQIP) databases.We reviewed patients enrolled between 2012 and 2013, with a total of 96,875 patients identified in the SRS dataset and 15,909 in the combined adult and pediatric NSQIP dataset. Patients were matched based on diagnostic category,and a univariate analysis was used to compare reported complication rates in the categories of perioperative infection, neurologic injury, and mortality. The SRS database only requires detailed demographic data reporting on patients that have had a complication event. We compared the demographics and comorbidities of this subgroup, and used this as a surrogate to assess the potential magnitude of confounders.Small differences existed between the SRS and NSQIP databases in terms of mortality (0.1% v. 0.2%), infection (1.2% v. 2%), and neurologic injury (0.8% v. 0.1%) (p0.001 for each comparison). Infection rates were consistently lower across multiple diagnostic sub-categories in the SRS database, whereas neurologic injury rates were consistently lower in the NSQIP database. These differences reached statistical significance across several diagnostic subcategories, but the clinical magnitude of the differences was small. Amongst the patients with a complication, modest differences in comorbidities existed between the two cohorts.Overall, the incidence of short-term morbidity and mortality was similar between the two databases. There were modest differences in comorbidities, which may explain the small differences observed in morbidity. Concerns regarding possible under-reporting of morbidity and mortality data by the SRS membership seem largely unfounded. This study may be useful for future investigators using the NSQIP and SRS datasets.

SUMMARYGenetic diversity of Trypanosoma cruzi may play a role in pathogenesis of Chagas disease forms. Natural populations are classified into 6 Discrete Typing Units (DTUs) Tc I-VI with taxonomical status. This study aimed to identify T. cruzi DTUs in bloodstream and tissue samples of Argentinean patients with Chagas disease. PCR-based strategies allowed DTU identification in 256 clinical samples from 239 Argentinean patients. Tc V prevailed in blood from both asymptomatic and symptomatic cases and Tc I was more frequent in bloodstream, cardiac tissues and chagoma samples from immunosuppressed patients. Tc II and VI were identified in a minority of cases, while Tc III and Tc IV were not detected in the studied population. Interestingly, Tc I and Tc II/VI sequences were amplified from the same skin biopsy slice from a kidney transplant patient suffering Chagas disease reactivation. Further data also revealed the occurrence of mixed DTU populations in the human chronic infection. In conclusion, our findings provide evidence of the complexity of the dynamics of T. cruzi diversity in the natural history of human Chagas disease and allege the pathogenic role of DTUs I, II, V and VI in the studied population.

Purpose: To compare the efficacy of nifedipine and fenoterol in the management of threatened preterm labor (TPL). Methods: A randomized and multicenter study assessing the tocolytic effect of nifedipine versus fenoterol in patients admitted to the participating maternity units with a diagnosis of TPL and a cost-savings study for economic assessment. For a power of 80% and an α error equal to 0.05, 132 consecutive patients were recruited during the study period; 66 patients were assigned to each group. A χ2 analysis and a mean differences test were performed according to variable types and survival curves per intention-to-treat. Results: Demographics were similar in both groups. The latency period was similar in both groups (26.7 vs. 25.6; p = 0.3). There were no differences in the results obtained. Nifedipine failed more frequently to obtain tocolysis when used as a first-line agent (80 vs. 90%, p = 0.0001). The group treated with fenoterol showed more drug adverse events (57.8 vs. 19.0%, p = 0.0001). The economic assessment did not evidence a significant difference in terms of cost savings between groups treated with either drug. Conclusion: The present study failed to demonstrate either clinical or economic superiority of any of the two drugs used in TPL management. The highest failure percentage of nifedipine when used as a first-line agent should encourage further research.

Aims To assess the efficacy of surgery and high-dose split-course radiotherapy in sinonasal head and neck mucosal melanoma (SHNMM). Material and methods Between 1991 and 2006, 23 patients (median age 73 years, male:female ratio 0.4) with non-metastatic SHNMM underwent surgery and postoperative radiotherapy, two had exclusive radiotherapy. Radiotherapy consisted of three series of 18Gy (3×6Gy every other day for 1 week) with 3 week planned treatment breaks. Chi-squared tests, Kaplan–Meyer method and Log-rank test were used to assess prognostic factors for survival and local control. Results There were 20 nasal cavity tumours; 12 of these involved more than one sinonasal site. One patient (4%) had lymphadenopathies at diagnosis. Six SHNMMs (24%) were amelanotic. The median follow-up was 39 months. Fourteen patients had en bloc surgery, 16 underwent radiation (14 postoperative, two exclusive). Eleven patients had local relapse, three had regional relapse and three had bone or liver metastases. Five year local control was 49±12%. Five year overall and SHNMM-specific survival was 38±12% and 62±12%, respectively. Five patients were alive without disease after 5 years and three after 10 years. En bloc excision (tumour removed in one piece) was prognostic for survival. Conclusions En bloc surgery was a prognostic factor on outcomes for local control and survival in this series. Data from the literature have shown that postoperative radiation therapy improves local control. Most series were carried out with conventional fractionation. The effect of planned breaks (split-course radiotherapy) may be deleterious, as suggested in this series. Therefore, split-course radiotherapy cannot be recommended for SHNMM.

International audience; Among drug delivery systems, catanionic vesicles now appear as powerful candidates for pharmaceutical applications because they are relatively cheap and easy to use, thus well corresponding to industrial requirements. Using labelled vesicles made of a tricatenar catanionic surfactant, the work reported here aims at exploring the mechanisms by which internalisation into a cell occurs. The study was performed on various cell types such as phagocytic as well as non-phagocytic cells using confocal laser scanning microscopy and flow cytometry. Using various inhibitors, endocytosis and also a passive process, as probably fusion, were highlighted as interaction phenomena between catanionic vesicles and cell membranes. Finally, the interaction modelled with giant liposomes as membrane models confirmed the hypothesis of the occurrence of a fusion phenomenon between the nanovectors and cell membranes. This process highlights the potential of catanionic vesicles for a future pharmaceutical application as a universal drug delivery system.

Background. The 2009 novel influenza A/H1N1 virus pandemic did not spare solid organ transplant (SOT) recipients. We aimed to describe the behavior of pandemic influenza infection in a group of SOT recipients in Argentina. Methods. Data from 10 transplant (Tx) centers were retrospectively collected for SOT that presented with a respiratory illness compatible with pandemic influenza A infection, between May and September 2009. Cases were defined as suspected, probable, or confirmed according to diagnostic method. Results. Seventy-seven cases were included. No significant differences in presenting symptoms, pulmonary infiltrates, and graft involvement were found among 35 suspected, 19 probable, and 23 confirmed cases. The 33 ambulatory cases had significantly more sore throat and headache when compared with 34 cases admitted to medical ward (MW) and 10 admitted to intensive care unit (ICU), 9 of whom required ventilatory support. MW and ICU cases had significantly more dyspnea, hypoxemia, pulmonary infiltrates, and graft dysfunction. Time from onset of symptoms to first visit and to treatment was significantly longer in MW and ICU cases (P=0.008). Coinfections were found in six cases. Most cases received oseltamivir for 5 to 10 days. Six patients (7.8%) died from viral infection at a median of 15 days from admission. No differences in outcome were seen related to the transplanted organ, the immunosuppressive regimen, time from Tx, or confirmation of diagnosis. Conclusions. Mortality is higher in Tx recipients than in the general population. Poor outcome seems to be related to a delay in the beginning of treatment.

Gonyautoxin are phycotoxins, whose molecular mechanism of action is a reversible block of the voltage-gated sodium channels at axonal level, impeding nerve impulse propagation.To evaluate clinical efficacy of gonyautoxin in the treatment of patients with chronic tensional-type headache.Open trial from September 2004 to 2005 in Hospital Clínico Universidad de Chile. Twenty-seven patients with chronic tension-type headache were locally infiltrated with gonyautoxins (50 micrograms) in ten sites considered as pain trigger points in a fixed infiltration protocol. In each site, a volume of 200 microlitres was injected. EMG recording was performed before and immediately after infiltrations. Main outcome measures are where a significantly drop-off in acute headache pain score occurs and number of days without headache pain.No side effects were detected in the follow-up period. From base line of 2 weeks, 19 patients of 27 (70%) are the successfully responders to the treatment. They showed the remarkable immediate effect after infiltration demonstrated by trapezium EMG recording. Patients reported a fall in pain score 5 minutes post-injection from 5.0 +/- 2.8 to 1.6 +/- 1.6 (mean +/- SD). The responder showed an average of 8.1 +/- 9.9 weeks of headache pain-free, all of them without a second infiltration or use of any additional analgesic medication.The therapeutic properties of gonyautoxin local infiltration in chronic tension-type headache patients are shown to be safe and effective. This report describes a new therapy for chronic tension-type headache involving local infiltrations of gonyautoxins. The immediate headache pain relief effect shown only minutes after toxin infiltrations were the most remarkable feature of this protocol. This is the first gonyautoxins testing report in the treatment of chronic tension-type headache.

Background: The prevalence of dysphagia after anterior cervical decompression and arthrodesis is estimated to be 50% within one month and 21% at twelve months. However, its exact etiology is not well understood. The objective of the present study was to explore the relationship between intraoperative intra-esophageal pressure due to surgical retraction, esophageal mucosal blood flow at the level of surgery, and postoperative dysphagia. Our hypothesis was that sustained elevated pressure on the esophagus during anterior cervical arthrodesis is associated with postoperative dysphagia. Methods: Seventeen selected patients scheduled for anterior cervical arthrodesis were studied. Throughout the procedure, intraluminal pressure in the upper esophageal sphincter was measured (mm Hg) with a custom-made manometer probe and mucosal perfusion was measured at the level of surgery with a laser Doppler flowmeter. The type of retraction chosen by the surgeon was noted. Postoperatively, the patients were specifically evaluated for dysphagia on the first postoperative day and at six weeks, three months, and six months postoperatively with use of the M.D. Anderson Dysphagia Inventory. Results: Four of the eleven patients who had dynamic retraction and five of the six patients who had static retraction during surgery had postoperative dysphagia. In the group of patients with dysphagia, the average M.D. Anderson Dysphagia Inventory score decreased from 93.8 ± 12.1 preoperatively to 67.7 ± 11.4 on the first postoperative day (p < 0.001). The patients with dysphagia had a significantly higher average intraluminal pressure (60.8 ± 54.3 compared with 54.4 ± 51.8 mm Hg; p < 0.0001) as well as significantly lower average mucosal perfusion (26.1 ± 18.1 compared with 40.8 ± 26.2 tissue perfusion units; p < 0.0001) in comparison with the asymptomatic patients. Conclusions: Patients with dysphagia following anterior cervical arthrodesis were exposed to higher intraoperative esophageal pressure and decreased esophageal mucosal blood flow during surgical retraction as compared with patients without dysphagia. In this small series, dynamic retraction seemed to be associated with a lower prevalence of postoperative dysphagia. Level of Evidence: Therapeutic Level II. See Instructions to Authors for a complete description of levels of evidence.

Retrospective cohort analysis.A growing number of publications have utilized the Scoliosis Research Society (SRS) Morbidity and Mortality (MM) database, but none have compared it to other large databases. The objective of this study was to compare SRS complications with those in administrative databases.The Nationwide Inpatient Sample (NIS) and Kid's Inpatient Database (KID) captured a greater number of overall complications while the SRS MM data provided a greater incidence of spine-related complications following adolescent idiopathic scoliosis (AIS) surgery. Chi-square was used to obtain statistical significance, with p.05 considered significant.The SRS 2004-2007 (9,904 patients), NIS 2004-2007 (20,441 patients) and KID 2003-2006 (10,184 patients) databases were analyzed for AIS patients who underwent fusion. Comparable variables were queried in all three databases, including patient demographics, surgical variables, and complications.Patients undergoing AIS in the SRS database were slightly older (SRS 14.4 years vs. NIS 13.8 years, p.0001; KID 13.9 years, p.0001) and less likely to be male (SRS 18.5% vs. NIS 26.3%, p.0001; KID 24.8%, p.0001). Revision surgery (SRS 3.3% vs. NIS 2.4%, p.0001; KID 0.9%, p.0001) and osteotomy (SRS 8% vs. NIS 2.3%, p.0001; KID 2.4%, p.0001) were more commonly reported in the SRS database. The SRS database reported fewer overall complications (SRS 3.9% vs. NIS 7.3%, p.0001; KID 6.6%, p.0001). However, when respiratory complications (SRS 0.5% vs. NIS 3.7%, p.0001; KID 4.4%, p.0001) were excluded, medical complication rates were similar across databases. In contrast, SRS reported higher spine-specific complication rates. Mortality rates were similar between SRS versus NIS (p = .280) and SRS versus KID (p = .08) databases.There are similarities and differences between the three databases. These discrepancies are likely due to the varying data-gathering methods each organization uses to collect their morbidity data.Level IV.

Few references are available describing the epidemiology of pediatric spine injuries. The purpose of this study is to examine the prevalence, risk factors and trends during the period from 1997 to 2009 of pediatric spine injuries in the United States using a large national database.Data was obtained from the Kid's Inpatient Database (KID) developed by the Healthcare Cost and Utilization Project (HCUP), for the years 1997-2009. This data includes3 million discharges from 44 states and 4121 hospitals on children younger than 20 years. Weighted variables are provided which allow for the calculation of national prevalence rates. The Nationwide Emergency Department Sample (NEDS), HCUP. net, and National Highway Traffic Safety Administration (NHTSA) data were used for verification and comparison.A prevalence of 107.96 pmp (per million population) spine injuries in children and adolescents was found in 2009, which is increased from the 77.07 pmp observed in 1997. The group 15 to 19 years old had the highest prevalence of all age groups in (345.44 pmp). Neurological injury was present in 14.6% of the cases, for a prevalence of 15.82 pmp. The majority (86.7%) of these injuries occurred in children15 years. Motor vehicle collisions accounted for 52.9% of all spine injuries, particularly in children15 years. Between 1997 and 2009 the hospital length of stay decreased, but hospital charges demonstrated a significant increase.Pediatric Spine Injuries continue to be a relevant problem, with rates exceeding those of other industrialized nations. Teenagers15 years of age were at greatest risk, and motor vehicle collisions accounted for the most common mechanism. An increase in prevalence was observed between 1997 and 2009, and this was matched by a similar increase in hospital charges.III.

Poor ovarian response (POR) often means low success rates after in vitro fertilisation (IVF). We aim to study the impact of a low-dose growth hormone (GH) supplementation in pregnancy rates in poor responders in a prospective, self-controlled study of 64 poor responders to previous IVF cycles, who failed to achieve pregnancy and were supplemented with low-doses of GH in a subsequent cycle using the same gonadotropin dose and protocol. Our primary endpoint was the clinical pregnancy rate (CPR), considering secondary endpoints, the number of retrieved oocytes, embryos, embryo quality and the proportion of cycles with embryo transfer. CPR in the GH group was 34.4%. Significant differences were observed for the GH group both in the number of top quality embryos (0.64 ± 0.88 versus 1.03 ± 1.17, p 0.05) and cryopreserved embryos (0.3 ± 0.81 versus 0.85 ± 1.49, p 0.05). This is, to our knowledge, the first clinical trial to use a low dose of GH as a supplement for IVF in POR patients. Despite this low dose, we achieved excellent success rates in patients with a very poor prognosis, at a reasonable cost and without side effects, which makes this a safe and cost-effective alternative.

Introduction The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR-145 correlated with nadir CD4+ T cell count. Discussion No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection.

STUDY DESIGN Retrospective review of prospectively collected data. OBJECTIVE To determine a cutoff below which worsening renal function is associated with increased risk of morbidity and to determine the types and magnitude of morbidity associated with renal impairment. SUMMARY OF BACKGROUND DATA Renal impairment is associated with an increased risk of morbidity after lumbar spine surgery. However, the degree to which increasing levels of renal dysfunction are associated with morbidity has not been well defined. METHODS A large, multicenter, clinical registry was queried for all adult patients undergoing lumbar spine surgery in 2012, and 13,576 cases were identified. An estimated glomerular filtration rate (eGFR) was calculated for each patient. Propensity scores were used to match patients on the basis of preoperative comorbidities and the procedure-type performed. The incidence of 30-day morbidity was then compared between patients with no or mild renal impairment (eGFR ≥60 mL/min/1.73 m) and those with moderate or severe disease (eGFR

Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with ≥3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR ≤ 60 ml/min/1.73 m2. Poisson regression was used to develop a risk score, externally validated on two independent cohorts. In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7–6.7; median follow-up 6.1 y, range 0.3–9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was −2 (interquartile range –4 to 2). There was a 1:393 chance of developing CKD in the next 5 y in the low risk group (risk score < 0, 33 events), rising to 1:47 and 1:6 in the medium (risk score 0–4, 103 events) and high risk groups (risk score ≥ 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166–3,367); NNTH was 202 (95% CI 159–278) and 21 (95% CI 19–23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506–1462), 88 (95% CI 69–121), and 9 (95% CI 8–10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3–12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6–8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD., Editors’ Summary Background About 35 million people are currently infected with HIV, the virus that causes AIDS. HIV destroys CD4 lymphocytes and other immune system cells, leaving infected individuals susceptible to other infections. HIV infection can be controlled, but not cured, using combination antiretroviral therapy (cART), and, nowadays, the life expectancy of many HIV-positive individuals is similar to that of HIV-negative people. HIV-positive individuals nevertheless experience some illnesses more frequently than HIV-negative people do. For example, up to a third of HIV-positive individuals develop chronic kidney disease (CKD), which is associated with an increased risk of cardiovascular disease and death. Persons with CKD may have an impaired effect of the filtration units in the kidneys that remove waste products and excess water from the blood to make urine, thereby leading to a reduced blood filtration rate (the estimated glomerular filtration rate [eGFR]) and waste product accumulation in the blood. Symptoms of CKD, which rarely occur until the disease is advanced, include tiredness, swollen feet, and frequent urination. Advanced stages of CKD cannot be cured, but its progression can be slowed by, for example, controlling hypertension (high blood pressure) and diabetes (two CDK risk factors) and by adopting a healthy lifestyle. Why Was This Study Done? The burden of CKD may increase among HIV-positive individuals as they age, and clinicians need to know which individuals are at high risk of developing CKD when choosing cART regimens for their patients. In addition, clinicians need to be able to identify those HIV-positive individuals at greatest risk of CKD so that they can monitor them for early signs of kidney disease. Some antiretroviral drugs—for example, tenofovir and atazanavir/ritonavir (a boosted protease inhibitor)—are associated with kidney damage. Clinicians may need to weigh the benefits and risks of giving such potentially nephrotoxic drugs to individuals who already have a high CKD risk. Here, the researchers develop and validate a simple, widely applicable risk score (a risk prediction model) for CKD among HIV-positive individuals and investigate the relationship between CKD and potentially nephrotoxic antiretroviral drugs among individuals with different CKD risk score profiles. What Did the Researchers Do and Find? To develop their CKD risk score, the researchers used clinical and demographic data collected from 17,954 HIV-positive individuals enrolled in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study who had an eGFR > 60 ml/min/1.73 m2 and were not taking a potentially nephrotoxic antiretroviral at baseline. During 103,185 person-years of follow-up, 641 individuals developed CKD. Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease predicted CKD. The researchers included these nine factors in their risk score model (which is available online) and defined three risk groups: low (risk score < 0), medium (risk score 0–4), and high (risk score ≥ 5) risk of CKD development in the next five years. Specifically, there was a 1 in 393, 1 in 47, and 1 in 6 chance of developing CKD in the next five years in the low, medium, and high risk groups, respectively. Because some patients started to use potentially nephrotoxic antiretroviral drugs during follow-up, the researchers were able to use their risk score model to calculate how many patients would have to be treated with one of these drugs for an additional patient to develop CKD over five years in each risk group. This “number needed to harm” (NNTH) for patients starting treatment with tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor was 739, 88, and 9 in the low, medium, and high risk groups, respectively. Finally, the researchers validated the accuracy of their risk score in two independent HIV study groups. What Do These Findings Mean? These findings provide a simple, validated risk score for CKD and indicate that the NNTH when starting potentially nephrotoxic antiretrovirals was low among HIV-positive individuals at the highest risk of CKD (i.e., treating just nine individuals with nephrotoxic antiretroviral drugs will likely lead to an additional case of CKD in five years). Although various aspects of the study, including the lack of data on race, limit the accuracy of these findings, these findings highlight the need for monitoring, screening, and chronic disease prevention to minimize the risk of HIV-positive individuals developing diabetes, hypertension, or cardiovascular disease, or becoming coinfected with hepatitis C, all of which contribute to the CKD risk score. Moreover, the development of a tool for estimating an individual’s five-year risk of developing CKD with or without the addition of potentially nephrotoxic antiretroviral drugs will enable clinicians and patients to weigh the benefits of certain antiretroviral drugs against the risk of CKD and make informed decisions about treatment options. Additional Information Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001809. Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS NAM/aidsmap provides basic information about HIV/AIDS, summaries of recent research findings on HIV care and treatment, and personal stories about living with AIDS/HIV Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS, including personal stories about living with HIV/AIDS The World Health Organization provides information on all aspects of HIV/AIDS (in several languages), including its guidelines on the use of ART for treating and preventing HIV infection The UNAIDS World AIDS Day Report 2014 provides up-to-date information about the AIDS epidemic and efforts to halt it The UK National Health Service Choices website provides information for patients on chronic kidney disease, including some personal stories The US National Kidney Foundation, a not-for-profit organization, provides information about chronic kidney disease (in English and Spanish) A tool for calculating the CDK risk score developed in this study is available Additional information about the D:A:D study is available, Amanda Mocroft and colleagues develop and validate a model for determining risk of developing chronic kidney disease for individuals with HIV if treated with different antiretroviral therapies.

The use of glycol ethers and their effects on health have recently attracted the attention of the French health authorities. At their request, INSERM, the French Institute of Health and Medical Research, conducted a collective expertise review on glycol ethers in 1999. INSERM Expertise Reviews are independent procedures performed by experts from several disciplines, to guarantee the objectivity and the relevance of the report. During several work sessions, the experts carried out a critical analysis of and reviewed studies concerning the toxicity of glycol ethers. This process resulted in a series of recommendations and conclusions. All these data have been published in the form of a report and have been used to help the public authorities to make decisions on how to prevent risks for professionals and consumers.

The mayor symptoms of chronic anal fissure are permanent pain, intense pain during defecation that lasts for hours, blood in the stools, and sphincter cramps. It is subsequent to formation of fibrosis infiltrate that leads to an increased anal tone with poor healing tendency. This vicious circle leads to fissure recurrence and chronicity. This study was designed to show the efficacy of gonyautoxin infiltration in healing patients with anal fissures.Gonyautoxin is a paralyzing phytotoxin produced by dinoflagellates. Fifty recruited patients received clinical examination, including proctoscopy and questionnaire to evaluate the symptoms. Anorectal manometries were performed before and after toxin injection. Doses of 100 units of gonyautoxin in a volume of 1 ml were infiltrated into both sides of the anal fissure in the internal anal sphincter.Total remission of acute and chronic anal fissures were achieved within 15 and 28 days respectively. Ninety-eight percent of the patients healed before 28 days with a mean time healing of 17.6 +/- 9 days. Only one relapsed during 14 months of follow-up. Neither fecal incontinence nor other side effects were observed. All patients showed immediate sphincter relaxation. The maximum anal resting pressures recorded after two minutes decreased to 56.2 +/- 12.5 percent of baseline.Gonyautoxin breaks the vicious circle of pain and spasm that leads to anal fissure. This study proposes gonyautoxin anal sphincter infiltration as safe and effective alternative therapeutic approach to conservative, surgical, and botulinum toxin therapies for anal fissures.

Background The purpose of this study was to determine the prevalence of concurrent spinopelvic fusion and THA and identify the risk of THA dislocation in patients with concurrent spinopelvic fusion. Methods We retrospectively reviewed an institutional database of spinal deformity patients and the Humana Inc data set to identify patients with concurrent THA and spinopelvic fusion. The prevalence of concurrent THA and spinopelvic fusion was identified, as was the risk of dislocation for all cohorts. Results Of 328 patients with spinopelvic fusions at our institution, 15 patients (4.6%) were found to have concurrent THA. Similarly, within the Humana database among 1049 patients with spinopelvic fusion, 4.6% had a concurrent THA. Among the 58,692 THA patients identified, only 0.1% had a concurrent spinopelvic fusion. A THA dislocation was observed in 3 of 15 patients (20.0%) and 3 of 18 THA (16.7%) within our institutional review. Within the Humana database, 8.3% of patients with THA and spinopelvic fusion went on to have a dislocation of their THA compared to 2.9% of patients with THA and no history of spinopelvic fusion (relative risk: 2.9 [1.2-7.6]). Conclusion Among patients with spinopelvic fusion, the prevalence of concurrent THA is 4.6%, and among primary THA patients, the prevalence of concurrent spinopelvic fusion is 0.1%. An alarmingly high THA dislocation rate has been demonstrated among THA patients with concurrent spinopelvic fusion at our institution (20%) and within a large national database (8.3%).

Background: Risk factors for complication after single-level anterior cervical discectomy and fusion remain poorly defined. The purpose of this study was to identify the incidence and risk factors for complication from a large, prospectively collected database, with a separate emphasis on the safety of outpatient procedures. Methods: The American College of Surgeons National Surgical Quality Improvement Program prospectively collects thirty-day morbidity and mortality data from more than 480 hospitals around the United States. We retrospectively queried this database to identify cases of single-level elective anterior cervical discectomy and fusion. Univariate and multivariate analyses were used to identify risk factors for complication, and a propensity score model was used to create matched inpatient and outpatient cohorts. Results: Of 2914 cases identified, 597 (20.5%) received outpatient treatment and 2317 (79.5%) received inpatient treatment. The overall incidence of any systemic morbidity was 3.2%. There were five mortalities (0.2%), four in the inpatient cohort and one in the outpatient cohort. Patient age over sixty-five years, body mass index of >30 kg/m2, American Society of Anesthesiologists class of 3 or 4, current dialysis, current corticosteroid use, recent sepsis, and operative times longer than 120 minutes were each independent risk factors for complication in the multivariate analysis. After propensity score matching to control for comorbidities, there were no significant differences in complication rates between inpatients and outpatients, and outpatient treatment was not a risk factor for complication in the multivariate analysis. Conclusions: Single-level elective anterior cervical discectomy and fusion had low complication rates, with no additional risk seen with outpatient as compared with inpatient procedures. It seems reasonable to consider inpatient admission for any patient with the risk factors identified here, particularly difficult airways. This information may be useful to surgeons performing informed consents for medical optimization and for selecting patients most appropriate for outpatient treatment. Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

STUDY DESIGN Retrospective cohort study. OBJECTIVE To determine the trends and causes for increases in hospital charges in adolescent idiopathic scoliosis (AIS) fusions. SUMMARY OF BACKGROUND DATA Trends in utilization rates, surgical procedure types, and hospital charges for AIS fusions have not been well investigated. METHODS We used International Classification of Diseases, Ninth Revision, billing codes to identify 29,594 AIS fusion cases from the National Inpatient Service (NIS) database between 2001 and 2011. Data were trended over time, and contrasted against other common procedures. To identify specific drivers of charges, we queried our own hospital's billing system, and averaged charges from 40 cases (10 cases for each of 4 yr studied). Dollar amounts were adjusted for inflation to 2011 dollars. RESULTS Utilization rates for AIS fusions have remained constant, whereas utilization of adult spinal fusions increased by 64% (P = 0.0004). Utilization of anterior thoracic fusions decreased by 80% (P < 0.0001). Mean hospital charges for AIS spinal fusions increased from $72,780 in 2001 to $155,278 in 2011 (113% increase), averaging 11.3% annually (P < 0.0001), with charges for adult spinal procedures increasing at a similar rate (13.4% annually, P < 0.0001). Charges for the other nonspine conditions increased to a lesser degree (range of 4.5%-6% annually, P < 0.001 for each). At our institution, spinal implant charges increased 27.6% annually, whereas surgeon charges decreased 0.5% annually, and all other charges increased only 5.2% annually. Over time, our surgeon used greater numbers of pedicle screws, and greater numbers of implants per surgery and per level fused (P < 0.05 for each). Implant charges were 28% of the total hospital bill in 2003, rising to 53% in 2012. CONCLUSION Although utilization rates for AIS fusions have remained constant over time, hospital charges have increased substantively, and there has been a shift toward performing posterior only surgical procedures. This corresponds to the widespread adoption of pedicle screw-based constructs. Spinal implants may be the primary driver of increased charges. Strategies directed toward implant cost savings may thus have the largest impact. LEVEL OF EVIDENCE 4.

This review addresses relevant aspects of Chagas disease in the immunocompromised host. Chagas disease—one of the world's most neglected diseases—has become a global public health concern. Novel transmission modalities, such as organ transplantation, evidence of parasite persistence in chronically infected individuals—with the potential for reactivation under immunosuppression—and the prolonged survival of immunosuppressed patients call for an appraisal of the disease in this particular setting. The management and outcome of solid organ transplantation in the infected recipient with special focus on heart transplantation is addressed. The guidelines for management and the outcome of the recipients of organs from infected donors are discussed, and comments on haematopoietic stem cell transplantation are included. Finally, Chagas disease in other situations of impairment of the immune system, such as HIV/AIDS and autoimmune diseases, are considered. Immunosuppression has become an increasingly frequent condition that might modify the natural history of Trypanosoma cruzi infection. A number of strategies are available for Chagas disease management in the immunosuppressed patient. First, according to recent recommendations from the health authorities in Argentina, most infected patients would benefit from being treated at diagnosis. This has not been validated for patients with different immunosuppressive disorders. A different strategy would involve treating only patients with documented reactivation (either parasitaemia or clinical manifestations). These different approaches are discussed. To reach a diagnosis of parasitaemia, monitoring is essential, either with conventional methods or with molecular techniques that are not yet available in all centres. Collaborative studies are needed to improve the level of evidence, which will allow for better guidelines.

We determined the characteristics of posttransplant tuberculosis and the impact of rifampin-based antituberculosis regimens on outcomes in the current era. Patients comprised 64 transplant recipients with tuberculosis, divided into 2 consecutive cohorts: an earlier cohort (cases occurring from 2003 to 2007) and a later cohort (cases from 2008 to 2011). Patients from the later versus earlier era had tuberculosis develop later after transplant (odds ratio, 1.01; 95% CI, 1.00–1.02; P = .05), were more likely to be liver transplant recipients (odds ratio, 4.52; 95% CI, 1.32–15.53; P = .02), and were more likely to receive tacrolimus-based immunosuppression (odds ratio, 3.24; 95% CI, 1.14–9.19; P = .03). Mortality rate was 10% in the later cohort and 21% in the earlier cohort ( P = .20). Rifampin-based treatment was less likely to be used in patients with prior rejection ( P = .04). However, neither rejection rate ( P = .71) nor mortality ( P = .93) after tuberculosis differed between recipients who received rifampin and recipients who did not. Thus, notable changes have occurred in the epidemiological characteristics of tuberculosis in transplant recipients. Overall mortality rate has improved, with about 90% of the patients now surviving after tuberculosis.

BACKGROUND: Because GB virus type C(GBV-C)/HGV (GBV-C/HGV) is blood-borne and sexually transmitted, persons at risk of infection with such viruses have a high prevalence of GBV-C/HGV markers. However, adults with no apparent risk factors, such as blood donors, frequently are positive for GBV-C/HGV markers. Mother-to-infant transmission could explain this high prevalence, but it has been studied only through small series of GBV-C/HGV-infected mothers co-infected with HCV or HIV. STUDY DESIGN AND METHODS: To determine the rate of mother-to-infant transmission of GBV-C/HGV RNA in women who are HCV- or HIV-negative, a prospective study was performed in a cohort of 288 mothers screened for viral RNA and in the infants born to GBV-C/HGV-infected mothers. RESULTS: Thirteen mothers (4.5%) were found positive for GBV-C/HGV RNA. Of the infants in whom at least one blood sample was collected between the third and the ninth months of life, 89 percent were positive for viral RNA. The majority of these newborns were negative for GBV-C/HGV RNA at birth and positive after the third month. The viral RNA titers of infants born to GBV-C/HGV-infected mothers appeared as elevated as those of their mothers. All the GBV-C/HGV-infected infants remained positive for viral RNA during the entire study period. No clinical events possibly linked to a primary GBV-C/HGV infection were reported in infants. Serum ALT level and blood count remained within normal values throughout the follow-up of all GBV-C/HGV-infected infants. CONCLUSION: The frequency of mother-to-infant GBV-C/HGV transmission is elevated and could explain the high prevalence of GBV-C/HGV markers (viral RNA and E2 antibody) in adults at low risk for blood-borne or sexually transmitted viruses, such as blood donors.

We report a case of intestinal hepatoid adenocarcinoma, confirmed by albumin m-RNA in situ hybridization, with subsequent metastatic spread to the liver in a male with a long-standing history of ulcerative colitis. This novel finding strongly suggests that ulcerative colitis can lead not only to conventional adenocarcinomas but also to hepatoid adenocarcinoma and highlights the mimicry of hepatocellular carcinoma by metastatic hepatoid adenocarcinoma liver nodules.

Two series of water-soluble dendritic catanionic assemblies, acting as multisite analogues of galactosylceramide (Galbeta1cer), have been prepared with the goal of blocking HIV infection prior to the entry of the virus into human cells. Trifunctional and hexafunctional cinnamic acid-terminated dendrimers have been synthesized from phosphorus-containing dendrimers bearing aldehyde end groups. A classical acid-base reaction performed in water between acid-terminated dendrimers and stoichiometric amounts of N-hexadecylamino-1-deoxylactitol provided the expected catanionic assemblies. Antiviral assays on these supramolecular entities confirmed the crucial roles both of multivalency effects and of lipophilicity on the biological activity of Galbeta1cer analogues. Moreover, correlation between in vitro tests and molecular modeling highlights the specific influence of the assembly shape on the anti-HIV efficiency, with the tri- and hexafunctional cored dendrimers, both decorated with 12 sugar moieties, exhibiting IC50 values of 1.1 and 0.12 microM, respectively.

Background. Incidence, characteristics, and risk factors for tuberculosis (TB)-associated immune reconstitution inflammatory syndrome (IRS) in solid-organ transplant (SOT) recipients are not known. Methods. Patients are composed of 64 consecutive SOT recipients with TB followed for 12 months. IRS was defined based on previously proposed criteria. Results. IRS developed in 14% (9/64) of the patients, a median of 47 days after the use of anti-TB therapy. Liver versus other types of organ transplant recipients (adjusted odds ratio [OR], 6.11; 95% confidence interval [CI], 1.08Y34.86), prior cytomegalovirus infection (adjusted OR, 5.65; 95% CI, 0.93Y34.47), and rifampin use (adjusted OR, 4.56; 95% CI, 0.74Y27) were associated with a higher risk of IRS. The presence of more than one factor (liver transplantation, cytomegalovirus infection, and rifampin use) when compared with none of these factors conferred a 19-fold increase in the risk of IRS (P=0.01). Mortality at 1 year after diagnosis was 33.3% in patients with IRS and 17.2% in those without IRS (P=0.31). Conclusions. IRS was documented in 14% of the SOT recipients with TB. We determined clinically identifiable factors that may be useful in assessing the risk of tuberculosis-associated posttransplantation IRS.

Objective: To examine the available evidence to assess if cryopreservation of all embryos and subsequent frozen embryo transfer (FET) results in better outcomes compared with fresh transfer. Design: Systematic review and meta-analysis. Setting: Centers for reproductive care. Patient(s): Infertility patient(s). Intervention(s): An exhaustive electronic literature search in MEDLINE, EMBASE, and the Cochrane Library was performed through December 2011. We included randomized clinical trials comparing outcomes of IVF cycles between fresh and frozen embryo transfers. Main Outcome Measure(s): The outcomes of interest were ongoing pregnancy rate, clinical pregnancy rate, and miscarriage. Result(s): We included three trials accounting for 633 cycles in women aged 27-33 years. Data analysis showed that FET resulted in significantly higher ongoing pregnancy rates and clinical pregnancy rates. Conclusion(s): Our results suggest that there is evidence that IVF outcomes may be improved by performing FET compared with fresh embryo transfer. This could be explained by a better embryo-endometrium synchrony achieved with endometrium preparation cycles. Copyright © 2013 American Society for Reproductive Medicine, Published by Elsevier Inc.

Two groups of patients with disseminated breast carcinomas who had failed radiotherapy, chemotherapy, and hormonotherapy were treated with natural interferon alpha (nIFN-alpha) alone or in combination with nIFN-gamma delivered in cycles of 10-12 intralesional (i.l.) injections to recurrent and metastatic lesions. In group, I, 16 skin lesions in 12 patients received nIFN-alpha alone resulting in 7 complete regressions verified histologically (CR), 7 partial regressions (PR), and no regressions (NR) in 2. Group II included 4 patients in whom 7 cutaneous recurrences were treated with nIFN-alpha/nIFN-gamma (5 CR, 2 PR), 2 were injected with nIFN-alpha alone (1 CR, 1 PR), and 1 received nIFN-gamma alone (PR). Two additional patients in group II were given i.l. injections of nIFN-alpha/nIFN-gamma to lymph node metastases (1 CR, 1 PR). Clinical toxicity was experienced by 5 of 12 patients in group I and by all the patients in group II and was controlled in most instances by antipyretics. Systemic antitumor effects were not appreciable clinically. Nevertheless, noninjected lesions exposed only to systemic levels of IFNs, when studied immunohistochemically, displayed an immunological response similar to that of IFN-injected lesions, although less intense. Therefore, IFNs can be useful in controlling locoregional recurrences of breast cancer even in patients who are not responding to other forms of therapy. Furthermore, in addition to the local antitumor actions, they appear to be capable of eliciting systemic immunological effects.

Nasopharingeal carcinoma (NPC) is frequently associated with Epstein-Barr virus (EBV), but little is known about its pathogenesis in Western countries, where its incidence is low and EBV is not endemic. We studied 26 Italian cases of NPC: 24 of the non-keratinizing subtype, and 2 keratinizing. We used immunohistochemistry to evaluate p53, bcl-2 and Ki-67 protein expression, and in situ hybridization (ISH) to assess bcl-2 mRNA and the EBV transcript, EBER1, with bcl-2 protein and mRNA expression being compared in serial sections. As regards bcl-2, the protein or mRNA was expressed in 15/26 (58%) and 17 (65%) cases respectively, with co-expression being found only in 9 (35%) cases; 23 (88%) cases were positive for one or the other. EBER1 was detected in 17/26 (65%) cases, of which 80% and 71% coexpressed bcl-2 protein or mRNA, respectively. Only 9/26 (35%) cases had a high Ki67 proliferative index; 3/26 (12%) overexpressed p53. This study of NPC in Italy confirms the importance of EBV and bcl-2 in Western cases. The discrepancy between bcl-2 mRNA and protein expression invites investigation into a possible internal bcl-2 regulation system.

Background: Spinal anesthesia has been associated with lower postoperative rates of deep-vein thrombosis, a shorter operative time, and less blood loss when compared with general anesthesia. The purpose of the present study was to identify differences in thirty-day perioperative morbidity and mortality between anesthesia choices among patients undergoing total knee arthroplasty. Methods: The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database was searched to identify patients who underwent primary total knee arthroplasty between 2005 and 2010. Complications that occurred within thirty days after the procedure in patients who had been managed with either general or spinal anesthesia were identified. Patient characteristics, thirty-day complication rates, and mortality were compared. Multivariate logistic regression identified predictors of thirty-day morbidity, and stratified propensity scores were used to adjust for selection bias. Results: The database search identified 14,052 cases of primary total knee arthroplasty; 6030 (42.9%) were performed with the patient under spinal anesthesia and 8022 (57.1%) were performed with the patient under general anesthesia. The spinal anesthesia group had a lower unadjusted frequency of superficial wound infections (0.68% versus 0.92%; p = 0.0003), blood transfusions (5.02% versus 6.07%; p = 0.0086), and overall complications (10.72% versus 12.34%; p = 0.0032). The length of surgery (ninety-six versus 100 minutes; p < 0.0001) and the length of hospital stay (3.45 versus 3.77 days; p < 0.0001) were shorter in the spinal anesthesia group. After adjustment for potential confounders, the overall likelihood of complications was significantly higher in association with general anesthesia (odds ratio, 1.129; 95% confidence interval, 1.004 to 1.269). Patients with the highest number of preoperative comorbidities, as defined by propensity score-matched quintiles, demonstrated a significant difference between the groups with regard to the short-term complication rate (11.63% versus 15.28%; p = 0.0152). Age, female sex, black race, elevated creatinine, American Society of Anesthesiologists class, operative time, and anesthetic choice were all independent risk factors of short-term complication after total knee arthroplasty. Conclusions: Patients undergoing total knee arthroplasty who were managed with general anesthesia had a small but significant increase in the risk of complications as compared with patients who were managed with spinal anesthesia; the difference was greatest for patients with multiple comorbidities. Surgeons who perform knee arthroplasty may consider spinal anesthesia for patients with comorbidities. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Objective To evaluate the impact of female smoking on early embryo development in vitro using a time-lapse system. Design Retrospective analysis of prospectively collected database. Setting Assisted reproductive technology (ART) program. Patient(s) A total of 135 infertile couples undergoing IVF-intracytoplasmic sperm injection (ICSI) cycle. Intervention(s) Embryo culture in a time-lapse incubator (Embryoscope, Unisense Fertilitech). Main Outcome Measure(s) Embryo morphokinetic parameters. Result(s) Of 135 women, 139 and 729 oocytes were cultured in 23 smokers and 112 nonsmokers, respectively. Basal characteristics and ovarian stimulation parameters were comparable in both groups. Serum antimullerian hormone level and antral follicle count were significantly lower in smokers than in nonsmokers. Conventional embryologic parameters were comparable in both groups, but time-lapse analysis showed that most cleavage events occurred significantly later in smokers than in nonsmokers, leading to poor cycle outcome in smokers. Conclusion(s) Female smoking impairs early embryo development, as reflected by time-lapse analysis. This might contribute to the dramatic decrease in pregnancy rates (PRs) in smokers undergoing IVF. Time lapse is a useful tool for the identification of deleterious components impairing early embryo development.

Syphilis has recently re-emerged in young adults. However, serological testing of patients undergoing assisted reproductive technology (ART) cycles and/or semen cryopreservation is not mandatory in every country.We conducted a retrospective analysis on our local database to evaluate the prevalence of syphilis among infertile couples, and discuss the interest of systematic syphilis serology testing in these patients.Between 2000 and 2010, only one patient out of 4314 was diagnosed with chronic syphilis.This study illustrates that systematic serological screening for syphilis in couples referred for semen cryopreservation or ART only allows exceptionally rare diagnosis. The cost-effectiveness of this strategy should be reconsidered.

Sex-Hormone Binding Globulin (SHBG) may be associated to Pre-eclampsia (PE) and Fetal Growth Restriction (RCIU).To determine if maternal serum SHBG concentrations during the first and second trimesters are predictive biomarkers of Pre-eclampsia and RCIU.Prospective cohort study carried out in the Fetal Medicine Unit, Universidad de Chile Clinical Hospital between January, 2005 and December, 2006. Blood samples were obtained from unselected pregnant women during routine 11-14 week and 22-25 week ultrasound examinations, conforming two different study groups. Posteriorly, serum SHBG concentrations were determined in women who developed Pre-eclampsia, RCIU and their respective controls.Fifty five patients were included in the 11-14 weeks group. Nine women that developed PE, 10 that developed RCIU and 36 controls were selected from this group. There were no significant differences in SHBG levels between patients with PE, RCIU or controls (324.7 (26.6), 336.8 (33.9) and 377.5 (24.3) nmol/L, respectively). Fifty four women were included in the 22-25 weeks group. Eight women who developed Pre-eclampsia, 15 who developed RCIU and 31 controls were selected. Again, there were no significant differences in SHBG levels between patients with PE, RCIU or controls (345.5 (151.1), 383.8 (143.4) and 345.5 nmol/l (151.1), respectively).Maternal SHBG serum levels did not predict subsequent development of Pre-eclampsia and RCIU.

Acute hepatitis has a very low incidence disease during pregnancy. However, it may be an important cause of jaundice during gestation which in cases of viral etiology can have a very high morbidity and mortality risk to the mother and the fetus. The purpose of this review is to update the available knowledge regarding viral hepatitis during pregnancy including description of the main etiologies, transmission route, maternal-fetal risk and possible management.

PROXIMAL JUNCTIONAL KYPHOSIS (PJK) IS DEFINED AS: 1) Proximal junction sagittal Cobb angle≥10°, and 2) Proximal junction sagittal Cobb angle of at least 10° greater than the pre-operative measurement PJK is a common complication which develops in 39% of adults following surgery for spinal deformity. The pathogenesis, risk factors and prevention of this complication are unclear.Of 54 consecutive adults treated with spinal deformity surgery (age≥59.3±10.1 years), 19 of 54 (35%) developed PJK. The average follow-up was 26.8 months (range 12 - 42). Radiographic parameters were measured at the pre-operative, early postoperative (4-6 weeks), and final follow-up visits. Sagittal alignment was measured by the ratio between the C7-plumbline and the sacral-femoral distance. Binary logistic regression model with predictor variables included: Age, BMI, C7-plumbline, and whether lumbar lordosis, thoracic kyphosis and sacral slope were presentPatients who developed PJK and those without PJK presented with comparable age, BMI, pelvic incidence and sagittal imbalance before surgery. They also presented with comparable sacral slope and lumbar lordosis. The average magnitude of thoracic kyphosis was significantly larger than the lumbar lordosis in the proximal junctional kyphosis group, both at baseline and in the early postoperative period, as represented by [(-lumbar )lordosis - (thoracic kyphosis)]; no- PJK versus PJK; 6.6°±23.2° versus -6.6°±14.2°; p≥0.012. This was not effectively addressed with surgery in the PJK group [(-LL-TK): 6.2°±13.1° vs. -5.2°±9.6°; p≥0.004]. This group also presented with signs of pelvic retroversion with a sacral slope of 29.3°±8.2° pre-operatively that was unchanged after surgery (30.4°±8.5° postoperatively). Logistic regression determined that the magnitude of thoracic kyphosis and sagittal balance (C7-plumbline) was the most important predictor of proximal junctional kyphosis.Proximal junctional kyphosis developed in those patients where the thoracic kyphosis remained greater in magnitude relative to the lumbar lordosis, and where the sagittal balance seemed corrected, but part of thise correction was secondary to pelvic retroversion.Prognostic case-control study - Level III.