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Medicaid reimbursements for physician services are determined by each state. However, how these reimbursements vary between states, and how these reimbursements vary in comparison to Medicare reimbursements is unknown for musculoskeletal radiology studies.To evaluate the variability in Medicaid and Medicare physician reimbursements for musculoskeletal imaging studies between states.We evaluated the Medicare and Medicaid physician reimbursements for the most commonly performed musculoskeletal radiology studies (15 radiographs and 10 MRIs) based on Medicare's 2017 National Summary Data File. Medicare and Medicaid reimbursements for these studies were compared by dollar difference (difference in reimbursement in dollars between Medicare and Medicaid). State-wide variability in these reimbursements was quantified by the coefficient of variation (COV) and by the dollar difference in reimbursement amounts. Medicaid and Medicare reimbursement rates were compared using a paired t-test, since the data was paired by state.The mean Medicaid reimbursement rates were lower for musculoskeletal radiographs (p 0.05) but higher for musculoskeletal MRI studies than the Medicare rates (p 0.05). As hypothesized, there was variation in both Medicare and Medicaid imaging reimbursements between states, however, the variation was substantially higher for Medicaid reimbursements. We found the Medicare reimbursement COV between states was 0.07 for all imaging studies, whereas the Medicaid reimbursement COV between states varied from 0.23 to 0.55 for radiographs and from 0.31 to 0.45 for MRIs.The data show that there is mild, but constant variation across imaging studies in Medicare reimbursement for musculoskeletal imaging studies between states. However, there is more variation in the Medicaid reimbursements across imaging studies and between states. More appropriate reimbursement may increase access to care for Medicaid patients.

Introduction: Coronavirus disease 2019 (COVID-19) has spread rapidly throughout the world. Smell and/or taste disorders have emerged as a very frequent symptom as the disease has spread in Europe. Spain is one of the European countries with the highest number of infections. Objective: This study aimed to investigate the clinical progression of smell and taste disorders in Spanish patients with mild COVID-19. Methods: An online survey was used to conduct a cross-sectional study of patients who presented sudden smell and/or taste disorders during the 2 months of total lockdown due to COVID-19 in Spain. Results: In our sample, 91.18% of respondents with impaired smell and/or taste and who were able to undergo PCR testing were positive for SARS-CoV-2 infection. Anosmia and ageusia presented in isolation in 6.5% of participants. The remaining 93.5% presented other mild symptoms: headache (51.6%), cough (51.6%), myalgia (45.2%), asthaenia (38.7%), nasal congestion or rhinorrhoea (35.5%), fever (41.9%), low-grade fever (29.0%), odynophagia (25.8%), or diarrhoea (6.5%). The mean duration of anosmia was 8.33 days, with patients subsequently manifesting hyposmia; complete resolution occurred after a mean of 17.79 days. In 22.6% of respondents, olfactory deficits persisted. All participants recovered their sense of taste. Conclusions: Olfactory and gustatory disorders are prevalent symptoms in mild COVID-19. Most patients do not present associated nasal congestion or rhinorrhoea and a small group of patients present these alterations in isolation. Resumen: Introducción: La enfermedad por coronavirus-2019 (COVID-19), se ha expandido con gran rapidez en todo el mundo. Las alteraciones del olfato y/o gusto han emergido como un síntoma muy frecuente a medida que la enfermedad se propagó en Europa. Uno de los países con mayor número de contagios en este continente ha sido España. Objetivo: Investigar la evolución clínica de los trastornos del olfato y el gusto en la enfermedad leve por COVID-19 en pacientes españoles. Métodos: Se realizó un estudio transversal a través de encuesta on‐line, en pacientes que presentaron afección súbita del olfato y/o el gusto, durante los dos meses de confinamiento total por COVID-19 en España. Resultados: El 91,18% de los sujetos con afectación del olfato y/o el gusto, que tuvieron a acceso a la realización de PCR, fueron positivos para COVID-19. El 6,5% presentó anosmia y ageusia de forma aislada. El 93,5% manifestó otros síntomas leves asociados: cefalea (51,6%), tos (51,6%), mialgias (45,2%), astenia (38,7%), congestión nasal o rinorrea (35,5%), fiebre (41,9%), febrícula (29,0%), odinofagia (25.8%) y diarrea (6,5%). La duración media de la anosmia fue de 8,33 días, posteriormente los pacientes manifestaron hiposmia, con resolución completa en 17,79 días de media. En el 22,6% de los pacientes el déficit olfatorio persistió. Todos los sujetos recuperaron el sentido del gusto. Conclusiones: Los trastornos olfativos y gustativos son síntomas prevalentes en la infección leve por COVID-19. Gran parte de los pacientes no presentan congestión nasal o rinorrea asociada y un grupo reducido de pacientes los presentan de forma aislada.

Fetuses with a diagnosis of congenital lung malformations (CLM) on prenatal imaging are commonly referred to a multi-disciplinary specialty team for prenatal assessment and postnatal management. The net effect of such services is broadly stated to improve the outcomes of affected newborns. However, these claims are relatively unsubstantiated.After IRB approval, a retrospective review of children diagnosed with CLM from 2008 to 2018 and referred to a large urban children's hospital was performed. A comparison was performed between prenatally diagnosed patients having a multi-disciplinary fetal center evaluation (FC) and prenatally diagnosed patients who did not receive a referral or were seen prior to the establishment of the center (NON-FC).Eighty-eight live-born patients with a prenatal diagnosis of CLM were identified, with 49 in the FC group and 39 NON-FC. Thirty-four (63%) and 23 (59%) patients underwent operative resection of CLM, respectively. FC patients presented earlier at first postnatal follow-up (42 vs. 145 days,Children with a prenatal diagnosis of CLM appear to benefit from an organized multi-specialty team approach in several impactful parameters. Hospital systems and providers that invest in similar strategies are likely to achieve improved outcomes in the care of newborns prenatally diagnosed with a CLM.

Background Despite improvements in fetal survival for pregnancies that are affected by twin-twin transfusion syndrome since the introduction of laser photocoagulation, prematurity remains a major source of neonatal morbidity and death. Objective To investigate the indications and factors that influence the timing of delivery after laser treatment, we collected delivery information regarding twin-twin transfusion syndrome cases in a large multicenter cohort. Study Design Eleven North American Fetal Therapy Network centers conducted a retrospective review of twin-twin transfusion syndrome patients who underwent laser photocoagulation. Clinical, demographic, and ultrasound variables that included twin-twin transfusion syndrome stage and gestational age at treatment and delivery were recorded. Primary and secondary maternal and fetal indications for delivery were identified. Univariate analysis was used to select candidate variables with significant correlation with latency and gestational age at delivery. Multivariable Cox regression with competing risk analysis was used to determine the independent associations. Results A total of 847 pregnancies were analyzed. After laser therapy, the average latency to delivery was 10.11±4.8 weeks, and the mean gestational age at delivery was 30.7±4.5 weeks. Primary maternal indications for delivery comprised 79% of cases. The leading indications included spontaneous labor (46.8%), premature rupture of membranes (17.1%), and placental abruption (8.4%). Primary fetal indications accounted for 21% of cases; the most frequent indications included donor nonreassuring status (20.5%), abnormal donor Doppler evaluations (15.1%), and donor growth restriction (14.5%). The most common secondary indications for delivery were premature rupture of membranes, spontaneous labor, and donor growth restriction. Multivariate modeling found gestational age at diagnosis, stage, history of previous amnioreduction, cerclage, intertwin membrane disruption, procedure complications, and chorioamniotic membrane separation to be predictors for both gestational age at delivery and latency. Conclusion Premature delivery after laser therapy for twin-twin transfusion syndrome is primarily the result of spontaneous labor, preterm premature rupture of membranes, and nonreassuring status of the donor fetus. Placental abruption was found to be a frequent complication that resulted in early delivery. Future research should be directed toward the goal of prolonging gestation after laser photocoagulation to further reduce morbidity and mortality rates that are associated with twin-twin transfusion syndrome.

Highlights • The coexistence of cervical cancer and pelvic organ prolapse is a rare scenario. • This is the first report of a cervical neuroendocrine cancer in a prolapsed uterus. • A pessary was used to optimize the accuracy and reproducibility of the target volume position during chemoradiation., Background The coexistence of cervical cancer and pelvic organ prolapse represents a rare clinical scenario. Small cell neuroendocrine histology likewise represents only 0.9–1.5% of all invasive cervical cancers. There is no consensus regarding the optimal management of patients with concomitant locally advanced cervical cancer and pelvic organ prolapse. Case summary The patient was a 32-year old woman with an 8-cm fungating cervical mass extruding from the introitus. Biopsy was consistent with small cell neuroendocrine carcinoma. Examination showed stage IIIC1r cervical cancer with stage IV pelvic organ prolapse. After manual reduction, a pessary was used to optimize target volume reproducibility during definitive chemoradiation. The patient was treated using cisplatin and etoposide chemotherapy with intensity modulated radiation therapy followed by intracavitary brachytherapy. The patient had no clinical evidence of disease and recurrence of symptomatic prolapse one year after treatment completion. Conclusion This is the first reported case of a cervical neuroendocrine carcinoma in a prolapsed uterus, and the youngest patient in literature to have concomitant cervical cancer and pelvic organ prolapse. The use of a pessary for optimizing target volume reproducibility during definitive chemoradiation is a viable option in managing this rare case scenario.

Programmed death-ligand 1 (PD-L1) is used as a biomarker for anti-programmed cell death protein-1 (PD-1) or anti-PD-L1 immunotherapies in NSCLC. We report here the results of population-based PD-L1 testing using the 22C3 IHC pharmDx Assay (Agilent Technologies) in a large Canadian regional reference pathology laboratory.Testing was conducted reflexively on biopsies and resections for NSCLC during an 8-month period. Tumor proportion score (TPS) cutoffs for low and high expression were 1% and 50%, respectively.Altogether, 2031 PD-L1 tests were performed on specimens from 1795 patients, with 107 inconclusive results (5.3%). Excluding cases with inconclusive/missing data, proportions for the remaining 1713 patients were 41.6% for TPS less than 1%, 28.6% for TPS 1% to 49%, and 29.8% for TPS greater than or equal to 50%. Higher PD-L1 expression rates were noted in EGFR wild-type versus mutant tumors (p0.001), squamous versus adenocarcinoma (p0.001), and metastatic versus primary tumors (p0.001). PD-L1 among 103 patients with paired biopsy and resection specimens revealed moderate concordance (κ = 0.67). A total of 52% (25 of 48) of biopsies with TPS less than 1% had TPS greater than 1% in resection, whereas 84.6% (22 of 26) of biopsies with TPS greater than or equal to 50% were concordant in resected tumors. Discordance rates between biopsy and resection were 71.4% for biopsies with less than 8 mmIntratumoral heterogeneity of PD-L1 expression may result in misclassification of PD-L1 status in a substantial proportion of PD-L1-negative small biopsy samples. Biopsy of metastatic site may increase proportion of patients with high PD-L1 expression.

Las innovaciones tecnicas han permitido realizar un sinnumero de cirugias endoscopicas y laparoscopicas, entre ellas la mastectomia preservadora de piel y pezon por puerto unico, que ha sido reportada como bien tolerada, con un excelente resultado cosmetico y con el mismo pronostico oncologico que la cirugia tradicional. Esta tecnica, comun en Asia, presenta diversos retos tecnicos y economicos. Presentamos la primera aproximacion en nuestro pais sobre este abordaje en una paciente con cancer de mama. Para realizar esta cirugia es preciso el entrenamiento en minima invasion y en cirugia mamaria, asi como una adecuada seleccion de las pacientes. Technical innovations and scientific advances have allowed to perform countless endoscopic and laparoscopic surgical procedures. Among these, Single port endoscopic Mastectomy has been reported as well tolerated, with great aesthetic results and the same oncologic prognosis as traditional surgery. This popular approach in Asian countries presents many technical and economic challenges. We present the first endoscopic approach in our country: a female patient with infiltrating ductal carcinoma in the left breast. We understand that to carry out this procedure, adequate patient selection, great minimal invasive and breast surgery skills are necessary.

Data from the routine surveillance systems have been extensively used to estimate the incidence of dengue. However, routine surveillance data frequently underestimate the diseases’ incidence. Underreporting of dengue cases is related to the varying spectrum of its clinical presentation, with a large proportion of mild and asymptomatic infections, to its unspecific signs and symptoms, to the limitations of access to health care, and to the performance of the surveillance system itself [1–3].In order to obtain accurate figures on dengue incidence, a cohort of children and adolescents was set up and followed during four years. The incidence of reported cases was used as a reference for the sample size calculation, which was stratified by age groups. A two-stage procedure was used to select the participants: census tracts were randomly selected, and within each one, a pre-determined number of children of each age group was randomly selected.The parents or legal guardians of the participating children and adolescents provided a written informed consent. In the first home visit, they responded to a questionnaire containing data on socio-demographic characteristics, housing, access to water, sewage, and garbage collection. Also, during the first visit a blood sample of the participating child/adolescent was collected for dengue baseline serology. Beginning in the week after the enrolment, the parent or legal guardian that was designated in the first visit received weekly phone calls for fever surveillance. If the child/adolescent had fever during the week, a nurse was dispatched to the family's home to collect more detailed data on the fever episode and collect a blood sample for dengue diagnosis (IgG, IgM, NS1 and PCR). If the dengue diagnosis was confirmed, a medical appointment was scheduled, and another blood sample for confirmatory tests was collected. It was also agreed that in every anniversary of their participation, they would receive another visit for a blood collection for dengue serology, regardless if they had a fever episode or a confirmed dengue diagnosis during the previous year.This article contains the description of the cohort's dataset. It is associated with the article published in Acta Tropica, under the title “A cohort study to assess the incidence of dengue, Brazil, 2014–2018” [4]. The associated article focused on the seroprevalence and incidence of dengue, and explored some associations between both outcomes and some explanatory variables. Keywords: Dengue, Incidence, Cohort study, Seroprevalence, Brazil

Infants prenatally suspected of having a choledochal cyst (CDC) typically undergo ultrasound imaging shortly after birth. This study sought to evaluate features on the initial postnatal ultrasound (IPU) that could identify newborns at risk for early complications.Following IRB approval, patients from four US fetal centers with prenatal suspicion for CDC and postnatal imaging from 2000 to 2017 were reviewed. Imaging and clinical courses were assessed.Forty-two patients had prenatal ultrasounds suspicious for CDC. Nineteen (45.2%) were excluded due to diagnostic revision (In newborns with prenatally diagnosed CDC, a cyst size ≥ 4.5 cm on IPU is associated with symptom development during the first month after birth and therefore early cyst excision is recommended.

Background Approximately 20% of fetuses diagnosed with congenital lung malformations (CLMs) are found to have additional anomalies. We aim to determine if additional anomalies have an impact on postnatal outcomes for patients with CLMs. Methods After institutional review board approval, we performed a retrospective review of live-born patients with CLMs from 2008 to 2018. All patients were prenatally diagnosed with CLMs. Clinical information pertaining to additional congenital anomalies and outcomes was collected from the electronic health record and analyzed. Results Of the 88 patients who had a prenatal diagnosis of CLMs, 20.5% had additional anomalies. Ten of the 18 patients (56%) were considered to have a major anomaly in addition to CLMs. Outcomes for patients electing nonoperative management of CLMs were similar between those with and without an additional anomaly. Although patients with an additional anomaly were more likely to have perinatal respiratory complications (44% versus 17%, P = 0.03), the number of preoperative clinic and emergency department visits, age at surgery, minimally invasive approach to surgical resection of CLM, estimated blood loss, length of hospital stay, intubation, duration of intubation, 30-day postoperative complications, and long term sequelae were not statistically different. This held true when stratified for major versus minor anomalies. Conclusions Twenty percent of fetuses diagnosed with CLM in our population have additional anomalies. Newborns with additional anomalies have a higher risk of pre-excision pulmonary complications. However, the overall outcomes of all patients with CLMs are similar.

Background To study the clinical outcomes of pigment epithelial detachment (PED) associated with neovascular age-related macular degeneration (nAMD) in patients switched from Ranibizumab to Aflibercept. Methods Retrospective non-comparative case series. 50 eyes with active nAMD and fovea involving PED of ≥100 μm measured manually using the caliper on the OCT, initially treated with intravitreal Ranibizumab (0.5 mg/0.05 ml) and later switched to Aflibercept (2.0 mg/0.05 ml). The outcome measures of best corrected visual acuity (BCVA), PED height, PED width and number of injections were measured at baseline and at time point of switch, 4 months, 1 year and at last follow up visit post-switch. Three paired t-tests and Pearson’s correlations were calculated to analyze variables at switch and change in variables at 1 year. Results After switch to Aflibercept, the improvement of BCVA was 1.84 (p = 0.11), 1.74 (p = 0.21) and 1.16 (p = 0.45) letters, the change in PED height was − 65.6μm (p

Background The aim of the article was to determine if anatomical findings on fetal magnetic resonance imaging (MRI) of venolymphatic malformations of the face and neck (VLMFN) can be used to create a staging system predictive of airway outcomes. Methods We reviewed 13 fetuses evaluated for VLMFN. Stage was assigned based on anatomical findings on fetal MRI. Stage I: no evidence of polyhydramnios with free egress of amniotic fluid and clear visualization of the aryepiglottic folds and larynx. Stage II: lesions of the tongue or epiglottis but with normal aryepiglottic folds without polyhydramnios. Stage III: lesions of the tongue or larynx; nonvisualization of the aryepiglottic folds without free egress of amniotic fluid along with polyhydramnios. Results Six met stage I criteria with no airway involvement, nor any subsequent issues. Two met stage II criteria and were managed by ex-utero intrapartum therapy and intubated. One had minimal involvement of the upper airway, was extubated, and had no subsequent issues. Child two had involvement of the tongue and larynx and received a tracheostomy. Five were assigned stage III, delivered by ex-utero intrapartum therapy and intubated. Postnatal evaluation showed involvement of the upper airway by the lesion and was managed with tracheostomy. All treated by tracheostomy remain cannulated because of persistent symptomatic lesions at follow-up (relative risk 4.0; confidence interval 1.2-13.3). Median follow-up was 4 y (range 2-7 y). Conclusions Although numbers are small, data suggest anatomical details obtained by antenatal fetal MRI appear to correlate with airway outcomes in children affected by a VLMFN. This information may be useful when counseling expectant families of affected fetuses.

Purpose Pre and post-operative administration of sevoflurane in myocardial revascularization surgery provides enhanced cardioprotective effects exerted by pharmacologic pre- and post-conditioning, as compared to propofol. The identification of the enzymes involved in conditioning mechanisms is crucial to the understanding of the effects of sevoflurane in cardiac surgery patients. The impact of sevoflurane on another crucial target organ—the kidney—was also assessed. Methods Ninety patients undergoing off-pump myocardial revascularization surgery were allocated to receive either intra- and postoperative sevoflurane (SS), intraoperative sevoflurane and postoperative propofol (SP), or intra- and postoperative propofol (PP)). Troponin I and hemodynamic parameters were monitored during the first 48 postoperative hours; blood and urine samples were collected at baseline and at 24h to determine Akt, ERK1/2, PKG, iNO, bradykinin receptor, caspase 3, NT proBNP and urinary NGAL. Results The enzymes were overexpressed in the SS group, remained unchanged in the SP group, and decreased in the PP group. Renal function was best preserved in the SS group. Conclusions The overexpression of enzymes induced by intraoperative anesthesia and postoperative sedation with sevoflurane reduces myocardial damage and improves renal function in patients undergoing off-pump myocardial revascularization surgery.

Background/AimsProspective data on switching anti-vascular endothelial growth factors in patients with neovascular age-related macular degeneration (nAMD) who have previously shown no/partial response are limited. This prospective study assessed the effect of switching from aflibercept to ranibizumab on anatomical and functional outcomes in patients with persistent/recurrent disease activity.MethodsSAFARI (NCT02161575) was a 6-month, prospective, single-arm study conducted in the UK and Germany. Patients, meeting strict eligibility criteria for one of two subgroups (primary treatment failure or suboptimal treatment response), received 3 monthly intravitreal ranibizumab injections (0.5 mg). Thereafter, ranibizumab was administered pro re nata at monthly visits. The primary endpoint was change from baseline (CfB) to day 90 in central subfield retinal thickness (CSRT). Best-corrected visual acuity (BCVA) and retinal morphology parameters were assessed.ResultsOne hundred patients were enrolled (primary treatment failure, 1; suboptimal treatment response, 99). In the overall population, there was a significant CfB in median CSRT of −30.75 µm (95% CI −59.50,–20.50; pConclusionSwitching from aflibercept to ranibizumab led to a significant improvement in CSRT, with ~60% experiencing stabilised/improved BCVA. Therefore, patients with nAMD who have shown a suboptimal response to aflibercept may benefit from switching to ranibizumab.

Aim: The aim of this study was to evaluate oxidative stress from glutathione depletion in critically ill patients with a septic shock through the abnormal presence of pyroglutamic acid (PyroGlu) in the urine (indirectly) and through its serum level (directly). Methods: This was a prospective analytical study of 28 critically ill patients with a septic shock who were monitored from admission (initial) to 3 days of stay (final) in the intensive care unit (ICU). Data collected included PyroGlu and glutamic acid (Glu) using liquid chromatography/mass spectrometry, and glutathione peroxidase (GPX) activity with a colorimetric assay. The differences in Glu, PyroGlu, and GPX activity between the septic shock group and healthy control group serving as reference values were evaluated using the Mann–Whitney test. The correlations between Glu, PyroGlu, and GPX activity and clinical outcomes were determined using Spearman’s correlation coefficient. Results: In patients with septic shock, serum and urine PyroGlu levels were higher, erythrocyte GPX activity/gr Hb was lower, and urine Glu levels were lower compared to healthy control reference values, for both initial and final values. Initial serum Glu levels were also lower. Serum PyroGlu levels had a correlation with both initial and final serum Glu levels; levels also correlated in the urine. Initial serum Glu correlated with the days of mechanical ventilation (P = 0.016) and the days of ICU stay (P = 0.05). Urine Glu/mg creatinine correlated with APACHE II (P = 0. 030). This positive correlation observed for serum Glu was not observed for PyroGlu. Conclusions: The current study found that septic patients have higher levels of PyroGlu, lower levels of Glu, and lower erythrocyte GPX activity, suggesting that these biomarkers could be used as an indicator of glutathione depletion. In addition, Glu is related to severity parameters. This study can guide future studies on the importance of monitoring the levels of pyroglutamic acidosis in critical patients with septic shock in order to preserve the oxidative status and its evolution during the stay in the ICU., Financial support for the study was provided by Project FIS PI10/1993 from the Spanish Carlos III Health Institute and FEDER European Funds.

Zika virus (ZIKV) clinical presentation and frequency/duration of shedding need further clarification. Symptomatic ZIKV-infected individuals identified in two hospitals in Sao Paulo State, Brazil, were investigated regarding clinical characteristics, shedding in body fluids, and serodynamics. Ninety-four of 235 symptomatic patients (Site A: 58%; Site B: 16%) had Real-Time PCR-confirmed ZIKV infection; fever, headache and gastrointestinal symptoms were less frequent, and rash was more frequent compared to ZIKV-negative patients. Real-Time PCR in serum had worse performance compared to plasma, while urine had the highest sensitivity. Shedding in genital fluids and saliva was rare. IgM positivity was the highest 28 days (24%); IgG positivity increased >14 days (96%) remaining positive in 94% of patients >28 days. ZIKV prevalence varied importantly in two neighboring cities during the same transmission season. Urine Real-Time PCR can improve diagnostic sensitivity; serum testing is less useful. Accurate serological tests are needed to improve diagnosis and surveillance.

Objectives This paper describes recommendations from a panel of UK retina experts on aflibercept in diabetic macular oedema (DMO). Methods A roundtable meeting was held in London, UK in March 2018. The meeting was sponsored by Bayer. Results Recommendations are based on clinical experience and level 1 evidence. Clinical experience supports the evidence base, reinforcing that aflibercept should be initiated with intensive proactive dosing at 2 mg every 4 weeks. Most panel members use six initial 4-weekly doses as in Protocol T, rather than five initial monthly doses as recommended in the Summary of product characteristics (SmPC). After intensive proactive dosing, patients with a good response (meet Protocol T ‘improvement’ criteria ≥5-letter improvement in visual acuity [VA] and/or ≥10% improvement in central subfield thickness [CST] from baseline) but who are not yet stable should continue with 4-weekly aflibercept until stability is reached. Patients with a good response and stability should initiate monitor-and-extend (not in line with SmPC). Those with a sub-optimal response (meet ‘improvement’ criteria but with additional concerns e.g. fluid worsening on macular volume map) should continue with 4-weekly aflibercept but additional treatments should be considered (aflibercept is not licensed for combination treatment). For patients with no response (no change, or meeting Protocol T ‘worsening’ criteria [≥5-letter decrease in VA and/or ≥ 10% increase in CST] from baseline), switching to a non-anti-vascular endothelial growth factor treatment should be considered. Conclusions Clinical experience reinforces that, when using aflibercept in DMO, the licensed posology or Protocol T regimens achieve the best outcomes.

Infectious agents are often considered potential triggers of chronic inflammatory disease, including autoimmunity; however, direct evidence is usually lacking. Here we show that following control of acute infection of mice with the myotropic Colombiana strain of Trypanosoma cruzi , parasites persisted in tissue at low levels associated with development of systemic necrotizing vasculitis. Lesions occurred in many but not all organs and tissues, with skeletal muscle arteries being the most severely affected, and were associated with myositis, atrophy, paresis/paralysis, and death. Histopathology showed fibrinoid vascular necrosis, rare amastigote nests within skeletal muscle myocytes, and massive leukocyte infiltrates composed mainly of inflammatory monocytes, F4/80 + macrophages, and T. cruzi tetramer-specific CD8 + T lymphocytes capable of producing gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α) but not interleukin-17 (IL-17). T. cruzi -specific IgG was detected in sera from infected mice, but antibody deposits and neutrophilic inflammation were not features of the lesions. Thus, T. cruzi infection of mice may be a specific infectious trigger of paralyzing systemic necrotizing vasculitis most severely affecting skeletal muscle, driven by pathogen-specific type I immune responses.

Objectives To use 3-dimensional endovaginal ultrasound to describe the location and distribution of bulking agent after an uncomplicated transurethral injection. Methods Endovaginal ultrasound was performed in 24 treatment-naive patients immediately after bulking agent was injected. The distance between the center of the hyperechoic density of bulking agent and the urethrovesical junction (UVJ) was measured in the sagittal and axial views. This was calculated in percentile length of urethra. Also, the pattern of tracking of bulking agent was assessed if it is presented. Results After the 2 subjects were excluded because of the poor quality of images, 22 patients were included in this study. Eighteen (82%) subjects showed 2 sites of bulking agents, and mostly, they were located around 3- and 9-o'clock positions. The average distance of bulking agent from left UVJ was at 16.9% of the length of the urethra (6.2 mm; range, 0.5-17 mm) and at 25.5% of the length of the urethra (8.9 mm; range, 0-24.8 mm) in the right side. The average length of urethra was 36.7 mm. Eleven of the 22 subjects (50%) had both sides within upper one third of urethra. The difference in distance between the 2 sides was less than 10 mm in 12 of 22 patients (54%). Nine of the 22 patients (41%) had a significant spread of bulking agent mostly either into the bladder neck or toward the distal urethra. Conclusions Although the bulking agent is most often found at 3- and 9-o'clock positions as intended, the distance from the UVJ is highly variable after an uncomplicated office-based transurethral injection. The bulking material does not form the characteristic spheres in 41% of cases and tracks toward the bladder neck or the distal urethra.

Purpose Aflibercept has the potential advantage of reducing capacity problems by allowing 2 monthly visits for patients with neovascular macular degeneration (nAMD) compared with monthly pro re nata regimens that are the most commonly used in the United Kingdom. This study aimed to report the visual outcomes achieved in routine clinical practice using the VEGF Trap-Eye: Investigation of Efficacy and Safety in Wet AMD (VIEW) protocol at 1 year and compare with trials data and other real-world reports. Design Retrospective data analysis from an electronic medical record. Participants Consecutive series of treatment-naive patients initiated on aflibercept for nAMD at least 1 year before data extraction. Methods Data were anonymized and remotely extracted from 16 centers in the United Kingdom that use the same electronic medical record (EMR) system (Medisoft Ophthalmology; Medisoft Limited, Leeds, UK). Main Outcome Measures The minimum data set defined before first data entry and mandated by the EMR included age, gender, visual acuity, injection episodes, and complications. Results The mean age was 80.0 years (median, 81.0 years) and 63.7% were women. During the first year of treatment with aflibercept, 1840 treatment-naive eyes of 1682 patients received a median of 8 (mean, 7.0) injections at a median of 8 (mean, 7.3) visits. The mean baseline visual acuity was 53.7 letters, improving to 58.8 letters (+5.1-letter gain) at 1 year. In first-treated eyes, the respective figures were 52.7 letters at baseline and 58.2 letters at 1 year, a gain of +5.5 letters. The proportion achieving 70 letters or more increased from 16.4% at baseline to 33.7% at 1 year, and 92% avoided moderate visual loss at 1 year. Conclusions The visual acuity outcomes are comparable to randomized trials and better than many previous real-world data collections, with a mean +5.1-letter gain at 1 year compared with +8.4 letters in the integrated analysis of the VIEW 1 and VIEW 2 studies. Early visual gains were maintained through the year. Collection of outcomes beyond clinical trials can have limitations but better reflect the full pool of patients actually treated and are important to determine whether a particular treatment is performing as expected. Such data also have the potential to improve services by setting up a mechanism to compare sites.

The short duration of viremia, low blood viral load, inaccessibility to timely specific diagnostic tests, and cross-reactions with other flaviviruses have hindered laboratory confirmation of Congenital Zika Syndrome (CZS). This study analyzes the positivity of the plaque reduction neutralization test (PRNT) in children with clinical or imaging characteristics of CZS and its association with laboratory, clinical, and imaging characteristics. The 94 clinical cases of CZS submitted to the ZIKV PRNT90 test were followed from 2016 to 2018. The mean age of children at PRNT90 collection was 22 &plusmn, 6 months Standard Deviation. The ZIKV PRNT90 was positive (titer &ge, 10) in 40 (42.5%) children. ZIKV PRNT90 positivity was associated with severe microcephaly in newborns (p = 0.016), lower head circumference z-score at birth (p = 0.043) and 24 months of age (p = 0.031), and severe reduction of the cerebral parenchyma volume (p = 0.021), expressing greater disease severity. Negative PRNT90 in children with characteristic signs of CZS may be due to false-negative results, indicating that the diagnosis of CZS should be primarily syndromic.

The purpose of this study is to determine which MRI parameters of fetal head and neck masses predict high-morbidity neonatal outcomes, including ex utero intrapartum treatment (EXIT) procedure.This retrospective study (2004-2016) included parameters of polyhydramnios (based on largest vertical pocket), mass effect on the trachea, mass midline extension, and morphologic grade and size of masses. The morbid cohort included those requiring an EXIT procedure, difficult intubation at delivery, or lethal outcome. Predictive modeling with a multivariable logistic regression and ROC analysis was then performed.Of 36 fetuses, five were delivered by EXIT procedures, there was one neonatal death within 12 hours after delivery, and another neonate required multiple intubation attempts. The remaining 29 fetuses were delivered at outside institutions with no interventions or neonatal morbidity. The largest vertical pocket and mass effect on the trachea were selected as independent predictors by the logistic regression. The cross-validated ROC AUC was 0.951 (95% CI, 0.8795-1).The largest vertical pocket measurement and mass effect on the trachea were the most contributory MRI parameters that predicted significant morbidity in fetuses with masses of the face and neck, along with other significant parameters. These parameters predict significant morbid neonatal outcomes, including the need for EXIT procedures.

Summary Background Yellow fever virus infection results in death in around 30% of symptomatic individuals. The aim of this study was to identify predictors of death measured at hospital admission in a cohort of patients admitted to hospital during the 2018 outbreak of yellow fever in the outskirts of Sao Paulo city, Brazil. Methods In this observational cohort study, we enrolled patients with yellow fever virus from two hospitals in Sao Paolo—the Hospital das Clinicas, University of Sao Paulo and the Infectious Diseases Institute “Emilio Ribas”. Patients older than 18 years admitted to hospital with fever or myalgia, headache, arthralgia, oedema, rash, or conjunctivitis were consecutively screened for inclusion in the present study. Consenting patients were included if they had travelled to geographical areas in which yellow fever virus cases had been previously confirmed. Yellow fever infection was confirmed by real-time PCR in blood collected at admission or tissues at autopsy. We sequenced the complete genomes of yellow fever virus from infected individuals and evaluated demographic, clinical, and laboratory findings at admission and investigated whether any of these measurements correlated with patient outcome (death). Findings Between Jan 11, 2018, and May 10, 2018, 118 patients with suspected yellow fever were admitted to Hospital das Clinicas, and 113 patients with suspected yellow fever were admitted to Infectious Diseases Institute “Emilio Ribas”. 95 patients with suspected yellow fever were included in the study, and 136 patients were excluded. Three (3%) of 95 patients with suspected yellow fever who were included in the study were excluded because they received a different diagnosis, and 16 patients with undetectable yellow fever virus RNA were excluded. Therefore, 76 patients with confirmed yellow fever virus infection, based on detectable yellow fever virus RNA in blood (74 patients) or yellow fever virus confirmed only at the autopsy report (two patients), were included in our analysis. 27 (36%) of 76 patients died during the 60 day period after hospital admission. We generated 14 complete yellow fever virus genomes from the first 15 viral load-detectable samples. The genomes belonged to a single monophyletic clade of the South America I genotype, sub-genotype E. Older age, male sex, higher leukocyte and neutrophil counts, higher alanine aminotransferase, aspartate transaminase (AST), bilirubin, and creatinine, prolonged prothrombin time, and higher yellow fever virus RNA plasma viral load were associated with higher mortality. In a multivariate regression model, older age, elevated neutrophil count, increased AST, and higher viral load remained independently associated with death. All 11 (100%) patients with neutrophil counts of 4000 cells per mL or greater and viral loads of 5·1 log10 copies/mL or greater died (95% CI 72–100), compared with only three (11%) of 27 (95% CI 2–29) among patients with neutrophil counts of less than 4000 cells per mL and viral loads of less than 5·1 log10 copies/mL. Interpretation We identified clinical and laboratory predictors of mortality at hospital admission that could aid in the care of patients with yellow fever virus. Identification of these prognostic markers in patients could help clinicians prioritise admission to the intensive care unit, as patients often deteriorate rapidly. Moreover, resource allocation could be improved to prioritise key laboratory examinations that might be more useful in determining whether a patient could have a better outcome. Our findings support the important role of the virus in disease pathogenesis, suggesting that an effective antiviral could alter the clinical course for patients with the most severe forms of yellow fever. Funding Sao Paulo Research Foundation (FAPESP).

Background The use of molecularly targeted therapy is becoming widespread in oncology. These agents cause tumour-specific genetic alterations in signal transduction pathways, hence less generalised toxicity. Dabrafenib, a BRAF inhibitor and Trametinib, a MEK inhibitor are two molecularly targeted agents recently approved for treatment of advanced, unresectable melanomas. MEK retinopathy is a recently introduced term describing retinal toxicity secondary to MEK inhibitors. Case presentation A 71-year-old man presented with ‘circular, green patches’ in his central vision for 2 weeks. He had multiple relapsed stage IV BRAF gene mutant malignant melanoma. He was on treatment with Dabrafenib (Tafinlar) for 7 months and Trametinib (Mekinist) for 4 months respectively. The fundus looked normal. The OCT scan showed bilateral symmetrical cystoid macular edema, intraretinal and subretinal fluid, thickening of elliposoid zone and subretinal granular deposits. The symptoms resolved with temporary cessation of chemotherapy but OCT signs persisted. Conclusion This case report identifies two new remarkable features of MEK retinopathy as thickening of ellipsoid zone and ‘starry sky’ pattern of distribution of subretinal granular deposits. These changes signify photoreceptors/ RPE toxicity and dysfunction. The subretinal granular deposits showed increased autofluorescence suggested abnormal lipofuscin clearance due to RPE dysfunction. The molecularly targeted therapy has revolutionized the cancer treatment and increased the survival rate. These agents are relatively new and recently approved for clinical use and most of them are associated with ocular toxicities. Awareness of ocular symptoms, side-effect profile of drugs, monitoring regime and liaison between oncologist and eye care professional with ocular imaging is key to early diagnosis and management of ocular adverse events.

Objectives: To asses the effect of a sports discipline called SINCROBOX® (consisting in stationary biking coordinated with different arm exercises, namely grip strength, light weightlifts, elastic band stretching, etc) in the functional capacity of mastectomized women’s shoulder. Methods: A randomized blinded cohort study was carried out, with 2 groups of mastectomized women (due to breast cancer). The first one (28 patients) was subjected to SINCROBOX® training for three months, while the second one (22 patients) served as control group. Every patient was subjected to physical exam (range of motion measurement of the affected shoulder) and to functional shoulder tests (DASH, Constant, STT and Oxford) before beginning the training and after 3 months of exercise. A Student’s T test was performed for statistical analysis in each group. Results: Every variable assessed showed statistically significant advantages in the training group: range of motion increased more than 10° in all directions; SST (+20.9; pConclusion: SINCROBOX® is a safe sports discipline that has the ability to improve mastectomized women’s shoulder’s functional capacity.

Zebrafish are increasingly used as a vertebrate model to study human cardiovascular disorders. Although heart structure and function are readily visualized in zebrafish embryos because of their optical transparency, the lack of effective tools for evaluating the hearts of older, nontransparent fish has been a major limiting factor. The recent development of high-frequency echocardiography has been an important advance for in vivo cardiac assessment, but it necessitates anesthesia and has limited ability to study acute interventions. We report the development of an alternative experimental ex vivo technique for quantifying heart size and function that resembles the Langendorff heart preparations that have been widely used in mammalian models. Dissected adult zebrafish hearts were perfused with a calcium-containing buffer, and a beat frequency was maintained with electrical stimulation. The impact of pacing frequency, flow rate and perfusate calcium concentration on ventricular performance (including end-diastolic and end-systolic volumes, ejection fraction, radial strain, and maximal velocities of shortening and relaxation) were evaluated and optimal conditions defined. We determined the effects of age on heart function in wild-type male and female zebrafish, and successfully detected hypercontractile and hypocontractile responses after adrenergic stimulation or doxorubicin treatment, respectively. Good correlations were found between indices of cardiac contractility obtained with high-frequency echocardiography and with the ex vivo technique in a subset of fish studied with both methods. The ex vivo beating heart preparation is a valuable addition to the cardiac function tool kit that will expand the use of adult zebrafish for cardiovascular research., Summary: Here, we describe a new experimental tool to assess contractility of the isolated zebrafish heart perfused in a Langendorff-like system, which will facilitate using zebrafish as a model for human cardiomyopathies.

OBJECTIVES The purpose of this study was to estimate the utility of sonography to detect small-for-gestational-age (SGA) neonates in pregnancies with gastroschisis and to evaluate neonatal outcomes according to birth weight percentile. METHODS We conducted a retrospective cohort study of singleton pregnancies with fetal gastroschisis delivered at our hospital between August 1997 and December 2012. Diagnosis of growth restriction was based on estimated fetal weight below the 10th percentile using the nomogram of Hadlock et al (Am J Obstet Gynecol 1985; 151:333-337), evaluated at 4-week intervals throughout gestation and compared with subsequent birth weight, to evaluate the accuracy of sonography to detect and exclude SGA neonates. Pregnancy and neonatal outcomes were evaluated according to birth weight percentile. RESULTS There were 111 births with gastroschisis (6 per 10,000), and one-third (n = 37) had birth weight below the 10th percentile. The sensitivity and negative predictive value of sonography for an SGA neonate both approached 90% by 32 weeks and were approximately 95% thereafter. Detection increased with advancing gestational age (P = .02). The birth weight percentile was not associated with preterm birth, infection, bowel complications requiring surgery, duration of hospitalization, or perinatal mortality. Delayed closure of the gastroschisis defect was more frequent with birth weights at or below the 3rd percentile (P = .03). CONCLUSIONS Sonography reliably identified SGA neonates with gastroschisis in our series, and its utility improved with advancing gestation. Apart from delayed closure of the defect, a low birth weight percentile was not associated with an increased risk of morbidity or mortality in the immediate neonatal period.

Neurogenic stunned myocardium is an unusual clinical entity. It mimics an acute coronary syndrome with electrocardiographic abnormalities, cardiac dysfunction and elevated cardiac enzymes with absence of obstructive coronary disease. It may occur after a neurosurgical procedure. A case is presented of neurogenic stunned myocardium occurring in a child after removal of a posterior fossa medulloblastoma. The patient developed nodal tachycardia with hemodynamic impairment. The clinical course was satisfactory due to antiarrhythmic therapy, with biochemical, echocardiographic, and clinical improvement within a week.

Excess intake of sodium is often associated with high risk for cardiovascular disease. More recently, some studies on the effects of high salt diets have also demonstrated that they are able to activate Th17 cells and increase severity of autoimmune diseases. The purpose of the present study was to evaluate the effects of a diet supplemented with NaCl in the colonic mucosa at steady state and during inflammation. We showed that consumption of high salt diet (HSD) by mice triggered a gut inflammatory reaction associated with IL-23 production, recruitment of neutrophils and increased frequency of the IL-17-producing type 3 innate lymphoid cells (ILC3) in the colon. Moreover, gut inflammation was not observed in IL-17-/- mice but it was present, although at lower grade, in RAG-/- mice suggesting that the inflammatory effects of high salt diet was dependent on IL-17 but only partially on Th17 cells. Expression of SGK1, a kinase involved in sodium homeostasis, increased 90 minutes after ingestion of 50% NaCl solution and decreased 3 weeks after HSD consumption. Colitis induced by oral administration of either dextran sodium sulfate (DSS) or 2,4,6-trinitrobenzenesulfonic acid (TNBS) was exacerbated by HSD consumption and this effect was associated with increased frequencies of RORt+ CD4+ T cells and neutrophils in the colon. Therefore, our results demonstrated that consumption of high-salt diet per se triggered a histologically detectable inflammation in the colon and also exacerbated chemically-induced models of colitis in mice by a mechanism dependent on IL-17 production most likely by both ILC3 and Th17 cells.

German Centre for Infection Research European Union's Horizon research and innovation program (ZIKAlliance) EVAg We conducted an external quality assessment of Zika virus molecular diagnostic tests in Brazil using a new Zika virus standard. Of 15 laboratories, 73% showed limited sensitivity and specificity. Viral load estimates varied significantly. Continuous quality assurance is required for adequate estimates of Zika virus-associated disease and determination of patient care. Charite, German Ctr Infect Res, Berlin, Germany Hosp Univ Prof Edgard Santos, LAPI, Salvador, BA, Brazil Fdn Prosangue Hemoctr Sao Paulo, Sao Paulo, Brazil Inst Oswaldo Cruz, Rio De Janeiro, Brazil Fed Univ Para, Belem, Para, Brazil Univ Brasilia, Brasilia, DF, Brazil Univ Sao Paulo, Sao Paulo, Brazil Fundacao Oswaldo Cruz, Pernambuco, Brazil Univ Fed Bahia, Salvador, BA, Brazil Diagnost Amer DASA, Sao Paulo, Brazil Hosp Israelita Albert Einstein, Sao Paulo, Brazil Fac Med Sao Jose do Rio Preto, Sao Jose De Rio Preto, Brazil Fdn Med Trop Dr Heitor Vieira Dourado, Manaus, Amazonas, Brazil Fundacao Oswaldo Cruz, Salvador, BA, Brazil Univ Fed Sao Paulo, Sao Paulo, Brazil Aix Marseille Univ, Marseille, France Assistance Publ Hop Marseille, Marseille, France Univ Bonn, Med Ctr, Bonn, Germany Robert Koch Inst, Berlin, Germany Univ Fed Sao Paulo, Sao Paulo, Brazil ZIKAlliance: 734548 EVAg: 653316 Web of Science

BACKGROUND The risk factors for acute episodes of respiratory disease in current and former smokers who do not have COPD are unknown. METHODS Eight thousand two hundred forty-six non-Hispanic white and black current and former smokers in the Genetic Epidemiology of COPD (COPDGene) cohort had longitudinal follow-up (LFU) every 6 months to determine acute respiratory episodes requiring antibiotics or systemic corticosteroids, an ED visit, or hospitalization. Negative binomial regression was used to determine the factors associated with acute respiratory episodes. A Cox proportional hazards model was used to determine adjusted hazard ratios (HRs) for time to first episode and an acute episode of respiratory disease risk score. RESULTS At enrollment, 4,442 subjects did not have COPD, 658 had mild COPD, and 3,146 had moderate or worse COPD. Nine thousand three hundred three acute episodes of respiratory disease and 2,707 hospitalizations were reported in LFU (3,044 acute episodes of respiratory disease and 827 hospitalizations in those without COPD). Major predictors included acute episodes of respiratory disease in year prior to enrollment (HR, 1.20; 95% CI, 1.15-1.24 per exacerbation), airflow obstruction (HR, 0.94; 95% CI, 0.91-0.96 per 10% change in % predicted FEV 1 ), and poor health-related quality of life (HR, 1.07; 95% CI, 1.06-1.08 for each 4-unit increase in St. George's Respiratory Questionnaire score). Risks were similar for those with and without COPD. CONCLUSIONS Although acute episode of respiratory disease rates are higher in subjects with COPD, risk factors are similar, and at a population level, there are more episodes in smokers without COPD.

El objetivo de este estudio fue comprobar el grado de cumplimiento y analizar el efecto de un programa intradiálisis de ejercicio físico sobre la condición física y salud del paciente con enfermedad renal crónica (ERC) que recibe hemodiálisis. Estudio de intervención con dos periodos de 14 semanas, uno sin intervención de ejercicio y otro con intervención, combinando trabajo de resistencia aeróbica y fuerza, en sesiones de 60 minutos, 3 días/semana. La condición física se evaluó a través de la capacidad de fuerza máxima de prensión manual, fuerza resistencia en extremidades inferiores y capacidad cardiorrespiratoria. El 62% de los pacientes cumplieron el 75% del programa. Durante el periodo sin ejercicio intradiálisis se observó una disminución significativa de la condición física, que se frenó durante el periodo con intervención de ejercicio. El programa de ejercicio intradiálisis es importante para frenar la pérdida de condición física ocasionada por la ERC. The aim of this study was to check the grade of enforcement and to assess the effect of an intradialytic exercise program on fitness and health in hemodi - alysis patients. The design of this study consisted of 2 periods of 14 weeks, the first one without exercise and the next one with exercise. The program included both aerobic endurance and strength exercise in sessions of 60 minutes, 3 days per week. Physical condition was evaluated through handgrip strength, lower extremity strength and aerobic capacit y . 62% of patients completed 75% of the exercise program. A statistically significant decrease in all fitness parameters was observed in period without exercise. This decrease stopped, due to the interven - tion of exercise program, without significance improvement. Intradialytic exercise program is important to reduce the loss of fitness associated to chronic kidney disease Cátedra Real Madrid - Universidad Europea (2016RM/09) Fundación Renal Íñigo Álvarez de Toledo (FRI A T) (P14 11 15303) 0.484 IDR (2019) C2, 20/43 Deporte No data JCR 2019 No data SJR 2019 UEM

Objective Neonatal jaundice (hyperbilirubinemia) remains present in 60% of births in the United States1. Current literature links hyperbilirubinemia with neurodevelopmental problems, particularly with attention deficit hyperactivity disorder (ADHD), general learning difficulties, and non-progressive developmental delays. Moderate elevations in bilirubin are also suggested to increase the risk for cognitive, perceptual, motor, and auditory disorders. Imaging studies have shown selective patterns of injury to specific brain regions associated with deficits in executive function, including impulse control and working memory as well as different subtypes of attention problems grounded in reward circuitry system dysfunction in children with bilirubin encephalopathy. Method Neuropsychological functioning of a 12-year old Hispanic female with a history of high levels of perinatal bilirubin, and subsequent developmental and cognitive difficulties in speech, learning, attention and memory as well as problems with socialization and anxiety is presented with the purpose of adding to existing literature. Comprehensive neuropsychiatric interview and neuropsychological testing was completed. Results Results revealed several areas of neurocognitive weaknesses with deficits in areas of intellectual functioning, learning (reading and mathematics), expressive language, visual memory, attention, and auditory processing. Emotional and behavioral measures evidenced significant deficits in social-emotional functioning, particularly with interpersonal skills, sense of adequacy, and self-reliance, which resulted in increased anxiety contributing to cognitive and academic deficits. Conclusions Neuropsychological profile was consistent with cognitive, academic, behavioral and emotional manifestations theoretically associated with neuropathological findings in hyperbilirubinemia. Furthermore, similar to existing literature, cognitive deficits were observed in the absence of a clear cause of neonatal jaundice following a full-term, uncomplicated pregnancy.

Resumen: Introducción: El objetivo del presente trabajo es demostrar si la aplicación del índice biespectral (BIS®) en la monitorización de la anestesia general en respiración espontánea en endoscopias digestivas altas (EDA) diagnósticas en el paciente pediátrico es útil para: a) disminuir la dosis de fármaco necesaria; b) disminuir el tiempo del despertar, y c) mejorar la seguridad del paciente. Pacientes y método: estudio prospectivo cuasi experimental de casos y controles en el ámbito de una unidad de cuidados intensivos pediátricos y neonatales de segundo nivel. Pacientes: niños entre 12 meses y 13 años. Caso: paciente ASA I que precisa EDA diagnóstica; sujetos elegibles 36, participantes 30. Población control: serie histórica de pacientes que precisaron EDA (años 2008-2010): 50 pacientes. Intervenciones: realización de EDA, aplicando protocolo de anestesia, monitorización de constantes vitales, nivel de sedación (escala de Ramsay) y nivel BIS. Variables de interés: dosis total de propofol (mg/kg), tiempo de inducción, tiempo de EDA y tiempo de despertar (min); índice BIS al inicio de la EDA (BISi) y durante la EDA; efectos adversos. Resultados: Sin diferencias significativas entre casos (B) y controles (C) respecto a sexo, edad y peso. Sin diferencias significativas en: dosis total de propofol (B 4,9 ± 1,4 mg/kg; C 5,2 ± 1,6 mg/kg, p = 0,492), Tiempo de despertar (B 12,2 ± 4,6 min; C 12,8 ± 4,4 min, p = 0,402), tiempo de procedimiento (B 9,5 ± 4,8 min; C 11,3 ± 6,5 min, p = 0,335) y tiempo de inducción (B 11,1 ± 2,6 min; C 10,1 ± 4,2 min, p = 0,059). BISi 55,4 ± 6,9. Sin diferencias significativas en efectos adversos (2 casos de desaturación leve en el grupo control). Conclusiones: La monitorización anestésica con índice biespectral en endoscopias digestivas altas en respiración espontánea en la población pediátrica es factible, pero no parece disminuir ni la dosis de fármaco necesaria ni el tiempo de despertar. Tampoco disminuye la incidencia de efectos adversos de forma significativa. Abstract: Introduction: The objective of this investigation is to determine whether bispectral index (BIS®) monitoring during intravenous anaesthesia with spontaneous breathing for upper gastrointestinal endoscopy (UGE) in a pediatric population is useful for: a) decreasing the amount of drug, b) decreasing the time for awakening, and c) improving patient safety. Patients and method: A quasi-experimental case-control prospective study was conducted in the setting of a second level hospital pediatric intensive care unit. Patients: Children aged 1-13 years. Case: ASA I patient who needed a diagnostic UGE; eligible, 36, participants, 30. Control: historical cohort of patients who needed UGE (years 2008-2010): 50 patients. Intervention: UGE performed with anaesthetic protocol, vital signs monitoring, sedation level (Ramsay scale) and BIS monitoring. Variables of interest: propofol total dose (mg/kg), induction time, time in performing the UGE, awakening time (min); initial BIS (iBIS), and BIS during the UGE; adverse effects. Results: There were no significant differences in sex, age or weight between case (B) and control (C) population. No significant differences in total propofol doses: (B 4.9 ± 1.4 mg/kg; C 5.2 ± 1.6 mg/kg, P=.492), awakening time (B 12.2 ± 4.6 min; C 12.8 ± 4.4 min, P=.402), time for execution of UGE (B 9.5 ± 4.8 min; C 11.3 ± 6.5 min, P=.335) and induction time (B 11.1 ± 2.6 min; C 10.1 ± 4.2 min, P=.059), iBIS 55.4 ± 6.9. There were no significant differences in adverse effects: 2 patients suffered from mild desaturation in the control group. Conclusions: BIS monitoring for diagnostic UGE in spontaneous breathing in a pediatric population is feasible, but does not appear to decrease awakening time or the amount of propofol needed. Furthermore, there was no statistically significant decrease in the number of adverse effects.

Ultrasound imaging has made it possible to clearly visualize the anatomy and to understand the functionality of the female pelvic floor. In this chapter, we will focus on the use of 2D/3D transperineal and 3D endovaginal ultrasound imaging in the assessment of the posterior compartment. Normal anatomy, ultrasound techniques, and equipment will be briefly reviewed. A detailed discussion of specific posterior compartment disorders, like rectocele, enterocele, intussusception, and pelvic floor dyssynergy, is included. Certain 3D endovaginal ultrasound findings that may help to explain the presence of obstructed defecation symptoms in a subset of patients with no gross abnormality on physical examination will also be discussed. The use of 3D endovaginal imaging to identify and characterize the presence of mesh in the posterior compartment will be covered as well.

Background. Currently, the number of obese people in the world has reached alarming proportions. During the expansion of adipose tissue, a number of functions such as activation and release of cytokines and hormones may be affected. This causes the body to take a pro-inflammatory pattern, which may affect the proper functioning of many tissues. Thus, studying the mechanisms by which obesity induces physiological disorders is necessary, and may be facilitated by the use of animal models, in particular rodents. We sought to investigate whether the gerbil (Meriones unguiculatus) would be a good experimental model for the study of obesity and metabolic changes resulting from a diet rich in fats and sugars. Methods. 14 gerbils were divided according to weight into two experimental groups and received a a standard diet with 4,15kcal/g (CT; n = 7) or a diet rich in simple carbohydrates and fats with 5,86kcal/g (OB, n = 7) for 11 weeks. The animals had free access to water and food. The weight of each animal and food consumption of each cage were measured weekly and at the end of the experiment, blood, adipose tissue and liver were collected. The following parameters were determined: cholesterol (COL), triglycerides (TGL) and glycemia (GLI) in the plasma; cytokines (IL-6, IL-10 and TNF-α) and hormones (adiponectin and leptin) in adipose tissue; activity of superoxide dismutase (SOD) and catalase (CAT), extraction and differentiation of fat in the liver and liver histology. Results. The consumption of a diet rich in simple fats and carbohydrates led to an increase of total body weight, relative weights of liver and adipose tissue, glucose and triglycerides levels, and TNF-α concentration in adipose tissue. Animals of this group also showed a significant increase of total fat, cholesterol and triglyceride content in the liver, contributing to higher intensity of hepatic steatosis. On the other hand, depletion in the enzyme activity of SOD and CAT in the liver, as well as reduction of IL-10 and adiponectin levels were found in adipose tissue of these animals. Conclusion. Diet consumption consisting of an excess in saturated fat and simple carbohydrates establish the gerbil as an experimental model for the study of obesity and metabolic and liver abnormalities resulting from this disease.

Background/aims:\ud Retinal screening programmes in England and Scotland have similar photographic grading schemes for background (non-proliferative) and proliferative diabetic retinopathy, but diverge over maculopathy. We looked for the most cost-effective method of identifying diabetic macular oedema from retinal photographs including the role of automated grading and optical coherence tomography, a technology that directly visualises oedema. \ud \ud Methods: Patients from seven UK centres were recruited. The following features in at least one eye were required for enrolment: microaneurysms/dot haemorrhages or blot haemorrhages within one disc diameter, or exudates within one or two disc diameters of the centre of the macula. Subjects had optical coherence tomography and digital photography. Manual and automated grading schemes were evaluated. Costs and QALYs were modelled using microsimulation techniques. \ud \ud Results: 3540 patients were recruited, 3170 were analysed. For diabetic macular oedema, England’s scheme had a sensitivity of 72.6% and specificity of 66.8%; Scotland’s had a sensitivity of 59.5% and specificity of 79.0%. When applying a ceiling ratio of £30 000 per quality adjusted life years (QALY) gained, Scotland’s scheme was preferred. Assuming automated grading could be implemented without increasing grading costs, automation produced a greater number of QALYS for a lower cost than England’s scheme, but was not cost effective, at the study’s operating point, compared with Scotland’s. The addition of optical coherence tomography, to each scheme, resulted in cost savings without reducing health benefits. \ud \ud Conclusions: Retinal screening programmes in the UK should reconsider the screening pathway to make best use of existing and new technologies.

When medical therapy fails for menorrhagia in a premenopausal woman, minimally invasive endometrial ablation can be used as a conservative management alternative to hysterectomy. Endometrial ablation alone is not considered effective contraception, and women of reproductive age can become pregnant after ablative therapy. We now present two cases of pregnancy after endometrial ablation and associated imaging where both cases required cesarean hysterectomy due to post-partum hemorrhage. Pregnancy after endometrial ablation incurs increased morbidity and diagnostic dilemmas.

The World Health Organization describes contraception as desirable for many reasons. It allows families to make informed choices about their reproductive years. It allows family planning, with spacing of children, leading to better bonding between mother and child, higher exclusive breastfeeding rates, and improved health of the mother for a future pregnancy.1 Unintended pregnancies continue to occur at an astronomically high rate in the US, as high as 35% by most recent data,2 and of course, since women with pulmonary arterial hypertension (PAH) are not exempt from this statistic, it is imperative that as care providers, we help our patients to plan ahead. In their case, maternal health is our main concern. Weiss and colleagues, reporting on pregnancy outcomes with PAH between 1978 and 1996, found a maternal mortality of 36% in Eisenmenger syndrome, 30% in idiopathic PAH, and 56% in secondary PAH.3 A more recent systematic review reported slightly more optimistic pregnancy outcomes from 1997 to 2007. Still, maternal mortality ranged from 17% to 33%, depending on the exact etiology of pulmonary hypertension.4 It is therefore very clear that in the setting of PAH, contraception is important and potentially lifesaving.

Objective To analyze various possibilities of using dimeric inhibin A (DIA) as a first-trimester marker, during week 13, for diverse sequential strategies together with the combined test (CT) [which uses pregnancy-associated plasma protein A, free beta-human chorionic gonadotrophin and nuchal translucency]. Method We analyzed three sequential strategies (nondisclosure, stepwise and contingent) for measuring DIA in week 13. Multivariate Gaussian modelling was used to estimate second-trimester, false-positive and detection rates. Model parameters were taken from the Serum, Urine and Ultrasound Screening Study (SURUSS) assay. Results The three sequential strategies provided high and comparable levels of effectiveness, with false-positive rate for fixed detection rate of 85% and detection rate for fixed false-positive rate of 5% values of about 91 and 2%, respectively. The contingent strategy (with two CT risk cutoffs, of 1 in 50 and 1 in 2000) produced a screening-positive rate of 0.8% with CT, while only 23% of the women needed subsequent DIA measurement. Conclusions First-trimester sequential screening using CT together with DIA measurement in week 13 is capable of producing results that are comparable with those of the integrated test, with the additional advantage that the final result is obtained earlier. It is recommended that this strategy be evaluated in large-scale prospective studies. Copyright © 2008 John Wiley & Sons, Ltd.

Chagas disease is a chronic disorder caused by the Trypanosoma cruzi protozoan. The infection causes alterations to the enteric nervous system such as megaesophagus and megacolon. There is evidence of denervation of myenteric ganglia. The intense parasitism of acute phase affects neuronal integrity but contrasts with the absence of parasites and the discreet inflammatory process of chronic phase, indicating a progressive injury mechanism that needs to be better understood in the megacolons. The potential selectivity of enteric neurons classes affected by the progression of the disease is not yet clear. Nitrergic neurons which co-localize other neurotransmitters represent the most common inhibitory neuron of the ENS. Recently a chronic stage of the Chagas disease was reproduced experimentally in a suitable murine model of megacolon. Considering the limitation of studying human intestine and the controversy on the pattern of nNOS involvement in chagasic megacolon, we decided to assess the nitrergic neurons in the myenteric plexus of mice. We used antibodies against structural protein gene product 9.5 (PGP 9.5) and functional neuronal nitric oxide synthase (n-NOS) at the acute and chronic phase of the disease to quantify myenteric ganglionar neurons in the colon of infected and non-infected mice. We found a reduction in the ganglionar number of neurons detected by anti-protein gene product 9.5 antibodies in colon from mice at the chronic stage. However, the number of nitrergic neurons per ganglia remained unchanged along the acute to phase chronic of the disease. Our findings indicate a long-term preservation of nitregic neurons detrimental to other classes of enteric in our model of experimental Chagas disease. We propose that differential loss of enteric neurons is at least one of the structural substrate for the development of the longterm morphfunctional changes that lead to the megacolon.

The zebrafish (Danio rerio) is an increasingly popular model organism in cardiovascular research. Major insights into cardiac developmental processes have been gained by studies of embryonic zebrafish. However, the utility of zebrafish for modeling adult-onset heart disease has been limited by a lack of robust methods for in vivo evaluation of cardiac function. We established a physiological protocol for underwater zebrafish echocardiography using high frequency ultrasound, and evaluated its reliability in detecting altered cardiac function in two disease models. Serial assessment of cardiac function was performed in wild-type zebrafish aged 3 to 12 months and the effects of anesthetic agents, age, sex and background strain were evaluated. There was a varying extent of bradycardia and ventricular contractile impairment with different anesthetic drugs and doses, with tricaine 0.75 mmol l−1 having a relatively more favorable profile. When compared with males, female fish were larger and had more measurement variability. Although age-related increments in ventricular chamber size were greater in females than males, there were no sex differences when data were normalized to body size. Systolic ventricular function was similar in both sexes at all time points, but differences in diastolic function were evident from 6 months onwards. Wild-type fish of both sexes showed a reliance on atrial contraction for ventricular diastolic filling. Echocardiographic evaluation of adult zebrafish with diphtheria toxin-induced myocarditis or anemia-induced volume overload accurately identified ventricular dilation and altered contraction, with suites of B-mode, ventricular strain, pulsed-wave Doppler and tissue Doppler indices showing concordant changes indicative of myocardial hypocontractility or hypercontractility, respectively. Repeatability, intra-observer and inter-observer correlations for echocardiographic measurements were high. We demonstrate that high frequency echocardiography allows reliable in vivo cardiac assessment in adult zebrafish and make recommendations for optimizing data acquisition and analysis. This enabling technology reveals new insights into zebrafish cardiac physiology and provides an imaging platform for zebrafish-based translational research., Summary: Standardization of zebrafish echocardiography provides insights into cardiac physiology in normal and diseased states, with application for functional studies in zebrafish models of heart disease.