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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.

The sugarcane cystatin (CaneCPI-5) was recently cloned and showed strong binding force to dental enamel and protection against initial erosion. However, evaluations on its safety and efficacy in a situation closer to the clinical condition are necessary. In the present study we analyzed 1) the cytotoxicity of CaneCPI-5 on human gingival fibroblasts (HGFs); 2) the ability of CaneCPI-5 to reduce enamel erosion and erosion+abrasion in situ. In part 1, HGFs were treated with CaneCPI-5 (0.025, 0.05, 0.1, 0.5 or 1.0 mg/mL) or no treatment (control). The cytotoxicity was assessed after 60 s and 24 h by mitochondrial activity (MTT), confocal microscopy, and hematoxylin/eosin staining. In part 2, 15 volunteers participated in a double-blind crossover protocol consisting of 3 phases, according to the following treatments: 1) 0.1 mg/mL CaneCPI-5; 2) SnCl2/NaF/AmF (Elmex; positive control); 3) water (negative control). The volunteers wore an appliance containing 4 bovine enamel specimens for 5 d. Each day, the specimens were individually treated with 50 µL of the tested solutions per 60 s and then subjected to erosive challenges (0.1% citric acid, pH 2.5, for 90 s, 4 times per day). After the first and last erosive challenge each day, 2 samples were abraded (toothbrushing, 15 s). Enamel wear was measured by contact profilometry. One or two-way analysis of variance (ANOVA)/Tukey’s or Sidak’s tests ( P < 0.05) were applied. Regardless of the concentration and the experimental time, CaneCPI-5 did not decrease the cell viability compared to the negative control ( P < 0.05). Erosion+abrasion led to significantly greater wear compared to erosion only. For both conditions, the lowest wear was found for SnCl2 and CaneCPI-5, which did not differ significantly from each other, but showed significant protection when compared to the negative control. In conclusion, CaneCPI-5 is safe on HGFs and reduces enamel erosive wear to the same extent as a commercial solution used to control erosive tooth wear (ETW).

Magnetic resonance imaging (MRI) assesses pulmonary hypoplasia in fetal congenital diaphragmatic hernia (CDH). Neonatal mortality may occur with CDH. To quantify MRI parameters associated with neonatal survival in fetuses with isolated CDH. Fetal MRI for assessing CDH included region of interest (ROI) measurements for total lung volume (TLV), herniated liver volume, herniated other organ volume and predicted lung volume. Ratios of observed lung volume and liver up volume to predicted lung volume (observed to predicted TLV, percentage of the thorax occupied by liver) were calculated and compared to neonatal outcomes. Analyses included Wilcoxon rank sum test, multivariate logistic regression and receiver operating characteristic (ROC) curves. Of 61 studies, the median observed to predicted TLV was 0.25 in survivors and 0.16 in non-survivors (P=0.001) with CDH. The median percentage of the thorax occupied by liver was 0.02 in survivors and 0.22 in non-survivors (P 28 weeks was greater compared to GA ≤28 weeks. The ROC analysis demonstrated an area under the curve of 0.96 (95% confidence interval 0.91–1.00) for the combined observed to predicted TLV, percentage of the thorax occupied by liver and GA. The percentage of the thorax occupied by liver and observed to predicted TLV was predictive of neonatal survival in fetuses with CDH.

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.

This work has as main objective to propose the identification of a small scale non-linear system through the Neural Network AutoRegressive with eXternal input. The use of this network requires an adequate methodology for its configuration and, consequently, a good training set. Then, it is proposed that the main definitions of the network parameters be obtained through the analysis of nonintrusive performance indices. Additionally, using a database based on the system’s response, excited by the Pseudo-Random Binary Sequence signal. The methodology will be applied in two specific open-loop identification situations: numerical simulation of a fourth order polynomial system (Case 01), and an experimental system that controls a nonlinear water tank level (Case 02). The results of the identified models were able to represent the system dynamics with high fidelity, presenting an average identification error of less than 0:14 and 0:34% for Case 1 and 2, respectively. Also, it is observed that the learning and generalization evidence could represent the process intrinsic nonlinearities satisfactorily. Besides, it will be possible to find the potentiality and usefulness of the developed network in nonlinear system identification.

Host immune responses contribute to dengue’s pathogenesis and severity, yet the possibility that failure in endogenous inflammation resolution pathways could characterise the disease has not been contemplated. The pro-resolving protein Annexin A1 (AnxA1) is known to counterbalance overexuberant inflammation and mast cell (MC) activation. We hypothesised that inadequate AnxA1 engagement underlies the cytokine storm and vascular pathologies associated with dengue disease. Levels of AnxA1 were examined in the plasma of dengue patients and infected mice. Immunocompetent, IFNα/βR-/-, AnxA1-/-and FPR2/ALX-/-mice were infected withDengue virus(DENV) and treated with the AnxA1 mimetic peptide Ac2-26for analysis. Additionally, the effect of Ac2-26on DENV-induced MC degranulation was assessedin vitroandin vivo. We observed that circulating levels of AnxA1 were reduced in dengue patients and DENV-infected mice. While the absence of AnxA1 or its receptor FPR2/ALX aggravated illness in infected mice, treatment with AnxA1 agonistic peptide attenuated disease manifestations. Both clinical outcomes were attributed to modulation of DENV-mediated viral load-independent MC degranulation. We have thereby identified that altered levels of the pro-resolving mediator AnxA1 are of pathological relevance in DENV infection, suggesting FPR2/ALX agonists as a therapeutic target for dengue disease.

Diffuse lung disease in early childhood due to mutations in the filamin A gene has been recently reported. Clinical outcomes vary among individuals indicating variability in phenotype but a substantial proportion of reported cases in early life have ended up in death or lung transplantation. We recently encountered a school-aged child in whom the diagnosis of a filamin A mutation was delayed and the natural history of emphysematous lung disease was altered by serial lung volume reduction surgeries. She eventually underwent a bilateral lung transplant and we report the natural history of her disease and treatments applied herein.

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.

Background Increased levels of inflammatory cytokines are associated with severe dengue evolution, but the source of such hypercytokinemia is elusive. We investigated the contribution of innate lymphocytes, innate lymphoid cells (ILCs), and natural killer (NK) cells in cytokine production in early dengue infection. Methods Peripheral blood mononuclear cells of individuals with dengue without warning signs (DWS–) and dengue with warning signs and severe dengue (SD) presentation combined (DWS+) were obtained between 2 and 7 days since fever onset and submitted to flow cytometry without specific antigen stimulation to evaluate cytokines in ILC and NK cell subpopulations. Results ILCs and NK cells were found to be important sources of cytokines during dengue. ILCs of the DWS+/SD group displayed higher production of interferon gamma (IFN-γ) and interleukin (IL) 4/IL-13 when compared to DWS– individuals. On the other hand, NK Eomes+ cells of DWS– patients displayed higher IFN-γ production levels compared with the DWS+/SD group. Interestingly, when NK cells were identified by CD56 expression, DWS+/SD displayed higher frequency of IL-17 production compared with the DWS– group. Conclusions These results indicate that ILCs and NK cells are important sources of inflammatory cytokines during acute dengue infection and display distinct profiles associated with different clinical forms.

In this article, an analysis of the current potentialities of social media and their impact on the daily life of human beings will be done. Leading to the presentation of software that helps to the generation of new knowledge based on different tools analysis applied to the users. The use of social media their strengths and orientation are analyzed by reviewing the advantages of the main ones used in the world and their focus. In this way, an analysis is presented on a global and local scale, looking for important acceptance indicators for users who remain active in the media. Finding the fields of interest, age groups, and gender according to the network and indistinct parameters that ultimately let us see the impact from the user. Base on different SM search engines on the main trends found we can define a friendly interface that can be implemented in the software model to be proposed. Finally, we put forward a proposal whose main orientation is to analyze personal and business interest groups, performing a benchmarking that has as its main input social media. It allows companies to innovate and improve in a certain line of business by obtaining knowledge of those who do things better at a given time. Organizations will be able to make decisions more efficient, agile, and appropriate to their own business.

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.

The quality of the images obtained from mobile cameras has been an important feature for modern smartphones. The camera Image Signal Processing (ISP) is a significant procedure when generating high-quality images. However, the existing algorithms in the ISP pipeline need to be tuned according to the physical resources of the image capture, limiting the final image quality. This work aims at replacing the camera ISP pipeline with a deep learning model that can better generalize the procedure. A Deep Neural Network based on the UNet architecture was employed to process RAW images into RGB. Pre-processing stages were applied, and some resources for training were added incrementally. The results demonstrated that the test images were obtained efficiently, indicating that the replacement of traditional algorithms by deep models is indeed a promising path.

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

Background In December 2018, a large, tertiary, university-affiliated hospital in the Philippines discovered that their legitimate supply chain was infiltrated with counterfeit rabies vaccines. Methods All vials suspected to be counterfeit were quarantined and surrendered to the Philippine Food and Drug Administration. Patients who may have received the counterfeit products were recalled, evaluated, and revaccinated accordingly. Vials of the counterfeit vaccines were sent to various laboratories for testing. Results Two batches of counterfeit rabies vaccines were found to have infiltrated the hospital’s supply chain between December 2017 and December 2018. Of the 1711 patients who may have received counterfeit vaccines, 1397 patients were successfully contacted, and 734 were revaccinated with at least 1 dose of authentic rabies vaccine. The counterfeit vials were sterile, contained no toxic substances, and both contained active antirabies ingredient. No report of rabies infection or other adverse events were noted. Conclusions Our experience demonstrates the need for strong intervention and collaborative response from all stakeholders—government and regulatory bodies, the pharmaceutical industry, and individual institutions and consumers—to effectively eradicate counterfeiting and protect our patients., This article describes how counterfeit rabies vaccines infiltrated one hospital’s supply chain, details its comprehensive response, including investigation, patient recall and revaccination, and vaccine testing, and illustrates how governments, the pharmaceutical industry, and individual institutions can collaborate to prevent recurrences.

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

Specific demand of lightweight and high efficient flexible energy unit is increased day by day for its integration into bendable electronics devices. Super-capacitor is one of the promising power unit to meet the current requirement. Flexible metal oxide and polypyrrole based flexible electrode materials are prepared using electrodeposition. The calculated specific capacitances of the devices shows 0.5 mill farad per gram. The super-capacitor is ultra-flexible, stable with operational voltage window expands from 0.8 to 2.5 V which can help to reduce the number of super-capacitor in series connection to obtain the same output. In this study, a conductive polymer can be coupled with MnO2 to improve capacitance and conductivity of a hybrid structure based on MnO2.

The Apicomplexa protozoanToxoplasma gondiiis a mandatory intracellular parasite and the causative agent of toxoplasmosis. This illness is of medical importance due to its high prevalence worldwide and may cause neurological alterations in immunocompromised persons. In chronically infected immunocompetent individuals, this parasite forms tissue cysts mainly in the brain. In addition,T.gondiiinfection has been related to mental illnesses such as schizophrenia, bipolar disorder, depression, obsessive-compulsive disorder, as well as mood, personality, and other behavioral changes. In the present study, we evaluated the kinetics of behavioral alterations in a model of chronic infection, assessing anxiety, depression and exploratory behavior, and their relationship with neuroinflammation and parasite cysts in brain tissue areas, blood-brain-barrier (BBB) integrity, and cytokine status in the brain and serum. Adult female C57BL/6 mice were infected by gavage with 5 cysts of the ME-49 type IIT.gondiistrain, and analyzed as independent groups at 30, 60 and 90 days postinfection (dpi). Anxiety, depressive-like behavior, and hyperactivity were detected in the early (30 dpi) and long-term (60 and 90 dpi) chronicT.gondiiinfection, in a direct association with the presence of parasite cysts and neuroinflammation, independently of the brain tissue areas, and linked to BBB disruption. These behavioral alterations paralleled the upregulation of expression of tumor necrosis factor (TNF) and CC-chemokines (CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1β and CCL5/RANTES) in the brain tissue. In addition, increased levels of interferon-gamma (IFNγ), TNF and CCL2/MCP-1 were detected in the peripheral blood, at 30 and 60 dpi. Our data suggest that the persistence of parasite cysts induces sustained neuroinflammation, and BBB disruption, thus allowing leakage of cytokines of circulating plasma into the brain tissue. Therefore, all these factors may contribute to behavioral changes (anxiety, depressive-like behavior, and hyperactivity) in chronicT.gondiiinfection.

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.

Quantum dots (QDs) are a hot topic in optoelectronic device research, due to tailorable absorption and emission properties. Unfortunately, the conventional methods of QD synthesis are hazardous and time-consuming. In this work, we present an alternative method of fabricating cadmium selenide (CdSe) QDs (via rapid microwave synthesis). This novel fabrication method provides a quick and efficient way to synthesize QDs that are almost identical to those commercially available. We also demonstrate the tuning of QD sizes by varying time and temperature during the growth process. Optical spectroscopy was used to measure the emission profile of QDs of various sizes. With ease repeatability, tunability, and scalability, this QD synthesis method can be integrated into a wide range of applications and optoelectronic devices.

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.

Introducción: el objetivo es analizar el estilo de vida, en función del ejercicio y la dieta, de un grupo de adolescentes de la Comunidad de Madrid, teniendo en cuenta género y patología y su relación con el estado nutricional, la distribución de grasa y la función pulmonar. Metodología: Estudio descriptivo de 207 sujetos que analizó el estilo de vida a partir del nivel de actividad física (AF) y la adherencia a la dieta mediterránea, el estado nutricional y la distribución de grasa, y la salud respiratoria. Resultados: El grupo de no asmáticos fue más activo (p=0,003) y presentó menor ICT (p=0,001) que el grupo de asmáticos. Se encontraron diferencias significativas dentro del grupo sin asma en nivel de AF siendo los varones más activos (p=0,01) y presentando menor índice cintura-talla (ICT) que las mujeres del mismo grupo (p=0,001). Conclusiones: Los adolescentes no asmáticos fueron más activos y presentaron mejor distribución de grasa que los asmáticos, Objectives: objective is to analyze the lifestyle, integrating exercise and diet, of a group of adolescents from the Community of Madrid, taking into account gender and pathology and its relationship with nutritional status, fat distribution and lung function in adolescents with or without asthma. Methods: This was a descriptive study including 207 subjects aged 13.20 ± 0.62 years. Lifestyle was assessed in terms of physical activity (PA) levels, Mediterranean diet, nutritional status, and respiratory health measured through FEV1 (z). Results: In the non-asthma group, boys were more active (p = 0.01) and showed a lower waist-to-height ratio (WHtR) than girls (p = 0.001). Participants without asthma were more active (p = 0.003), and had a better WHtR (p = 0.001) and FEV1 (p = 0.001) than those with asthma. Conclusions: In this Spanish population sample, non-asthmatic adolescents were more active and showed a better nutritional status, fat distribution and respiratory health than their peers with asthma, Financiado a través de la VII Convocatoria Real Madrid-Universidad Europea (Ref 2015/03RM); Tercer premio en los XV Premios Neumomadrid; Beca Jóvenes Investigadores de la SENP 2015.

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.

Transgenic corn and cotton expressing Cry and/or Vip3Aa proteins from Bacillus thuringiensis (Bt) have been planted for managing lepidopteran and coleopteran insect pests for more than two decades in the U.S. Evolution of insect resistance to these Bt proteins is a major threat for the continued efficacy of Bt technology. Understanding patterns of cross-resistance and dominance of resistance in target insects is essential for resistance management and pest control. The bollworm, also called corn earworm, Helicoverpa zea (Boddie), is a major target pest of pyramided Bt crops in the U.S. In this study, we evaluated the responses of Cry2Ab2-resistant (RR), susceptible (SS), and heterozygous (RS) strains of H. zea to the Cry1Ac, Cry1A.105, Cry2Ab2 and Vip3Aa39 proteins using diet-overlay bioassays. The Cry2Ab2-resistant H. zea also possessed high levels of resistance to Cry1Ac and Cry1A.105, but were very susceptible to Vip3Aa. The resistance to Cry1 and Cry2 proteins in RR H. zea varied from incompletely recessive to completely dominant depending on the protein concentration. These data suggest that the RR H. zea possess multiple non-recessive resistance to Cry1/Cry2 proteins. These results have significant implications for understanding field-evolved resistance of H. zea to Cry1 and Cry2 proteins in U.S. Bt corn and cotton fields and should contribute to developing effective management strategies for control of H. zea.

Silicon photonics enables the fabrication of optical devices with standard semiconductor processing technology. With high transparency and modal confinement, Si has matured into a well-established infrared optical material. Nanostructured silicon has been studied extensively due to its optical properties, especially silicon nanowires due to the myriad of available fabrication techniques, the broad range of physical dimensions, and the resulting optical characteristics. In this study, we fabricate silicon nanowires using a wet chemical process and modify their absorptive properties via atomic layer deposition passivation. The passivated nanowires absorb 95% of light from the visible to infrared, with a minimal angular dependence, making them excellent candidates for broadband absorber applications.

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.

Mercury Cadmium Telluride (MCT) is a primary absorber material used in most infrared (IR) detection technologies. Our previous studies show that the optical absorbance profile of MCT in the mid-infrared region can be enhanced by 13% under ambient conditions via integrating periodic Indium Tin Oxide (ITO) nanostructures. Here, we focus on the geometrical parameterization and optimization of ITO nanostructure arrays. We simulate several types of geometries, their corresponding effective absorption profiles, E-field distribution, and optimal geometric parameters. This work may lead to improved light collection and absorption edge engineering, as MCT continues to be the material of choice in IR detection architectures.

Objectives: This study was performed to determine whether neutralizing antibodies against yellow fever virus (YFV) generated by YFV vaccine could interfere in the specificity of dengue virus (DENV) and Zika virus (ZIKV) IgG ELISA tests. Methods: Seventy-nine pairs of serum samples (pre- and post-vaccination), collected during the years 1997–1998 from children with no history of yellow fever disease who had been vaccinated against YFV, were tested. The seroconversion post-vaccination was evaluated through plaque reduction neutralization test (PRNT), and four different commercial ELISA kits were used for the detection of DENV and ZIKV IgG antibodies. Results: A cross-reactivity rate of 3.9% with DENV IgG antibodies was found only with the Dengue Virus IgG Dx Select kit (Focus Diagnostics). Conclusions: As several countries have local transmission of multiple arboviruses, the absence of cross-reactivity or minimum cross-reactivity of YFV neutralizing antibodies with DENV and ZIKV antigens is a relevant finding, since the interpretation of sero-epidemiological investigations would be seriously impacted in many regions where YFV vaccination is mandatory. Keywords: Serological tests, Yellow fever, Dengue, Zika, Cross-reactivity

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.