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ENG is an accessory receptor molecule that, in association with TGF-β family receptors types I and II, binds TGF-β1, TGF-β3, activin A, bone morphogenetic protein (BMP)-2, and BMP-7, regulating TGF-β dependent cellular responses. ENG, predominantly expressed in vascular endothelial cells, is also detected in fibroblasts, vascular smooth muscle cells and mesangial cells, among others. Since ENG negatively regulates extracellular matrix (ECM) levels, this molecule may be relevant to DN, which is primarily a disorder of ECM accumulation. 125 T1D pts were ranked based on their electron microscopy estimated rate of mesangial expansion (ME) or ME score (MES). The 20 pts with the highest MES and proteinuria ("fast-track") and the 20 with the lowest MES and normoalbuminuria ("slow-track"), along with 20 healthy controls without D family history, were studied. SF ENG mRNA expression levels were assessed by microarray (Affimetrix HG-U133A GeneChip) and by QRT-PCR. Four subjects from each group, representing a wide range of microarray ENG mRNA expression levels, were selected for western blot using a mouse anti-human ENG monoclonal antibody. Age [36 ± 10 (mean ± SD); 38 ± 8; 41 ± 8 years] and sex (8; 9; 8 males) were similar among "slow-" and "fast-track" pts and controls, respectively. D duration was similar (20 ± 8 vs. 24 ± 7 years), while Ale (8.4 ± 1.2 vs. 9.4 ± 1.5%) and mean blood pressure (85 ± 8 vs. 96 ± 8 mmHg) were lower and glomerular filtration rate (115 ± 13 vs. 72 ± 20 ml/min/1.73m²) higher in "slow" vs. "fast-track" pts. Controls and "fast-track" pts had similar microarmy ENG expression levels (p=0.91), whereas these levels were higher in "slow-track" pts than controls (13=0.015) and "fast-track" pts (p=0.0069). These findings were confirmed by QRT-PCR, where ENG mRNA expression levels were higher in "slow-" (2.07 ± 0.39) than in "fast-track" pts (1.75 ± 0.27; p--0.009) or controls (1.78 ± 0.5; p=0.02). ENG microarmy and QRT-PCR mRNA levels were correlated (r=0.65; p=0.022), and ENG protein expression correlated with ENG mRNA expression levels measured by microarray (r=0.59; p=0.044) and QRT-PCR (r=0.61; p=0.034). Monocyte cell line studies have shown that cells transfected with ENG have lower fibronectin synthesis after TGF-β exposure than control cells. Given this background, our studies are compatible with the idea that "slow-track" T1D pts, strongly protected from DN, have distinct cellular behaviors consistent with reduced ECM production. [ABSTRACT FROM AUTHOR]

Sporadic Creutzfeldt-Jakob disease (sCJD) is a fatal and rapidly progressive form of dementia caused by the spread of a prion protein within the brain. Its real incidence is unknown since its definitive diagnosis requires histopathological analysis of brain specimens. However, novel tests that detect prion proteins in cerebrospinal fluid samples, such as the real-time quaking-induced conversion (RT-QuIC) technique, now allow the pre-mortem diagnosis of sCJD. Here, we report the first case of sCJD confirmed by RT-QuIC in Latin America, providing evidence of its diagnostic performance and clinical correlation. [ABSTRACT FROM AUTHOR]

Presents several questions on various literary subjects. Early references to acupuncture in the tales of travellers to the Orient; Names of printed books that first employed the use of color printing; List of French and German author clubs or newsletters.

Purpose: 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. Methods: 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). Results: 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, p=.03), had fewer preoperative office visits (2.1 vs. 3.4, p=.0003), received fewer preoperative chest radiographs (0.5 vs. 1.3; p=.002) and chest computed tomography (0.9 vs. 1.4; p=.001), and had fewer preoperative pneumonias (0 vs. 17.4%; p=.02) compared to their NON-FC counterparts. FC patients were also more likely to undergo resection at an earlier age (217 vs. 481 days, p=.003) and were more likely to undergo a minimally invasive resection (75% vs. 39.1%, p=.015). There were no differences in post-operative outcomes between the two groups. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Background: Salmonella species now represent a leading cause of Gram-negative bacterial meningitis in the developing world. Various drugs have been used for the treatment of Salmonella meningitis over the past decades, but mortality, neurologic sequelae and relapse rates remain high. In this report we describe two children aged 8 and 9 months who presented within a week to our hospital with Salmonella meningitis. They were treated with penicillin and chloramphenicol but progressed rapidly to death within 48 h. Aim: The aim of this article is to review all published English literature on the treatment of Salmonella meningitis and identify the best drug option for its treatment. This was done by comparing the outcomes such as cure, failure, relapse, and death rates. Method: A Medline electronic search was carried out to find and retrieve articles that have been published since 1987, when the last review of Salmonella meningitis was done. Results: Salmonella typhimurium was the commonest organism reported, and 89.7% of infections occurred in children less than 1 year old. Fluoroquinolones had a cure rate of 88.9%, while the third-generation cephalosporins had a cure rate of 84.6%. Conventional antibiotics (chloramphenicol, ampicillin, and cotrimoxazole) had a cure rate of 41.2%, a relapse rate of 11.8%, and an associated mortality of 44.7%. Treatment with fluoroquinolone and imipenem resulted in no deaths. There were, however, only two cases that were treated with imipenem. Conclusion: When Salmonella meningitis is suspected, third-generation cephalosporins, with or without a fluoroquinolone, may be the best option for treatment. [ABSTRACT FROM AUTHOR]

Background: Magnetic resonance imaging (MRI) assesses pulmonary hypoplasia in fetal congenital diaphragmatic hernia (CDH). Neonatal mortality may occur with CDH. Objective: To quantify MRI parameters associated with neonatal survival in fetuses with isolated CDH. Materials and methods: 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. Results: 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<0.001). The association of observed to predicted TLV and percentage of the thorax occupied by liver with survival for gestational age (GA) >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. Conclusion: The percentage of the thorax occupied by liver and observed to predicted TLV was predictive of neonatal survival in fetuses with CDH. [ABSTRACT FROM AUTHOR]

Background: Data are lacking on the pneumococcal serotypes present in many developing regions, including the Caribbean. We examined the serotypes of nasopharyngeal (NP) isolates of pneumococci obtained from Jamaican children. Methods: We obtained NP samples from children seen in the Emergency Department at the Bustamante Children's Hospital. The samples were transported to Canada for isolation and serotyping of pneumococci. Results: We obtained 94 isolates from 276 children; median age 3.4 years. The majority (57%) had symptoms of acute respiratory infection at the time of sampling. The main serotypes carried were 6B (20.5%), 19F (14.5%), and 14 (8.4%). Non-typable isolates accounted for 10.8% of the isolates. Fifty-nine percent of the serotypes were present among the 11 being considered for candidate pneumococcal conjugate vaccines (95% CI 48-70%); the corresponding proportion present in the recently licensed 7-valent vaccine was 57% (95% CI 45-67%). A significant proportion of the serotypes found is absent from those to be included in future conjugate vaccines (P < 0.0001; reference = 85% expected serotype representation). Less than 5% of isolates were non-susceptible to penicillin (3.2%), cefotaxime-ceftriaxone (3.2%) and cefuroxime (3.2%), while 8.4% and 1.l% of isolates were resistant to trimethoprim-sulfamethoxazole and erythromycin respectively. There were three isolates with resistance to two or more classes of drug. These isolates were all resistant to penicillin (MIC 2 µg/mL); the serotypes were 14, 23F, and 19F. Conclusion: A significant proportion of the serotypes found is absent from those to be included in future conjugate vaccines. [ABSTRACT FROM AUTHOR]

Background: Enterohemorrhagic Escherichia coli (EHEC) O26 has emerged as a significant cause of hemolyticuremic syndrome (HUS). The source and the vehicle of contamination with EHEC O26 are not often identified. We report two Austrian cases of HUS due to E. coli O26:H - affecting an 11-month-old boy and a 28-month-old girl in which transmission through unpasteurized cow's milk was positively identified. Methods and Results: Using automated ribotyping and pulsed-field gel electrophoresis (PFGE), the isolates (which yielded the virulence genes stx2, eae , and hly) were indistinguishable from each other. An epidemiologic investigation revealed that the children had stayed in the same hotel. Both patients had consumed unpasteurized cow's milk from the breakfast buffet. Fecal samples were taken from the cows of the farm producing the incriminating milk, and one of three cattle EHEC O26:H - isolates had a PFGE pattern indistinguishable from that of the patients' strains. Conclusions: These two cases of E. coli O26 infection illustrate the hazards associated with the consumption of raw milk, and underline the importance of microbiological diagnostic approaches able to detect sorbitol-fermenting, nonO157 EHEC. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to characterize phenotypically enterotoxins, colonization factors (CFs) and the antibiotic susceptibility of enterotoxigenic Escherichia coli (ETEC) strains isolated from cases of acute diarrhea that occurred in Europeans traveling to resorts in Mombasa, Kenya; this information is critical for the development of vaccines and empirical treatment. Methods: Over a 1-year period from 1996 to 1997, five E. coli -like colonies were obtained from each of 463 cases with acute diarrhea. These strains were characterized for enterotoxins using GM-1 ELISA, for CFs using a dot-blot assay, and for antibiotic susceptibility using antibiotic disks. Results: Of 164 strains characterized for ETEC phenotype, 30 (18%) expressed heat-labile toxin (LT) only, 83 (51%) heat-stable toxin (ST) only, and 51 (31%) both LT and ST. Analysis for CF expression demonstrated that 107 (65%) of the strains were positive for CFs, including CFA/IV (46%), CFA/II (35%), and CFA/I (5%), while less than 4% expressed less common CFs. All ETEC strains tested were resistant to erythromycin and sensitive to ceftriaxone. Over one-third of the strains were resistant to sulfamethoxazole-trimethoprim or tetracycline. Six strains were resistant to nalidixic acid; none of these were resistant to ciprofloxacin. Conclusions: Cumulatively, our findings indicate that ETEC in this region comprises a highly diverse group of bacterial enteropathogens, and that the development of prophylactic agents against ETEC faces major challenges because of this diversity. [ABSTRACT FROM AUTHOR]

Background: The more widespread use of peripheral venous catheters (PVC) has led to more frequent complications, not only in PVC-associated bacteremia, but also in phlebitis. This requires the catheter to be removed and increases healthcare costs. Our aim was to assess the PVC-associated complications in an endoscopy department., Methods: We performed a cross-sectional, descriptive study on patients admitted to our center and undergoing a procedure in the endoscopy department. We analyzed the appearance of the following PVC-associated complications: obstruction, phlebitis, redness, extravasation, pain, and infection on the day of the study. All catheter tips were sent to the microbiology laboratory for culture using the roll-plate semiquantitative technique. Clinical and microbiological data were collected., Results: We included a total of 46 patients with 50 PVCs. The median (IQR) age was 70.0 (55.0-81.5) years, and 58.7% were female. The median (IQR) hospital stay was 9.00 (6.00-14.25) days. Of the 50 PVCs, most were inserted in the emergency room (74.0%), and the median (IQR) indwelling time was 5.00 (3.00-7.00) days. The phlebitis rate was 78.0%, which occurred mainly in PVCs inserted in the emergency room (74.3%). The tip was colonized in 9 PVCs (18.0%)., Conclusion: The endoscopy department can alert clinicians to PVC-associated complications. PVCs inserted in the emergency room were subject to a higher risk of phlebitis and/or colonization. Therefore, we recommend systematically replacing PVCs inserted in the emergency room within 48 h if preventive measures during insertion cannot be guaranteed., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Uncommon, or rare, yeast infections are on the rise given increasing numbers of patients who are immunocompromised or seriously ill. The major pathogens include those of the genera Geotrichum, Saprochaete, Magnusiomyces, and Trichosporon (ie, basidiomycetes) and Kodamaea, Malassezia, Pseudozyma (ie, now Moesziomyces or Dirkmeia), Rhodotorula, Saccharomyces, and Sporobolomyces (ie, ascomycetes). A considered approach to the complex, multidisciplinary management of infections that are caused by these pathogens is essential to optimising patient outcomes; however, management guidelines are either region-specific or require updating. In alignment with the One World-One Guideline initiative to incorporate regional differences, experts from diverse geographical regions analysed publications describing the epidemiology and management of the previously mentioned rare yeasts. This guideline summarises the consensus recommendations with regards to the diagnostic and therapeutic options for patients with these rare yeast infections, with the intent of providing practical assistance in clinical decision making. Because there is less clinical experience of patients with rare yeast infections and studies on these patients were not randomised, nor were groups compared, most recommendations are not robust in their validation but represent insights by use of expert opinions and in-vitro susceptibility results. In this Review, we report the key features of the epidemiology, diagnosis, antifungal susceptibility, and treatment outcomes of patients with Geotrichum, Saprochaete, Magnusiomyces, and Trichosporon spp infections., Competing Interests: Declaration of interests KA, DEA, JC, LD-G, CG, P-RH, MI, SSK, OL, LP, TP, RR-R, MR, JS-G, ES, DS, AS, IS, RS, JS, ET, LT, AMT, MH, and FFT declare no competing interests. SA-A reports speaker honoraria from Gilead Sciences and travel grants from Astellas and Pfizer, outside the submitted work. TB reports grants from Gilead Sciences and personal fees from Gilead Sciences and Pfizer, outside the submitted work. SC-AC reports untied educational grants from Merck Sharp and Dohme Australia and F2G and is on the antifungal advisory boards of Merck Sharp and Dohme Australia, Gilead Sciences, and F2G, outside the submitted work. ALC reports grants from Astellas and Pfizer; personal fees from Astellas, Pfizer, Eurofarma, Merck Sharp and Dohme, Gilead Sciences, and Biotoscana-United Medical; and non-financial support from Eurofarma, Gilead Sciences, and Biotoscana-United Medical, outside the submitted work. OAC is supported by the German Federal Ministry of Research and Education; is funded by the Deutsche Forschungsgemeinschaft under Germany's Excellence Strategy (Cologne Cluster of Excellence on Cellular Stress Responses in Aging-associated Diseases, EXC 2030—390661388); has received research grants from Actelion, Amplyx, Astellas, Basilea, Cidara, Da Volterra, F2G, Gilead Sciences, Janssen, Medicines Company, Melinta, Merck/Merck Sharp and Dohme, Octapharma, Pfizer, and Scynexis; is a consultant to Actelion, Allecra, Amplyx, Astellas, Basilea, Biosys, Cidara, Da Volterra, Entasis, F2G, Gilead Sciences, Matinas, MedPace, Menarini, Merck/Merck Sharp and Dohme, Mylan, Nabriva, Noxxon, Octapharma, Paratek, Pfizer, PSI, Roche Diagnostics, Scynexis, and Shionogi; and has received lecture honoraria from Al-Jazeera Pharmaceuticals, Astellas, Basilea, Gilead Sciences, Grupo Biotoscana, Merck/Merck Sharp and Dohme, and Pfizer, outside the submitted work. JNdAJ reports grants from Fundação de Amparo à Pesquisa do Estado de São Paulo, outside the submitted work. TF reports grants from Ministry of Health, Czech Republic, outside the submitted work. GG-E reports grants from Gador SA Laboratory (Argentina) and travel grants from Pfizer and Grupo Biotoscana, outside the submitted work. NG reports honoraria from Merck Sharp and Dohme, Australia, in 2019 and has participated in educational activities under the auspices of the Australia–New Zealand Mycology Interest Group. The Australia–New Zealand Mycology Interest Group workshops and meetings receive pharmaceutical sponsorship (from Pfizer, Gilead Sciences, Merck Sharp and Dohme, and Mayne Pharma), outside the submitted work. NPG reports grants from the National Institutes of Health, US Center for Disease Control and Prevention, Bill & Melinda Gates Foundation, UK Medical Research Council, and National Health Laboratory Service Research Trust and non-financial support from Gilead Sciences, outside the submitted work. AHG reports grants from Gilead Sciences, Merck Sharp and Dohme, and Pfizer and personal fees from Amplyx, Astellas, Basilea, Gilead Sciences, Merck Sharp and Dohme, Pfizer, F2G, and Synexis, outside the submitted work. CL-F reports grants from Gilead Sciences and Astellas and personal fees from Gilead Sciences, Astellas, Merck Sharp and Dohme, Basilea, and Angelini, outside the submitted work. JM reports grants from Astellas, Gilead Sciences, Merck Sharp and Dohme, and Pfizer, outside the submitted work. PM reports personal fees from Angelini, Basilea, Gilead Sciences, Merck Sharp and Dohme, Nabriva, Pfizer, and Fundación Ciencias de la Salud, outside the submitted work. LO-Z reports grants from Cidara, Scynexis, Amplyx, Pfizer, and Astellas and personal fees from Cidara, Scynexis, F2G, Pfizer, Astellas, Merck, and Gilead Sciences, outside the submitted work. JP reports grants from Merck, Astellas, Pfizer, Amplyx, and Minnetronix and personal fees from Merck, F2G, Scynexis, Amplyx, and Ampili, outside the submitted work. AV reports research grants from Procter and Gamble, L'Oréal Paris, Pfizer, and Astellas and honorarium from Merck Sharp and Dohme, outside the submitted work. NW reports grants from Astellas, bioMerieux, Cepheid, Cidara, Covance, F2G, and Viamet and personal fees from Gilead Sciences and Mayne Pharma, outside the submitted work. Y-CC reports personal fees for lectures from Pfizer, Merck Sharp and Dohme, and Gilead Sciences, outside the submitted work., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Despite improvements in fetal survival for pregnancies affected by twin-twin transfusion syndrome since the introduction of laser photocoagulation, prematurity remains a major source of neonatal morbidity and mortality., Objective: To investigate the indications and factors influencing the timing of delivery following 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 (NAFTNet) centers conducted a retrospective review of twin-twin transfusion syndrome patients who underwent laser photocoagulation. Clinical, demographic and ultrasound variables including 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 GA at delivery. Multivariable Cox regression with competing risk analysis was utilized to determine the independent associations., Results: A total of 847 pregnancies were analyzed. After laser, 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 and the most frequent indications included donor non-reassuring status (20.5%), abnormal donor Dopplers (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 prior amnioreduction, cerclage, interwin membrane disruption, procedure complications and chorioamniotic membrane separation as predictors for both gestational age at delivery and latency., Conclusion: Premature delivery after laser therapy for twin-twin transfusion syndrome is primarily due to spontaneous labor, preterm premature rupture of membranes and non-reassuring status of the donor fetus. Placental abruption was found to be a frequent complication resulting in early delivery. Future research should be directed toward the goal of prolonging gestation after laser photocoagulation to further reduce morbidity and mortality associated with twin-twin transfusion syndrome., Competing Interests: The authors report no conflicts of interest.

Objective: 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., Materials and Methods: 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., Results: 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)., Conclusion: 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.

Background: Seasonal influenza infection may cause significant morbidity and mortality in transplant recipients. The purpose of this study was to assess the epidemiology of symptomatic influenza infection posttransplant and determine risk factors for severe disease., Methods: Twenty centers in the United States, Canada, and Spain prospectively enrolled solid organ transplant (SOT) or hematopoietic stem cell transplant (HSCT) recipients with microbiologically confirmed influenza over 5 consecutive years (2010-2015). Demographics, microbiology data, and outcomes were collected. Serial nasopharyngeal swabs were collected at diagnosis and upto 28 days, and quantitative polymerase chain reaction for influenza A was performed., Results: We enrolled 616 patients with confirmed influenza (477 SOT; 139 HSCT). Pneumonia at presentation was in 134 of 606 (22.1%) patients. Antiviral therapy was given to 94.1% for a median of 5 days (range, 1-42 days); 66.5% patients were hospitalized and 11.0% required intensive care unit (ICU) care. The receipt of vaccine in the same influenza season was associated with a decrease in disease severity as determined by the presence of pneumonia (odds ratio [OR], 0.34 [95% confidence interval {CI}, .21-.55], P < .001) and ICU admission (OR, 0.49 [95% CI, .26-.90], P = .023). Similarly, early antiviral treatment (within 48 hours) was associated with improved outcomes. In patients with influenza A, pneumonia, ICU admission, and not being immunized were also associated with higher viral loads at presentation (P = .018, P = .008, and P = .024, respectively)., Conclusions: Annual influenza vaccination and early antiviral therapy are associated with a significant reduction in influenza-associated morbidity, and should be emphasized as strategies to improve outcomes of transplant recipients.

Transplantation activity is increasing, leading to a growing number of patients at risk for toxoplasmosis. We reviewed toxoplasmosis prevention practices, prevalence, and outcomes for hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT; heart, kidney, or liver) patients in Europe. We collected electronic data on the transplant population and prevention guidelines/regulations and clinical data on toxoplasmosis cases diagnosed during 2010-2014. Serologic pretransplant screening of allo-hematopoietic stem cell donors was performed in 80% of countries, screening of organ donors in 100%. SOT recipients were systematically screened in 6 countries. Targeted anti-Toxoplasma chemoprophylaxis was heterogeneous. A total of 87 toxoplasmosis cases were recorded (58 allo-HSCTs, 29 SOTs). The 6-month survival rate was lower among Toxoplasma-seropositive recipients and among allo-hematopoietic stem cell and liver recipients. Chemoprophylaxis improved outcomes for SOT recipients. Toxoplasmosis remains associated with high mortality rates among transplant recipients. Guidelines are urgently needed to standardize prophylactic regimens and optimize patient management.

Background: Prognostic implications of cryptococcal antigen and outcomes associated with central nervous system (CNS) cryptococcal lesions in solid organ transplant recipients have not been fully defined., Methods: Patients were derived form a cohort of 122 solid organ transplant recipients with cryptococcosis in a multicenter study from 1999 to 2006., Results: Central nervous system cryptococcosis was documented in 61 patients. Serum or cerebral spinal fluid antigen titers did not correlate with mortality at 90 days or cerebral spinal fluid sterilization at 2 weeks. Central nervous system lesions were identified in 16 patients and included leptomeningeal lesions in eight, parenchymal lesions in six, and hydrocephalus in two. Overall, 13/16 CNS lesions were present at the time of diagnosis. One parenchymal and two hydrocephalus lesions, however, developed after diagnosis and fulfilled the criteria for immune reconstitution syndrome. Cerebral spinal fluid antigen titers were higher with meningeal versus parenchymal lesions, and hydrocephalus (P=0.015). Mortality was 50% (3/6) for patients with parenchymal, 12.5% (1/8) for those with leptomeningeal, and 0/3 for patients with hydrocephalus. Mortality was 31% (4/13) for patients with CNS lesions at baseline and 0/3 in those with new onset lesions., Conclusions: Despite a higher antigen titer with meningeal lesions, outcomes tended to be worse with parenchymal compared with meningeal lesions or hydrocephalus. New onset CNS lesions may represent immune reconstitution syndrome and seemed to be associated with better outcome.

Synergistic interactions were observed between CIs and antifungal agents against 53 (90%) of 59 Cryptococcus neoformans isolates from solid organ transplant recipients with cryptococcosis and may account for better outcomes in patients with cryptococcosis receiving these immunosuppressive agents.

Background/aims: Transforming growth factor-beta1 (TGF-beta1) plays a pivotal role in the extracellular matrix accumulation observed in fibrotic diseases. Endoglin is an important component of the TGF-beta receptor complex highly expressed in tissues undergoing fibrotic processes. Endoglin expression regulates the effect of TGF-beta on extracellular matrix synthesis. The purpose of our study has been to understand the molecular mechanism by which endoglin exerts its effects on fibrosis and the possible role of MAP kinases in these effects., Methods: We have assessed in mock and in endoglin-transfected L6E9 myoblasts the effect of TGF-beta1 on collagen mRNA by Northern blot and effect of TGF-beta1 on collagen content in the cultured medium by [(3)H]-Proline incorporation into collagen proteins. Total and activated MAPK and their role on collagen synthesis were assessed by Western blot., Results: TGF-beta1 induced an increase on alpha(2) (I) collagen mRNA expression and collagen accumulation in mock-transfected myoblasts, whereas the response was much lower in endoglintransfected cells. TGF-beta1 activated the ERK1/2 and p38 MAPK pathways but not the JNK pathway in L6E9 myoblasts. TGF-beta1-induced alpha(2) (I) collagen mRNA expression and collagen accumulation were completely inhibited by SB203580, in either mock or endoglintransfected myoblasts. PD98059 increased TGF-beta1 induced-collagen synthesis and accumulation in endoglin-transfected myoblasts but not in mock cells., Conclusion: Our studies demonstrate that TGF-beta1- induced collagen synthesis is mediated by p38 MAPK activation in L6E9 myoblasts. Furthermore, endoglin expression reduces basal and TGF-beta1 induced collagen synthesis when ERK1/2 pathway is operating.