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Bromodomain-containing protein 9 (BRD9), a member of the bromodomain and extra terminal domain (BET) protein family, works as an epigenetic reader. BRD9 has been considered an essential drug target for cancer, inflammatory diseases, and metabolic disorders. Due to its high similarity among other isoforms, no effective treatment of BRD9-associated disorders is available. For the first time, we performed a detailed comparative analysis among BRD9, BRD7, and BRD4. The results indicate that residues His42, Gly43, Ala46, Ala54, Val105, and Leu109 can confer the BRD9 isoform selectivity. The predicted crucial residues were further studied. The pharmacophore model’s features were precisely mapped with some key residues including, Gly43, Phe44, Phe45, Asn100, and Tyr106, all of which play a crucial role in BRD9 inhibition. Docking-based virtual screening was utilized with the consideration of the conserved water network in the binding cavity to identify the potential inhibitors of BRD9. In this workflow, 714 compounds were shortlisted. To attain selectivity, 109 compounds were re-docked to BRD7 for negative selection. Finally, four compounds were selected for molecular dynamics studies. Our studies pave the way for the identification of new compounds and their role in causing noticeable, functional differences in isoforms and between orthologues.

Bromodomain-containing protein 9 (BRD9), a member of the bromodomain and extra terminal domain (BET) protein family, works as an epigenetic reader. BRD9 has been considered an essential drug target for cancer, inflammatory diseases, and metabolic disorders. Due to its high similarity among other isoforms, no effective treatment of BRD9-associated disorders is available. For the first time, we performed a detailed comparative analysis among BRD9, BRD7, and BRD4. The results indicate that residues His42, Gly43, Ala46, Ala54, Val105, and Leu109 can confer the BRD9 isoform selectivity. The predicted crucial residues were further studied. The pharmacophore model's features were precisely mapped with some key residues including, Gly43, Phe44, Phe45, Asn100, and Tyr106, all of which play a crucial role in BRD9 inhibition. Docking-based virtual screening was utilized with the consideration of the conserved water network in the binding cavity to identify the potential inhibitors of BRD9. In this workflow, 714 compounds were shortlisted. To attain selectivity, 109 compounds were re-docked to BRD7 for negative selection. Finally, four compounds were selected for molecular dynamics studies. Our studies pave the way for the identification of new compounds and their role in causing noticeable, functional differences in isoforms and between orthologues. [ABSTRACT FROM AUTHOR]

The increasing gap between the number of patients who could benefit from liver transplantation and the number of available donors has fueled efforts to maximize the donor pool using marginal grafts that usually were discarded for transplantation. This study included data of all patients who received decreased donor liver grafts between January 2004 and January 2013 (n = 218) with the use of a prospectively collected database. Patients with acute liver failure, retransplantation, pediatric transplantation, and split liver transplantation were excluded. Donors were classified as standard donor (SD), extended criteria donor (ECD), and overextended criteria donor (OECD). The primary endpoints of the study were early allograft primary dysfunction (PDF), primary nonfunction (PNF), and patient survival (PS), whereas incidence of major postoperative complications was the secondary endpoint. In our series we demonstrated that OECD have similar outcome in terms of survival and incidence of complication after liver transplantation as ideal grafts. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: The aim of this study was to evaluate the incidence, clinical characteristics, treatment, and outcome of de novo tumors (DNT) of the upper aerodigestive tract in patients with alcoholic cirrhosis after orthotopic liver transplantation (OLT). Methods: Among 225 consecutive OLT performed between January 2002 and January 2012, a total of 205 patients received a first liver allograft. Eleven (4.9%) patients developed DNT (lung, pancreas, bowel, esophagus, larynx, tongue, tonsil, and lymphoma). Among these, we observed 5 patients with DNT of the upper aerodigestive tract. Results: The 5 patients with DNT of the upper aerodigestive tract underwent OLT for alcoholic cirrhosis. There were 4 men and 1 woman with a mean age at transplantation of 47 years. The mean period of alcohol abuse was 90 months. The tumors occurred after a mean post-transplantation time of 39 months. The immunosuppressive regimen included Tacrolimus, mTOR, mycophenolate mofetil (MMF), and low-dose steroids. We observed 2 cases of squamous cell carcinoma of the esophagus, 1 case of tonsillar cancer, 1 case of larynx carcinoma, and 1 case of tongue carcinoma. All patients underwent surgical excision. After surgery, 4 patients received chemotherapy and 2 patients radiotherapy. At present, among the 5 patients with DNT of the upper aerodigestive tract, only 2 are alive without disease and 1 is alive with a local recurrence. Conclusion: The incidence of DNT of the upper aerodigestive tract after OLT is higher among patients receiving a transplant for alcoholic cirrhosis. This could be due to an additional effect of post-transplantation immunosuppression in patients exposed to alcohol before transplantation. We suggest a careful post-transplantation follow-up and more attention to improve early diagnosis. [Copyright &y& Elsevier]

Background We assessed the usefulness of color Doppler imaging in diagnosis and monitoring hepatic artery complications after liver transplantation. Methods Subjects were 421 liver transplant recipients who underwent serial ultrasound (US) color Doppler evaluations of the hepatic arteries after surgery. Results We saw 4 hepatic arterial complications after liver transplantation (13 thrombosis, 29 stenosis, 2 kinking, 2 pseudo-aneurysm, and 2 pseudo-aneurysm rupture). All subjects underwent US color Doppler examination periodically after surgery. In 6 cases of early thrombosis, hepatic arterial obstruction was diagnosed with absence of Doppler signals; in the other 7 cases (late hepatic artery thrombosis), thrombosis was suspected for the presence of intra-parenchymal “tardus-parvus” waveforms. In all of the cases, computed tomography angiography showed obstruction of the main arterial trunk and the development of compensatory collateral circles (late hepatic artery thrombosis). In 10 of the 29 cases of stenosis, Doppler ultrasonography examination revealed stenotic tract and intra-hepatic tardus-parvus waveforms; in 17 stenosis cases, the site of stenosis could not be identified, but intra-parenchymal tardus-parvus waveforms were recorded. In 2 patients, hepatic artery stenosis occurred with ischemic complications. Conclusions The use of US color Doppler examination allows the early diagnosis of hepatic arterial complications after liver transplantation. Tardus-parvus waveforms indicated severe impairment of hepatic arterial perfusion from either thrombosis or severe stenosis. The presence of these indirect signs enhanced the accuracy of color Doppler diagnosis, and detection should prompt therapy. [ABSTRACT FROM AUTHOR]

Background Fungal infections, although less frequent than bacterial infections, represent a severe comorbidity with an exponential increase in mortality rate in liver transplantation patients. The incidence of invasive fungal infections (IFIs) after solid organ transplantation ranges from 7% to 42%, with Candida spp. and Aspergillus spp. as the most common pathogens. Fungal infections in liver transplant recipients have been associated with poor outcome and mortality rates ranging from 65% to 90% for invasive aspergillosis and 30% to 50% for invasive candidiasis. The results largely depend on early diagnosis and early initiation of specific treatment for IFIs. Therefore, the diagnosis must be prompt, preferably based on microbiological data, both cultures and biomarkers, and/or based on clinical features and known risk factors. Materials and Methods This study evaluated the incidence of fungal infections in patients after liver transplantation in our center between January 2003 and December 2012. The retrospective analysis of 215 consecutive liver transplantation patients was undertaken to estimate incidence, risk factors, and clinical courses of IFIs in the first 3 months after liver transplantation. Results Candidemia and invasive candidiasis microbiologically proven were found in 26 patients (12%), whereas in 6 patients (2.8%) invasive fungal infections from other non- Candida fungi developed: Aspergillus (4 cases: 2 A fumigatus , 2 A terreus ), Fusarium oxysporum (1 case), and Rhodotorula rubra (1 case). Two patients with Aspergillus and the patient with Fusarium died. The patient with Rhodotorula as well as 22 of the patients with candidemia (85%) survived. All of the episodes developed during the first 3 months posttransplantation. All cases have followed a previous polymicrobial bacterial infection (especially in the biliary tract) with large use of combined antibiotic therapies. Conclusions The rate of fungal infection was found to increase in parallel with the number of risk factors. Prophylactic strategies can decrease the risk of fungal infections. Early detection and treatment with adequate early empiric therapy is the key to obtaining a better outcome in liver transplantation patients. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Hepatic artery stenosis (HAS) is an important complication after liver transplantation. However, studies are not conclusive in terms of definition, incidence, best treatment, and timing of intervention. The aim of this study was to evaluate the incidence of SSHA that occurred in a single center over the past 12 years, pointing out diagnostic and therapeutic strategies. Methods: The incidence of HAS was reviewed in 258 liver transplant recipients between January 1999 and December 2011. All patients underwent Doppler ultrasound (DUS) at fixed times. Multidetector computed tomographic angiography (MDCTA) was performed to confirm the DUS findings. Results: HAS occurred in 23 cases (9.3%). In all cases diagnosis was performed by DUS resulting in a sensitivity of 100% and a specificity of 99.6%. Based on DUS and MDCTA data integration, in 10 cases we adopted the “wait and see” strategy, whereas 13 patients underwent interventional radiology techniques. Conclusion: DUS monitoring is efficacious in the diagnosis of HAS after liver transplantation. Interventional radiology procedures are safe and efficacious. [Copyright &y& Elsevier]

Abstract: Orthotopic liver transplantation (OLT) is a life-saving procedure for the treatment of many end-stage diseases, but infectious and acute rejection episodes remain major causes of morbidity and mortality. Bacterial and fungal infections can be due to intra-abdominal, biliary, respiratory, urinary, wound, central venous catheters (CVC) or unknown sources. Using the computerized database of our microbiology laboratory, we analyzed all the bacterial and fungal infections in the first three months following OLT among 151 consecutive adult recipients at single center between January 2005 and December 2011. Samples included blood, bile CVC, urine, and bronchoalveolar lavage (BAL) specimen. Culture and identification of the isolated microorganisms was done in accordance with standard microbiological procedures. Three hundred thirteen samples from the above sites showed positive results for gram-positive cocci (n = 137; 43.8%), gram-negative rods (n = 156; 49.8%), and Candida species (n = 19; 6.1%). One patient (0.3%) experienced a CVC-related infection caused by Fusarium oxysporum. Bacterial and particularly biliary tract infections seem to play major roles in morbidity and mortality in the first three months following OLT. The major contributors to patient morbidity and mortality were candidemia and/or invasive candidiasis mainly from the biliary tract and/or CVC-related infections. [Copyright &y& Elsevier]

Abstract: Introduction: In the last years, the incidence of Candida infections in liver transplant recipients has increased with still higher morbidity and mortality. Anidulafungin, a new echinocandin that does not interfere with cytochrome p450, shows no need for dosage adjustment based upon renal or hepatic function or weight. Aim: To analyze tolerance to and microbiologic and clinical efficacy of Anidulafungin to treat Candida infections in liver transplant patients. Materials and Methods: This phase 3b, prospective, open-label, single-center study focused on liver transplant patients with a suspected and/or diagnosed Candida infection. The patients received Anidulafungin intravenously, optionally followed by oral therapy with azoles. The primary endpoint was the global response at the end of therapy; secondary endpoints were the efficacy of intravenous therapy, 90-day survival, as well as tolerance for and interaction with immunosuppresants. Results: We considered 42 consecutive liver recipients transplanted between 2009 and 2010 among whom 13 (31%) were recruited for the study and four patients were treated with Anidulafungin as empirical therapy, six as preemptive therapy, and three as targeted treatment for documented candidemia (7.1%). The immunosuppressive regimen consisted of tacrolimus and low dose of steroids. The Candida species were: C albicans (50%), C glabrata (12.5%), C parapsilosis (12.5%), C krusei (12.5%), C lusitaniae (6.2%), C tropicalis (6.2%), and multiple others (25%). The principle site of isolation was the bile (53.8%), followed by the bloodstream (23.1%), central venous catheters (15.4%), bronchoalveolar lavage (15.4%), peritoneum (7.7%), and other locations (7.7%). Two patients (15.4%) died of severe sepsis with multiple organ failure. There was no alteration of hepatic enzymes, indices of cholestasis or changes in immunosuppressant drug levels. Conclusion: Anidulafungin was an effective, safe, and well-tolerated drug. There were neither toxic effects to the grafts or adverse interactions with immunosuppresants. [Copyright &y& Elsevier]

Abstract: Liver transplantation (OLT) is a lifesaving procedure for the treatment of many end-stage liver diseases, but infection and acute rejection episodes still remain the main causes of morbidity and mortality. Bloodstream infections (BSIs), particularly, are the major cause of mortality among these patients. BSIs in OLT, are from intra-abdominal, biliary, respiratory, urinary, wound and/or central venous catheter sources. A certain percentage are of unknown origin. Using the computerized database of our microbiology laboratory, we analyzed all BSIs in 75 consecutive adult liver transplant patients in a single center between January 2008 and July 2011. BSIs occurred in 21/75 (28%) patients. Thirteen subjects had a single; two, two episodes, and the other six patients each >4 episodes. All episodes occurred in the first 60 days following OLT; the majority (74%), in the first month. Among 44 microorganisms recovered, 52.3% were gram-negative, the most frequent being Pseudomonas aeruginosa and Klebsiella pneumoniae; 47.7% were gram-positive, the most frequent being coagulase-negative staphylococci, particularly Staphylococcus epidermidis. Overall 65.9% of the isolates were resistant to several antibiotics: 40.9% displayed the multiding-resistant and 25% the panding-resistant phenotype. There was a high incidence of gram-negative and most importantly, resistant bacteria, which required appropriate therapy. These data showed that it is imperative to promote strategies to prevention and contain antimicrobial resistance. [Copyright &y& Elsevier]

Abstract: MELD and PELD scores of 255 consecutive grafts were calculated (236 adult cases and 19 pediatric cases). No correction for the etiology of liver disease was performed. Retransplants were excluded. Three categories of patients were identified: low MELD (scores <12, n = 61); intermediate MELD (scores between 12–24, n = 159); high MELD (scores ≥25, n = 35). Grafts were categorized according to donor quality: standard livers (n = 199), vs nonstandard livers (n = 56). Nonstandard livers were identified by age ≥60, or at least by two of the following conditions: severe hemodynamic instability, ultrasound evidence of steatosis, natriemia ≥155 mEq/L, ICU stay >7 days, liver trauma, protracted anoxia as cause of brain death, transaminases levels × 4. In standard livers, the 12-month graft survival (GS) for low, intermediate, and high MELD classes were 88%, 74%, and 77%, respectively. In nonstandard livers, the 12-month GS for the low, intermediate, and high MELD classes were 84%, 55%, and 44%, respectively; differences between low MELD class and both intermediate and high MELD classes were significant (P < .05). Cox regression analysis of all cases identified the following parameters as independent predictors of GS: donor status; donor age; and recipient creatinine. The highest correlation with GS was found using donor age and recipient creatinine as covariates. In standard livers no variable was able to predict GS. In nonstandard livers the MELD-PELD score was the unique variable able to predict GS. We suggest avoiding the use of nonstandard livers for patients with high MELD scores. [Copyright &y& Elsevier]

Alagille syndrome (AS) is an autosomal-dominant, multisystem disorder affecting the liver, heart, eyes, skeleton, and face. The manifestations are predominantly pediatric. Diagnosis is based on findings of a paucity of bile ducts on liver biopsy combined with ≥3 of 5 major clinical criteria. Orthotopic liver transplantation (OLT) is the only option for treating patients who developed liver failure, portal hypertension, severe itching, and xanthomatosis. It is difficult to establish clear criteria for OLT; indications are controversial because of the wide variety of clinical symptoms and the multisystem involvement. Generally, AS-associated liver disease is never an acute illness. We report the case of a 28-year-old woman with AS who underwent urgent OLT for acute liver failure. At 24 months posttransplant, the patient is in good clinical condition and with normal hepatic and renal function. [ABSTRACT FROM AUTHOR]

Abstract: Among biliary complications, ischemic-type biliary lesions (ITBLs) remain a major cause of morbidity in liver transplant recipients, significantly affecting the chance of survival of both patients and grafts. We retrospectively reviewed 10 years of prospectively collected donor and recipient data from April 2001 to April 2011. We evaluated the incidence of ITBL occurrence, exploring the possible predisposing factors, including donor and recipient data. Two hundred fifty-one grafts were harvested: 222 of them were transplanted at our institution, the remaining 29 (11.6%) discarded by our donor team as showing >40% macrovesicular steatosis. Mild-moderate (20%–40%) macrovesicular steatosis (P < .001) and cold ischemia time (P = .048) significantly increased the risk of ITBL, also as an independent risk factor after multivariate analysis. [Copyright &y& Elsevier]

Ischemic-type biliary lesions (ITBLs) are now a discussed cause of morbidity and mortality in liver transplant recipients, even if not definitively characterized. We reviewed 13 years of donor and recipient data between April 2001 and April 2013. We evaluated the incidence of ITBL occurrence, exploring the possible predisposing factors, focusing on the relationship between severe macrovesicular steatosis of the graft and incidence of ITBL. A total of 445 grafts were harvested: 416 of them were transplanted at our institution, the remaining 29 were discarded by our donor team as showing more than 40% macrovesicular steatosis. Mild-moderate (20% to 40%) macrovesicular steatosis ( P < .001) and cold ischemia time ( P = .048) significantly increased the risk of ITBLs, also resulting in independent risk factors at multivariate analysis. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma is the most common primary liver tumor. Orthotopic liver transplant is one of the best treatment options, but its waiting list has to be considered. Bridge therapies have been introduced in order to limit this issue. The aim of this study is to evaluate if bridge therapies in advanced hepatocellular carcinoma can improve overall survival and reduce de-listing. We selected 185 articles. The search was limited to English articles involving only adult patients. These were deduplicated and articles with incomplete text or irrelevant conclusions were excluded. Sorafenib is the standard of care for advanced hepatocellular carcinoma and increases overall survival without any significant drug toxicity. However, its survival benefit is limited. The combination of transarterial chemoembolization + sorafenib, instead, delays tumor progression, although its survival benefit is still uncertain. A few studies have shown that patients undergoing transarterial chemoembolization + radiation therapy have similar or even better outcomes than those undergoing transarterial chemoembolization or sorafenib alone for rates of histopathologic complete response (89% had no residual in the explant). Also, the combined therapy of transarterial chemoembolization + radiotherapy + sorafenib was compared to the association of transarterial chemoembolization + radiotherapy and was associated with a better survival rate (24 vs. 17 months). Moreover, immunotherapy revealed new encouraging perspectives. Combination therapies showed the most encouraging results and could become the gold standard as a bridge to transplant for patients with advanced hepatocellular carcinoma.

Background: Women who have undergone liver transplantation (LT) enjoy better health, and possibility of childbearing. However, maternal and graft risks, optimal immunosuppression, and fetal outcome is still to clarify., Aim: Aim of the study was to assess outcomes of pregnancy after LT at national level., Methods: In 2019, under the auspices of the Permanent Transplant Committee of the Italian Association for the Study of the Liver, a multicenter survey including 14 Italian LT-centers was conducted aiming at evaluating the outcomes of recipients and newborns, and graft injury/function parameters during pregnancy in LT-recipients., Results: Sixty-two pregnancies occurred in 60 LT-recipients between 1990 and 2018. Median age at the time of pregnancy was 31-years and median time from transplantation to conception was 8-years. During pregnancy, 4 recipients experienced maternal complications with hospital admission. Live-birth-rate was 100%. Prematurity occurred in 25/62 newborns, and 8/62 newborns had low-birth-weight. Cyclosporine was used in 16 and Tacrolimus in 37 pregnancies, with no different maternal or newborn outcomes. Low-birth-weight was correlated to high values of AST, ALT and GGT., Conclusion: Pregnancy after LT has good outcome; however, maternal complications and prematurity may occur. Compliance with the immunosuppression is fundamental to ensure the stability of graft function and prevent graft-deterioration., (Copyright © 2021 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: With the increasing use of extended-criteria donor organs, the interest around T-tubes in liver transplantation (LT) was restored whilst concerns regarding T-tube-related complications persist., Aim: To describe insertion and removal protocols implemented at our institution to safely use pediatric rubber 5-French T-tubes and subsequent outcomes in a consecutive series of adult patients., Methods: Data of consecutive adult LT patients from brain-dead donors, treated from March 2017 to December 2019, were collected ( i.e. , biliary complications, adverse events, treatment after T-Tube removal). Patients with upfront hepatico-jejunostomy, endoscopically removed T-tubes, those who died or received retransplantation before T-tube removal were excluded., Results: Seventy-two patients were included in this study; T-tubes were removed 158 d (median; IQR 128-206 d) after LT. In four (5.6%) patients accidental T-tube removal occurred requiring monitoring only; in 68 (94.4%) patients Nelaton drain insertion was performed according to our protocol, resulting in 18 (25%) patients with a biliary output, subsequently removed after 2 d (median; IQR 1-4 d). Three (4%) patients required endoscopic retrograde cholangiopancreatography (ERCP) due to persistent Nelaton drain output. Three (4%) patients developed suspected biliary peritonitis, requiring ERCP with sphincterotomy and nasobiliary drain insertion (only one revealing contrast extravasation); no patient required percutaneous drainage or emergency surgery., Conclusion: The use of pediatric rubber 5-French T-tubes in LT proved safe in our series after insertion and removal procedure refinements., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Liver cirrhosis has been known to be associated with increased intestinal permeability (IP); however, little is known about the modification of IP after liver transplantation (LT). The present study was aimed to assess IP after LT and evaluated its association with laboratory tests and clinical parameters, as well as with the development of infections., Methods: LT recipients were consecutively enrolled and compared with an equal number of patients with liver cirrhosis and healthy subjects. IP was assessed by urinary excretion of chromium-51 ethylenediaminetetraacetic acid (51Cr-EDTA)., Results: The median 51Cr-EDTA excretion was found to be higher in 35 LT recipients as compared with that in the healthy controls [4.77% (2.79-6.03) vs. 2.07% (1.57-2.42), p<0.0001], and comparable to that in the cirrhotic patients [3.69% (2.34-6.57), p = 0.445]. 51Cr-EDTA excretion was not associated with clinical variables, the type of immunosuppressive therapy, donor-related factors, comorbidities and incidence of infections [infection/no infection: 4.97% (3.14-7.03) vs 4.62% (2.79-5.82), p = 0.938]., Conclusion: LT recipients show an increased IP, similar to that in patients with liver cirrhosis. However, it is not associated with a high risk of infections. Further investigations into the pathogenesis of this persistent impairment of the intestinal barrier are warranted., Competing Interests: The authors have declared that no competing interests exist.

Background: Today, women who have undergone liver transplantation enjoy better health, so they encounter more frequently the possibility of living pregnancy. Many questions about the safety of pregnancy are pending. This study analyzes pregnancy outcomes in women with a liver transplant managed at Policlinico Universitario "A.Gemelli.", Results: We identified 17 childbirths in 13 women who had undergone a liver transplant. Causes of transplant include congenital or acquired disorders. The mean age at transplant was 22 ± 9 years, mean maternal age at delivery was 33 ± 5 years, and transplant-to-pregnancy interval was 12 ± 6 years. The mean gestational week was 36.1 ± 3.5. All women had normal liver function after pregnancy. Immunosuppressive therapy before and during pregnancy included tacrolimus (n = 8), cyclosporine (n = 5) and mycophenolate mofetil (n = 1). No maternal death was registered. Maternal complications included increase of aspartate transaminase and alanine transaminase, graft deterioration requiring liver retransplantation, increase of bile acids (n = 1), itch (n = 1), and anemia (n = 1). Twelve women had a high adherence to an immunosuppressive regimen during pregnancy. A woman with poor compliance continued therapy with mycophenolic acid during pregnancy, showing preterm birth (25th week) with fetal respiratory failure. Another woman continued therapy with tacrolimus during breastfeeding without adverse effects., Conclusion: Liver transplant does not influence women's fertility; during pregnancy, we report low rates of minor graft complications and no major issues. There are no adverse effects on babies. An evaluation by a multidisciplinary team is recommended. Compliance to an immunosuppressive regimen is fundamental to ensure the stability of graft function and to prevent graft deterioration in pregnancy. Moreover, it is suggested to avoid teratogenic drugs, such as mycophenolic acid., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Wheat rust diseases pose one of the greatest threats to global food security, including subsistence farmers in Ethiopia. The fungal spores transmitting wheat rust are dispersed by wind and can remain infectious after dispersal over long distances. The emergence of new strains of wheat rust has exacerbated the risks of severe crop loss. We describe the construction and deployment of a near realtime early warning system (EWS) for two major wind-dispersed diseases of wheat crops in Ethiopia that combines existing environmental research infrastructures, newly developed tools and scientific expertise across multiple organisations in Ethiopia and the UK. The EWS encompasses a sophisticated framework that integrates field and mobile phone surveillance data, spore dispersal and disease environmental suitability forecasting, as well as communication to policy-makers, advisors and smallholder farmers. The system involves daily automated data flow between two continents during the wheat season in Ethiopia. The framework utilises expertise and environmental research infrastructures from within the cross-disciplinary spectrum of biology, agronomy, meteorology, computer science and telecommunications. The EWS successfully provided timely information to assist policy makers formulate decisions about allocation of limited stock of fungicide during the 2017 and 2018 wheat seasons. Wheat rust alerts and advisories were sent by short message service and reports to 10 000 development agents and approximately 275 000 smallholder farmers in Ethiopia who rely on wheat for subsistence and livelihood security. The framework represents one of the first advanced crop disease EWSs implemented in a developing country. It provides policy-makers, extension agents and farmers with timely, actionable information on priority diseases affecting a staple food crop. The framework together with the underpinning technologies are transferable to forecast wheat rusts in other regions and can be readily adapted for other wind-dispersed pests and disease of major agricultural crops., (© 2019 The Author(s).)

Early everolimus (EVR) introduction and tacrolimus (TAC) minimization after liver transplantation may represent a novel immunosuppressant approach. This phase 2, multicenter, randomized, open-label trial evaluated the safety and efficacy of early EVR initiation. Patients treated with corticosteroids, TAC, and basiliximab were randomized (2:1) to receive EVR (1.5 mg twice daily) on day 8 and to gradually minimize or withdraw TAC when EVR was stable at >5 ng/mL or to continue TAC at 6-12 ng/mL. The primary endpoint was the proportion of treated biopsy-proven acute rejection (tBPAR)-free patients at 3 months after transplant. As secondary endpoints, composite tBPAR plus graft/patient loss rate, renal function, TAC discontinuation rate, and adverse events were assessed. A total of 93 patients were treated with EVR, and 47 were controls. After 3 months from transplantation, 87.1% of patients with EVR and 95.7% of controls were tBPAR-free (P = 0.09); composite endpoint-free patients with EVR were 85% (versus 94%; P = 0.15). Also at 3 months, 37.6% patients were in monotherapy with EVR, and the tBPAR rate was 11.4%. Estimated glomerular filtration rate was significantly higher with EVR, as early as 2 weeks after randomization. In the study group, higher rates of dyslipidemia (15% versus 6.4%), wound complication (18.32% versus 0%), and incisional hernia (25.8% versus 6.4%) were observed, whereas neurological disorders were more frequent in the control group (13.9% versus 31.9%; P < 0.05). In conclusion, an early EVR introduction and TAC minimization may represent a suitable approach when immediate preservation of renal function is crucial., (Copyright © 2018 by the American Association for the Study of Liver Diseases.)

Objective: The usefulness, the methods and the criteria of intra-operative monitoring of the parathyroid hormone (ioPTH) during parathyroidectomy (PTX) for renal secondary hyperparathyroidism (rSHPT) in patients on chronic hemodialysis remain still matter of debate. The present study aimed to evaluate the ability of a low cost central-laboratory second generation PTH assay to predict an incomplete resection of parathyroid glands (PTG)., Methods: The ioPTH decay was determined In 42 consecutive patients undergoing PTX (15 subtotal and 27 total without auto-transplant of PTG) for rSHPT. The ioPTH monitoring included five samples: pre-intubation, post-manipulation of PTG and at 10, 20 and 30min post-PTG excision. The patients with PTH exceeding the normal value (65pg/ml) at the first postoperative week, 6 and 12months were classified as persistent rSHPT., Results: The concentrations of ioPTH declined significantly over time in patients who received total or subtotal PTX; however, no difference was found between the two types of PTX. Irrespective of the type of PTX and the number of PTG removed, combining the absolute and percentage of ioPTH decay at 30min after PTG excision, we found high sensitivity (100%), specificity (92%), negative predictive value (100%) and accuracy (93%) in predicting the persistence of rSHPT., Conclusions: The monitoring of the ioPTH decline by a low cost central-laboratory second generation assay is extremely accurate in predicting the persistence of disease in patients on maintenance hemodialysis undergoing surgery for rSHPT., (Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Fibrolamellar hepatocellular carcinoma (FHCC) is a rare malignant tumor of hepatocyte origin occurring earlier in life than typical hepatocellular carcinoma (HCC). We describe a distinctive case of FHCC with biliary tumor thrombus (BTT) in a 25-year-old Caucasian patient, pointing out the imaging features supported by histopathology.