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Thrombotic microangiopathy after renal transplantation: Current insights in de novo and recurrent disease

World Journal of Transplantation 2018年第5期8卷 122-141页

作者： Fedaey Abbas Mohsen El Kossi Jon Jin Kim ajay sharma Ahmed Halawa Nephrology Department Jaber El Ahmed Military Hospital Faculty of Health and Science University of Liverpool Institute of Learning and Teaching School of Medicine Doncaster Renal Unit Doncaster Royal Infirmary Nottingham Children Hospital Transplant Surgery Royal Liverpool University Hospitals Department of Transplantation Surgery Sheffield Teaching Hospitals

Thrombotic microangiopathy(TMA) is one of the most devastating sequalae of kidney transplantation. A number of published articles have covered either de novo or recurrent TMA in an isolated manner. We have, hereby, in this article endeavored to address both types of TMA in a comparative mode. We appreciate that de novo TMA is more common and its prognosis is poorer than recurrent TMA; the latter has a genetic background, with mutations that impact disease behavior and, consequently, allograft and patient survival. Post-transplant TMA can occur as a recurrence of the disease involving the native kidney or as de novo disease with no evidence of previous involvement before transplant. While atypical hemolytic uremic syndrome is a rare disease that results from complement dysregulation with alternative pathway overactivity, de novo TMA is a heterogenous set of various etiologies and constitutes the vast majority of post-transplant TMA cases. Management of both diseases varies from simple maneuvers, e.g., plasmapheresis, drug withdrawal or dose modification, to lifelong complement blockade, which is rather costly. Careful donor selection and proper recipient preparation, including complete genetic screening, would be a pragmatic approach. Novel therapies, e.g., purified products of the deficient genes, though promising in theory, are not yet of proven value.

关键词： Kidney transplantation De novo thrombotic microangiopathy Thrombotic microangiopathy Recurrent thrombotic microangiopathy Atypical hemolytic uremic syndrome

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De novo glomerular diseases after renal transplantation:How is it different from recurrent glomerular diseases?

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World Journal of Transplantation 2017年第6期7卷 285-300页

作者： Fedaey Abbas Mohsen El Kossi Jon Kim Jin ajay sharma Ahmed Halawa Department of Nephrology Jaber El Ahmed Military Hospital Faculty of Health and Science University of LiverpoolInstitute of Learning and TeachingSchool of Medicine Doncaster Royal Infirmary Nottingham Children Hospital Royal Liverpool University Hospitals Department of Transplantation Surgery Sheffield Teaching Hospitals

The glomerular diseases after renal transplantation can occur de novo,i.e.,with no relation to the native kidney disease,or more frequently occur as a recurrence of the original disease in the native *** may not be any difference in clinical features and histological pattern between de novo glomerular disease and recurrence of original glomerular ***,structural alterations in transplanted kidney add to dilemma in *** changes in architecture of histopathology can happen due to:(1) exposure to the immunosuppression specifically the calcineurin inhibitors(CNI);(2) in vascular and tubulointerstitial alterations as a result of antibody mediated or cellmediated immunological onslaught;(3) post-transplant viral infections;(4) ischemia-reperfusion injury; and(5) hyperfiltration *** pathogenesis of the de novo glomerular diseases differs with each *** of B-cell clones with subsequent production of the monoclonal Ig G,particularly Ig G3 subtype that has higher affinity to the negatively charged glomerular tissue,is suggested to be included in PGNMID *** novo membranous nephropathy canbe seen after exposure to the cryptogenic podocyte *** role of the toxic effects of CNI including tissue fibrosis and the hemodynamic alterations may be involved in the de novo FSGS *** well-known deleterious effects of HCV infection and its relation to MPGN disease are frequently *** new concepts have emerged that demonstrate the role of dysregulation of alternative complement pathway in evolution of MPGN that led to classifying into two subgroups,immune complex mediated MPGN and complement-mediated *** latter comprises of the dense deposit disease and the C3 GN *** novo C3 disease is rather *** of de novo diseases varies with each type and their management continues to be empirical to a large extent.

关键词： De novo glomerulonephritis Renal transplantation New concepts of therapy

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Structural and Electrical Characteristics of Ba(Fe0.5Nb0.5)O3-SrTiO3Ceramic System

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Materials Sciences and Applications 2011年第11期2卷 1593-1600页

作者： Narendra Kumar Singh Pritam Kumar ajay Kumar sharma Ram Naresh Prasad Choudhary 不详

A complex structure of barium iron niobate, Ba(Fe0.5Nb0.5)O3 (BFN) and strontium titanate SrTiO3 (ST) was fabricated by a solid-state reaction method. The phase formation of Ba(Fe0.5Nb0.5)O3-SrTiO3 was checked using X-ray diffraction (XRD) technique. The X-ray structural analysis of BFN and BFN-ST ceramics, showed the formation of single-phase compound in the monoclinic system, which is a distorted structure of an ideal cubic perovskite. Careful examination of microstructures of the individual compounds of the system was done by the scanning electron micrograph (SEM), and confirms the polycrystalline nature of the systems. Detailed studies of dielectric and electrical impedance properties of the systems in a wide range of frequency (100Hz - 5MHz) and different temperatures (30°C-285°C) showed that these properties are strongly dependent on temperature and frequency.

关键词： Dielectrics Perovskite Oxides X-Ray Diffraction Scanning Electron Micrograph

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Systemic meta-analysis assessing the short term applicability of early conversion to mammalian target of rapamycin inhibitors in kidney transplant

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World Journal of Transplantation 2017年第2期7卷 144-151页

作者： Jayant Kumar Isabella Reccia Tomokazu Kusano Bridson M Julie ajay sharma Ahmed Halawa Department of Cancer and Surgery Imperial College Faculty of Health and Sciences Institute of Learning and TeachingUniversity of Liverpool Department of Surgery Royal Liverpool University Hospital Department of Surgery Sheffield Teaching Hospitals

AIM To consolidate the present evidence of effectiveness in renal functioning and graft survival following early introduction of mammalian target of rapamycin(m TOR) inhibitors with or without calcineurin inhibitors(CNIs) in renal transplant *** We analysed the current literature following PROSPERO approval describing the role of immunosuppressive agent, m TOR inhibitors as an alternative to CNI within six months of renal transplant by searching the Pub Med, EMBASE, Cochrane, Crossref, and Scopus using Me SH terms. RESULTS Six articles of early withdrawal of CNI and introduction of m TOR-inhibitors within six months of renal transplantation were sought. Glomerular filtration rate(GFR) and serum creatinine were significantly better in m TOR inhibitor group with equivalent survival at 12 mo, even though Biopsy Proven Acute rejection was significantly higher in m TOR-inhibitor group. CONCLUSION The evidence reviewed in this meta-analysis suggests that early introduction m TOR-inhibitors substantial CNI minimization. The m TOR inhibitors such as everolimus and sirolimus, due to their complementary mechanism of action and favourable nephrotoxicity profile; better glomerular filtration, lower serum creatinine with equivalent survival. Having said that, due to the higher rejection rate, may influence the use of these regimens to patients with moderate to high immunological risk patients.

关键词： Adverse events Calcineurin inhibitors Graft failure Kidney transplantation Mammalian target of rapamycin inhibitors

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Dielectric Relaxation in Complex Perovskite Oxide Sr(Gd0.5Nb0.5)O3

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Materials Sciences and Applications 2012年第6期3卷 369-376页

作者： Pritam Kumar ajay Kumar sharma Bhrigunandan Prasad Singh Tripurari Prasad Sinha Narendra Kumar Singh Department of Physics Bose Institute Kolkata India University Department of Physics T. M. Bhagalpur University Bhagalpur India University Department of Physics V. K. S. University Ara India

The complex perovskite oxide a strontium gadolinium niobate (SGN) synthesized by solid-state reaction technique has single phase with tetragonal structure. X-ray diffraction (XRD) technique and scanning electron microscopy (SEM) were used to study the structural and microstructural properties of the ceramics, respectively. The XRD patterns of SGN at room temperature show a tetragonal structure. Studies of the dielectric constant and dielectric loss of compound as a function of frequency (50 Hz to 1 MHz) at room temperature, and as a function of temperature (60°C to 420°C) indicate polydispersive nature of the material. The logarithmic angular frequency dependence of the loss peak is found to obey the Arrhenius law with activation energy ~0.18 eV. The small value of activation energy of the compound (~0.18 eV) can be explained by mixed ionic-polaronic conductivity mechanism. The grain size of the pellet sample was found to be 1.92 μm. The frequency-dependant electrical data are analyzed in the framework of conductivity and electric modulus formalisms. The complex plane impedance plot shows the grain boundary contribution for higher value of dielectric constant in the law frequency region.

关键词： Dielectrics Perovskite Oxides X-Ray Diffraction Scanning Electron Micrograph

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Human leukocyte antigen typing and crossmatch:A comprehensive review

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World Journal of Transplantation 2017年第6期7卷 339-348页

作者： Mohammed Mahdi Althaf Mohsen El Kossi Jon Kim Jin ajay sharma Ahmed Mostafa Halawa Jack Pryor Renal Unit Norfolk and Norwich University Hospital-NHS Foundation Trust Faculty of Health and Science University of LiverpoolInstitute of Learning and TeachingSchool of Medicine Doncaster Royal Infirmary Nottingham Children Hospital Royal Liverpool University Hospitals Department of Transplantation Surgery Sheffield Teaching Hospitals

Renal transplantation remains the best option for patients suffering from end stage renal disease(ESRD).Given the worldwide shortage of organs and growing population of patients with ESRD,those waitlisted for a transplant is ever *** crossmatch methods and human leukocyte antigen(HLA) typing play a pivotal role in improving organ allocation and afford better matches to *** crossmatch as well as HLA typing for renal transplantation and applying it in clinical practice is the key step to achieve a successful *** of crossmatch results can be quite challenging where clinicians have not had formal training in applied transplant *** review aims to provide a worked example using a clinical ***,each technique is discussed in detail with its pros and *** index case is that of a young male with ESRD secondary to Lupus *** is offered a deceased donor kidney with a 1-0-0 *** complement dependent cytotoxicity(CDC) crossmatch reported positive for B lymphocyte,but flow cytometry crossmatch(FCXM) was reported negative for both B and T ***-SAB(single antigen bead) did not identify any donor specific antibodies(DSA).He never had a blood *** positive CDCcrossmatch result is not concordant with DSA *** implausible results are due to underlying lupus erythematosus,leading to false-positive B-lymphocyte crossmatch as a result of binding immune complexes to *** positive report of CDC crossmatch can be caused by the underlying autoimmune diseases such as lupus erythematosus,that may lead to inadvertent refusal of adequate kidney *** study of DSA by molecular technique would prevent wrong exclusion of such *** on these investigations this patient is deemed to have "standard immunological risk" for renal transplantation.

关键词： Human leukocyte antigen typing Cytotoxic crossmatch Flow cytometry crossmatch Virtual crossmatch Human leukocyte antigen null alleles

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Complement-mediated renal diseases after kidney transplantation-current diagnostic and therapeutic options in de novo and recurrent diseases

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World Journal of Transplantation 2018年第6期8卷 203-219页

作者： Fedaey Abbas Mohsen El Kossi Jon Jin Kim Ihab Sakr Shaheen ajay sharma Ahmed Halawa Nephrology Department Jaber El Ahmed Military Hospital Faculty of Health and Science University of Liverpool Institute of Learning and Teaching School of Medicine Doncaster Royal Infirmary Nottingham Children Hospital Royal Hospital for Children Glasgow G51 4TF United Kingdom Royal Liverpool University Hospitals Sheffield Teaching Hospitals

For decades, kidney diseases related to inappropriate complement activity, such as atypical hemolytic uremic syndrome and C3 glomerulopathy(a subtype of membranoproliferative glomerulonephritis), have mostly been complicated by worsened prognoses and rapid progression to end-stage renal failure. Alternative complement pathway dysregulation, whether congenital or acquired, is well-recognized as the main driver of the disease process in these patients. The list of triggers include: surgery, infection, immunologic factors, pregnancy and medications. The advent of complement activation blockade, however, revolutionized the clinical course and outcome of these diseases, rendering transplantation a viable option for patients who were previously considered as non-transplantable *** less-costly therapeutic lines and likely better efficacy and safety profiles are currently underway. In view of the challenging nature of diagnosing these diseases and the long-term cost implications, a multidisciplinary approach including the nephrologist, renal pathologist and the genetic laboratory is required to help improve overall care of these patients and draw the optimum therapeutic plan.

关键词： Complement-related diseases Kidney transplantation De novo Recurrent diseases

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Echocardiographic predictors and associated outcomes of multiple vegetations in infective endocarditis:A pilot study

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World Journal of Cardiology 2024年第6期16卷 318-328页

作者： ajay Kumar Mishra Kannu Bansal Ibragim Al-Seykal Pradnya B Bhattad Anu Anna George Anil Jha Nitish sharma Jennifer Sargent Mark J Kranis Division of Cardiology Saint Vincent HospitalWorcesterMA 01608United States Department of Internal Medicine Saint Vincent HospitalWorcesterMA 01608United States Department of Medicine Division of CardiologySaint Vincent HospitalWorcesterMA 01608United States Division of Cardiovascular Medicine Saint Vincent HospitalWorcesterMA 01608United States

BACKGROUND Infective endocarditis(IE)is a life-threatening infection with an annual mortality of 40%.Embolic events reported in up to 80%of *** of>10 mm size are associated with increased embolic events and poor *** is a paucity of literature on the association of multiple vegetations with *** To study the echocardiographic(ECHO)features and outcomes associated with the presence of multiple *** In this retrospective,single-center,cohort study patients diagnosed with IE were recruited from June 2017 to June 2019.A total of 84 patients were diagnosed to have IE,of whom 67 with vegetation were *** demographic,clinical,laboratory,and ECHO parameters were *** that were studied included recurrent admission,embolic phenomenon,and *** Twenty-three(34%)patients were noted to have multiple vegetations,13(56.5%)were male and 10(43.5%)were *** mean age of these patients was ***(35%)had a prior episode of *** features of moderate to severe valvular regurgitation[odds ratio(OR)=4],presence of pacemaker lead(OR=4.8),impaired left ventricle(LV)relaxation(OR=4),and elevated pulmonary artery systolic pressure(PASP)(OR=2.2)are associated with higher odds of multiple *** these moderate to severe valvular regurgitation(P=0.028),pacemaker lead(P=0.039)and impaired relaxation(P=0.028)were statistically *** patients were noted to have an increased association of recurrent admissions(OR=3.6),recurrent bacteremia(OR=2.4),embolic phenomenon(OR=2.5),intensive care unit stay(OR=2.8),hypotension(OR=2.1),surgical intervention(OR=2.8)and device removal(OR=4.8).Of this device removal(P=0.039)and recurrent admissions(P=0.017)were statistically *** This study highlights the associations of ECHO predictors and outcomes in patients with IE having multiple *** features of moderate to severe regurgitation,presence of pacemaker lead,impai

关键词： Endocarditis Echocardiography Vegetations Predictors Outcome

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Comprehensive analysis of uncertainty quantification for the^(58)Ni(n,p)^(58)Co reaction cross section

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Chinese Physics C 2024年第9期48卷 170-175页

作者： Mahesh Choudhary Aman sharma Namrata Singh Mahima Upadhyay Punit Dubey A.Gandhi Akash Hingu G Mishra Sukanya De L.S.Danu ajay Kumar R.G.Thomas Saurav Sood Sajin Prasad S.Mukherjee I.N.Ruskov Yu.N.Kopatch A.Kumar Department of Physics Banaras Hindu UniversityVaranasi 221005India Horia Hulubei National Institute of Physics and Nuclear Engineering-IFIN-HH Bucharest 077125Romania Department of Physics The Maharaja Sayajirao University of BarodaVadodara 390002India Nuclear Physics Division Bhabha Atomic Research CentreMumbai 400085India Health Physics Division Bhabha Atomic Research CentreMumbai 400085India Department of Electrical Power Engineering Brno University of TechnologyBrno 61600Czech Republic Institute for Nuclear Research and Nuclear Energy Bulgarian Academy of SciencesSofia 1784Bulgaria Joint Institute for Nuclear Research(JINR) Dubna 141980Russia

In this study,we measured the^(58)Ni(n,p)^(58)Co reaction cross section with neutron energies of 1.06,1.86,and 2.85 *** cross section was measured using neutron activation techniques andγ-ray spectroscopy,and it was compared with cross section data available in the ***,we calculated the covariance matrix of the measured cross section for the aforementioned nuclear *** uncertainties of the theoretical calculation for^(58)Ni(n,p)^(58)Co reaction cross section were calculated via Monte Carlo *** this study,we used uncertainties in the optical model and level density parameters to calculate uncertainties in the theoretical cross *** theoretical calculations were performed by using *** this study,we aim to analyze the effect of uncertainties of the nuclear model input as well as different experimental variables used to obtain the values of reaction cross section.

关键词： ^(58)Ni(n p)^(58)Co reaction γ-ray spectroscopy uncertainty quantification of cross section covariance analysis

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Infertility,pregnancy and breastfeeding in kidney transplantation recipients:Key issues

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World Journal of Meta-Analysis 2023年第3期11卷 55-67页

作者： Mohamad Habli Dawlat Belal ajay sharma Ahmed Halawa Department of Internal Medicine Division of NephrologyKingdom HospitalRiyadh 11564Saudi Arabia Kasr El-Ainy School of Medicine Cairo UniversityCairo 11562Egypt Royal Liverpool University Hospital Royal Liverpool University HospitalLiverpool L78YEUnited Kingdom Department of Transplantation Sheffield Teaching HospitalsSheffield S102JFUnited Kingdom

Chronic kidney disease(CKD),especially in advanced stages,is an important cause of *** CKD patients,infertility has been linked to multiple *** pathophysiology of infertility related to CKD is complex and *** of modifiable factors can improve fertility in both *** males as well as females,successful kidney transplantation offers good chances of restoration of reproductive *** female renal allograft recipients,recovery of reproductive functions in the post-transplant period will manifest as restoration of normal menses and *** to this improvement,there is a significant risk of unplanned pregnancy,hence the need to discuss methods of contraception before *** kidney transplant recipients,different contraceptive options for pregnancy planning,have been *** selection of one contraception over another is based on preference and ***,in renal transplanted females,is associated with physiologic changes that occur in pregnant women with native *** medications during pregnancy,in a recipient with a single functioning kidney,expose the mother and fetus to unwanted *** immunosuppressive drugs are contraindicated during *** medications should be discussed with renal transplant recipients who are planning to breastfeed their *** addition to antirejection drugs,other medications should be managed accordingly,whenever pregnancy is planned.

关键词： Infertility Chronic kidney disease Pregnancy Kidney transplantation Immunosuppression Breastfeeding

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