Third-party cytomegalovirus-specific T cells improved survival in refractory cytomegalovirus viremia after hematopoietic transplant.

BackgroundRefractory CMV viremia and disease are associated with significant morbidity and mortality in recipients of hematopoietic stem cell transplant (HCT).MethodsIn phase I/II trials, we treated 67 subjects for CMV viremia or disease arising after HCT with adoptive transfer of banked, third-party, CMVpp65-sensitized T cells (CMVpp65-VSTs). All were evaluable for toxicity and 59 for response. Evaluable subjects had CMV disease or persisting viremia that had failed at least 2 weeks of induction therapy with a median of 3 antiviral drugs; 84.7% had more than 3 of 11 high-risk features. CMVpp65-VSTs were specific for 1 to 3 CMVpp65 epitopes, presented by a limited set of HLA class I or II alleles, and were selected based on high-resolution HLA matching at 2 of 10 HLA alleles and matching for subject and subject's HCT donor for 1 or more alleles through which the CMVpp65-VSTs were restricted.ResultsT cell infusions were well tolerated. Of 59 subjects evaluable for response, 38 (64%) achieved complete or durable partial responses.ConclusionsRecipients responding to CMVpp65VSTs experienced an improved overall survival. Of the risk factors evaluated, transplant type, recipient CD4+ and CD8+ T cell levels prior to adoptive therapy, and the HLA restriction of CMVpp65-VSTs infused each significantly affected responses. In addition, CMVpp65-specific T cells of HCT donor or recipient origin contributed to the durability of both complete and partial responses.Trial RegistrationNCT00674648; NCT01646645; NCT02136797 (NIH).FundingNIH (P01 CA23766, R21 CA162002 and P30 CA008748); Aubrey Fund; Claire Tow Foundation; Major Family Foundation; "Rick" Eisemann Pediatric Research Fund; Banbury Foundation; Edith Robertson Foundation; Larry Smead Foundation.

Impact of Donor, Recipient, and Graft Characteristics on Corneal Transplantation Outcomes.

Purpose: Although several donor, recipient, and graft characteristics have been studied in relation to corneal transplantation outcomes, no study to our knowledge has assessed the impact of donor cooling times on postoperative outcomes longitudinally. With only one corneal graft available for every 70 needed worldwide, this study seeks to identify any factors that could alleviate this shortage. Methods: Patients undergoing corneal transplantation at the Manhattan Eye, Ear & Throat Hospital over a 2-year period were retrospectively studied. Study metrics included age, diabetic history, hypertensive history, endothelial cell density, death-to-preservation time (DTP), death-to-cooling time (DTC), and time-in-preservation (TIP). Postoperative transplantation outcomes, including best corrected visual acuity (BCVA) at 6- and 12-month follow-up visits, need for re-bubbling, and need for re-grafting, were assessed. Unadjusted univariate and adjusted multivariate binary logistic regressions were performed to determine the association of cooling and preservation parameters with corneal transplantation outcomes. Results: Among 111 transplants, our adjusted model found that DTC ≥4 hours was associated with significantly worse BCVA, but only at 6-month postoperative follow-up (odds ratio [OR]: 0.234; 95% confidence interval [CI]: 0.073-0.747; p = 0.014). By 12-month follow-up, DTC >4 hours was no longer associated with BCVA in a statistically significant manner (OR: 0.472; 95% CI: 0.135-1.653; p = 0.240). A similar trend was found at a DTC cutoff of ≥3 hours. None of the other studied parameters, including DTP, TIP, donor age, or medical history were significantly correlated with transplantation outcomes. Conclusion: Longer DTC or DTP did not have a statistically significant effect on corneal graft outcomes after one year, though short-term outcomes were improved in donor tissues with DTC below four hours. None of the other studied variables correlated with transplantation outcomes. Given the global shortage of corneal tissue, these findings should be considered when determining suitability for transplantation.

Effect of Body Mass Index on complications and success rates of percutaneous nephrolithotomy-A tertiary care hospital experience.

Background and Objectives: Urolithiasis is prevalent globally. Over time, innovation in endoscopic instruments and miniaturization has untangled the interventional strategy for carrying out remedial surgical procedures for renal stones. However, studies have been scarce as for sequelae of Percutaneous Nephrolithotomy (PCNL) in varying body mass index group patients in the developing world. We aimed to report success rates and complications in different BMI groups. Methods: This was a retrospective study wherein data of 359 patients was reviewed in charts. These patients went through PCNL at our department from July 2011 till September 2019. Three groups of patients were made in agreement with WHO BMI classification. Information concerning study variables was noted in designated and then processed in SPSS version 16 for the statistical computations. Results: On the whole, the mean age of patients was 44.6± 14.4 years. While the mean calculus size was 3.1± 1.4 cm. Moreover, the majority of stones in all the three groups belonged to Guy's stone score 1 and 2 (see Table-I). The overall mean procedure time and inpatient stay were almost comparable in the obese group. The highest stone-free rate was observed in the normal weight group (77.69 %), however, stone-free status in overweight and obese groups was not comparatively too lower (p=0.74). Complication rates were being close among the three groups. Conclusion: PCNL can be ventured with safety and in an effectual manner for attaining stone treatment goals alike in obese and non-obese group patients.

Biomarker correlates with response to NY-ESO-1 TCR T cells in patients with synovial sarcoma.

Autologous T cells transduced to express a high affinity T-cell receptor specific to NY-ESO-1 (letetresgene autoleucel, lete-cel) show promise in the treatment of metastatic synovial sarcoma, with 50% overall response rate. The efficacy of lete-cel treatment in 45 synovial sarcoma patients (NCT01343043) has been previously reported, however, biomarkers predictive of response and resistance remain to be better defined. This post-hoc analysis identifies associations of response to lete-cel with lymphodepleting chemotherapy regimen (LDR), product attributes, cell expansion, cytokines, and tumor gene expression. Responders have higher IL-15 levels pre-infusion (p = 0.011) and receive a higher number of transduced effector memory (CD45RA- CCR7-) CD8 + cells per kg (p = 0.039). Post-infusion, responders have increased IFNγ, IL-6, and peak cell expansion (p < 0.01, p < 0.01, and p = 0.016, respectively). Analysis of tumor samples post-treatment illustrates lete-cel infiltration and a decrease in expression of macrophage genes, suggesting remodeling of the tumor microenvironment. Here we report potential predictive and pharmacodynamic markers of lete-cel response that may inform LDR, cell dose, and strategies to enhance anticancer efficacy.

Dominant epitopes presented by prevalent HLA alleles permit wide use of banked CMVpp65 T cells in adoptive therapy.

We established and characterized a bank of 138 CMVpp65 peptide-specific T-cell (CMVpp65CTLs) lines from healthy marrow transplant donors who consented to their use for treatment of individuals other than their transplant recipient. CMVpp65CTL lines included 131 containing predominantly CD8+ T cells and 7 CD4+ T cells. CD8+ CMVpp65CTLs were specific for 1 to 3 epitopes each presented by one of only 34 of the 148 class I alleles in the bank. Similarly, the 7 predominantly CD4+ CMVpp65CTL lines were each specific for epitopes presented by 14 of 40 HLA DR alleles in the bank. Although the number of HLA alleles presenting CMV epitopes is low, their prevalence is high, permitting selection of CMVpp65CTLs restricted by an HLA allele shared by transplant recipient and hematopoietic cell transplant donor for >90% of an ethnogeographically diverse population of hematopoietic cell transplant recipients. Within individuals, responses to CMVpp65 peptides presented by different HLA alleles are hierarchical. Furthermore, within groups, epitopes presented by HLA B*07:02 and HLA A*02:01 consistently elicit immunodominant CMVpp65CTLs, irrespective of other HLA alleles inherited. All dominant CMVpp65CTLs exhibited HLA-restricted cytotoxicity against epitope loaded targets and usually cleared CMV infections. However, immunodominant CMVpp65CTLs responding to epitopes presented by certain HLA B*35 alleles were ineffective in lysing CMV-infected cells in vitro or controlling CMV infections post adoptive therapy. Analysis of the hierarchy of T-cell responses to CMVpp65, the HLA alleles presenting immunodominant CMVpp65 epitopes, and the responses they induce may lead to detailed algorithms for optimal choice of third-party CMVpp65CTLs for effective adoptive therapy.

Outcome of tubeless percutaneous nephrolithotomy in elder patients: A single-center experience from a developing country.

Background: Percutaneous nephrolithotomy (PCNL) has evolved as a standard procedure to treat large-sized renal stones. A nephrostomy tube is used frequently in this procedure; however, data regarding tubeless PCNL procedures in elder patients is scarce. Aim: The aim of this study was to review the results and outcomes associated with tubeless PCNL procedures in the elderly population. Materials and Methods: A retrospective review of patients aged ≥60 years at our hospital that was treated for renal stones by PCNL procedure. The patients were separated into two groups: Group 1 underwent tubed PCNL procedures and Group 2 received tubeless PCNL procedures. Information regarding variables were recorded in specified pro forma and then processed in Statistical Package for the Social Sciences statistics analyses. Statistical tests were utilized for continuous and categorical variables and a P<0.05 was considered statistically significant. Results: 121 patients with a mean age of 65±5 years were included in the analysis. Mean stone size and body mass index were 3.4±1.5 cm and 26.2±4.3 kg/m2, respectively. Mean operative time was longer in tubed PCNL as compared to the tubeless group. Mean hospital stay was similar among the tubed and tubeless PCNL treated groups. Mean analgesic doses were significantly lower in the tubeless group. The overall stone-free rate was 89/121 patients (74%). Conclusion: Tubeless PCNL can be safely undertaken in geriatric patients and has potential advantages associated with shorter operative times and reduced necessity for analgesia. Relevance for Patients: Tubeless PCNL is considered advantageous as it can reduce post-operative pain and analgesia necessity; shorten hospitalization and lower cost in young patients. However, there is no clear evidence with reference to virtue of tubeless PCNL in the elderly age groups. This study will analyze and review results and outcomes associated with tubeless PCNL in a cohort of elderly patients.

Use Of Computed Tomography-Based Nomogram In Adult Age Patients To Predict Success Rates After Shock Wave Lithotripsy For Renal Stones: A Single Center Experience.

BACKGROUND: The Triple D score is a novel and easy to use nomogram to predict shock-wave lithotripsy (SWL) outcomes. It is based on Computed Tomography (CT scan) parameters including stone density, skin-to-stone distance, and stone volume. However, its use has not been validated much as studies are sparse regarding its use. Our aim was to validate and evaluate accuracy of the Triple D scoring system in predicting SWL success rates. METHODS: It was a prospective study of 277 patients who had undergone SWL procedure for renal stones. They were evaluated by using non-contrast tomography, before undergoing SWL. CT scan-based parameters including distance of stone to skin (SSD), stone volume (SV), stone density was assessed. Computation of Cut off values was done with receiver operating characteristics analysis. Score was assigned on the basis of these cut-off values and success rate of SWL was determined. This score ranged from 0 (least favourable score) to 3 (most favourable score). RESULTS: Stone-free status was attained in 160 patients (57.7%), and 117 (42.3%) patients were labelled to have failed the procedure. Differences between these two groups in terms of Stone volume, stone density and skin to stone distance were significant. Triple D scores of zero,1, 2, and 3 had stone-free rates of 3.6%, 52.56%, 53.3%, and 93.1% respectively (p-vaue<0.001). CONCLUSIONS: Shock-wave lithotripsy outcomes can be predicted with use of Triple D score and hence, it's externally corroborated. It may help urologist in appropriate patient selection and hence decision making and patient counselling.

Role of Stone Heterogeneity Index in Determining Success of Shock Wave Lithotripsy in Urinary Calculi.

INTRODUCTION: Various stone factors can affect the outcome of shock wave lithotripsy (SWL). A novel factor called the stone heterogeneity index (SHI) may have an impact on stone free rates. The objective of this study was to assess the role of SHI in SWL outcomes. METHODS: Patients' medical records were reviewed for the collection of data variables. They were subjected to SWL, using an electromagnetic lithotripter machine (Storz Modulith SLX-MX). Computation of mean stone density (mean value of the Hounsfield units) and SHI was accomplished by generating elliptical regions of interest on the computed tomography (CT) scan images. Grouping was performed on the basis of stone free and failure outcomes. Relevant statistical tests were applied for continuous and categorical variables. P ≤ 0.05 was considered statistically significant. RESULTS: Overall, 385 subjects were included having a mean age of 38.4 ± 14.7 years. The cohort comprised 276 (71.7%) males and 109 (28.3%) female patients. A total of 234 (60.8%) patients were rendered successful (stone free after one session) while 151 (39.2%) of the patients were declared to have failed the SWL procedure. Stone length, stone density, and SHI values were 13.7 ± 7.6 mm, 935 ± 404, and 201 ± 107, respectively. The stone density, SHI, and stone length were significantly different between the two groups (p-values of 0.001, 0.02, and 0.04, respectively). CONCLUSIONS: SHI can be a helpful CT scan-based parameter to assess stone fragility. It can help clinicians in the judicious selection of patients before implementing SWL procedure. RELEVANCE FOR PATIENTS: Non-contrast CT-based stone parameters have been found to be effective for predictions of outcomes. SHI can be a helping tool to better predict SWL success rates when treating the renal stones.

Outcomes Of Percutaneous Nephrolithotomy In Elder Age Patients-Single Center Experience.

BACKGROUND: Urolithiasis is a prevailing ailment affecting all age groups across global population. In modern innovative industry endoscopic instruments alterations and miniaturization has simplified the interventional strategy for undertaking these procedures for renal stones. However, there has been paucity of studies regarding outcomes of Percutaneous Nephrolithotomy (PCNL) in elder age group. We aimed to report success rates and complications in elder age group. METHODS: This was a retrospective review of the charts for subjects that underwent unilateral PCNL from 2012 till 2018 November at a tertiary care hospital at capital of Pakistan. Patients of age ≥60 years were chosen for this study. PCNL procedures were done in prone position. We implemented the Guy stone scoring (stone complexity) to forecast the net results of PCNL. Information regarding variables were recorded in specified proforma and then processed in SPSS version 16 for the statistical computations. RESULTS: On the whole 79 patients were incorporated for this study. Most common presenting complaint in clinic was flank pain followed by haematuria and fever respectively. Mean age in this analysis was calculated as 63.36±5.19 years. Mean size for calculi was 449±163mm2. One patient underwent transfusion after surgery while only 2.5% of these patients had sepsis (post PCNL procedure). Stone free rate was significantly affected by Guys stone score (GSS). CONCLUSIONS: PCNL can be undertaken safely and effectually for achieving treatment goals even in elder subjects. Stone free rates are higher in lower Guys stone score as compared to the higher scores.

Ocular Outcomes after Treatment of Cytomegalovirus Retinitis Using Adoptive Immunotherapy with Cytomegalovirus-Specific Cytotoxic T Lymphocytes.

PURPOSE: To describe ocular outcomes in eyes with cytomegalovirus (CMV) retinitis treated with adoptive immunotherapy using systemic administration of CMV-specific cytotoxic Tlymphocytes (CMV-specific CTLs). DESIGN: Retrospective cohort study. PARTICIPANTS: Patients with active CMV retinitis evaluated at a tertiary care academic center. METHODS: Treatment of CMV retinitis with standard-of-care therapy (systemic or intravitreal antivirals) or CMV-specific CTLs (with or without concurrent standard-of-care therapies). MAIN OUTCOME MEASURES: The electronic medical record was reviewed to determine baseline characteristics, treatment course, and ocular outcomes, including best-corrected visual acuity (BCVA), treatments administered (CMV-specific CTLs, systemic antivirals, intravitreal antivirals), resolution of CMV retinitis, any occurrence of immune recovery uveitis, cystoid macular edema, retinal detachment, or a combination thereof. RESULTS: Seven patients (3 of whom had bilateral disease [n = 10 eyes]) were treated with CMV-specific CTLs, whereas 20 patients (6 of whom had bilateral disease [n = 26 eyes]) received standard-of-care treatment. Indications for CMV-specific CTL therapy included persistent or progressive CMV retinitis (71.4% of patients); CMV UL54 or UL97 antiviral resistance mutations (42.9%); side effects or toxicity from antiviral agents (57.1%); patient intolerance to longstanding, frequent antiviral therapy for persistent retinitis (28.6%); or a combination thereof. Two patients (28.6%; 4 eyes [40%]) received CMV-specific CTL therapy without concurrent systemic or intravitreal antiviral therapy for active CMV retinitis, whereas 5 patients (71.4%; 6 eyes [60%]) continued to receive concurrent antiviral therapies. Resolution of CMV retinitis was achieved in 9 eyes (90%) treated with CMV-specific CTLs, with BCVA stabilizing (4 eyes [40%]) or improving (4 eyes [40%]) in 80% of eyes over an average follow-up of 33.4 months. Rates of immune recovery uveitis, new-onset cystoid macular edema, and retinal detachment were 0%, 10% (1 eye), and 20% (2 eyes), respectively. These outcomes compared favorably with a nonrandomized cohort of eyes treated with standard-of-care therapy alone, despite potentially worse baseline characteristics. CONCLUSIONS: CMV-specific CTL therapy may represent a novel monotherapy or adjunctive therapy, or both, for CMV retinitis, especially in eyes that are resistant, refractory, or intolerant of standard-of-care antiviral therapies. More generally, adoptive cell transfer and adoptive immunotherapy may have a role in refractory CMV retinitis. Larger prospective, randomized trials are necessary.

Laparoscopic Orchiopexy For Management Of Bilateral Non-Palpable Testes

BACKGROUND: Despite numerous clinical studies regarding the management of unilateral impalpable testes by laparoscopy, there is a paucity of such studies regarding the management of bilateral 'non-palpable' testes. We shared the outcome of the laparoscopic management of bilateral 'non-palpable' testes in terms of successful orchiopexy and complications in children. METHODS: A total of 22 children underwent bilateral diagnostic laparoscopy for undescended testes who presented to our department from January 2010 till March 2018. We did chart review for variables such as the age of children, operative time, hospital stay, single-stage or 2 stage procedure, and operative complications. Preoperatively history and physical examination were done along with baseline investigations and Ultrasound abdomen and scrotum before surgery for general anaesthesia fitness. They were managed by single or two steps laparoscopic orchiopexy according to suitability for each case. RESULTS: We performed bilateral laparoscopic orchidopexies in 22 children having a mean age of 4.1±1.98 years (49.2 months) Mean operative time for single setting bilateral single-stage orchiopexy was 136±32 minutes. Out of twenty-two children with bilateral impalpable testes, 12 boys (54.5%) were managed with a single-stage Bilateral Laparoscopic technique while the other 10 (45.45%) were managed in 2 staged laparoscopic intervention using Fowler-Stephens technique. Testicular atrophy was seen in 2/44 testes (4.54%). While 1 /44 (2.27%) testis had ascended to the inguinal region requiring redo surgery. CONCLUSIONS: Laparoscopic management of bilateral 'non-palpable' testes in a single or double setting is a safe and effective method of bringing testes down to the scrotum. It has no major morbidities.

Incidental Findings Of Polypoid Cystitis In A 6-Year Old Child Without Any History Of Lower Urinary Tract Symptoms And Previous Urinary Catheterization.

A 6-year-old boy presented to ER with acute pain in right iliac fossa without any history of lower urinary tract symptoms, haematuria and urinary catheterization. Ultrasound showed loculated cystic area in pelvis with non-visualized appendix. A CT scan abdomen and pelvis revealed loculated, multi-septated cystic lesion in right hemipelvis thought to be a collection from possible appendicular inflammation / perforation. The laboratory findings revealed raised CRP and normal urine routine examination and culture. Exploratory laparotomy revealed cystic urinary bladder growth involving dome with normal appendix, partial cystectomy was done. Histopathology confirmed polypoid cystitis with no evidence of malignancy. This is a very rare presentation of polypoidal cystitis, not previously reported in literature.

Association of single nucleotide polymorphism of transforming growth factor ß1 (T29C) in breast cancer patients: a case control study in Rawalpindi.

OBJECTIVE: To determine the association of single nucleotide polymorphism in three CC, TT and TC genotypes of transforming growth factor ß1 T29C in breast cancer patients. METHODS: The case-control study was conducted from April 2017 to April 2018 at the Islamic International Medical College, Rawalpindi, Pakistan, in collaboration with Nuclear Oncology Medicine and Radiotherapy Institute and Holy Family Hospital, Rawalpindi. Using convenience sampling, breast cancer cases and healthy controls were enrolled. All investigations were done using standardized laboratory protocols. The outcomes were determined in terms of association of single nucleotide polymorphism of transforming growth factor ß1with breast cancer. Data was analysed using SPSS 21. RESULTS: Of the 150 subjects, 80(53.3%) were cases and 70(47.7%) were healthy controls. Among the cases, the most frequent genotype was CC 38(47.5%) followed by TC 26(32.5%) and TT 16(20%). Among the controls, the corrsesponding values were 50(71.42%), 13(18.5%) and 7(10%). Transforming growth factor ß1 TC genotype was strongly associated with the increased risk of developing breast cancer (odds ratio: 3.79). CONCLUSIONS: The incidence of breast cancer was markedly lower among women with CC genotype compared to those with CT or TT genotypes.

Off-the-shelf EBV-specific T cell immunotherapy for rituximab-refractory EBV-associated lymphoma following transplantation.

BACKGROUNDAdoptive transfer of donor-derived EBV-specific cytotoxic T-lymphocytes (EBV-CTLs) can eradicate EBV-associated lymphomas (EBV-PTLD) after transplantation of hematopoietic cell (HCT) or solid organ (SOT) but is unavailable for most patients.METHODSWe developed a third-party, allogeneic, off-the-shelf bank of 330 GMP-grade EBV-CTL lines from specifically consented healthy HCT donors. We treated 46 recipients of HCT (n = 33) or SOT (n = 13) with established EBV-PTLD, who had failed rituximab therapy, with third-party EBV-CTLs. Treatment cycles consisted of 3 weekly infusions of EBV-CTLs and 3 weeks of observation.RESULTSEBV-CTLs did not induce significant toxicities. One patient developed grade I skin graft-versus-host disease. Complete remission (CR) or sustained partial remission (PR) was achieved in 68% of HCT recipients and 54% of SOT recipients. For patients who achieved CR/PR or stable disease after cycle 1, one year overall survival was 88.9% and 81.8%, respectively. In addition, 3 of 5 recipients with POD after a first cycle who received EBV-CTLs from a different donor achieved CR or durable PR (60%) and survived longer than 1 year. Maximal responses were achieved after a median of 2 cycles.CONCLUSIONThird-party EBV-CTLs of defined HLA restriction provide safe, immediately accessible treatment for EBV-PTLD. Secondary treatment with EBV-CTLs restricted by a different HLA allele (switch therapy) can also induce remissions if initial EBV-CTLs are ineffective. These results suggest a promising potential therapy for patients with rituximab-refractory EBV-associated lymphoma after transplantation.TRIAL REGISTRATIONPhase II protocols (NCT01498484 and NCT00002663) were approved by the Institutional Review Board at Memorial Sloan Kettering Cancer Center, the FDA, and the National Marrow Donor Program.FUNDINGThis work was supported by NIH grants CA23766 and R21CA162002, the Aubrey Fund, the Claire Tow Foundation, the Major Family Foundation, the Max Cure Foundation, the Richard "Rick" J. Eisemann Pediatric Research Fund, the Banbury Foundation, the Edith Robertson Foundation, and the Larry Smead Foundation. Atara Biotherapeutics licensed the bank of third-party EBV-CTLs from Memorial Sloan Kettering Cancer Center in June 2015.

A Comparison of Complications and Success Rates after PCNL in Younger and Elderly Patients.

OBJECTIVE: To compare the outcomes of percutaneous nephrolithotomy (PCNL) across younger and elderly, especially PCNL complications in terms of modified Clavian grading system. STUDY DESIGN:  Cros-sectional comparative study. PLACE AND DURATION OF STUDY: Department of Urology, Shifa International Hospital, Islamabad, from 2010 till 2018 December at a tertiary care hospital. METHODOLOGY: Patients who underwent unilateral PCNL were reviewed group 1 (younger, age < 60 years) had 594 patients; while group 2 (elderly, age >60 years) had 137 patents. Information regarding complication and success rate were recorded by residents in proforma and then processed for statistical computations. RESULTS: There were total of 731 subjects. The mean age in group 1 was 39.7±11.2 years and that of group B was 65.66±4.55 years. The mean size for calculi in group 1 was 2.83±1.32 cm while in group 2 stone size reached 2.81±1.04 cm. A total of 174 (23.8%) complications and stone free rate of 81.8% (598/731) was recorded in this study. Overall when compared, no notable difference in complications, hospital duration and success rates was observed between the young and elderly age group. CONCLUSION: Despite old age, the success rates and complications were not remarkably different from that of the younger subjects for prone PCNL. Key Words: Percutaneous nephrolithotomy, Geriatrics, Renal stone, Complications.

Comparison of asymmetric dimethylarginine levels between pre- and post-menopausal women - a cross-sectional study from Rawalpindi.

OBJECTIVE: To compare serum levels of asymmetric dimethylarginine between premenopausal and postmenopausal women, and to evaluate its relationship with time since onset of menopause. METHODS: The cross-sectional comparative study was conducted at Islamic International Medical College, Rawalpindi, Pakistan, from April 2017 to March 2018, and comprised individuals recruited from the Gynaecology and Obstetrics outpatient department of the Pakistan Railway Hospital in the city. The subjects were divided into two groups; pre-menopausal women in Group I and postmenopausal in Group II. Group II was subdivided into three categories according to time since onset of menopause. Serum asymmetric dimethylarginine levels were estimated in each subject. Data was analysed using SPSS 21. RESULTS: Of the 80 subjects, there were 40(50%) in Group I with a mean age of 36.25}6.8 years, 40(50%) in Group II with a mean age of49.83}4.35 years. There was a significant increase in mean asymmetric dimethylarginine levels in Group II compared to Group I (p<0.05). There was also a significant increase in asymmetric dimethylarginine levels with increase in duration since the onset of menopause (p<0.001). CONCLUSIONS: Levels of asymmetric dimethylarginine increased significantly after menopause.

Outcome Of Percutaneous Nephrolithotomy In Preschool And School-Age Children-Single Center Experience.

BACKGROUND: Efficacy of percutaneous nephrolithotomy in adults has been studied well in past. However, such studies are sparse within paediatric age group. As this procedure is being adopted in smaller and older children alike, we wanted to determine its safety and efficacy in two different age groups of children (preschool age and school age). METHODS: The records of 59 children undergoing PCNL at our department from December 2009 to May 2017 were reviewed retrospectively. Patients were placed into 2 age groups including children ≤7 years old (group 1) and those ≥7 years (group 2). Twenty-seven patients were put in preschool group with mean age of 4.8±2.1 years while 32 patients in school age group having mean age of 11.8±4.6 years. RESULTS: Stone size was calculated showing mean 309±55 mm2 in preschool and 324±63 mm2 in school age group respectively (p=0.1). The mean operative time was 150.1±38.7 minutes and 166.3±39.6 minutes in the preschool and school age children respectively (p=0.1). The mean length of hospital stay was 3.1±1.4 days and 2.9±1.3 days in preschool and school going children (p=0.5). The stone clearance with PCNL was seen in 96.3% (pre-school group) and 93.75% (school age group) as monotherapy (p=0.1), which increased to 100% after combining it with extracorporeal shock wave lithotripsy. CONCLUSIONS: PCNL is equally effective in both pre-school and school age groups in terms of stone free rates. Complication rates were not different between the two groups.

Therapeutic advantages provided by banked virus-specific T-cells of defined HLA-restriction.

We have developed banks of EBV and CMV-specific T-cell lines generated from healthy seropositive third party donors and characterized them as to their HLA type, virus specificity, lack of alloreactivity, and HLA restriction. We here summarize results of studies employing these immediately accessible, broadly-applicable third party virus-specific T-cells for adoptive therapy of EBV lymphomas and CMV infections in allo-HCT recipients. We describe the characteristics contributing to their safety. We also discuss several distinctive advantages of banked third party virus-specific T-cells selected on the basis of their HLA restriction, particularly in the treatment of Rituximab-non-responsive EBV+ lymphomas and drug refractory CMV infections complicating HLA non-identical transplants.