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PURPOSE: The objective was to predict proliferative diabetic retinopathy (PDR) in non-Hispanic Black (NHB) and Latino (LA) patients by applying machine learning algorithms to routinely collected blood and urine laboratory results. METHODS: Electronic medical records of 1124 type 2 diabetes patients treated at the Bronxcare Hospital eye clinic between January and December 2019 were analysed. Data collected included demographic information (ethnicity, age and sex), blood (fasting glucose, haemoglobin A1C [HbA1c] high-density lipoprotein [HDL], low-density lipoprotein [LDL], serum creatinine and estimated glomerular filtration rate [eGFR]) and urine (albumin-to-creatinine ratio [ACR]) test results and the outcome measure of retinopathy status. The efficacy of different machine learning models was assessed and compared. SHapley Additive exPlanations (SHAP) analysis was employed to evaluate the contribution of each feature to the model's predictions. RESULTS: The balanced random forest model surpassed other models in predicting PDR for both NHB and LA cohorts, achieving an AUC (area under the curve) of 83%. Regarding sex, the model exhibited remarkable performance for the female LA demographic, with an AUC of 87%. The SHAP analysis revealed that PDR-related factors influenced NHB and LA patients differently, with more pronounced disparity between sexes. Furthermore, the optimal cut-off values for these factors showed variations based on sex and ethnicity. CONCLUSIONS: This study demonstrates the potential of machine learning in identifying individuals at higher risk for PDR by leveraging routine blood and urine test results. It allows clinicians to prioritise at-risk individuals for timely evaluations. Furthermore, the findings emphasise the importance of accounting for both ethnicity and sex when analysing risk factors for PDR in type 2 diabetes individuals.
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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.
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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.
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Neoplasias da Mama/genética , Fator de Crescimento Transformador beta1/genética , Adulto , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Pessoa de Meia-Idade , Paquistão/epidemiologia , Polimorfismo de Nucleotídeo ÚnicoRESUMO
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.
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Arginina/análogos & derivados , Pós-Menopausa/sangue , Pré-Menopausa/sangue , Adulto , Arginina/sangue , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Paquistão/epidemiologiaRESUMO
PURPOSE: To investigate predictors of success, visual outcomes, and complications of intravitreal ocriplasmin for the treatment of symptomatic vitreomacular adhesion in a clinical care setting. METHODS: Retrospective chart review of 49 consecutive eyes of 47 patients who received intravitreal ocriplasmin. Spectral domain optical coherence tomography scans were examined for vitreomacular traction (VMT) release, full-thickness macular hole (FTMH) closure, and other changes in retinal anatomy. RESULTS: Pharmacologic VMT release occurred in 41% of eyes; positive predictors included age ≤75 years (P = 0.001), phakic status (P = 0.016), VMT width ≤750 µm (P = 0.001), and absence of retinal comorbidities (P = 0.035). Pharmacologic FTMH closure occurred in 25% of cases; positive predictors included successful VMT release (P = 0.042), better preinjection best-corrected visual acuity (P = 0.036), and smaller FTMH aperture width (P = 0.033). Eyes that achieved VMT release and did not undergo surgery attained significant improvement in best-corrected visual acuity (P = 0.015). Complications included subfoveal lucency (33%), ellipsoid zone disruption (33%), and FTMH base enlargement (75%). Only FTMH base enlargement resulted in worse visual outcomes (P = 0.024). Subgroup analysis of 14 eyes with ideal characteristics (all positive predictors listed above) yielded a 93% VMT release rate. CONCLUSION: Proper case selection may facilitate successful pharmacologic vitreolysis with ocriplasmin, improve visual outcomes, and minimize potential complications.
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Fibrinolisina/administração & dosagem , Fragmentos de Peptídeos/administração & dosagem , Perfurações Retinianas/tratamento farmacológico , Tomografia de Coerência Óptica/métodos , Acuidade Visual , Descolamento do Vítreo/tratamento farmacológico , Idoso , Feminino , Seguimentos , Humanos , Injeções Intravítreas , Masculino , Perfurações Retinianas/diagnóstico , Estudos Retrospectivos , Aderências Teciduais/diagnóstico , Aderências Teciduais/tratamento farmacológico , Resultado do Tratamento , Descolamento do Vítreo/diagnósticoRESUMO
We conducted a phase I trial of allogeneic T cells sensitized in vitro against a pool of pentadecapeptides (15-mer peptides) spanning the sequence of CMVpp65 for adoptive therapy of 17 allogeneic hematopoietic cell transplant recipients with cytomegalovirus (CMV) viremia or clinical infection persisting despite prolonged treatment with antiviral drugs. All but 3 of the patients had received T cell-depleted transplants without graft-versus-host disease (GVHD) prophylaxis with immunosuppressive drugs after transplantation. The CMVpp65-specific T cells (CMVpp65CTLs) generated were oligoclonal and specific for only 1 to 3 epitopes, presented by a limited set of HLA class I or II alleles. T cell infusions were well tolerated without toxicity or GVHD. Of 17 patients treated with transplant donor (n = 16) or third-party (n = 1) CMVpp65CTLs, 15 cleared viremia, including 3 of 5 with overt disease. In responding patients, the CMVpp65CTLs infused consistently proliferated and could be detected by T cell receptor Vß usage in CMVpp65/HLA tetramer + populations for period of 120 days to up to 2 years after infusion. Thus, CMVpp65CTLs generated in response to synthetic 15-mer peptides of CMVpp65 are safe and can clear persistent CMV infections in the post-transplantation period.
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Infecções por Citomegalovirus , Citomegalovirus/imunologia , Transplante de Células-Tronco Hematopoéticas , Transfusão de Linfócitos , Peptídeos/imunologia , Fosfoproteínas/imunologia , Linfócitos T , Doadores de Tecidos , Proteínas da Matriz Viral/imunologia , Viremia , Idoso , Aloenxertos , Criança , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/patologia , Infecções por Citomegalovirus/terapia , Feminino , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/patologia , Doença Enxerto-Hospedeiro/prevenção & controle , Neoplasias Hematológicas/imunologia , Neoplasias Hematológicas/patologia , Neoplasias Hematológicas/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeos/farmacologia , Fosfoproteínas/farmacologia , Linfócitos T/imunologia , Linfócitos T/patologia , Linfócitos T/transplante , Proteínas da Matriz Viral/farmacologia , Viremia/imunologia , Viremia/patologia , Viremia/terapiaRESUMO
Human herpesvirus 6B (HHV-6B) is a ubiquitous pathogen with frequent reactivation observed in immunocompromised patients such as BM transplant (BMT) recipients. Adoptive immunotherapy is a promising therapeutic avenue for the treatment of opportunistic infections, including herpesviruses. While T-cell immunotherapy can successfully control CMV and EBV reactivations in BMT recipients, such therapy is not available for HHV-6 infections, in part due to a lack of identified protective CD8(+) T-cell epitopes. Our goal was to identify CD8(+) T-cell viral epitopes derived from the HHV-6B immediate-early protein I and presented by common human leukocyte Ag (HLA) class I alleles including HLA-A*02, HLA-A*03, and HLA-B*07. These epitopes were functionally tested for their ability to induce CD8(+) T-cell expansion and kill HHV-6-infected autologous cells. Cross-reactivity of specific HHV-6B-expanded T cells against HHV-6A-infected cells was also confirmed for a conserved epitope presented by HLA-A*02 molecule. Our findings will help push forward the field of adoptive immunotherapy for the treatment and/or the prevention of HHV-6 reactivation in BMT recipients.
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Linfócitos T CD8-Positivos/imunologia , Epitopos de Linfócito T/imunologia , Antígeno HLA-A2/imunologia , Antígeno HLA-A3/imunologia , Antígeno HLA-B7/imunologia , Herpesvirus Humano 6/imunologia , Proteínas Imediatamente Precoces/imunologia , Adolescente , Transferência Adotiva , Adulto , Animais , Linfócitos T CD8-Positivos/patologia , Proliferação de Células/genética , Epitopos de Linfócito T/genética , Feminino , Antígeno HLA-A2/genética , Antígeno HLA-A3/genética , Antígeno HLA-B7/genética , Herpesvirus Humano 6/genética , Humanos , Proteínas Imediatamente Precoces/genética , Imunidade Celular/genética , Masculino , Camundongos , Camundongos Transgênicos , Pessoa de Meia-Idade , Infecções por Roseolovirus/genética , Infecções por Roseolovirus/imunologia , Infecções por Roseolovirus/patologia , Infecções por Roseolovirus/terapiaRESUMO
The Wilms tumor protein (WT-1) is widely recognized as a tumor antigen that is expressed differentially by several malignancies. However, WT-1 peptides known to induce tumoricidal T cells are few. In the present study, we evaluated T-cell responses of 56 healthy donors to in vitro sensitization with autologous APCs loaded with a pool of overlapping 15-mer peptides spanning the sequence of WT-1. Thereafter, we mapped the WT-1 peptides eliciting responses in each individual, defined the immunogenic peptides, and identified their presenting HLA alleles. We report 41 previously unreported epitopes of WT-1: 5 presented by class II and 36 by class I alleles, including 10 that could be presented by more than 1 class I allele. IFNγ(+) T cells responding to 98% of the class I and 60% of the class II epitopes exhibited HLA-restricted cytotoxicity against peptide-loaded targets. T cells specific for 36 WT-1 peptides were evaluable for leukemocidal activity, of which 27 (75%) lysed WT-1(+) leukemic targets sharing their restricting HLA allele. Each epitope identified induced T-cell responses in most donors sharing the epitopes' presenting allele; these responses often exceeded responses to flanking peptides predicted to be more immunogenic. This series of immunogenic epitopes of WT-1 should prove useful for immunotherapies targeting WT-1(+) malignancies.
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Epitopos de Linfócito T/imunologia , Antígenos HLA/imunologia , Leucemia/imunologia , Peptídeos/imunologia , Linfócitos T/imunologia , Proteínas WT1/imunologia , Alelos , Sequência de Aminoácidos , Linhagem Celular Tumoral , Mapeamento de Epitopos , Antígenos HLA/genética , Humanos , Leucemia/genética , Dados de Sequência Molecular , Peptídeos/química , Linfócitos T Citotóxicos/imunologia , Células Tumorais Cultivadas , Proteínas WT1/químicaRESUMO
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.
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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.
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Infecções por Citomegalovirus , Transplante de Células-Tronco Hematopoéticas , Humanos , Criança , Citomegalovirus , Viremia/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Infecções por Citomegalovirus/terapia , Infecções por Citomegalovirus/etiologia , Linfócitos T CD8-PositivosRESUMO
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.
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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.
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Infecções por Citomegalovirus , Transplante de Células-Tronco Hematopoéticas , Alelos , Linfócitos T CD8-Positivos , Infecções por Citomegalovirus/terapia , Epitopos , Humanos , Epitopos ImunodominantesRESUMO
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.
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Sarcoma Sinovial , Antígenos de Neoplasias/metabolismo , Biomarcadores/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Humanos , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/metabolismo , Sarcoma Sinovial/genética , Sarcoma Sinovial/patologia , Sarcoma Sinovial/terapia , Microambiente TumoralRESUMO
Adoptive transfer of virus-specific T cells can treat infections complicating allogeneic hematopoietic cell transplants. However, autologous APCs are often limited in supply. In this study, we describe a panel of artificial APCs (AAPCs) consisting of murine 3T3 cells transduced to express human B7.1, ICAM-1, and LFA-3 that each stably express one of a series of six common HLA class I alleles. In comparative analyses, T cells sensitized with AAPCs expressing a shared HLA allele or autologous APCs loaded with a pool of 15-mer spanning the sequence of CMVpp65 produced similar yields of HLA-restricted CMVpp65-specific T cells; significantly higher yields could be achieved by sensitization with AAPCs transduced to express the CMVpp65 protein. T cells generated were CD8(+), IFN-gamma(+), and exhibited HLA-restricted CMVpp65-specific cytotoxicity. T cells sensitized with either peptide-loaded or transduced AAPCs recognized epitopes presented by each HLA allele known to be immunogenic in humans. Sensitization with AAPCs also permitted expansion of IFN-gamma(+) cytotoxic effector cells against subdominant epitopes that were either absent or in low frequencies in T cells sensitized with autologous APCs. This replenishable panel of AAPCs can be used for immediate sensitization and expansion of virus-specific T cells of desired HLA restriction for adoptive immunotherapy. It may be of particular value for recipients of transplants from HLA-disparate donors.
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Alelos , Citomegalovirus/imunologia , Antígenos de Histocompatibilidade Classe I/genética , Epitopos Imunodominantes/imunologia , Imunoterapia Adotiva , Ativação Linfocitária/imunologia , Fosfoproteínas/imunologia , Linfócitos T Citotóxicos/transplante , Proteínas da Matriz Viral/imunologia , Animais , Células Cultivadas , Epitopos de Linfócito T/imunologia , Antígenos HLA-A/genética , Antígeno HLA-A2 , Antígeno HLA-A24 , Antígeno HLA-A3 , Antígenos HLA-B/genética , Antígeno HLA-B7 , Antígeno HLA-B8 , Antígenos de Histocompatibilidade Classe I/biossíntese , Humanos , Epitopos Imunodominantes/administração & dosagem , Camundongos , Células NIH 3T3 , Fosfoproteínas/administração & dosagem , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/transplante , Subpopulações de Linfócitos T/virologia , Linfócitos T Citotóxicos/imunologia , Linfócitos T Citotóxicos/virologia , Proteínas da Matriz Viral/administração & dosagemRESUMO
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.
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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.
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Cálculos Renais/cirurgia , Nefrolitotomia Percutânea , Idoso , Transfusão de Sangue , Endoscopia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nefrolitotomia Percutânea/efeitos adversos , Paquistão , Complicações Pós-Operatórias , Estudos Retrospectivos , Resultado do TratamentoRESUMO
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.
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Cálculos Renais , Litotripsia , Adulto , Humanos , Cálculos Renais/diagnóstico por imagem , Cálculos Renais/terapia , Nomogramas , Estudos Prospectivos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
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.
Assuntos
Antivirais/administração & dosagem , Retinite por Citomegalovirus/tratamento farmacológico , Citomegalovirus/imunologia , Infecções Oculares Virais/tratamento farmacológico , Imunoterapia Adotiva/métodos , Linfócitos T Citotóxicos/imunologia , Acuidade Visual , Adulto , Idoso , Anticorpos Antivirais/análise , Retinite por Citomegalovirus/imunologia , Retinite por Citomegalovirus/virologia , Infecções Oculares Virais/imunologia , Infecções Oculares Virais/virologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
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.