Impact of pre-transplant donor specific antibodies detected by Luminex with negative microlymphocytotoxicity assay and flow crossmatch in live-related renal transplant recipients.

INTRODUCTION/AIM: The Luminex assay, where beads are coated with a single HLA antigen, has been shown to detect HLA antibodies with more sensitivity and specificity as compared to microlymphocytotoxicity (CDC) assay and flow cross match (FCXM). We report the impact of low Mean Flourescence intensity (MFI) pre-transplant DSA by Luminex with negative CDC and FCXM on acute rejection, graft function, and survival. METHODS: In this retrospective study between January 2015 to December 2021, 45 recipients had pre-transplant anti-HLA donor-specific antibodies (DSAs) detected by Luminex. Two control groups of 45 patients each matched for age and gender, first with non-DSA HLA antibodies and second with no antibodies by Luminex were selected to compare outcomes with DSA group. RESULTS: In the DSA group of 45, 22 (48.8%) had class I (MFI mean 4043 ± 1909, range: 1096-7111), 20 (44.4%) class II (MFI mean 3601 ± 2310, range: 1031-9259), and 3 (6.6%) both class I (MFI mean 4746 ± 1922) and class II (MFI mean 3940 ± 2312) antibodies. Acute rejection episodes were reported in 15.6%, DSA group, 17.8% in non-DSA, and 24.4% in no antibody group (p = .538). Death censored graft survival at 1 and 5 years was 98% and 93% in DSA group, 100% and 95% in non-DSA and 93% and 85% in the no antibody group (p = .254). CONCLUSIONS: Patients with low MFI DSA pre-transplant, with a negative CDC and FCXM under ATG induction, have similar graft outcomes at 1 and 5 years when compared to non-DSA and no antibody groups.

HOGA1 gene pathogenic variants in primary hyperoxaluria type III: Spectrum of pathogenic sequence variants, and phenotypic association.

Primary hyperoxalurias (PH) are a group of rare heterogeneous disorders characterized by deficiencies in glyoxylate metabolism. To date, three genes have been identified to cause three types of PH (I, II, and III). The HOGA1 gene caused type III in around 10% of the PH cases. Disease-associated pathogenic variants have been reported from several populations and a comprehensive spectrum of these mutations and genotype-phenotype correlation has never been presented. In this study, we describe new cases of the HOGA1 gene pathogenic variants identified in our population. We report the first case of ESKD with successful kidney transplantation with 5 years of follow-up. Furthermore, a comprehensive overview of PH type III associated HOGA1 gene variants was carried out. Compiling the data from the literature, we reviewed 57 distinct HOGA1 gene pathogenic variants in 175 patients worldwide. The majority of reported variants are missense variants that predicted a loss of function mechanism as the underlying pathology. There has been evidence of the presence of founder mutations in several populations like Europeans, Ashkenazi Jews, Arab, and Chinese populations. No significant genotype-phenotype correlation was identified concerning the ages of onset of the disease and biochemical and metabolic parameters. Nephrocalcinosis was rare in patients with disease-associated variants. Most of the patients were presented with urolithiasis early in life; only five cases reported disease progression after the second decade of life. The establishment of impairment of renal function in 8% of all the reported cases makes this type a relatively severe form of primary hyperoxaluria, not a benign etiology as suggested previously.

Whipple's disease in renal transplant recipients: Management experience of seven cases from Pakistan.

INTRODUCTION: Whipple's disease (WD) is a rare multi-systemic disorder caused by actinomycetes, Tropheryma whipplei. It presents with weight loss, arthralgia, and diarrhea and may involve the heart, lung, or central nervous system. The use of immunosuppressive medications or underlying immunodeficiency states are associated risk factors. Six cases in transplant recipients have so far been reported worldwide. We describe our experience of WD in renal transplant recipients. METHODS: All renal transplant recipients who presented with diarrhea and were diagnosed with WD on duodenal biopsy from 2016 till 2019 were included. Their data regarding duration since transplantation, immunosuppressive therapy, symptoms, treatment response, and outcome were analyzed. RESULTS: Seven cases were diagnosed as WD based on duodenal biopsy, with histological findings of periodic acid Schiff-positive granules in macrophages. All were males. The most common symptoms were chronic diarrhea and weight loss. Average time since transplantation was 4.8 years. All patients were on azathioprine and everolimus. Clinical relapse or adverse effects was seen in five of seven patients treated with doxycycline and hydroxychloroquine which was discontinued. Trimethoprim/sulfamethoxazole for 1 year, with initial intravenous ceftriaxone in two patients, resulted in complete remission in all patients at a follow-up period averaging 1.5 years. CONCLUSION: WDs in renal transplant recipients most commonly presents as an intestinal disorder. Treatment of 1 year with trimethoprim/sulfamethoxazole has good response with complete remission at 1.5 years of follow up.

The efficacy of isoniazid prophylaxis in renal transplant recipients in a high tuberculosis burden country.

INTRODUCTION: Renal transplant recipients are at high risk of tuberculosis (TB). We started isoniazid (INH) prophylaxis of 1 year duration in all renal transplant recipients from April 2009. Our aim was to assess the incidence of TB on INH prophylaxis and its tolerability. METHODS: This was a retrospective observational study. The files of renal transplant recipients from April 2009 to December 2011 were reviewed till June 2015. We noted the incidence of TB, INH tolerability, and development of resistance. We compared the incidence of TB with the historical controls who never received the prophylaxis. RESULTS: A total of 910 patients were reviewed and followed up for 4.8 years. INH prophylaxis was completed by 825 (91%) patients. A total of 46 patients (5%) developed active TB as compared to 15% in the historical controls. The median time of TB diagnosis from transplantation was 2.8 years. In the first-year post transplant, out of total TB cases, 52% occurred in the historical controls whereas 13% occurred in study cohort. Around 67% had TB >2 years after transplant. Overall 1.43% had hepatotoxicity. There was a significant reduction in TB among those who completed prophylaxis to those who did not (p < 0.001). Of 14 cultures, one isolate was INH resistant (7%). CONCLUSION: INH prophylaxis was well tolerated. The incidence of TB decreased in the first 2 years. However there was a surge in TB cases 1 year after stopping INH therapy. We should consider prolonging the duration of INH prophylaxis in high TB burden countries in renal transplant recipients.

A case series of multidrug-resistant tuberculosis in renal transplant recipients: Challenges in management from a TB endemic country.

Multidrug-resistant tuberculosis (MDR-TB) is caused by Mycobacterium tuberculosis that is resistant to isoniazid and rifampicin (Rif). The use of immunosuppressive drugs in solid organ transplant recipients can increase the risk of TB. Management of MDR-TB is quite challenging in the general population with poor compliance owing to lengthy treatment duration and drug toxicities. New drugs as well as shorter regimen have been used to increase the likelihood of adherence. The experience of treating MDR-TB in the transplant recipients is limited. New drugs like bedaquiline, linezolid, clofazimine, and delamanid have rarely been used in transplant recipients. To the best of our knowledge, only 14 cases of MDR-TB in transplant population have been reported in the literature and no case from Pakistan, a high TB burden country. We are reporting our experience of treating 4 renal transplant recipients. We used new drug regimen and found many side effects. Treatment outcome was successful with complete cure in 3 of our patients, however one died of severe drug toxicity. The most worrisome drug interaction was between azathioprine and linezolid, with life-threatening thrombocytopenia. There was no graft dysfunction noted at the end of the therapy. The management of MDR-TB in transplant recipients is challenging; excellent coordination between transplant team and Infectious Diseases Physician for close monitoring and follow-up is needed.

Furunculosis and its complications: A cause of morbidity in renal transplant recipients: A retrospective observational study from Sindh Institute of Urology and Transplantation Karachi.

Furunculosis in renal transplant recipients may be associated with increased morbidity. With the aim to study the presentation, morbidity, and risk factors for furunculosis, this observational study was conducted at the Sindh Institute of Urology and Transplantation, between January to December 2014. All patients with furuncles or abscesses were included. The clinical presentation and risk factors were recorded. A morbidity scale of 0 and 1 was made on the basis of hospital stay for ≥7 days, bacteraemia, large abscesses and repeated furunculosis. Out of 38 patients, 29 (76%) had large abscesses and 9 (24%) had furuncles, with gluteal region being the most common site. Twelve (32%) had severe disease; 29 (76%) had morbidity scale of ≥1. High dose immunosuppression was significantly associated with severe disease while repeated furunculosis had significantly more risk factors. Furunculosis is a severe disease with high morbidity in renal transplant recipients and more studies are needed on skin colonisation and preventive strategies.

Overcoming the Immunological Barrier in Highly HLA Sensitized Renal Transplant Recipients - A Desensitization Experience from a Transplant Center in Pakistan.

Highly Human Leukocyte antigen sensitized patients have relatively fewer chances of being transplanted successfully and may remain dialysis dependent for a long time. In the last few years with the development of immunomodulatory therapies and advancements in immunological investigations, the chance s of transplantation in these sensitized patients have improved. Desensitization therapies in these patients include plasma exchange, intravenous immune globulins and immunomodulatory agents such as rituximab and bortezomib. These agents used together in desensitization protocols across the world have shown encouraging results in highly Human Leukocyte Antigen sensitized recipients awaiting renal transplant. We used a desensitization protocol using rituximab followed by bortezomib with concurrent plasma exchange sessions and Intravenous Immune Globulins. Our aim was to assess improvement in renal function and quality of life in these patients after desensitization and renal transplantation. To the best of our knowledge, this is the first account of desensitization prior to renal transplantation from Pakistan.

Living donor risk model for predicting kidney allograft and patient survival in an emerging economy.

AIM: Living donor kidney is the main source of donor organs in low to middle income countries. We aimed to develop a living donor risk model that predicts graft and patient survival in an emerging economy. METHODS: We used data from the Sindh Institute of Urology and Transplantation (SIUT) database (n = 2283 recipients and n = 2283 living kidney donors, transplanted between 1993 and 2009) and conducted Cox proportional hazard analyses to develop a composite score that predicts graft and patient survivals. RESULTS: Donor factors age, creatinine clearance, nephron dose (estimated by donor/recipient body weight ratio) and human leukocyte antigen (HLA) match were included in the living donor risk model. The adjusted hazard ratios (HRs) for graft failures among those who received a kidney with living donor scores (reference to donor score of zero) of 1, 2, 3 and 4 were 1.14 (95%CI: 0.94-1.39), 1.24 (95%CI:1.03-1.49), 1.25 (95%CI:1.03-1.51) and 1.36 (95%CI:1.08-1.72) (P-value for trend =0.05). Similar findings were observed for patient survival. CONCLUSIONS: Similar to findings in high income countries, our study suggests that donor characteristics such as age, nephron dose, creatinine clearance and HLA match are important factors that determine the long-term patient and graft survival in low income countries. However, other crucial but undefined factors may play a role in determining the overall risk of graft failure and mortality in living kidney donor transplant recipients.

The association of urinary interferon-gamma inducible protein-10 (IP10/CXCL10) levels with kidney allograft rejection.

BACKGROUND: Interferon-gamma inducible protein-10 (IP-10/CXCL10) is a chemokine involved in the alloimmune response against kidney allograft. We aimed to investigate the association of urinary CXCL10 protein levels with rejection in renal transplant patients. METHODS: A total of 273 urine samples from (biopsy-proven) rejection and non-rejection patients and controls were included in this study. CXCL10 levels were analyzed for association with rejection. RESULTS: The data showed statistically significant differences in the CXCL10 levels between rejection vs. non-rejection (p < 0.001). Among the rejection groups, statistically significant differences for CXCL10 levels were found between ACR vs. NAD (p < 0.001), ACR vs. BLR (p = 0.019) and AVR vs. NAD (p = 0.009). Receiver Operating Characteristic (ROC) curve analysis of CXCL10 showed an area under the curve (AUC) of 0.74 with 72% sensitivity and 71% specificity at 27.5 pg/ml between rejection and non-rejection group. Kaplan-Meier curve analysis among different levels of CXCL10 showed a better rejection-free graft survival in patients with <100 pg/ml when compared to >200 pg/ml (38 ± 6 vs. 12 ± 1.0 weeks; log-rank p < 0.001) and 100-200 pg/ml (38 ± 6 vs. 22 ± 9 weeks; log-rank p = 0.442) concentration. CONCLUSION: The results indicate significantly increased levels of CXCL10 protein in the urine at the time of allograft rejection. This association of urinary CXCL10 protein levels with rejection could provide an additional tool for the non-invasive monitoring of allograft rejection.

Monocyte Chemoattractant Protein-1 (MCP-1/CCL2) Levels and Its Association with Renal Allograft Rejection.

BACKGROUND: CCL2 is a chemoattractant for monocytes/macrophages, T cells, and natural killer cells. It is shown to be involved in the immunological responses against renal allograft. This study was conducted to access the role of urinary CCL2 expression in predicting the rejection episodes in renal transplant patients. METHOD: A total of 409 urine samples included in this study. The samples were consisted of (a) biopsy-proven graft rejection (n = 165); (b) non-rejection (n = 93); (c) non-biopsy stable-graft (n = 42), and (d) healthy renal donors (n = 109). The samples were quantified for the CCL2 using the MCP-1/CCL2 ELISA kit. The data were analyzed using the Statistical Package for Social Sciences (SPSS®) and MedCalc® statistical software. RESULTS: Results showed that the CCL2 levels were significantly increased in rejection group when compared with the non-rejection, stable-graft, and control, P < 0.05. The receiver operating curve's characteristics illustrated that the urinary CCL2 level is a good predictor for graft rejection, with an area under the curve of 0.81 ± 0.03 with optimum sensitivity and specificity of 87% and 62%, respectively, at a cut-off value of 198 pg/mL. Kaplan-Meier curve also showed better cumulative rejection-free graft survival time in group with less than 198 pg/mL of CCL2 as compared to those with expression levels of more than 198 pg/mL (30 weeks vs. 3 weeks; log-rank test, P < 0.001). CONCLUSION: In our study, noninvasive investigation of CCL2 levels in urine has showed potential to predict rejection episodes. It is suggested that the CCL2, with others markers, may help in early detection and monitoring of graft rejection episodes.

Plasma cell-rich acute rejections in living-related kidney transplantation: a clinicopathological study of 50 cases.

BACKGROUND: Acute rejections (ARs) with plasma cell-rich infiltrates (PCARs) are associated with poor outcomes. PATIENTS AND METHODS: Between February 2012 and December 2013, 1630 dysfunctional renal graft biopsies were performed. Of these, 50 (3%) showed PCAR. ARs with >10% plasma cells were defined as PCAR. Human leukocyte antigen (HLA) antibodies were tested in historic sera and at the time of PCAR. Treatment for PCAR comprised methylprednisolone, antithymocyte globulin, plasmapheresis, and anti-CD20 antibody. RESULTS: Of the 1630 dysfunctional biopsies, 50 (3%) had PCAR which occurred 3.1 ± 2.55 yr after transplant. The percentage of plasma cells was 28.8 ± 11.7, and CD138, 29.0 ± 12.4. Donor-specific antibodies (DSAs) were found in 32 (64%) overall, Class I in 15% and Class II in 65%. Post-treatment serum creatinine improved from 3.80 ± 2.59 to 2.66 ± 1.59 mg/dL in DSA positive (p < 0.003) and from 2.59 ± 1.09 to 2.08 ± 0.86 mg/dL in DSA negative (p < 0.008). One- and two-yr graft survival after PCAR was 72%, 42% in the DSA-positive vs. 89%, 82% in the DSA-negative group, respectively (p = 0.071). CONCLUSIONS: Our results show that PCAR occurs late after transplant and in many cases is associated with DSAs. Graft outcome was poor when PCAR was associated with DSAs.

Chest X-ray: an unfair screening tool.

BACKGROUND: Chest radiography is considered as the sole screening tool for chest pathologies as prerequisite for overseas employment during their medical examinations. The aim was to evaluate the role of CXR as a screening tool in the diagnosis of different lung pathologies in general and TB in particular. METHODS: In this descriptive case series, reports of 63,648 Pakistani candidates, who took chest X-rays during medical screening for employment abroad under the rules of Gulf Coordination Council (GCC), were analysed. The reports were collected over a three year period (2008-2011). All the candidates were apparently healthy males of ages ranging between 18-50 years with average age of 27.4 years. RESULTS: Out of 63,648 candidates examined over a three year period, 1368 (2.15%) were declared unfit on the basis of CXR. There were 359 cases of calcified granulomas, 318 of costophrenic angle obliteration, 174 of apical scaring; 144 of pulmonary scars, 123 of fibrocalcific lesion, 82 of soft shadows in lung, 51 of nodular lung shadows, 42 of lymphadenopathy, 30 of pleural effusion, 26 of interstitial lung shadow and 19 of calcification. A closer scrutiny of these cases revealed that over 90% of the CXRs of the candidates declared as having lung pathologies displayed scars rather than active disease. CONCLUSION: A normal CXR by itself, neither categorically rules out problems in the chest nor does any finding in it confirm some disease. Unfitness on the basis of CXR alone, unless substantiated by further investigation, is questionable to say the least.

Knowledge and Attitudes Regarding Depression Among a Sample of Iraqi Non-Psychiatric Nurses: A Cross-Sectional Study.

Introduction: Nurses, comprising the largest profession in healthcare, play a significant role in the identification and management of mental health disorders in hospitals. Objectives: The study assessed the knowledge and attitudes of non-psychiatric nurses and their encounters with depressive patients throughout their careers. Methods: This was a cross-sectional descriptive study with 400 non-psychiatric nurses from different hospitals in the Kurdistan Region of Iraq during October and November 2022. The independent Student's t-test, one-way analysis of variance, and binary logistic regression were used to assess possible factors associated with knowledge and attitude toward depression. Results: In this study, 400 non-psychiatric nurses were examined, revealing a mean age of 31.57 ± 8.59 years. Their mean scores for knowledge and attitude toward depression were 5.41 out of a maximum of 11 (standard deviation 1.15) and 5.15 out of 18 (standard deviation 1.83), respectively. Notably, differences in mean knowledge scores were observed concerning participant marital status (P = .044), while disparities in mean attitude scores are related to participant gender (P = .010). Upon binary logistic regression analysis, none of the independent variables exhibited an association with good knowledge. Nevertheless, gender emerged as a significant factor influencing attitude toward depression (odds ratio: 0.51; 95% confidence interval: 0.30-0.86; P = .012). Subsequently, in the multivariate binary logistic regression analysis, gender sustained significance (adjusted odds ratio: 0.573; 95% confidence interval: 0.348-0.942; P = .028) as the key variable impacting attitudes toward depression among non-psychiatric nurses. Conclusion: Based on the results of this study, nurses have insufficient awareness and management skills for depression. It has been experienced and reported that nurses lack knowledge and an attitude toward depression management. The study highlights a significant gap in nurses' skills for managing depression, urging the immediate improvement of training programs. Customizing these programs to enhance nurses' abilities in identifying and managing depression is crucial.

Comparison of resistive index and shear-wave elastography in the evaluation of chronic kidney allograft dysfunction.

BACKGROUND: Detection of early chronic changes in the kidney allograft is important for timely intervention and long-term survival. Conventional and novel ultrasound-based investigations are being increasingly used for this purpose with variable results. AIM: To compare the diagnostic performance of resistive index (RI) and shear wave elastography (SWE) in the diagnosis of chronic fibrosing changes of kidney allograft with histopathological results. METHODS: This is a cross-sectional and comparative study. A total of 154 kidney transplant recipients were included in this study, which was conducted at the Departments of Transplantation and Radiology, Sindh Institute of Urology and Transplan tation, Karachi, Pakistan, from August 2022 to February 2023. All consecutive patients with increased serum creatinine levels and reduced glomerular filtration rate (GFR) after three months of transplantation were enrolled in this study. SWE and RI were performed and the findings of these were evaluated against the kidney allograft biopsy results to determine their diagnostic utility. RESULTS: The mean age of all patients was 35.32 ± 11.08 years. Among these, 126 (81.8%) were males and 28 (18.2%) were females. The mean serum creatinine in all patients was 2.86 ± 1.68 mg/dL and the mean estimated GFR was 35.38 ± 17.27 mL/min/1.73 m2. Kidney allograft biopsy results showed chronic changes in 55 (37.66%) biopsies. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of SWE for the detection of chronic allograft damage were 93.10%, 96.87%%, 94.73%, and 95.87%, respectively, and the diagnostic accuracy was 95.45%. For RI, the sensitivity, specificity, PPV, and NPV were 76.92%, 83.33%, 70.17%, and 87.62%, respectively, and the diagnostic accuracy was 81.16%. CONCLUSION: The results from this study show that SWE is more sensitive and specific as compared to RI in the evaluation of chronic allograft damage. It can be of great help during the routine follow-up of kidney transplant recipients for screening and early detection of chronic changes and selecting patients for allograft biopsy.

Risk Factors and Outcome of Gram-Negative Bloodstream Infection in Living-Donor Renal Transplant Recipients: A Case-Control Study From Pakistan.

OBJECTIVES: Gram-negative rods are the most common cause of bloodstream infection in renal transplant recipients. Acute rejection, urologic abnormalities, and ureteral stents are risk factors. Graft dysfunction is independently associated with gram-negative rod bloodstream infection. Our aim is to investigate the incidence, risk factors, and outcome among living donor renal transplant recipients from Pakistan. MATERIALS AND METHODS: In this case-control study, we reviewed the medical records until June 2021 of renal transplant recipients seen from 2015 to 2019 for gram negative bacteremia. For every case, controls were matched by age, date of transplant, and sex. Demographics, risk factors, graft function, and mortality were compared. Clinical features, immunosuppression, source of blood stream infection, and microbiology were noted in cases. RESULTS: Of 1677 renal transplant recipients, 44 developed gram negative bacteremia. The incidence was 5.9 per 1000 person-years. Median time since transplant was 5 months. The most common source was urinary tract infection. On univariate analysis, antithymocyte globulin, urinary tract infection, and recurrent urinary tract infections were associated with gram negative bacteremia. On multivariate analysis, urinary tract infection (adjusted odds ratio = 3.46; 95% CI, 1.27-9.37) and recurrent urinary tract infections (adjusted odds ratio = 4.03; 95% CI, 1.15-14.15) were significant risk factors. We found no difference in 30-day mortality and estimated glomerular filtration rate on last follow-up between cases and controls. Kaplan-Meier survival curves showed significant differences in graft survival in patients with gram negative bacteremia. Escherichia coli was the most common organism, with 75% ceftriaxone and 13% imipenem resistance. CONCLUSIONS: The most significant risk factor for gram negative rod bloodstream infection was recurrent urinary tract infections. Timely treatment and prevention of recurrent urinary tract infections areimperative for prevention of gram negative bacteremia.

Recurrent urinary tract infection by Burkholderia cepacia in a live related renal transplant recipient.

Burkholderia cepacia is high virulent organism usually causing lower respiratory tract infections especially in Cystic fibrosis (CF) patients and post lung transplant. Urinary tract infections with Burkholderia cepacia have been associated after bladder irrigation or use of contaminated hospital objects. Post renal transplant urinary tract infection (UTI) is the most common infectious complications. Recurrent urinary tract infection with Burkholderia cepacia is a rare finding. Complete anatomical evaluation is essential in case recurrent urinary tract infections (UTI) after renal transplant. Vesico-ureteric reflux (VUR) and neurogenic urinary bladder was found to be important risk factors.

A retrospective study of cardiotoxicities induced by 5-fluouracil (5-FU) and 5-FU based chemotherapy regimens in Pakistani adult cancer patients at Shaukat Khanum Memorial Cancer Hospital & Research Center.

OBJECTIVE: To study cardiotoxicities, especially bradycardia in cancer patients treated with 5-Fluouracil and 5-Fluouracil based chemotherapy regimens in Pakistani population. METHODS: Data was extracted from the medical records of all diagnosed cancer patients at Shaukat Khanum Memorial Cancer Hospital and Research Center registered between January 2002 and December 2004 receiving 5- Fluouracil based chemotherapy regimens. The data was analysed retrospectively, including electrocardiogram and cardiac markers. Pearson's Correlation coefficient was calculated to see any possible correlation between 5-Fluouracil alone and 5-Fluouracil based regimens and cardiotoxicity, and other variables. RESULTS: Symptomatic cardiotoxicity was observed in 60 (19.93%) out of 301 patients whose cases were part of the study. Bradycardia was the most common cardiotoxicity and was observed in 36 (11.96%) patients. Nine (2.99%) mortalities were also observed. The incidence of cardiotoxicity was not significantly different between the patients with and without pre-existing cardiovascular disease (p = 0.095) and having negative correlation - 0.305. Cardiotoxicities were more common with Continuous Infusion (CI) of 5-Fluouracil, radiotherapy concurrent with 5-Fluouracil and when 5-Fluouracil was used in combination with Cisplatinum (CDDP). CONCLUSION: Cardiotoxicities were more prevalent when 5-Fluouracil was used along with concurrent radiotherapy and with Cisplatinum and when administered in continuous infusion pattern. Hence, 5-Fluouracil and 5-Fluouracil based chemotherapy regimens cause cardiotoxicities, especially bradycardia, in a significant number of cancer patients in Pakistani population.

Chronic necrotizing pulmonary aspergillosis in a renal transplant recipient.

Chronic necrotizing pulmonary aspergillosis is a chronic semi invasive pulmonary disease. It is an uncommon disease and has never been reported in transplant recipients. We report a case of chronic necrotizing pulmonary aspergillosis in a renal transplant recipient.

Use of sofosbuvir based regimen in patients with end-stage renal disease and chronic hepatitis C; an open label, non-randomized, single arm, single center study from Pakistan.

AIM: we aimed to determine the virological response and safety of Sofosbuvir-based direct-acting antiviral agents (DAAs) in chronic hepatitis C (CHC) patients on long-term hemodialysis (HD). BACKGROUND: With the advent of interferon-free DAAs, the treatment of CHC has been revolutionized. Pakistan is among the countries where novel sofosbuvir (SOF)-free antiviral agents are not available. METHODS: This non-randomized, single-arm, open-label study enrolled all HD patients with chronic HCV infection after informed consent. They were treated with SOF in combination with Ribavirin (RBV) with either interferon (IFN group) or daclatasvir (DAC group), with the virological response assessed according to standard guidelines. Data were analyzed using SPSS version 20.00. RESULTS: Out of 133 patients, the majority (72.9%) were males with the mean age of 31.92 ± 9.88 years. Most patients (50.3%) had HCV genotype (GN) 1, followed by GN 3 in 42.9%, 4 in 1.48% and 2 in 0.7%, while mix GN was documented in 6 (4.4%) patients. Among these, 60 (45.1 %) patients received standard SOF, IFN, and RBV (IFN group) and 73 (54.9 %) received SOF, DAC and RBV (DAC group). End of treatment and sustained virological response at 12 weeks post-treatment were achieved in 133 (100%) and 129 (97 %) patients, respectively. The adverse effects were anemia in 58 (43.6 %) patients and elevated alanine transaminases in 11 (8.1%) patients. CONCLUSION: SOF in combination with either IFN or DAC is an equally efficacious and effective treatment regimen for patients on maintenance HD, especially in resource-poor countries.