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Desensitization allows successful transplantation of patients with a positive crossmatch (PXM) against their live donor. We evaluated outcomes following PXM renal transplant despite failure to convert to negative flow cytometric crossmatch (FCXM) after desensitization. Patients that underwent desensitization before PXM transplant between 1/1/00 and 11/1/11 were identified for analysis. Patients who received a transplant despite failure to convert to negative FCXM were identified as the not converted group. Patients who converted to negative FCXM after desensitization comprised the converted group control arm. 108 patients were desensitized before PXM transplant, (not converted group=42; converted group=66). Mean eGFR was comparable between groups at all time points, and 3-year eGFR was 57.8 mL/min vs. 57.1 mL/min, p=0.91. Patients with eGFR < 30mL/min at 3 years did not differ significantly (28% vs. 14%, p=0.15). Biopsy-proven rejection rates were numerically higher within the not converted group for each type of rejection and time point, but the values did not differ significantly. Opportunistic infections rates were comparable. Patient survival (95% vs. 91%) and death-censored allograft survival (84% vs. 95%, p=0.07) were similar between arms at 3 years post-transplant.

Background: In sickle cell anemia (SCA), compromise of the renal vasculature due to sickled red cells has been recognized. Objectives: To assess the renal function and blood pressure pattern in children with sickle cell anaemia (SCA) presenting in a tertiary institution. Method: A cross-sectional study of patients with sickle cell anaemia (SCA) over six months involving the use of questionnaires, general physical examination, blood pressure, investigations for haemoglobin genotype, urinalysis, serum creatinine, screening for hepatitis B and HIV. Results: 51 children with SCA were seen. The prevalence of impaired renal function as defined by reduced eGFR <90mL/min/1.73m2 in this study was 27.5%, previous hospital admission and blood transfusion were associated with reduction in eGFR but blood pressure did not have significant correlation with the eGFR. The overall mean age at diagnosis of SCA was 4.09 ± 3.33 (years). Conclusion: Impaired renal function is a major comorbid condition in children with SCA. In countries/locations where there is no newborn screening for sickle cell disease, diagnosis is delayed, thus detecting impaired renal function may be delayed, therefore the need for early detection and management is imperative.Introduction

Background: In 2004 we started a phase II trial in non-small lung cancer (NSCLC), stage III, with erlotinib followed by a combination with a platinum-based doublet in unselected patients to identify molecular subgroups benefitting from an EGFR targeting approach. Patients and methods: Induction with erlotinib (E, 150 mg, d1-42) was followed by three cycles of gemcitabine (G, 1250 mg/m², d1+d8, q3w) and cisplatin (P, 80 mg/m², d1, q3w). Patients with at least stable disease after E were treated with a GP + E combination. Induction was followed by surgery and radiation. The trial was conducted as a prospective, multi-center, open label, exploratory phase II study to determine pathological response rate (pRR), as well as secondary endpoints disease free survival (DFS) and overall survival (OS). Results: Of 38 prescreened patients 16 were included in the main study. Due to slow recruitment the study had to be terminated early. Combination of E and GP was well tolerated, surgery was feasible after induction therapy in 12 of 16 patients, 7/12 (58%) patients had a major pathological response (MPR). Median overall survival for patients with MPR was 57.7 months (confidence interval (CI), 37.4 to 78.0; n = 7) and for patients without MPR 11.9 months (CI, 6.4 to 17.4; n = 5). 2/16 patients had an epidermal growth factor receptor (EGFR) mutation. Conclusion: Before discovery of distinct molecular mechanisms in NSCLC our study was an attempt to identify clinical and pathological subgroups that would benefit from E induction. Two patients with an EGFR mutation were identified. MPR was a predictor of long term disease free and overall survival.

Background: Glomerular hyperfiltration (GH) is a common feature of sickle cell nephropathy (SCN) starting at infancy and represents an early marker of incipient glomerular injury and renal dysfunction. Methods: This study aimed to determine the prevalence and correlates of GH among children (≤ 16 years) with sickle cell disease (SCD) at their steady state, recruited over 6 months at the Pediatric Outpatient Clinic in Al-Sadaqa General Teaching Hospital, Aden, Yemen. Glomerular filtration rate (eGFR) was estimated using the Schwartz formula. Data on clinical history, anthropometry, blood pressure (BP) and laboratory investigations were collected. Results: Of 101 children (mean age 7.2 ± 3.9 years), 65 (64.4%) were males. The prevalence of GH was observed in 36 (35.6%) children, who were significantly older (10.7 ± 3.2 vs. 5.2 ± 2.7 years, p < 0.001) and had a lower fetal Hb level (5 ± 3.3 vs. 9 ± 7.1, p = 0.02). All children were normotensive, but hyperfiltrating children showed significantly higher systolic (97.2 ± 7.3 vs. 89.7 ± 5.2 mmHg) and diastolic pressure (55.1 ± 5.0 vs. 49 ± 4.3 mmHg) (all p < 0.001). Among evaluated children, 25.7% had hyperfiltration alone, whereas 9.9% had an associated microalbuminuria (MA), and no significant difference in eGFR between those with and without MA (158.4 ± 33.7 vs. 160.7 ± 29.8 ml/min/173m2, p = 0.84). Conclusion: This study demonstrated a relatively high prevalence of GH in Yemeni children with SCD that increased with age. Recognition of hyperfiltration and other early markers of nephropathy in this population could help to develop renal protective strategies to prevent progressive loss of kidney function.

Background: There is enough evidence to suggest that vancomycin increases the risk of acute kidney injury (AKI) but the exact mechanism is not well understood. This study aims to understand the incidence of vancomycin-associated acute kidney injury (VA-AKI) among hospitalized patients and to identify the risk factors for VA-AKI. Methods: Patients aged 18 and above who received a minimum of 24 hours of intravenous vancomycin and who had serial creatinine measurements over a 13-month period were identified through electronic records. Patients with pre-existing AKI, or eGFR of less than 30ml/min, and patients with end stage kidney disease were excluded. Results were analyzed using t-test and Fisher’s test. A logistic regression model was used to identify the predictors for VA-AKI. Results: From the 598 patients who met the inclusion criteria, 70 developed AKI. Compared to those without AKI, patients with VA-AKI had higher mean serum vancomycin trough levels (22.6 mg/L vs. 14.6 mg/L), and a statistically significant longer duration of vancomycin use (6.7 vs. 5.2 days). Multivariate analysis revealed that serum vancomycin level of > 20 mg/L was associated with a six-fold increase in odds of VA-AKI when compared to those with vancomycin levels < 15 mg/L. The presence of hypotension, iodinated contrast use, and concomitant use of piperacillin-tazobactam were all associated with increased odds of VA-AKI. Conclusion: The incidence of VA-AKI in hospitalized patients with eGFR > 30 ml/min was 11.7%. Serum vancomycin levels of > 20 mg/L, hypotension and administration of iodinated contrast significantly increased the risk of VA-AKI. Piperacillin-tazobactam, when used with vancomycin, was noted to be an independent predictor of AKI, regardless of serum vancomycin trough levels, prompting a reevaluation of the safety of this widespread practice as empiric therapy. Close monitoring of kidney function, avoiding high serum vancomycin levels, maintaining hemodynamic stability, and avoiding unnecessary use of iodinated contrast seem to be essential for the prevention of VA-AKI.

Background: Currently there are three available formulations of tacrolimus in the United States; these include immediate-release capsules (TAC-IR), extended-release capsules (TAC-XL),and extended-release tablets (TAC-XR). Previous studies have demonstrated non-inferiority between the three formulations in terms of efficacy. The purpose of this study was to compare three formulations of tacrolimus (TAC) and assess differences in time within the therapeutic range (TTR) and variability in levels. Results: Renal transplant recipients from January 2013 to October 2017 were retrospectively identified for analysis. Deviation from standard TAC protocol or formulation changes excluded patients. The primary outcome compared percent TTR (TTR %) among 3 TAC formulations over the first 90 days post-transplant. TTR was calculated using the Rosendaal method. Secondary outcomes included differences in TAC levels, TAC dose, eGFR, rejection, patient and graft survival between the TAC formulations. TAC-XR demonstrated a significantly higher TTR % compared to TAC-IR and TAC-XL (62.8% vs. 53.3% vs. 60.9%, p = 0.048). In post-hoc analysis, TAC-XR had a higher TTR % compared to TAC-IR (p = 0.065), which approached statistical significance. Average TAC levels, weight-normalized TAC doses, median dose-normalized TAC levels, rejection rates, eGFR, and graft or patient survival were similar among groups. Conclusion: In the early transplant period, TTR was significantly different among the groups. TAC-XR demonstrated numerically superior time within the therapeutic range. Patient-specific factors such as race, obesity, genetic polymorphisms may impact this variability and clinical outcomes. Further analysis is necessary to understand the effect of each patient-specific factor on TAC exposure.

Chronic Kidney Disease (CKD) by definition is a disease characterized by irreversible elimination of renal function, which keeps propagating as corroborated by an estimated glomerular filtration rate (eGFR) of < 60 ml/min/1.73m2, the constant existence of presentation which pointed to Kidney injury (proteinuria, active sediments of urine, histological injury, structural aberrations or prior history with regards to Kidney transplantation) or both that are persistent for greaterthan 3 mths [1].

Non-small-cell lung cancer (NSCLC) accounts for 85% of lung cancer cases and is associated with different risk factors (smoking habits, gender, and age). In this scenario, many studies have been conducted to pursue improvement of survival, faster and better therapy response, reduced adverse events, and expanded available therapies and treatments against tumor resistance to drugs. These studies have focused on defining the most prevalent NSCLC biomarkers (EGFR, HER2, ALK, MET, ROS1, BRAF, KRAS G12C, HER3, NTRK, and NRG1) and their actionability. It is noteworthy that expressed kinase receptors can have overlapping mechanisms of activation of different pathways (JAK-STAT, MAPK, PI3K-AKT-mTOR, and PLC-c), which can lead to the same outcome of cell proliferation, migration, and survival resulting in increased tumor resistance to treatment. This review provides an overview of the latest findings regarding NSCLC treatment, emphasizing particular biomarkers and potential molecularly altered pathways implicated as targeted therapies. Additionally, it explores the clinical significance of the proposed treatments, their implication on progression-free survival, ongoing clinical trials, and their perspective of evolution so far.

Chronic Kidney Disease (CKD) is a significant public health issue with a rising prevalence globally. Diabetic kidney disease (DKD), a leading cause of CKD, necessitates improved biomarkers for early detection and effective management. Traditional markers such as serum creatinine, estimated glomerular filtration rate (eGFR), and albuminuria have notable limitations in sensitivity and specificity, especially for early detection. Fetuin-A, specifically its post-translationally modified form (PTM-Fetuin-A), has emerged as a potential novel biomarker for DKD. This study evaluates PTM-Fetuin-A in a cohort of Bulgarian patients with type 1 and type 2 diabetes, assessing its correlation with traditional markers such as albuminuria and eGFR. Significant correlations were observed between PTM-Fetuin-A and these indicators (e.g., Pearson’s r = 0.447, p = 0.025 for albuminuria), highlighting its ability to detect early kidney function decline. Furthermore, PTM-Fetuin-A demonstrated potential as a non-invasive tool for identifying normoalbuminuric DKD, addressing gaps left by conventional biomarkers. By offering additional prognostic value, PTM-Fetuin-A could improve the early diagnosis and clinical management of diabetic patients, reducing the burden of CKD.

Introduction: Pleomorphic Carcinoma (PC) is a subset of poorly differentiated non–small cell lung cancer that is diagnostically challenging because it is a rare malignancy of the lung. It shows varying dual-cell components; spindle or giant cells and epithelial cells.Method: We report a case of 68-year-old non-smoking female who presented with cough, fever, pain in the left side of chest & weight loss of recent onset and an abnormal shadow on her chest X-ray. Computed tomography of chest revealed a well defined heterogeneously enhancing cavitatory soft tissue lesion in the posterior basal segment of the left lower lobe with mediastinal lymphadenopathy.Results: Fine needle aspiration cytology& percutaneous lung biopsy confirmed poorly differentiated malignant tumor. Patient underwent a left lower lobectomy. A diagnosis of PC was confirmed after Immunohistochemistry (IHC). Mutation analysis revealed an EGFR exon 21 mutation within the tumor cells. The patient is on Gefitinib based chemotherapy and has remained disease-free for three years post-surgery.Conclusion: PC of the lung is a rare pathological entity. Definite diagnosis may only be made on a resected tumor along with the use of IHC. Surgical resection is the main modality of the treatment. Such rare cases should be documented to establish an optimal management plan and to provide a further insight to targeted therapy.