The impact of Treosulfan-based conditioning for inborn errors of immunity: Is dose monitoring crucial?

INTRODUCTION: In children with inborn errors of immunity (IEI) who will receive a hematopoietic stem cell transplant (HSCT) treosulfan-based conditioning is currently preferred. The aim of this study was to investigate early and late outcomes in pediatric IEI patients receiving pre-HSCT treosulfan and to examine the effect of treosulfan dose monitoring on outcomes. METHODS: Seventy-three pediatric patients receiving this management between 2015 and 2022 were included. RESULTS: Overall survival rate was 80%, and event-free survival was 67.8%. A larger treosulfan dose AUC after first application increased the rate of early toxicity (p = .034) and slowed lymphocyte engraftment (r = .290; p = .030). Underlying disease, treosulfan AUC, donor type, stem cell type, number of immunosuppressive agents, the dose of anti-thymocyte globulin, and post-transplantation cyclophosphamide did not to increase risk of acute graft-versus-host disease. The risk of mixed chimerism (MC) in patients with autoimmune lymphoproliferative syndrome and leukocyte adhesion deficiency were higher than those with severe combined immunodeficiency (p = .021 and p = .014, respectively). The risk of MC was lower in those receiving peripheral blood stem cells (SC) compared with bone marrow derived SC (OR = .204, p = .022). CONCLUSION: The AUC of the treosulfan dose was not associated with poorer late outcomes. Treosulfan is an agent that can be used safely in the IEI patient group,  level measurement appears essential to identify early toxicities. Prospective studies with more extended follow-up periods are needed.

Can serum progranulin level be used as a prognostic biomarker in non-small cell lung cancer?

Progranulin has been considered to be a poor prognostic biomarker for some types of malignancies. However, the clinical significance of serum progranulin level and the prognostic value are still not explored in advanced stages of lung cancer.  The current study investigates the prognostic significance of progranulin serum levels in advanced-stage non-small cell lung cancer (NSCLC) patients. This study involved 94 subjects (70 advanced-stage NSCLC patients and 24 healthy controls). Serum progranulin level was measured by enzyme-linked immunosorbent assay (ELISA) and was correlated with patient outcome. The association between circulating progranulin level and clinicopathological parameters was detected. Serum progranulin cut-off level predicting six-month survival was determined. Serum progranulin level was found significantly elevated in NSCLC patients than in the control group (p<0.001). We did not determine a significant difference between stage IIIB and stage IV NSCLC patients for serum progranulin levels (p=0.166). When we evaluated the laboratory parameters, only serum LDH level was found significantly correlated with serum progranulin level (p=0.043), also bone and liver metastasis showed a significant correlation with progranulin level (p=0.008 and p = 0.024, respectively). The cut-off level of serum progranulin in predicting six months of survival was determined as 16.03 ng/ml (AUC = 0.973, 95%Cl: 0.903-0.997, p<0.001) with 97.06% sensitivity and 88.89% specificity. Overall survival was determined shorter in patients with progranulin level ≥16 ng/ml than those with <16 ng/ml (p<0.001). Also, in the multivariate analysis using the Cox regression model serum progranulin level was found as an independent prognostic factor for NSCLC (p=0.001). Serum progranulin level may be a useful biomarker for predicting poor survival in advanced-stage NSCLC patients.

Relationship between renal volume and atherosclerosis in nondiabetic hypertensive patients with normal glomerular filtration rate.

Background: The association between cystatin C (CysC) and atherosclerosis has been shown in numerous studies in hypertensive patients and in various patient groups with high cardiovascular risk. The study examining the association between renal volume and atherosclerosis is very limited. This study aimed to investigate whether there is an association between the presence of atherosclerosis with CysC and renal volume in hypertensive patients.Methods: 133 hypertensive patients and 80 healthy volunteers were evaluated. CysC level was studied in the blood sample taken from all participants. Carotid intima media thickness (CIMT) and renal volume were measured with ultrasound always by the same radiologist. Laboratory findings, CysC, CIMT, and renal volume measurements of the groups were compared statistically.Results: There was no significant difference in mean renal volume values between hypertension and control groups. There was no significant correlation between renal volume with albuminuria and proteinuria. CIMT was significantly higher in hypertension group than in control group (p = .003). There was a significant correlation between renal volume and CIMT, which is an indicator of subclinical atherosclerosis (r = 0.213, p = .001). Renal volume was found to be an independent predictor of CIMT when corrected with variables such as age, BMI, serum LDL-cholesterol level, creatinine, CysC, and albumin-to-creatinine ratio.Conclusion: Ultrasonographic renal volume measurement, which is easy to perform and does not take a long time, can be a useful method for predicting the presence of atherosclerosis in hypertensive patients with GFR >60 ml/min.

The importance of plasma arginine level and its downstream metabolites in diagnosing prostate cancer.

PURPOSE: There is still no certain threshold value of prostate-specific antigen (PSA) for prostate cancer diagnosis. We aimed to investigate the predictive value of arginine and its metabolites for diagnosing prostate cancer in patients with PSA 4-10 ng/ml and evaluate their usefulness as prognostic tumor markers. METHODS: Seventy-eight patients with a mean age of 64.50 ± 5.49 years were included in our prospective observational study between November 2016 and March 2017. They were divided into two equal groups according to the pathologic results of prostate biopsy (benign vs. malignant). Plasma arginine and ornithine levels were analyzed before biopsy by liquid chromatography-tandem mass spectrometry. ELISA was used for analyzing urinary diacetylspermine. RESULTS: In PSA-adjusted analysis, the malignant group had lower plasma arginine levels (p = 0.021) and arginine to ornithine ratio (AOR) (p = 0.010), but higher plasma ornithine levels (p = 0.012) and urinary diacetylspermine levels (p < 0.001) as compared with the benign group. While arginine (r = - 0.628, p < 0.001) and AOR (r = - 0.714, p < 0.001) were negatively correlated with D'Amico clinical classification (p < 0.001), ornithine (r = 0.659, p < 0.001) and diacetylspermine (r = 0.710, p < 0.001) were found to be positively correlated (p < 0.001). In multivariate analysis, ornithine [OR 3.264, 95% CI (1.045-10.196), p = 0.042] and diacetylspermine [OR 6.982, 95% CI (2.403-20.290), p < 0.001] were found to be more significant in detection of prostate cancer. CONCLUSION: Plasma arginine, ornithine, AOR and urinary diacetylspermine levels may be used as molecular markers to predict prostate biopsy outcomes in patients with PSA 4-10 ng/ml. But according to our results, the use of ornithine and diacethylspermine prior to biopsy seems to be the most cost-effective diagnostic strategy.

A Simple Method for Quantification of Five Urinary Porphyrins, Porphobilinogen and 5-Aminolevulinic Acid, Using Liquid Chromatography Tandem Mass Spectrometry.

Analysis of porphyrins and 5-aminolevulinic acid (ALA), porphobilinogen (PBG) in physiological liquids is required for diagnosis and follow-up of porphyrias. High performance liquid chromatography (HPLC) and liquid chromatography tandem mass spectrometry (LC-MS) methods with higher specificity and sensitivity have been developed. The major disadvantage of those methods is that they require longer extraction times due to their matrix effects. The present study suggests a simple, fast, sensitive, and specific assay for determination of Coproporphyrin, 5-carboxylporphyrin, 6-carboxylporphyrin, 7-carboxylporphyrin, Uroporphyrin I and ALA, PBG in urine sample by direct injection without sample pre-treatment using LC-MS. For the purposes of the present study LC-MS device was set to multiple reaction monitoring (MRM) and positive ion mode. Porphyrins and ALA, porphobilinogen were characterized by their MS/MS product ion, spectra. ALA, PBG and 5 porphyrins were detected simultaneously. Limit of detection for Coproporphyrin, 5-carboxylporphyrin, 6-carboxylporphyrin, 7-carboxylporphyrin, Uroporphyrin I were 2 nmol/L, where it was 5 µmol/L for ALA and 2 µmol/L for porphobilinogen. The present study suggests that the present method is very effective compared to many other available methods for it does not require pre-treatment, provides simultaneous results of ALA, PBG and 5 porphyrins quantitatively in a shorter span of time, and has suitable sensitivity and selectivity. LC-MS technique was used clinically for the determination of urine porphyrin levels.

Sleeve gastrectomy relieves exocrine pancreatic insufficiency in morbidly obese patients: a prospective case-control study.

INTRODUCTION: Bariatric surgery is the most effective treatment modality in morbidly obese patients. Compared to Roux-en Y gastric bypass (RYGB), sleeve gastrectomy (SG) has better metabolic and nutritional outcomes after surgery. Exocrine pancreatic insufficiency (EPI) can be seen after RYGB but there is not any knowledge about EPI-SG association. AIM: To assess exocrine pancreatic functions before and after the SG procedure. MATERIAL AND METHODS: This is a single-center, prospective and case-control study. Forty morbidly obese patients were included in the study. Their pre-operative and post-operative, third month fecal samples were collected. Exocrine pancreatic insufficiency was determined by using fecal elastase-1 and diagnosed when fecal elastase-1 levels were < 200 µg/g. RESULTS: The mean fecal elastase-1 level was 256.25 ±137.16 µg/g and the mean post-surgical fecal elastase-1 level was 437.7 ±212.43 µg/g (p = 0.001). In the pre-operative period, half of patients had FE levels under 200 µg/g. In the third month after surgery, only 4 patients had fecal elastase-1 levels under 200 µg/g. Comparison of fecal elastase-1 between pre-surgery and post-surgery revealed a significant difference (p = 0.001). CONCLUSIONS: This is the first study to investigate EPI-SG association. Surgery-associated morbidity and mortality are the leading limitations of bariatric surgery procedures. Exocrine pancreatic insufficiency is one of them; prior studies demonstrate its increased frequency after RYGB. Our study revealed that SG relieves exocrine pancreatic insufficiency.

Could plasma asymmetric dimethylarginine level be a novel predictor beyond the classic predictors of stent restenosis?

OBJECTIVE: The aim of this study was to investigate the factors associated with coronary stent restenosis and if there is an association between plasma asymmetric dimethylarginine (ADMA) levels and stent restenosis. METHODS: Ninety-one patients, who had a history of coronary bare metal stent implantation due to any cause in the last one year period, were admitted to this observational cross-sectional study. Coronary angiography was performed to all patients and quantitative angiography was used to determine the presence of stent restenosis. Laboratory parameters and angiographic features that contribute to stent restenosis were evaluated. Plasma ADMA levels were measured by using high performance liquid chromatography. Logistic regression analysis was used to determine the independent factors of stent restenosis. RESULTS: Angiographic restenosis was found in 35 patients (38.5%). Stent diameter (p=0.038) and left ventricular ejection fraction (p=0.023) were lower and stent implantation history due to acute coronary syndrome (p=0.029), plasma ADMA level (5.0±1.8x10-4 mmol/L vs. 3.9±1.0x10-4 mmol/L, p=0.001), C-reactive protein concentration (p=0.016), white blood cell count (p=0.044) and stent length (p=0.005) were higher in patients with restenosis. Plasma ADMA level (ß=0.536; OR: 1.710; CI: 1.022-2.861; p=0.041), C-reactive protein concentration (ß=0.062; OR: 1.064; CI: 1.003-1.129; p=0.041), stent diameter (ß=-3.047; OR: 0.048; CI: 0.007-0.313; p=0.002) and length (ß=0.165; OR: 1.179; CI: 1.036-1.343; p=0.013) were found to be the independent predictors of stent restenosis in logistic regression analysis. CONCLUSION: We conclude that plasma ADMA levels may be used as a novel marker for stent restenosis beyond the classic stent restenosis markers.