NT-proCNP levels predict higher atherosclerotic cardiovascular risk profile in patients with proliferative diabetic retinopathy.

AIMS: In this study, we aimed to demonstrate the effectiveness of serum amino-terminal proCNP (NT-proCNP) levels in predicting coronary heart disease (CHD) and cardiovascular risk in type 2 diabetes mellitus (T2DM) patients. METHODS: We recruited 73 patients with T2DM in the study. Additionally, we grouped the patients according to their status of diabetic retinopathy (DR) as no DR, non-proliferative DR, or proliferative DR. Serum NT-proCNP levels of the patients were measured and their atherosclerotic cardiovascular disease (ASCVD) risk scores were calculated. RESULTS: There was no significant difference in terms of NT-proCNP levels between the groups (p = 0.3) and in terms of CHD and ASCVD risk scores (p = 0.4 and p = 0.4, respectively). In the correlation analysis, a significant correlation was observed between the NT-proCNP levels and the ASCVD risk score (r = 0.373; p = 0.008 among the entire cohort and r = 0.555; p = 0.01 in the non-proliferative-DR group), smoking status (r = 0.280; p = 0.03 among the entire cohort and r = 0.362; p = 0.035 in the non-proliferative-DR group), sBP (r = 0.278; p = 0.038 among the entire cohort), and dBP (r = 0.284; p = 0.034 among the entire cohort and r = 0.482; p = 0.004 in the proliferative-DR group). In the ROC analysis, we found that the NT-proCNP level predicted a high ASCVD risk score with 83.3% sensitivity and 70.8% specificity and a very high ASCVD risk score with 100% sensitivity and 69.2% specificity among the proliferative-DR patients. No cut-off value was calculated for the prediction of high and very-high ASCVD risk scores in patients with non-proliferative DR. Similarly, no cut-off value was revealed for the prediction of established coronary artery disease in all groups. CONCLUSIONS: Our study revealed a significant association between NT-proCNP levels and high ASCVD risk scores in patients with proliferative DR.

Vaccine Adherence and Postvaccination Serological Status of Pediatric Allogeneic Hematopoietic Stem Cell Transplant Recipients: A Single-center Experience.

Despite developing consensus guidelines addressing immunization after hematopoietic stem cell transplantation (HSCT), studies showed deviations from recommended immunization practices commonly occur. Difference between the ideal scenario presented in guidelines and real-life scenarios is one of the most recognized barriers to implementing recommended practices. Therefore, this study aimed to evaluate pediatric allogeneic HSCT recipients' adherence to revaccination schedule and evaluate the serological status after immunization. Transplant and vaccination records of children who were followed up at least 2 years after HSCT, postvaccination antibody results of vaccine-preventable diseases were evaluated retrospectively. Total of 173 patients have enrolled in this study. Median revaccination onset time was post-transplant 15 months. Adherence to revaccination program was 30% for inactive and 11.4% for live vaccines. Oral polio vaccine was given to 22 patients, and Bacille-Calmette-Guerin vaccine was applied to 3. Seropositivity after revaccination was >90% for Hepatitis B, Hepatitis A, pertussis, and measles, and it was 88.5% for rubella, 80% for mumps and varicella. Measles seropositivity was low in children with hemoglobinopathy. In subgroup assessments of pertussis, patients vaccinated with low antigen-containing pertussis vaccine (Tdap) had higher seropositivity of adenylate cyclase toxin. Our findings revealed the importance of careful monitoring of current practices in pediatric HSCT recipients.

The impact of the COVID-19 pandemic on Fabry Disease Patients: an examination of Mood Status, Therapy Adherence, and COVID-19 infection.

BACKGROUND: Fabry disease (FD) is a rare metabolic disorder, in which a lifelong enzyme replacement therapy (ERT) constitutes the cornerstone of disease-specific therapy. In this study, we examined the effects of the COVID-19 pandemic and lockdown measures on the management of FD patients. METHODS: We collected data in three main domains; mood status, adherence to ERT, and COVID-19 infection. We used the Hospital Anxiety and Depression Scale (HADS) to evaluate the mood statuses of FD patients and the Morisky Medication Adherence Scale (MMAS) and the Medication Adherence Report Scale (MARS) to assess patients' adherence to non-disease specific therapy. We also examined a control group to compare the mood status data. RESULTS: A total of 67 FD patients (males: 47.8%, mean age: 37.0 years) were recruited to the study, of which 58 were receiving ERT. Both the HADS depression and anxiety scores were higher in the control group compared to FD patients. During the first wave of the pandemic, 25 patients reported to have missed an infusion for a mean of 2.3 ± 1.7 doses and half of the patients had adopted a home-based infusion treatment regimen. COVID-19 infection developed in 25 patients, of which one died. The majority of our patients (71.6%) have had at least one shot of the vaccine. CONCLUSION: We found that FD patients were more resilient to the negative psychological effects of lockdown. Traumatic growth may be an important factor in explaining this finding. Government-supported home therapy programs might be beneficial for FD patients to increase the therapy adherence.

Effects of SGLT2 inhibitors on patients with diabetic kidney disease: A preliminary study on the basis of podocyturia.

BACKGROUND: The aim of this study was to investigate the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on the glomerulus through the evaluation of podocyturia in patients with diabetic kidney disease (DKD). METHODS: The study population was composed of 40 male patients with type 2 diabetes mellitus; 22 of them received SGLT2i (SGLT2i group), and the others who did not were the control. The DKD-related parameters of patients were monitored before SGLT2i initiation, and then in the third and sixth month of the follow-up period. Patients' demographic, clinical, laboratory, and follow-up data were obtained from medical charts. Microalbuminuria was measured in 24-h urine. The number of podocytes in the urine was determined by immunocytochemical staining of two different markers, namely podocalyxin (podx) and synaptopodin (synpo). Concentrations of urine stromal cell-derived factor 1a and vascular endothelial growth factor cytokines were quantified with an enzyme-linked immunosorbent assay kit. RESULTS: At the end of the follow-up period, decreases in glycosylated hemoglobin, glucose, systolic and diastolic blood pressure, uric acid level, and microalbuminuria, and improvement in body mass index level and weight loss were significant for the SGLT2i group. On the other hand, there was no significant difference in terms of these parameters in the control group. The excretion of synaptopodin-positive (synpo+ ) and podocalyxin-positive (podx+ ) cells was significantly reduced at the end of the follow-up period for the SGLT2i group, while there was no significant change for the control. CONCLUSIONS: At the end of the follow-up period, male patients receiving SGLT2i had better DKD-related parameters and podocyturia levels compared to baseline and the control group. Our data support the notion that SGLT2i might have structural benefits for glomerular health.

Blood Pressure Variability in Fabry Disease Patients.

INTRODUCTION: Fabry disease is a rare metabolic, multisystemic, and X-linked lysosomal storage disorder. The involvement of the autonomic nervous system is well defined; however, data on the variability of the blood pressure (BP) and heart rate in Fabry disease are largely missing. In this study, we aimed to examine the circadian variations of BP and heart rate variability in Fabry disease patients. METHODS: We recruited 31 consecutive adult (age >18 years) Fabry disease patients (16 males and 15 females) who were regularly followed up in our outpatient clinic between July 2019 and March 2020. We performed ambulatory blood pressure monitoring and echocardiography in all patients. We used standard deviation (SD), coefficient of variation (CV), and average real variability as the measures of variability. We constructed 2 control groups for propensity score matching using age, sex, and eGFR parameters in the first group and adding antihypertensive drug use to the above parameters in the second group. RESULTS: All BP measurements were significantly lower in the FD group compared to that of the control groups, except the nighttime systolic BP. Regarding nondipping and reverse dipping statuses, FD patients and controls were similar. We found that none of the BP variability measures were higher in FD patients. Regarding heart rate variability data, both the nighttime SD and CV were significantly lower in FD patients compared to those of the controls. CONCLUSION: A decrease in heart rate variability, rather than an increase in BP variability, might be an early marker of autonomic involvement in FD.

Reflex Decay Test Can Reveal Ear Involvement in Fabry Disease.

OBJECTIVES: Fabry disease (FD) is an X-linked lysosomal storage disorder that causes multisystem involvement, including ear disease. In this study, we aimed to investigate the nature of auditory issues in FD using a wide spectrum of audiological tests. DESIGN: This cross-sectional study was conducted between June 2017 and December 2018. We collected the clinical and laboratory data of 40 eligible FD patients, 45 healthy subjects, and 26 diabetic controls. All patients and controls completed audiologic evaluations that included tympanometry, acoustic reflex threshold test, reflex decay test, pure-tone audiometry, speech audiometry, transient otoacoustic emissions (TEOAEs), high-frequency audiometry, and distortion product otoacoustic emission (DPOAE). RESULTS: In our study population, hearing was reduced at higher frequencies starting at 4 kHz in both the FD and diabetic groups. Regarding the acoustic reflex threshold test, FD and diabetic patients had similar results. In all frequencies, positive decay was significantly more frequent in FD patients when compared with the diabetic patients and healthy controls (p < 0.001 for each ear). The FD patients and healthy controls had similar results for DPOAE testing. CONCLUSIONS: We showed that FD patients had a higher rate of reflex decay, indicating retrocochlear involvement. Thus, further investigation of factors associated with retrocochlear involvement could be investigated, such as ABR and speech in noise tests.

Evaluation of the reasons for the microvascular changes in patients with Fabry disease using optic coherence tomography angiography.

PURPOSE: To investigate the blood flow changes in the choriocapillaris and the superficial and deep capillary plexus of the retina using optic coherence tomography angiography (OCTA) in patients with Fabry disease (FD) and reveal any possible association of these changes with the systemic findings. METHODS: This cross-sectional study included 38 patients with FD and age- and gender-matched 40 healthy controls. OCTA images were obtained from all patients. Superficial (sCVD) and deep capillary vascular density (dCVD) in the foveal, parafoveal, and perifoveal zones and the whole image were recorded for each patient. Flow area in the choriocapillaris and central macular thickness (CMT) were also recorded. RESULTS: Patients with FD showed a lower whole image (54.45 ± 5.99% vs 57.32 ± 6.71%, p = 0.004), foveal (34.94 ± 7.60% vs 39.65 ± 7.03%, p = 0.003), parafoveal (57.41 ± 4.85% vs 59.19 ± 4.67%, p = 0.043), and perifoveal (55.87 ± 6.43% vs 58.87 ± 7.02%, p = 0.003) dCVD compared to the healthy controls without a significant difference in the sCVD and choriocapillaris blood flow (p > 0.05). A significantly lower whole image and foveal dCVD in the FD patients with renal involvement was observed compared to the healthy controls (p = 0.027 and p = 0.024, respectively) without any significant difference between the FD patients without renal involvement and healthy controls (p = 0.17 and p = 0.13, respectively). CMT was significantly higher in FD patients with renal involvement compared to the ones without renal involvement (252.1 ± 18.5 µm vs 235.5 ± 17.6 µm, p = 0.016). CONCLUSION: Patients with FD showed a lower dCVD without any change in sCVD and choriocapillaris compared to the healthy controls. This decrease was associated mostly with the renal involvement and duration of treatment.

Clinical utility of noninvasive scores in assessing advanced hepatic fibrosis in patients with type 2 diabetes mellitus: a study in biopsy-proven non-alcoholic fatty liver disease.

BACKGROUND/AIM: Simple noninvasive fibrosis scores based on routine blood tests have been increasingly investigated as screening tools in different clinical settings. Here, we sought to examine whether the Fibrosis-4 Index (FIB-4) and the non-alcoholic fatty liver disease (NAFLD) fibrosis score (NFS) could perform differently in diabetic versus non-diabetic patients with biopsy-proven NAFLD. METHODS: We examined 349 patients with biopsy-proven NAFLD (166 with type 2 diabetes and 183 without). Patients with FIB-4 scores < 1.3 and > 2.67 or NFS scores < - 1.455 and > 0.676 were considered at low and high risk of advanced fibrosis, respectively. RESULTS: A FIB-4 cutoff value of 1.3-which denotes a low risk of advanced fibrosis-had a specificity of 67% in patients with diabetes and 69% in those without. Conversely, a FIB-4 cutoff value of 2.67-which denotes a high risk of advanced fibrosis-had a sensitivity of 22% in patients with diabetes and 0% in those without. NFS performed similar to FIB-4. CONCLUSION: Both FIB-4 and NFS scores have an acceptable clinical utility in the exclusion of advanced fibrosis in patients with NAFLD, regardless of the presence of type 2 diabetes. However, their usefulness in identifying advanced fibrosis is limited-especially in the absence of diabetes.

Simple Noninvasive Scores Are Clinically Useful to Exclude, Not Predict, Advanced Fibrosis: A Study in Turkish Patients with Biopsy-Proven Nonalcoholic Fatty Liver Disease.

Background/Aims: Advanced fibrosis (F≥3) indicates poor outcomes in nonalcoholic fatty liver disease (NAFLD). Here, we examined the diagnostic performance of the fibrosis-4 index (FIB-4) and NAFLD fibrosis score (NFS) for detecting (or excluding) advanced fibrosis in patients with biopsy-proven NAFLD. Methods: The diagnostic performance of each noninvasive test according to previously identified cutoff points indicating low and high risk for advanced fibrosis was determined in 463 patients with NAFLD. Patients who scored <1.3 and >2.67 on the FIB-4 were considered at low and high risk for advanced fibrosis, respectively. Patients who scored <-1.455 and >0.676 on the NFS were considered at low and high risk for advanced fibrosis, respectively. Results: Eighty-one patients (17.5%) had biopsy-proven advanced fibrosis (F≥3). The published FIB-4 cutoff values for low and high risk were able to exclude advanced fibrosis with negative predictive values (NPVs) of 0.907 and 0.843 and specificities of 74% and 97%, respectively. The published NFS cutoff values for low and high risk were able to exclude advanced fibrosis with NPVs of 0.913 and 0.842 and specificities of 63% and 96%, respectively. If biopsies were performed in only patients with a FIB-4 above the low cutoff point (≥1.3), 67.1% could be avoided. Conversely, if biopsies were performed in only patients with an NFS above the low cutoff point (≥-1.455), 57.0% could be avoided. Conclusions: The main clinical utility of the FIB-4 and NFS in patients with NAFLD lies in the ability to exclude, not identify, advanced fibrosis.

The interaction between current smoking and hemoglobin on the risk of advanced fibrosis in patients with biopsy-proven nonalcoholic fatty liver disease.

BACKGROUND: Higher hemoglobin levels have been associated with an increased risk for nonalcoholic fatty liver disease. Although the mechanism underlying this association is elusive, smoking has been previously related to both higher hemoglobin concentrations and an increased risk of fibrosis in nonalcoholic fatty liver disease. The present study was conducted to investigate formally the interaction among current smoking, hemoglobin levels, and risk for advanced fibrosis in patients with biopsy-proven nonalcoholic fatty liver disease. PATIENTS AND METHODS: We examined 433 Turkish patients with biopsy-proven nonalcoholic fatty liver disease. Advanced fibrosis (F ≥ 3) was identified on liver biopsy in 80 cases, whereas 84 patients were current smokers. Logistic regression models were used to evaluate the effect of current smoking on risk for advanced fibrosis, after adjusting for the effects of age, sex, BMI, diabetes, and metabolic syndrome. RESULTS: Preliminary analyses revealed the presence of substantial statistical interaction between current smoking and hemoglobin levels (P < 0.001). In separate multivariable analyses conducted in the entire cohort and in the subgroups of patients with high and low hemoglobin levels (according to median value in the study cohort: 14.4 g/l), current smoking was associated with increased risk for advanced fibrosis in patients with high hemoglobin (odds ratio: 3.32, 95% confidence interval: 1.23-7.21, P < 0.01) but neither in those with low hemoglobin (odds ratio: 0.71, 95% confidence interval: 0.28-1.81, P = 0.52) nor in the entire study cohort (odds ratio: 1.18, 95% confidence interval: 0.73-2.14, P = 0.79). CONCLUSION: Hemoglobin acts as a modifier in the association between current smoking and advanced fibrosis in nonalcoholic fatty liver disease.

The diagnostic utility of fibrosis-4 or nonalcoholic fatty liver disease fibrosis score combined with liver stiffness measurement by fibroscan in assessment of advanced liver fibrosis: a biopsy-proven nonalcoholic fatty liver disease study.

BACKGROUND/AIM: The clinical guidelines recommend the use of nonalcoholic fatty liver disease fibrosis score and fibrosis-4 score for estimating the advanced liver fibrosis in nonalcoholic fatty liver disease. However, these scores are used confidently in eliminating advanced fibrosis, rather than detecting it. Therefore, paired combination with liver stiffness measurement by transient elastography is recommended. In this study, we aimed to validate this combined algorithm in our study population. METHODS: A total of 139 consecutive biopsy-proven nonalcoholic fatty liver disease patients were enrolled in the study. We calculated the noninvasive scores and performed liver stiffness measurement examination for each patient. RESULTS: The optimal cutoff of liver stiffness measurement for advanced fibrosis was 11.0 kPa (area under curve: 0.856) with a sensitivity of 84% and a specificity of 78%. Using the fibrosis-4 score (< 1.45 for low risk of advanced fibrosis and > 3.25 for high risk of advanced fibrosis) in combination with the liver stiffness measurement cutoffs revealed the best diagnostic performance (< 8.8 kPa for low risk of advanced fibrosis and > 10.9 kPa for high risk of advanced fibrosis). This paired combination had the positive predictive value of 0.735 at a sensitivity of 89% and the negative predictive value of 0.932 at a specificity of 82%. CONCLUSION: A paired combination of the fibrosis-4 score and liver stiffness measurement (< 8.8 kPa for exclusion of advanced fibrosis and > 10.9 kPa for inclusion of advanced fibrosis) is able to diagnose the patients with advanced fibrosis with the highest diagnostic accuracy.

The utility of noninvasive scores in non-alcoholic fatty liver disease patients with normal and elevated serum transaminases.

Background and Aim: Noninvasive scores are developed for the estimation of advanced fibrosis, including parameters in addition to transaminases in non-alcoholic fatty liver disease (NAFLD). In this study, we aimed to investigate the diagnostic performances of Fibrosis-4 (FIB-4) and NAFLD Fibrosis Score (NFS) in the estimation of advanced fibrosis comparing patients with normal and elevated transaminases. Material and Methods: We retrospectively analyzed the prospectively collected data of a total of 407 consecutive patients with biopsy-proven NAFLD. FIB-4 scores of <1.3 and >2.67 or <1.45 and >3.25 indicated a low and high risk for advanced fibrosis, respectively. NFS scores of <-1.455 and >0.676 were used to assess low and high risk for advanced fibrosis, respectiv. Results: FIB-4 cutoffs of <1.3 and <1.45 for low risk of advanced fibrosis had a sensitivity of 70% and 54% in patients with elevated transaminases and 70% and 52% in patients with normal transaminases, respectively. The specificities for the cutoffs of >2.67 and >3.25 were 97% and 98% in patients with elevated transaminases and 99% and 100% in patients with normal transaminases, respectively. Concerning NFS, we found similar results. Conclusion: FIB-4 and NFS showed acceptable diagnostic performance in the exclusion of advanced fibrosis in both populations with normal and elevated transaminases.

Association of Nutritional Assessment by Phase Angle With Mortality in Kidney Transplant Patients in an 8-Year Follow-Up.

BACKGROUND: Phase angle is a bioimpedance analysis parameter that indirectly shows body cell mass. Its association with mortality has been shown in patients receiving dialysis treatment. However, assessment with mortality in kidney transplant recipients has not been studied previously. METHODS: We examined 158 kidney transplant recipients who underwent bioimpedance analysis 8 years ago in a cross-sectional study. We contacted them again and investigated the presence of cardiovascular events, cancer, angina pectoris, and claudication. Data regarding mortality, graft failure, and creatinine values were collected from recipients' files. FINDINGS: During the follow-up period, 15 recipients died, 26 lost graft function, 36 experienced cardiovascular events, and 4 developed cancer. Phase angle was significantly associated with mortality during the 8-year follow-up period of kidney transplant recipients (P < .001). The cutoff value for phase angle as a predictor of mortality was ≤5.85. Moreover, a phase angle value lower than 5.85 indicated 5.33 times higher risk of mortality. DISCUSSION: Phase angle was a predictor of mortality in kidney transplant recipients. Since phase angle is an inexpensive, easy-to-perform, and noninvasive method, it might be considered as an additional tool to assess survival in kidney transplant recipients.

A dilemma at gray scale thyroid ultrasound: microcalcification or not? Differentiation with Acoustic Radiation Force Impulse Imaging-Virtual Touch Imaging.

AIMS: To evaluate the capacity of virtual touch imaging (VTI) of the acoustic radiation force impulse (ARFI) techniquein the differential diagnosis of micro-echogenicities in thyroid nodules. MATERIAL AND METHODS: The study comprised 28patients. Gray scale and ARFI displacement maps were used during ultrasound examination.In the same session, fine needleaspiration biopsy (FNAB) samples were obtained from the dominant nodule hav-ing micro-echogenicities. Two radiologists blinded to the FNAB results and clinical data of the patients evaluated these images and rated ARFI echogenicities according to the degree of shining points on the displacement maps and classified them as isohypoechogenic, isohyperechogenic, and obvious hyperechogenic. To differentiate between benignancy and malignancy, "a new sign" was defined as follows: in the ARFI maps obtained by VTI, iso-echogenic or hyper-echogenic appearance of micro-echogenic foci was evaluated as benignancy and hypo-echogenic appearance of micro-echogenic foci was evaluated as malignancy. RESULTS: The FNAB results indicated 14 cases and benign nodules in the other 14 cases. Interobserver agreement between the two radiologists was highly significant for the classification of the micro-echogenic foci (Kappa=0.659, p<0.001). When we reclassified the hyperechoic and isohyperechoic foci as "benign" and isohypoechoic foci as "malignant", the interobserver agreement between the two radiologists increased (Kappa=0.772, p<0.001). The evaluation of the first and second radiologists were highly concordant with the gold standard pathology results (Kappa=0.786, p<0.001 and Kappa=0.714, p<0.001, respectively). CONCLUSIONS: ARFI method with specific VTI features could be a very useful tool in the differentiation of malignant microcalcifications in thyroid nodules.

Elastography in Distinguishing Benign from Malignant Thyroid Nodules.

AIM: The aim of this study is to test the diagnostic success of strain elastography in distinguishing benign from malignant thyroid nodules. MATERIALS AND METHODS: The size, echogenicity, and halo integrity of 293 thyroid nodules and the presence of microcalcification in these nodules were evaluated on gray-scale examination. Doppler characteristics and elastography patterns were also evaluated and recorded. Nodules were classified in four categories (patterns 1-4) based on elastographic examination. RESULTS: According to the cytopathological findings, 222 nodules were benign, and 71 nodules were malignant. The risk of a nodule to be malignant was 3.8 times increased by hypoechogenicity, 7.7 times increased by the presence of microcalcification, and 11.5 times increased by the absence of halo. On Doppler patterns, the presence of central vascularity increased the malignancy risk of a nodule by 5.8 times. According to the receiver operating characteristic analysis, patterns 3 and 4 were malignant, and patterns 1 and 2 were benign. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of elastography were 100%, 80.2%, 61.7%, 100%, and 85%, respectively. CONCLUSION: Strain elastography can be used as a noninvasive method in distinguishing benign from malignant thyroid nodules and in identifying the patients who would undergo surgery.