A Novel Time-Aware Deep Learning Model Predicting Myopia in Children and Adolescents.

Objective: To quantitatively predict children's and adolescents' spherical equivalent (SE) by leveraging their variable-length historical vision records. Design: Retrospective analysis. Participants: Eight hundred ninety-five myopic children and adolescents aged 4 to 18 years, with a complete ophthalmic examination and retinoscopy in cycloplegia prior to spectacle correction, were enrolled in the period from January 1, 2008 to July 1, 2023 at the University Hospital "Sveti Duh," Zagreb, Croatia. Methods: A novel modification of time-aware long short-term memory (LSTM) was used to quantitatively predict children's and adolescents' SE within 7 years after diagnosis. Main Outcome Measures: The utilization of extended gate time-aware LSTM involved capturing temporal features within irregularly sampled time series data. This approach aligned more closely with the characteristics of fact-based data, increasing its applicability and contributing to the early identification of myopia progression. Results: The testing set exhibited a mean absolute prediction error (MAE) of 0.10 ± 0.15 diopter (D) for SE. Lower MAE values were associated with longer sequence lengths, shorter prediction durations, older age groups, and low myopia, while higher MAE values were observed with shorter sequence lengths, longer prediction durations, younger age groups, and in premyopic or high myopic individuals, ranging from as low as 0.03 ± 0.04 D to as high as 0.45 ± 0.24 D. Conclusions: Extended gate time-aware LSTM capturing temporal features in irregularly sampled time series data can be used to quantitatively predict children's and adolescents' SE within 7 years with an overall error of 0.10 ± 0.15 D. This value is substantially lower than the threshold for prediction to be considered clinically acceptable, such as a criterion of 0.75 D. Financial Disclosures: The author(s) have no proprietary or commercial interest in any materials discussed in this article.

The CroMyop study: myopia progression in Croatian children and adolescents-a 15-year retrospective analysis.

Purpose: Myopia is a major global health issue, especially among children and adolescents. Understanding its traits and progression is vital for proper management and prevention. This study aimed to fill a gap in research by analyzing demographic and refractive data concerning myopia among children and adolescents in Croatia, with the goal of providing insights into myopia prevalence, progression rates, and associated risk factors within the Croatian population. Design: This retrospective study utilized a comprehensive dataset from pediatric ophthalmology clinics at the University Eye Department, University Hospital "Sveti Duh," Zagreb, Croatia. The dataset included electronic medical records spanning from January 2008 to July 2023, encompassing demographic and refractive data. Methods: Data analysis focused on individuals aged 4 to 18 years who were diagnosed with primary myopia and/or compound myopic astigmatism. Ophthalmic examinations, including visual acuity tests, cycloplegic refraction, and assessments for eye comorbidities, were conducted by experienced pediatric ophthalmologists. Statistical analysis, including t-tests, survival analysis, and logistic regression, was performed to assess myopia prevalence, progression rates, and associated factors. These analyses were adjusted for covariates such as age, parental myopia, and gender. Results: The study included 895 individuals, 51 premyopes, 813 low myopes, and 31 high myopes. The average age of diagnosis was 11.37 ± 3.59 years for premyopes, 11.18 ± 3.53 years for low myopes, and 11.44 ± 4.35 years for high myopes. The fastest progression occurred in 2021 and 2022, -0.5 ± 0.12 D/y for premyopes and - 0.45 ± 0.1 D/y for low myopes. Premyopic progression to low myopia was associated with age 7-9 years (HR 2.42, 1.53 to 3.21) and both parents being myopic (HR 920.27. 850.16 to 950.53). Low myopic individuals with both myopic parents displayed the fastest 11-24 months after first visit progression rates, -0.69 (-0.52 to -0.87) D/y, while the 7-9 age group demonstrated -0.36 (-0.24 to -0.45) D/y. Low myopes aged 7-9 years with baseline SE between -6 D and -4 D were more strongly associated with ≤ - 0.5 D progression (OR = 2.0, 95% CI -1.00 to 2.39). Conclusion: This study highlights the importance of environmental factors, genetics, and age in addressing myopia progression among Croatian youth, urging further research for effective local intervention strategies.

Retrospective analysis between total laparoscopic and vNOTES hysterectomy in obese patients: single-center study.

INTRODUCTION: Hysterectomy is one of the most common major gynecological surgeries, and it is performed for benign and malignant reasons. Currently, five types of hysterectomies are described: vaginal (VH), abdominal (AH), laparoscopic (LH), robotic, and vNOTES (vaginal natural orifice transluminal endoscopic surgery). This paper compares these two types of surgery in obese patients by analyzing the surgeries performed by our team. MATERIALS AND METHODS: The research was conducted from January 2022 to December 2023 at the Department of Gynecology and Obstetrics of the General Hospital in Zadar. The study included female patients aged 18-75 years with a BMI > 30 kg/m2, regardless of parity, who were operated on for benign pathology. RESULTS: There were 24 patients included in total. One conversion was observed in the TLH group because of excessive bleeding. Median operative time (IQR) was significantly lower in the vNOTES group (p < 0.05) than in the TLH group 35 (10.9) vs 125 (74.0) min. CONCLUSION: The results concerning the duration of surgery, conversion rate, and postoperative bleeding and complications show that vNOTES hysterectomies seem to be feasible for obese patients. Further studies are needed to confirm these observations.

Prevalence of posttraumatic stress disorder following acute coronary syndrome and clinical characteristics of patients referred to cardiac rehabilitation.

BACKGROUND: Studies have demonstrated that patients who have experienced acute coronary syndrome (ACS) have an increased risk of developing posttraumatic stress disorder (PTSD) and experiencing worse survival outcomes than those who do not develop PTSD. Nevertheless, the prevalence rates of PTSD following ACS vary widely across studies, and it is noteworthy that in most cases, the diagnosis of PTSD was based on self-report symptom questionnaires, rather than being established by psychiatrists. Additionally, the individual characteristics of patients who develop PTSD after ACS can differ widely, making it difficult to identify any consistent patterns or predictors of the disorder. AIM: To investigate the prevalence of PTSD among a large sample of patients undergoing cardiac rehabilitation (CR) after ACS, as well as their characteristics in comparison to a control group. METHODS: The participants of this study are patients who have experienced ACS with or without undergoing percutaneous coronary intervention and are enrolled in a 3-wk CR program at the largest CR center in Croatia, the Special Hospital for Medical Rehabilitation Krapinske Toplice. Patient recruitment for the study took place over the course of one year, from January 1, 2022, to December 31, 2022, with a total of 504 participants. The expected average follow-up period for patients included in the study is about 18 mo, and currently ongoing. Using self-assessment questionnaire for PTSD criteria and clinical psychiatric interview, a group of patients with a PTSD diagnosis was identified. From the participants who do not have a PTSD diagnosis, patients who would match those with a PTSD diagnosis in terms of relevant clinical and medical stratification variables and during the same rehabilitation period were selected to enable comparability of the two groups. RESULTS: A total of 507 patients who were enrolled in the CR program were approached to participate in the study. Three patients declined to participate in the study. The screening PTSD Checklist-Civilian Version questionnaire was completed by 504 patients. Out of the total sample of 504 patients, 74.2% were men (n = 374) and 25.8% were women (n = 130). The mean age of all participants was 56.7 years (55.8 for men and 59.1 for women). Among the 504 participants who completed the screening questionnaire, 80 met the cutoff criteria for the PTSD and qualified for further evaluation (15.9%). All 80 patients agreed to a psychiatric interview. Among them, 51 patients (10.1%) were diagnosed with clinical PTSD by a psychiatrist according to Diagnostic and Statistical Manual of Mental Disorders criteria. Among the variables analyzed, there was a noticeable difference in the percentage of theoretical maximum achieved on exercise testing between the PTSD and non-PTSD groups. Non-PTSD group achieved a significantly higher percentage of their maximum compared to the PTSD group (P = 0.035). CONCLUSION: The preliminary results of the study indicate that a significant proportion of patients with PTSD induced by ACS are not receiving adequate treatment. Furthermore, the data suggest that these patients may exhibit reduced physical activity levels, which could be one of the possible underlying mechanisms in observed poor cardiovascular outcomes in this population. Identifying cardiac biomarkers is crucial for identifying patients at risk of developing PTSD and may derive benefits from personalized interventions based on the principles of precision medicine in multidisciplinary CR programs.

Long-Term Outcome of Differentiated Thyroid Cancer Patients-Fifty Years of Croatian Thyroid Disease Referral Centre Experience.

Background: Indolent nature but a high incidence of differentiated thyroid cancer (DTC) remains a challenge for optimizing patient care. Therefore, prognostic factors present valuable information for determining an adequate clinical approach. Methods: This study assessed prognostic features of 1167 papillary (PTC) and 215 follicular (FTC) thyroid cancer patients that had undergone surgery between 1962 and 2012, and were followed-up up to 50 years in a single institution, till April 2020. Age, gender, tumor size, presence of local and distant metastases at presentation, extrathyroidal extension, disease recurrence, and cancer-specific survival were evaluated. Results: In multivariate analysis, factors affecting the worse outcome were age (p = 0.005), tumor size (p = 0.006), and distant metastases (p = 0.001) in PTC, while extrathyroidal extension (p < 0.001), neck recurrence (p = 0.002), and distant metastases (p < 0.001) in FTC patients. Loco-regional recurrence rate was 6% for PTC and 4.7% for FTC patients, while distant metastases were detected in 4.2% PTC and 14.4% of FTC patients. The 10-year cancer-specific survival rates for PTC and FTC were 98.6% and 89.8%, respectively (p < 0.001). Conclusions: Negative prognostic factors, besides distant metastases, were older age and greater tumor size in PTC, and extrathyroidal extension and neck recurrence in FTC patients. The recurrence and mortality rates were very low.

Astaxanthin Relieves Testicular Ischemia-Reperfusion Injury-Immunohistochemical and Biochemical Analyses.

Testicular torsion potentially leads to acute scrotum and testicle loss, and requires prompt surgical intervention to restore testicular blood flow, despite the paradoxical negative effect of reperfusion. While no drug is yet approved for this condition, antioxidants are promising candidates. This study aimed to determine astaxanthin's (ASX), a potent antioxidant, effect on rat testicular torsion-detorsion injury. Thirty-two prepubertal male Fischer rats were divided into four groups. Group 1 underwent sham surgery. In group 2, the right testis was twisted at 720° for 90 min. After 90 min of reperfusion, the testis was removed. ASX was administered intraperitoneally at the time of detorsion (group 3) and 45 min after detorsion (group 4). Quantification of caspase-3 positive cells and oxidative stress markers detection were determined immunohistochemically, while the malondialdehyde (MDA) value, superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities were determined by colorimetric assays. The number of apoptotic caspase-3 positive cells and the MDA value were lower in group 4 compared to group 2. A significant increase in the SOD and GPx activity was observed in group 4 compared to groups 2 and 3. We conclude that ASX has a favorable effect on testicular ischemia-reperfusion injury in rats.

Geographic distribution and risk of upper urothelial carcinomas in Croatia, 2001-2011.

BACKGROUND: Strong associations exist between Balkan endemic nephropathy (BEN) and upper urothelial carcinomas (UUCs). However, the common etiology between the two remains unclear and there are no studies to date that visualize UUC risks in Croatia. In Croatia, 14 villages in the southwestern part of Brod-Posavina County are considered endemic for BEN. The aim of this ecological study is to map cancer risks and describe the case distribution of UUCs in Croatia at the county level during 2001-2011. METHODS: A total of 608 incident cases from the Croatian National Cancer Registry were identified. Indirect standardization was employed to compute standardized incidence ratios (SIRs). RESULTS: Counties with SIRs greater than 1 were concentrated around the agricultural region of Slavonia and the coastal region of Dalmatia. However, only Brod-Posavina County and Vukovar-Srijem County had a statistically significant risk of UUC development, where there were 390 and 210% more UUC cases observed than expected, respectively. Only unique to Brod-Posavina County, females were at higher risk (SIR 4.96; 95% CI 3.59-6.34) of developing UUCs than males (SIR 3.03; 95% CI 2.04-4.01) when compared to their Croatian counterparts. Although Brod-Posavina County only made up 3.7% of the total Croatian population (as of 2011), it had the highest frequency of incident UUC cases after the capital City of Zagreb. No elevated cancer risks were noted in the City of Zagreb, even after stratifying by sex. CONCLUSION: Our findings suggest that Brod-Posavina County had the highest cancer risk for UUCs, especially among females, when compared to Croatia as a whole during 2001-2011. Given that a majority of BEN patients develop associated UUCs, concurrent screening programs for UUCs and BEN should be considered not only in endemic areas of BEN but also the surrounding rural areas and amongst at-risk groups such as those undergoing hemodialysis, who frequently develop UUCs, to help clarify BEN-UUC associations by identifying common risk factors while standardizing disease estimates across endemic regions for BEN.

Correlation between Family History and the Age of Onset of Childhood Acne in Relation to Sex and Type of Acne.

Acne vulgaris is a common chronic skin disorder of the pilosebaceous unit with a wide range of clinical presentations, which depend on the age of onset of acne, sex, family history of acne, and genetic factors, especially the genes affecting keratinization and desquamation. This retrospective study investigated pediatric acne using the patients' past medical history, with patients aged from newborns to 15 years of age. Acne were further stratified by 5 parameters: sex, age, family history, acne type, and localization. Our main aim was to investigate the possible association between selected parameters and the presence or absence of family history of acne. We did not find statistically significant correlation between sex, age of onset, and positive family history of acne. Furthermore, we did not find any association between age of onset and family history according to family members (mother/father/brother or sister). However, we found statistically significant correlation between sex and type of acne. This retrospective analysis of pediatric acne in Croatia did not reveal statistically significant correlation between positive family history and sex, age of onset, and clinical type of acne. In analyzing the correlation between family history and localization of acne, however, we found that the number of patients with acne localized on both the face and trunk and positive family history was statistically significant higher than expected.

Association of MAPT haplotype-tagging polymorphisms with cerebrospinal fluid biomarkers of Alzheimer's disease: A preliminary study in a Croatian cohort.

INTRODUCTION: Alzheimer's disease (AD) is the world leading cause of dementia. Early detection of AD is essential for faster and more efficacious usage of therapeutics and preventive measures. Even though it is well known that one ε4 allele of apolipoprotein E gene increases the risk for sporadic AD five times, and that two ε4 alleles increase the risk 20 times, reliable genetic markers for AD are not yet available. Previous studies have shown that microtubule-associated protein tau (MAPT) gene polymorphisms could be associated with increased risk for AD. METHODS: The present study included 113 AD patients and 53 patients with mild cognitive impairment (MCI), as well as nine healthy controls (HC) and 53 patients with other primary causes of dementia. The study assessed whether six MAPT haplotype-tagging polymorphisms (rs1467967, rs242557, rs3785883, rs2471738, del-In9, and rs7521) and MAPT haplotypes are associated with AD pathology, as measured by cerebrospinal fluid (CSF) AD biomarkers amyloid ß1-42 (Aß1-42 ), total tau (t-tau), tau phosphorylated at epitopes 181 (p-tau181 ), 199 (p-tau199 ), and 231 (p-tau231 ), and visinin-like protein 1 (VILIP-1). RESULTS: Significant increases in t-tau and p-tau CSF levels were found in patients with AG and AA MAPT rs1467967 genotype, CC MAPT rs2471738 genotype and in patients with H1H2 or H2H2 MAPT haplotype. CONCLUSIONS: These results indicate that MAPT haplotype-tagging polymorphisms and MAPT haplotypes should be further tested as potential genetic biomarkers of AD.

Event-related Potentials Improve the Efficiency of Cerebrospinal Fluid Biomarkers for Differential Diagnosis of Alzheimer's Disease.

INTRODUCTION: The pathological process of Alzheimer's disease (AD) in the brain likely begins 20-30 years earlier than the emergence of its first clinical symptoms and symptoms of AD often overlap with the symptoms of other primary causes of dementia. Therefore, it is crucially important to improve early and differential diagnosis of the disease. Event-related potentials (ERP) measured non-invasively by electroencephalography have shown diagnostic potential in AD. AIMS: The aim of this study was to compare the efficiency of P300 and N200 potentials and reaction time (RT) with commonly used protein biomarkers measured in the cerebrospinal fluid (CSF), including amyloid ß peptide (ß1-42), total tau (t-tau), tau protein phosphorylated at threonine 181 (p-tau181), tau protein phosphorylated at serine 199 (p-tau199), tau protein phosphorylated at threonine 231 (p-tau231), and visinin-like protein 1 (VILIP-1) in differential diagnosis of AD in mild cognitive impairment (MCI) and AD patients. SUBJECTS: The study involved 49 AD patients, 28 patients with MCI, 4 healthy control subjects and 16 patients with other primary causes of dementia. RESULTS: ERP (P300RT, N200RT, P300 counting and N200 counting) showed a moderate to strong correlation with protein CSF biomarkers. We confirmed previous observations of moderate to strong correlation between ERP and neuropsychological testing and showed that P300 latency and RT are shortened in AD patients on therapy with acetylcholinesterase inhibitors. Using ERP and RT, a predictive model for determination of AD likelihood in MCI patients was developed, detecting 56.3% of MCI patients with high risk for development of AD in our cohort. MCI patients with pathological levels of Aß1-42 had prolonged P300 latency, indicating that a combination of ERP and CSF protein biomarkers could improve the differential diagnosis of AD in MCI patients. Additionally, the results suggested the potential of P300 latency in differentiating AD and FTD patients. CONCLUSION: Our data provide possible solutions for improvement of differential diagnosis of AD, and reveal that the diagnostic efficiency of CSF protein biomarkers t-tau, p-tau181, p-tau199, p-tau231 and VILIP-1 could be improved by adding ERP in clinical practice.

Evaluation of cerebrospinal fluid phosphorylated tau231 as a biomarker in the differential diagnosis of Alzheimer's disease and vascular dementia.

BACKGROUND: The diagnosis of either Alzheimer's disease (AD) or vascular dementia (VaD) is still largely based on clinical guidelines and exclusion of other diseases that may lead to dementia. AIMS: In this study, we assessed whether the use of sensitive and specific biomarkers such as phosphorylated tau proteins could contribute to an earlier and more accurate diagnosis of AD and VaD, as well as to their differentiation. MATERIAL AND METHODS: A total of 198 patients, of which 152 had AD, 28 VaD, and 18 were healthy controls (HC), were included in the analyses. We analyzed cerebrospinal fluid (CSF) levels of total tau protein (t-tau), tau protein phosphorylated at threonine 231 (p-tau231), and factor score (FS) determined by combination of p-tau231 and Mini-Mental State Examination (MMSE) in patients with AD and VaD, as well as in HC. We tested the diagnostic accuracy of these biomarkers in the CSF and FS (p-tau231, MMSE) in differentiating AD from VaD and HC. RESULTS: Total tau levels were significantly elevated in subjects with AD compared to HC, as well as in VaD subjects compared to HC. DISCUSSION: p-tau231 levels were significantly higher in patients with ADvsHC as well in patients with VaD vsHC. p-tau231 levels did not distinguish AD from VaD patients. Importantly, FS(p-tau231 and MMSE) showed statistically significant differences in the distribution of subjects with AD and VaD. CONCLUSION: These results indicate that FS (p-tau231 and MMSE) has a strong potential to provide an early distinction between AD and VaD.

Myofascial pain of the head and neck among Croatian war veterans treated for depression and posttraumatic stress disorder.

BACKGROUND: During the Croatian War of Independence, 1991-1995, Croatian soldiers were exposed to traumatic and stressful events. Certain number of soldiers who took part in the war, developed depression and posttraumatic stress disorder (PTSD). Stress is one of the etiological factors in the development of myofascial pain (MPS), although the mechanism of these processes is not entirely understood. The aims of this study were to determine the frequency of myofascial pain among Croatian war veterans with depression and PTSD, association between MPS and severity of depression, to describe the most common locations of trigger points in the region of head and neck, and to find out if there is any association in frequency between MPS and endotracheal intubation. SUBJECTS AND METHODS: A total of 101 Croatian war veterans suffering from PTSD and depression participated in the current study. Diagnosis of myofascial pain was based on detailed anamnestic history and careful clinical examination. RESULTS: Our findings showed a high rate of myofascial pain among Croatian war veterans, with occipital region and right temporal region as the most common places of trigger points. Higher severity of depression was accompanied by a higher percentage of subjects with MPS. Finally, there was no significant association between endotracheal intubation and development of MPS among the war veterans. CONCLUSIONS: It can be concluded that the rate of myofascial pain among Croatian war veterans is high and therefore it must be considered in patients with depression and PTSD. Moreover, the severity of depressive symptomatology seems to be related to the presence of myofascial pain.

Assessment of apoptosis in the native vein used for hemodialysis access.

AIM: To determine whether apoptosis is more common in previously punctured native veins than in non-punctured native veins among patients who undergo surgical creation of arteriovenous fistula (AVF) for dialysis access. METHODS: Cephalic vein specimens were obtained from January 1, 2013 to December 31, 2014 from 60 patients, 30 with previously punctured native veins and 30 with non-punctured native veins. Before AVF placement, a 1-cm vein segment was excised from distal part of the vein for histological, histochemical, and immunohistochemical analysis. Vein specimens were divided into two portions along the longitudinal axis and stained with hematoxylin and eosin for routine histological evaluation. Immunohistochemical analysis was used to localize Bax, p53, caspase 3, and Bcl-2 expression. RESULTS: The group with previously punctured veins showed significantly increased caspase 3 (P<0.001, two-sided Fisher`s Exact Test) and Bax expression (P=0.002, two-sided Fisher`s Exact Test) and significantly decreased Bcl-2 expression (P<0.001, two-sided Fisher`s Exact Test) compared with the control group. There were no significant differences between the groups in p53 expression (?2=0.071, df=1, P=0.791). Fistula failure was significantly more common in the study group (26.7% vs 6.7%, ?2=4.32, df=1, P=0.038). CONCLUSION: Our study indicates a possible role of venipuncture in apoptosis development and a possible role of apoptosis in fistula failure, but we do not have sufficient evidence to conclude that it represents its main cause.

Does Diabetes Have an Influence on Regional Deformation Parameters in Patients with Normal Systolic Function during Off-Pump Coronary Artery Bypass Grafting?

OBJECTIVES: The aim of this study was to assess the recovery of regional myocardial function of the left-ventricular septal wall and the septal site of the mitral valve (MV) annulus by tissue Doppler imaging (TDI). METHODS: In 63 (32 diabetic and 31 control) patients having off-pump coronary artery bypass grafting (OPCABG), including the left internal mammary artery (LIMA) and the left anterior descending coronary artery (LAD), TDI measurements were performed before operation (baseline), 5 min after LIMA-LAD revascularization (early reperfusion) and after completion of all anastomoses (after revascularization). RESULTS: Compared to the patients with diabetes, the controls had higher peak systolic velocities of the mid septal segments in the early reperfusion measurement (p = 0.002). After revascularization, values of peak systolic strain at the basal (-10.13 vs. -13.36%, p = 0.044) and mid septal segments (-8.25 vs. -12.69%, p = 0.009) were decreased in the diabetic patients compared to the controls. There was no difference between the groups with respect to the velocities acquired at the septal site of the MV annulus. CONCLUSIONS: This study demonstrates an insufficient recovery of regional myocardial function in patients with type II diabetes undergoing OPCABG.

Cardiovascular disease (CVD) risk factors in older adults - Perception and reality.

OBJECTIVE: CVD are the leading causes of death and disability in the world. Since there are no published data about the knowledge of CVD risk factors among Croatian older adults, this was the primary aim of this study. Another aim was to determine relationship between actual CVD risk (total cholesterol - TC and triglyceride levels - TG, blood pressure - BP, body mass index - BMI, smoking) and self-assessed CVD risk among older adults. METHODS: We used a cross-sectional epidemiological study in which participants (969 subjects aged >70 years) answered a written questionnaire. Participants' BMI, BP, TC and triglycerides were measured. RESULTS: The actual presence of CVD risk factors in participants did not appear to alter their perceptions of risk compared to participants without CVD risk factors (the percentage of participants who think that they have moderate/high CVD risk is almost the same: 75.5% among participants with actual CVD risk factors; 75.7% among those without CVD risk factors). Accordingly, 24.5% of participants with actual CVD risk factors failed to recognize that risk. Only 23.4% of participants correctly recognized BP target values, while 49.8% participants successfully recognized TC target levels. The knowledge of target BP and/or TC levels did not influence participants' ability to assess their own CVD risk. Surprisingly, 41.8% of participants reported that they have not discussed CVD risk factors with their physicians. CONCLUSION: The results suggest insufficient awareness of CVD risk factors among Croatian older adults and a need for improved promotion of CVD prevention in this population segment.

The risk of developing endemic nephropathy in subjects with proteinuria.

Endemic nephropathy is a chronic tubulointerstitial disease characterized by early damage to the proximal tubule, with low-molecular weight proteinuria being an important hallmark and possible tool for early diagnosis. The aim of this retrospective cohort study was to assess the risk of developing endemic nephropathy in subjects with proteinuria from the endemic region in Croatia. The cohort study included subjects with proteinuria determined by the sulfosalicylic acid method (after 1988 with strip method), involved in the field survey conducted in the Croatian endemic village of Kaniza in 1975 and followed up until 1997. Subjects with endemic nephropathy established at the first visit and patients that failed to present for follow up visits after 1975. were excluded. In the field survey group that consisted of 624 subjects (286 male and 338 female), proteinuria was established in 157 subjects. Upon the application of exclusion and inclusion criteria, the study cohort included 111 of 157 subjects. The mean follow up was 7.26 years (95% confidence interval 4.06-10.46 years). During the follow up period, 19 (17%) subjects with initial proteinuria developed endemic nephropathy. The incidence density of endemic nephropathy among subjects with proteinuria was 1.3 per 100 persons/year. Estimated risk was 0.0137 (confidence interval 0.0087-0.0214) per year of exposure. The presence of proteinuria determined by the sulfosalicylic acid or test strip in subjects from the endemic village indicated that endemic nephropathy would develop in 1.3 of 100 subjects with proteinuria per year.