Central sensitization: its prevalence and impact on quality of life among hemodialyzed patients.

BACKGROUND/AIM: Data on the role of central sensitization in hemodialyzed patients are scarce. The aim was to identify the impact of central sensitization on quality of life and elucidate the risk factors for the development of central sensitization in patients receiving hemodialysis. METHODS: Central sensitization, quality of life, psychological well-being, and sleep were assessed by the Central Sensitization Inventory (CSI), abbreviated version of the World Health Organization Quality of Life Instrument (WHOQOL-BREF), Hospital Anxiety and Depression Scale (HADS), and Jenkins Sleep Evaluation Scale (JSS), respectively. The effect of central sensitization on quality of life and the predictors of the development of central sensitization were assessed by regression analyses. RESULTS: The frequency of central sensitization was 48% in the study population (n = 100). Patients with central sensitization had significantly higher pain intensity, worse sleep quality, and more impaired psychological status (p < 0.05 for all). The CSI score negatively affected all quality of life domains on its own (p < 0.001 for all, adjusted R2 ranged from 0.17 to 0.47). Dialysis vintage (OR, 0.8; 95% CI, 0.7 to 1.0), pain (OR, 1.5; 95% CI, 1.1 to 2.0), JSS (OR, 1.3; 95% CI, 1.1 to 1.5), and HADS-total (OR, 1.1; 95% CI, 1.0 to 1.2) were determined as the independent risk factors for central sensitization (p < 0.05 for all). CONCLUSION: This study confirms that given the high frequency of central sensitization and its significant negative impact on quality of life, the presence of central sensitization should be investigated in patients undergoing hemodialysis.

A Novel Approach: Evaluating ChatGPT's Utility for the Management of Thyroid Nodules.

Background and objective Artificial intelligence (AI) applications such as Chat Generative Pre-Trained Transformer (ChatGPT) created by OpenAI, which represent the revolutionary aspects of today's technology, have benefitted professionals in many fields and society at large. In this study, we aimed to assess how effective is ChatGPT in helping both the patient and the physician manage thyroid nodules, a very common pathology. Methods Fifty-five questions frequently asked by patients were identified and asked to ChatGPT. Subsequently, three cases of thyroid nodules were progressively presented to ChatGPT. The answers to patient questions were scored for correctness and reliability by two endocrinologists. As for the cases, diagnostic and therapeutic approaches provided by ChatGPT were analyzed and scored by two endocrinologists for correctness, safety, and usability. The responses were evaluated by using 7-point Likert-type scales designed by us. Results The answers to patient questions were found to be mostly correct and reliable by both raters (Rater #1: 6.47 ± 0.50 and 6.27 ± 0.52; Rater #2: 6.18 ± 0.92 and 6.09 ± 0.96). Regarding the management of cases, ChatGPT's approach was found to be largely correct, safe, and usable by Rater #1, while Rater #2 evaluated the approaches as partially or mostly correct, safe, and usable. Conclusion Based on our findings, ChatGPT can be used as an informative and reliable resource for managing patients with thyroid nodules. While it is not suitable to be used as a primary resource for physicians, it has the potential to be a helpful and supportive tool.

Ultrasonographical, clinical and histopathological features of 1264 nodules with papillary thyroid carcinoma and microcarcinoma based on tumor size.

OBJECTIVE: We aimed to evaluate the patients diagnosed with papillary thyroid carcinoma (PTC) and papillary thyroid microcarcinoma (PTMC) in terms of clinical, ultrasonographical (US) and histopathological features and their relationships with tumor size. METHODS: We retrospectively evaluated 881 patients who underwent thyroid surgery in our clinic and diagnosed with PTC histopathologically were enrolled the study. Demographic characteristics, US findings and histopathological features were evaluated. RESULTS: In total, 1264 nodules were identified in the 881 patients. The incidentality rates were higher in the PTMC group and also in the ≤ 5 mm group. In total multifocality rate was 32.9%, and was significantly higher in PTMC group than the PTC group. PTC and > 5 mm PTMC groups compared to PTMC and ≤ 5 mm groups respectively, were more aggresive histopathological features. CONCLUSION: Since the incidentality rates were found significantly more common in our patients with PTMC and those with ≤ 5 mm, ultrasonographic features of the nodules should be evaluated carefully and for cases which are suspicious with US, US-guided fine needle aspiration biopsy (FNAB) should be considered in order to make the correct treatment strategy. Also our study revealed that PTC and > 5 mm PTMC groups compared to PTMC and ≤ 5 mm groups respectively, have more aggresive histopathological features.

Serum fibroblast growth factor 23 levels do not correlate with carotid intima-media thickness in patients with chronic kidney disease.

High levels of fibroblast growth factor 23 (FGF 23) are associated with mortality and cardiovascular events in patients with chronic kidney disease (CKD). Carotid intima-media thickness (CIMT) is a useful marker of subclinical atherosclerosis. This study aimed to investigate the relationship between serum FGF23 levels and CIMT of CKD patients. In this cross-sectional study, CIMT was measured in 162 patients with CKD Stage of 2-5 (age range 18-79 years, 61.7% males). Serum FGF23 levels were determined by enzyme-linked immunosorbent assay. CIMT was measured by ultrasonography. Serum FGF-23 levels were significantly higher (P = 0.046) in advanced CKD patients. CIMT was thicker in patients with advanced CKD patients (P = 0.01). CIMT was correlated with age (r = 0.486, P <0.001), smoking (r = 0.411, P <0.001), and 25-OH Vitamin D (r = -0.195, P= 0.045). There was no correlation between serum FGF23 and CIMT. Multivariate analysis showed that age (ß = 0.373, P <0.001), smoking (ß = 0.228, P = 0.004), and serum 25-hydroxyvitamin D levels (ß = -0.164, P = 0.042) were associated with CIMT. There was no relationship between FGF23 and CIMT. The CIMT was found to be related to increased age, smoking, and 25-hydroxyvitamin D in CKD patients.

Loss of vision and renal function in a patient with miliary tuberculosis.

INTRODUCTION: Visual loss is a rare complication of tuberculosis; it can be related to anti-tuberculous drugs or to the infection itself. For the treatment of visual loss, differential diagnosis is important between infection and adverse effect of anti-tuberculous drugs. CASE: A 48-year-old male patient with a history of tuberculosis and visual loss during anti-tuberculous drug therapy was admitted to our hospital. Anti-tuberculous drugs had been stopped on the 2nd day of therapy due to development of optic neuritis secondary to ethambutol administration at another hospital. He had miliary tuberculosis, renal failure requiring dialysis and visual disturbances. Anti-tuberculous drugs, including ethambutol, were initiated at our clinic because the period between the ethambutol therapy and visual loss was too short and the dose of ethambutol was not very high. Computed brain tomography was normal. Fundoscopic examination revealed only hypertensive retinopathy. Our diagnosis was tuberculosis-related visual loss, which could be due to neuroretinitis, intraocular tuberculosis or chiasmal tuberculoma. In addition, ethambutol rarely causes visual loss during the early period or when given at lower doses. In our case no complications developed from the treatment and the patient's visual loss and renal function improved. At his last visit, 12 months later, his vision had improved and his serum creatinine was lower, at 2.2 mg/dL. CONCLUSION: With anti-tuberculous treatment, renal functions and visual disturbances were improved in a patient with miliary tuberculosis. During the anti-tuberculous therapy, visual loss can be related to ethambutol toxicity or the tuberculosis infection itself. Differential diagnosis is very important and anti-tuberculous drugs must be continued if the diagnosis is tuberculosis.

Severe acute renal failure due to tubulointerstitial nephritis, pancreatitis, and hyperthyroidism in a patient during rifampicin therapy.

It is well known that rifampicin can cause nephrotoxicity. Rifampicin-related pancreatitis and hyperthyroidism are rarely reported in the same patient in the presence of tubulointerstitial nephritis. Reported herein is the medical management of a patient with hemolytic anemia, acute renal failure, pancreatitis, and hyperthyroidism during with rifampicin therapy. A 50-year-old man was admitted to the hospital owing to abdominal colic and acute renal failure. He was treated with 2 courses of tetracycline-rifampicin for brucellosis 3 weeks and 4 months prior to admission. Physical examination showed blood pressure of 130/70 mm Hg, pulmonary crackles, and edema. Laboratory findings are detailed in the case report. Findings of abdominal ultrasonography suggested edematose pancreatitis and thyroid ultrasonography showed several solid nodules. Renal biopsy showed tubulointerstitial nephritis. Although rifampicin-related tubulointerstitial nephritis and acute renal failure are not uncommon during rifampicin therapy, the convergence of hyperthyroidism, pancreatitis, tubulointerstitial nephritis, and acute renal failure rarely presents in the same patient. Although pancreatitis, tubulointerstitial nephritis, and acute renal failure were ameliorated with corticoid therapy within 2 months, hyperthyroidism continued and required antithyroid therapy. In conclusion, rifampicin may trigger hyperthyroidism in patients with goiter.

Ultrasonographical, clinical and histopathological features of 1264 nodules with papillary thyroid carcinoma and microcarcinoma based on tumor size

ABSTRACT Objective: We aimed to evaluate the patients diagnosed with papillary thyroid carcinoma (PTC) and papillary thyroid microcarcinoma (PTMC) in terms of clinical, ultrasonographical (US) and histopathological features and their relationships with tumor size. Subjects and methods: We retrospectively evaluated 881 patients who underwent thyroid surgery in our clinic and diagnosed with PTC histopathologically were enrolled the study. Demographic characteristics, US findings and histopathological features were evaluated. Results: In total, 1264 nodules were identified in the 881 patients. The incidentality rates were higher in the PTMC group and also in the ≤ 5 mm group. In total multifocality rate was 32.9%, and was significantly higher in PTMC group than the PTC group. PTC and > 5 mm PTMC groups compared to PTMC and ≤ 5 mm groups respectively, were more aggresive histopathological features. Conclusions: Since the incidentality rates were found significantly more common in our patients with PTMC and those with ≤ 5 mm, ultrasonographic features of the nodules should be evaluated carefully and for cases which are suspicious with US, US-guided fine needle aspiration biopsy (FNAB) should be considered in order to make the correct treatment strategy. Also our study revealed that PTC and > 5 mm PTMC groups compared to PTMC and ≤ 5 mm groups respectively, have more aggresive histopathological features.

Effects of cyclosporine and tacrolimus on maintenance therapy after renal transplantation.

The immunosuppressive agents cyclosporine A and tacrolimus have demonstrated efficacy in preventing acute organ rejection after renal transplantation, but no comparative studies of these 2 agents have been published. This study compared the effects of tacrolimus and cyclosporine A on the renal function, blood pressure, and serum glucose and lipid levels of patients who underwent cyclosporine A therapy and C2 monitoring or tacrolimus therapy and standard monitoring during the first 24 months after transplantation. By the end of the follow-up period, no significant difference between either treatment group was noted in the measures of creatine clearance; BUN, glucose, uric acid, and lipid levels; or diastolic blood pressure (P>.05 for all), which were maintained at normal values throughout the study. Systolic blood pressure was significantly lower in the cyclosporine A group at the end of the 1 st month (P<.025) but this difference was not evident at months 6, 12, and 24 (P>.05). These results indicate that tacrolimus and cyclosporine (when combined with C2 monitoring) were equally effective and safe in preventing acute organ rejection.

Nonsynergistic effects of trimetazidine and selenium combination therapy on renal ischemic-reperfusion injury in rats.

Reactive oxygen species (ROS) have been postulated to play a major role in postischemic acute renal injury. Moreover, lipid peroxidation has been described as an important pathway of ROS-induced postischemic acute renal failure. To evaluate effects of selenium (Se) and trimetazidine (TMZ) on postischemic renal failure, renal tissue malondialdehyde (MDA) and superoxide dismutase (SOD) concentrations were measured in Wistar rats with ischemic renal failure. Treatment groups consisted of rats treated with TMZ (5 mg/kg orally) or Se (30 microg/kg orally) or TMZ+Se for 15 days. Ischemic groups consisted of rats with clamped left renal arteries for 1 hour. Before left renal arterial clamping, right nephrectomy was performed; after 24 hours, left nephrectomy was done. The animals were divided into 5 groups. Group 1 (n=7) was the nonischemic control group without treatment; Group 2 (n=6) was the ischemic control group treated with physiologic solution; Group 3 (n=5) received TMZ; Group 4 (n=5) received Se; and Group 5 (n=6) received TMZ+Se for 15 days. After TMZ and Se treatment, right renal tissue MDA significantly decreased in Groups 3-5 when compared with those in Group 1. There was no significant difference between nonischemic and ischemic renal tissue MDA in Groups 3, 4, and 5. Postischemic renal tissue SOD levels were higher than nonischemic levels in Group 3. In Groups 4 and 5, no significant differences were observed between nonischemic and ischemic renal tissue SOD levels. Moreover, total scores obtained from histopathologic evaluation of ischemic and nonischemic kidney samples in Groups 3, 4, and 5 were similar, but these scores in Group 2 were significantly different from those of Groups 3, 4, and 5. These results indicate that, under these study conditions, TMZ, Se, and TMZ+Se treatments prevent lipid peroxidation in ischemic and nonischemic renal tissue. Moreover, these treatments prevent histologic findings of postischemic-perfusion renal injury.

Is there any relationship between serum levels of interleukin-10 and atherosclerosis in hemodialysis patients?

OBJECTIVE: Cardiovascular complications due to atherosclerosis (AS) are the major cause of mortality in hemodialysis (HD) patients. Inflammation may play an important role in the development of AS. Several studies have demonstrated an association between AS and acute-phase proteins and cytokines in the general population and in HD patients. Interleukin-10 (IL-10) is an anti-inflammatory cytokine. The aim of this study was to compare serum levels of inflammatory and anti-inflammatory indicators in HD patients according to the presence or absence of AS. MATERIAL AND METHODS: A total of 33 HD patients were studied. AS was defined as the presence of plaques as detected by Doppler ultrasonography. The patients were subgrouped according to the presence or absence of plaques. Serum levels of IL-1, -2, -6 and -10, C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-alpha) were measured. Risk factors for AS, such as age, gender, hypertension, hyperlipidemia and duration of HD, were also evaluated. RESULTS: Patients with AS had significantly higher high sensitivity (hs)-CRP and lower IL-10 levels. Blood pressure was also elevated in patients with AS. There was an inverse correlation between CRP and IL-10 levels in patients with AS. CONCLUSION: Patients with AS undergoing HD had low serum levels of the anti-inflammatory cytokine IL-10 and high serum levels of hs-CRP. These results may suggest that limitation of the anti-inflammatory response in atherosclerotic uremic patients is a triggering or contributory factor for AS.

Permanent improvement of renal dysfunction and proteinuria with colchicine in a patient with tumoral amyloidosis and basal cell carcinoma.

Basal cell carcinoma and amyloid deposition was reported not uncommonly, but renal failure and nephrotic syndrome were rare. Here in, we reported a 72 years old male patient with nephrotic syndrome, renal failure and relatively small basal cell carcinoma. In this patient toumoral excision caused temporary improvement. When the proteinuria reappeared, due to amyloid deposition in toumoral tissue, colchicine was began. With colchicine therapy permanent improvement of nephrotic syndrome was achieved in follow-up 18 months.

A unique form of polycythemia associated with minimal change disease.

OBJECTIVE: To present a case with nephrotic syndrome due to minimal change disease and polycythemia. CLINICAL PRESENTATION AND INTERVENTION: A 20-year-old female was admitted to our clinic for edema and severe proteinuria present with minimal change disease since the age of 7 years. Polycythemia was found during the last activation of nephrotic syndrome. The patient was placed on glucocorticoid therapy that caused disappearance of edema, proteinuria and polycythemia. Ten months later both hemoglobin and hematocrit levels were within normal range. CONCLUSION: This patient with nephrotic syndrome due to minimal change disease and polycythemia was successfully treated with glucocorticoid.

Which parameter is more influential on the development of arteriosclerosis in hemodialysis patients?

Arteriosclerosis is characterized by stiffening of arteries. The incremental elastic modulus (Einc) measurement is a good marker of arterial wall stiffness. Metabolic, inflammatory and hemodynamic alterations cause structural changes and vascular complications in end stage renal disease. The aim of the present study was to evaluate the factors that may affect the development of arteriosclerosis by measurement of Einc in hemodialysis (HD) patients. Thirty-two patients (16 men; 16 female) on chronic HD with a mean age of 42.2 +/- 19.3 (range: 15-80) were included in the study. The carotid Einc was measured to determine arteriosclerosis by high-resolution echo-tracking system (Acuson Aspen, Acuson Corp., Mountain View, California, USA). Einc measurement was calculated from transcutaneous measurements of common carotid arterial (CCA) internal diameter and wall thickness and carotid pulse pressure. Common carotid compliance and distensibility were determined from changes in carotid artery diameter during systole and simultaneously measured carotid pulse pressure. Common carotid artery stuffiness (Einc) was influenced by age, systolic blood pressure (SBP), pulse pressure (PP), calcium (Ca) and alkaline phosphatase (ALP). The distensibility of CCA was correlated with age, SBP, diastolic blood pressure (DBP), PP, Ca, ALP, and parathormone (PTH). The inflammatory parameter, hs-CRP, was increased with Einc. The mean Einc measurement was found significantly increased in patient receiving vitamin D. In conclusion, the stiffening of carotid artery in HD patients is related not only to hemodynamic changes (increased SBP, PP) but also to metabolic (increased Ca) and to inflammation (increased hs-CRP). Carotid Einc is accepted independent risk factor for cardiovascular mortality. Because of the positive correlation between Einc and serum Ca, vitamin D and Ca containing phosphorus (P) binders should be used carefully.

Oxidative-antioxidative system in peripartum acute renal failure and preeclampsia-eclampsia.

BACKGROUND: Preeclampsia-eclampsia and acute renal failure in peripartum women can be the cause of mortality and morbidity. There are many different reports about oxidative-antioxidative systems in preeclampsia-eclampsia. Until now, products of activated oxidative-antioxidative systems were not evaluated in peripartum women with acute renal failure. In this study, our aim was to evaluate the oxidative-antioxidative systems in peripartum women with acute renal failure and/or preeclampsia-eclampsia. METHODS: The study groups consisted of 17 peripartum women (first week of delivery) with acute renal failure (G I), 11 preeclamptic (G II), 11 healthy pregnancy (> or = 30 weeks of pregnancy) (G III), and 11 healthy women (G IV) aged between 18-38 years. Superoxide dismutase (SOD), glutathione peroxidase (GSHPx) in erythrocytes, and plasma malondialdehyde (MDA) levels were measured in all groups. SOD, GSHPx, and MDA levels were also measured at the onset of acute renal failure (G IA), regression of renal dysfunction (G IB) and recovery of renal functions (G IC). RESULTS: MDA levels were 11.95+/-4.25, 9.22+/-3.62, 5.10+/-3.65, 3.40+/-1.27, 4.91+/-2.06, 4.24+/-1.67 mmol/mL in G IA, G IB, G IC, G II, G III, and G IV, respectively. SOD activity in erythrocyte were 3269.23+/-1437.83, 2641.35+/-1411.13, 2056.35+/-1143.11, 924+/-160.04, 1057.91+/-257.03, 861.63+/-243.28 Ug/Hb in G IA, G IB, G IC, G II, G III, and G IV, respectively. GSHPx activity in erythrocyte was 70.17+/-23.52, 58.27+/-23.75, 45.44+/-17.60, 24.48+/-6.77, 26.28+/-7.27, 32.95+/-8.24 Ug/Hb in G IA, G IB, G IC, G II, G III, and G IV, respectively. MDA levels and activities of SOD, GSHPx in erythrocytes were highest in GIA The values of MDA, SOD, and GSH-Px in G IA, G IB, and G IC were significantly different from each other and decreased while regaining of renal functions. Preeclampsia-eclampsia or normal pregnancy did not cause elevation of plasma MDA levels and GSHPx, SOD in erythrocyte. CONCLUSION: Although SOD and GSHPx in erythrocytes and plasma MDA level were found to be similar in healthy women, pregnant women, and preeclamptic women; SOD, GSHPx, and MDA increased at the beginning and decreased during recovery of renal functions in peripartum women with acute renal failure.

Other glomerular pathologies in three patients with diabetes mellitus.

Diabetic nephropathy is the common cause of end stage renal disease in diabetes mellitus. But other glomerular pathologies have been also described in diabetic patients. We described 3 cases with diabetes mellitus and other glomerular diseases. Case I: A 59-year-old male patient with type 2 diabetes mellitus for 4 years was evaluated for generalized edema. Physical examination showed pretibial edema and no diabetic retinopathy. The cause of nephrotic syndrome was membranoproliferative glomerulonephritis. Conservative therapy could not control the severe proteinuria and renal dysfunction. With corticosteroid and cyclophosphamide therapy partial remission was obtained. Case II: A 46-year-old diabetic woman was evaluated for severe proteinuria. Diabetic retinopathy was not found on her funduscopic examination. Mesangioproliferative glomerulonephritis was found on renal biopsy. Proteinuria did not regress with conservative therapy and corticosteroid and cyclophosphamide. Case III: A 48-year-old male patient with diabetes mellitus type 2 for 2 years was admitted to the hospital because of nephrotic syndrome and weakness. At another hospital his diagnosis with biopsy showed minimal change disease. He was treated with corticosteroid since 3 months. His renal biopsy was reevaluated and found amyloid deposition but not diabetic nephropathy or minimal change disease. In diabetic patients, nondiabetic nephropathy is not uncommon and it was reported as common as about 30%. In addition to therapy for diabetes mellitus these patients can need specific therapy.

Heart rate variability, left ventricular functions, and cardiac autonomic neuropathy in patients undergoing chronic hemodialysis.

OBJECTIVE: Autonomic neuropathy and impairment of left ventricular functions (LVF) have been frequently encountered in chronic renal failure (CRF). The aim of the present study was to evaluate the relationship of cardiac autonomic modulation impairments, as assessed by means of heart rate variability (HRV), with clinical characteristics, and left ventricular function in the patients with CRF undergoing hemodialysis (HD). METHODS: Twenty control subjects (Group I) and 22 comparable by age and gender patients with CRF undergoing hemodialysis (Group II) were enrolled in the study. After routine clinical and biochemical evaluations, electrocardiography, and 2 Dimensional, M Mode echocardiography were performed in all participants. Frequency domain HRV analysis was studied by using Kardiosis System. The powers (P1 and P2) and the central frequencies (F1 and F2) of low and of high frequency spectral bands were recorded. RESULTS: End systolic (ESV) and end diastolic volumes (EDV) were significantly higher in Group II (59.3 +/- 21.1mL vs. 34.0 +/- 14.3 mL and 131.5 +/- 37.3 mL vs. 96.9 +/- 18.9 mL, p < 0.01, p < 0.05, respectively) when compared to those of Group I. Ejection fraction (EF) and fractional shortening (FS) were significantly lower in Group II than in control subjects (52.3 +/- 2.4% vs. 63.7 +/- 10.1% and 0.29 +/- 0.01 vs. 0.34 +/- 0.07, p < 0.001, p < 0.05, respectively). P and P2 were decreased in Group II than in Group I (136.2 +/- 173.9 m s2 vs. 911.0 +/- 685.5 and 96.5 +/- 149.6 vs. 499.7 +/- 679.5, p < 0.001, p < 0.01, respectively). Significant correlations were found between high frequency spectral power and dialysis duration (DD), ESV, EDV, EF, FS (r = 0.52 p < 0.01, r = 0.68 p < 0.001, r = 0.65 p < 0.002, r = 0.66 p < 0.02, and r = 0.69 p < 0.01). CONCLUSION: As a result, the dependence of cardiac autonomic neuropathy on the disease duration and degree of left ventricular function impairment was shown in the patients undergoing chronic hemodialysis.

The prevalence and clinical features of tuberculous peritonitis in CAPD patients in Turkey, report of ten cases from multi-centers.

OBJECTIVE: To determine the rate, risk factors and outcome of Tuberculous Peritonitis (TBP) in patients treated with continuous ambulatory peritoneal dialysis (CAPD) in our units. DESIGN: Retrospectively, we reviewed the medical data of all CAPD patients from 12 centers for TBP, covering the period between 1986 and December 2002. SETTING: All patients were from 12 renal clinics at tertiary-care university hospitals. RESULTS: Ten cases of TBP were identified among the CAPD patients in our centers. There were five male and five female patients with a mean age of 37.2 years. None of the patients had tuberculosis history, 6 patients had predominance of PNL. One patient had coincidental bacterial peritonitis. Two patients were successfully treated without the removal of the Tenckhoff catheter. CONCLUSION: TBP in CAPD patients is a very rare complication. In contrast to predominance of lymphocytes in nonuremic patients with tuberculous peritonitis, CAPD patients with tuberculous peritonitis may have predominance of PNL on examination of the peritoneal fluid. Since TBP has high morbidity and mortality, early diagnosis and treatment of disease are extremely important for improving outcome.