Validation of the International IgA Nephropathy Prediction Tool in the Greek Registry of IgA Nephropathy.

BACKGROUND: Immunoglobulin A nephropathy (IgAN) is among the commonest glomerulonephritides in Greece and an important cause of end-stage kidney disease (ESKD) with an insidious chronic course. Thus, the recently published International IgAN prediction tool could potentially provide valuable risk stratification and guide the appropriate treatment module. This study aimed to externally validate this prediction tool using a patient cohort from the IgAN registry of the Greek Society of Nephrology. METHODS: We validated the predictive performance of the two full models (with or without race) derived from the International IgAN Prediction Tool study in the Greek Society of Nephrology registry of patients with IgAN using external validation of survival prediction models (Royston and Altman). The discrimination and calibration of the models were tested using the C-statistics and stratified analysis, coefficient of determination ( R D 2 ) for model fit, and the regression coefficient of the linear predictor (ßPI), respectively. RESULTS: The study included 264 patients with a median age of 39 (30-51) years where 65.2% are men. All patients were of Caucasian origin. The 5-year risk of the primary outcome (50% reduction in estimated glomerular filtration rate or ESKD) was 8%. The R D 2 for the full models with and without race when applied to our cohort was 39 and 35%, respectively, and both were higher than the reported R D 2 for the models applied to the original validation cohorts (26.3, 25.3, and 35.3%, respectively). Harrel's C statistic for the full model with race was 0.71, and for the model without race was 0.70. Renal survival curves in the subgroups (<16th, ~16 to <50th, ~50 to <84th, and >84th percentiles of linear predictor) showed adequate separation. However, the calibration proved not to be acceptable for both the models, and the risk probability was overestimated by the model. CONCLUSIONS: The two full models with or without race were shown to accurately distinguish the highest and higher risk patients from patients with low and intermediate risk for disease progression in the Greek registry of IgAN.

A multicenter, open-label, comparative study of B-cell depletion therapy with Rituximab for systemic sclerosis-associated interstitial lung disease.

OBJECTIVES: Rituximab (RTX) may favorably affect lung function and skin fibrosis in patients with systemic sclerosis (SSc). We aimed to assess long-term efficacy and safety of RTX in SSc compared to standard treatment. METHODS: A total of 51 patients with SSc-associated interstitial lung disease were recruited and treated with RTX (n = 33) or conventional treatment (n = 18). Median follow-up was 4 years (range: 1-7). Conventional treatment consisted of azathioprine (n = 2), methotrexate (n = 6), and mycophenolate mofetil (n = 10). RESULTS: Patients in the RTX group showed an increase in FVC at 2 years (mean ± SD of FVC: 80.60 ± 21.21 vs 86.90 ± 20.56 at baseline vs 2 years, respectively, p = 0.041 compared to baseline). In sharp contrast, patients in the control group had no change in FVC during the first 2 years of follow-up. At the 7 year time point the remaining patients in the RTX group (n = 5) had higher FVC compared to baseline (mean ± SD of FVC: 91.60 ± 14.81, p = 0.158 compared to baseline) in contrast to patients in the control group (n = 9) where FVC deteriorated (p < 0.01, compared to baseline). Direct comparison between the 2 groups showed a significant benefit for the RTX group in FVC (p = 0.013). Improvement of skin thickening was found in both the RTX and the standard treatment group; however, direct comparison between groups strongly favored RTX at all-time points. Adverse events were comparable between groups. CONCLUSIONS: Our data indicate that RTX has a beneficial effect on lung function and skin fibrosis in patients with SSc. Randomized controlled studies are highly needed.

Radiobiologic comparison of helical tomotherapy, intensity modulated radiotherapy, and conformal radiotherapy in treating lung cancer accounting for secondary malignancy risks.

The aim of the present study is to examine the importance of using measures to predict the risk of inducing secondary malignancies in association with the clinical effectiveness of treatment plans in terms of tumor control and normal tissue complication probabilities. This is achieved by using radiobiologic parameters and measures, which may provide a closer association between clinical outcome and treatment delivery. Overall, 4 patients having been treated for lung cancer were examined. For each of them, 3 treatment plans were developed based on the helical tomotherapy (HT), multileaf collimator-based intensity modulated radiation therapy (IMRT), and 3-dimensional conformal radiation therapy (CRT) modalities. The different plans were evaluated using the complication-free tumor control probability (p+), the overall probability of injury (pI), the overall probability of control/benefit (pB), and the biologically effective uniform dose (D¯¯). These radiobiologic measures were used to develop dose-response curves (p-D¯¯ diagram), which can help to evaluate different treatment plans when used in conjunction with standard dosimetric criteria. The risks for secondary malignancies in the heart and the contralateral lung were calculated for the 3 radiation modalities based on the corresponding dose-volume histograms (DVHs) of each patient. Regarding the overall evaluation of the different radiation modalities based on the p+ index, the average values of the HT, IMRT, and CRT are 67.3%, 61.2%, and 68.2%, respectively. The corresponding average values of pB are 75.6%, 70.5%, and 71.0%, respectively, whereas the average values of pI are 8.3%, 9.3%, and 2.8%, respectively. Among the organs at risk (OARs), lungs show the highest probabilities for complications, which are 7.1%, 8.0%, and 1.3% for the HT, IMRT, and CRT modalities, respectively. Similarly, the biologically effective prescription doses (DB¯¯) for the HT, IMRT, and CRT modalities are 64.0, 60.9, and 60.8Gy, respectively. Regarding the risk for secondary cancer, for the heart, the lowest average risk is produced by IMRT (0.10%) compared with the HT (0.17%) and CRT (0.12%) modalities, whereas the 3 radiation modalities show almost equivalent results regarding the contralateral lung (0.8% for HT, 0.9% for IMRT, and 0.9% for CRT). The use of radiobiologic parameters in the evaluation of different treatment plans and estimation of their expected clinical outcome is shown to provide very useful clinical information. The radiobiologic analysis of the response probabilities showed that different radiation modalities appear to be more effective in different patient geometries and target sizes and locations. Furthermore, there is not a clear pattern between the plans that appear to be more effective for the treatment and the risk of secondary malignancy. It seems that radiobiologically based treatment planning taking into account the risk of secondary cancer can be established as an effective clinical tool for a more clinically relevant treatment optimization.

Ureteric response to abdominal radiotherapy and metallic double-pigtail ureteric stents: a pig model.

OBJECTIVE: To examine the safety and compatibility of full-length metal ureteric stents with abdominal radiotherapy. MATERIALS AND METHODS: Four ureteric stents (Resonance(TM), Cook Urological, Ireland) (RS) and four RSs specially modified to contain thermocouples were placed unilaterally in eight pigs. The contralateral ureters of the same pigs served as their controls, and contained two polymeric ureteric catheters and two similar specially modified to contain thermocouples, while the remaining four control ureters remained intact. All pigs were exposed to abdominal radiotherapy. The dose rate was approximately 5.3 Gy/min and a total radiation dose of 10 Gy was administered. Throughout the treatment the temperature was monitored by the RSs and catheters containing the thermocouples. The pigs were killed at 1 day (four), 7 days (two) and 15 days (two) after treatment, and all ureters examined histologically. RESULTS: There was no statistically significant increase in RS and catheter temperature throughout the treatment in any of the treated pigs (P > 0.05). All histological lesions reported were due to radiation treatment. There were no differences in histology between the ureters containing RSs and controls. CONCLUSION: RS usage is unrelated to any increase in stent temperature during abdominal radiotherapy and does not cause any further deterioration in the histology of the ipsilateral ureter, additional to that caused by the initial treatment.

Interictal alterations of cardiovagal function in chronic epilepsy.

AIM: To assess the function of parasympathetic heart control in patients with epilepsy by means of clinical routine neurophysiology. MATERIALS AND METHODS: Seventy-one consecutive epileptic patients (mean age+/-S.D. 37.8+/-12.9 years) with partial or generalized seizures manifested for more than 6 months and receiving various therapeutic regimes and 71 matched for sex and age healthy controls undertook a battery of neurophysiological tests which consisted of sensory conduction of sural nerve; R-R interval variation during normal and deep breathing; Valsalva manoeuvre and tilt test for calculation heart rate changes to respiratory strain and standing. RESULTS: The patient group showed a significant difference in all parasympathetic parameters studied compared to the control group. Overall, 42.2% of patients had abnormal measurement in at least one of the parameters and Valsalva was the most frequently abnormal one (31% of patients). Sural nerve amplitude was significantly lower in the patients than in the controls and its measurements were associated with those of the tilt test. Long epilepsy duration (more than 10 years) and treatment with phenytoin showed a negative effect on data of R-R interval variation during deep breathing. No other correlations between measurements of parasympathetic parameters and epilepsy related characteristics i.e. type and frequency of seizure, monotherapy or combined therapy with seven other antiepileptic medications, were proven. CONCLUSIONS: Our results suggested that simple neurophysiological tests, suitable for screening purposes were able to demonstrate suppressed cardiovagal control in epileptic patients and to identify those in need for further analysis of cardiovagal function.

Evaluation of conduction properties of somatic and sympathetic sudomotor fibers in patients with epilepsy.

To assess the function of fast somatic nerve fibers and sympathetic sudomotor system in patients with partial or generalized seizures, receiving various therapeutic regimes. The authors studied 60 patients (mean age 36.7 +/- 12.5 years) and 60 matched healthy controls by clinical, conventional nerve conduction study, and sympathetic skin responses (SSR) from hand and foot. Compared with controls, patients showed a tendency, occasional reaching significant level, to conduction slowing and amplitude reduction in the sensory and less often in the motor nerve study. Clinical signs of neuropathy were disclosed in 8.3% of patients, whereas at least one abnormal sensory parameter was evident in 18.3%. Mean SSR latencies in the patients were significantly prolonged. At least one SSR abnormality was shown in 20 (33.3%) patients; six of these had absent SSR from the hand or/and the foot. Polytherapy (vs. monotherapy) and topiramate, but not any other particular drug, seemed to have a negative effect on SSR measurements. The results suggested that despite the insignificant clinical manifestations of neuropathy, an electrophysiological examination was able to demonstrate some subclinical abnormalities of the fast somatic fibers in the peripheral nerves and of the sympathetic sudomotor function in a considerable number of epileptic patients.

Inheritance and perinatal consequences of inherited thrombophilia in Greece.

OBJECTIVE: To investigate the impact of inherited thrombophilic factors on the gestational outcome of unselected pregnant women. METHOD: A total of 392 women with spontaneous pregnancy were investigated for Factor V Leiden, prothrombin G20210A, and MTHFR C677T mutations. Adverse pregnancy outcomes were recorded. RESULTS: Thrombophilic genotypes were significantly higher in women with placental abruption. Heterozygocity for Factor V Leiden increased the risk for placental abruption 9.1 times. The MTHFR T677T genotype increased the risk for placental abruption 4.8 times despite folate supplements, and normal serum folate and B(12) levels. Women with inherited thrombophilia and previous obstetric complications were at significant risk for complications in a subsequent pregnancy (P<0.05). CONCLUSION: Women with placental abruption should be screened for thrombophilic factors and plasma homocysteine should be measured. Subgroups of women with inherited thrombophilia and obstetric complications might benefit from prophylactic anticoagulation in subsequent pregnancies.