Hypothyroidism Induced Severe Rhabdomyolysis in a Hemodialysis Patient

Hypothyroidism occurs relatively common and is a significant cause of morbidity and mortality during the course of chronic kidney disease. Rhabdomyolysis is a potentially life-threatening condition characterised by necrosis of muscular tissue and rarely associates with hypothyroidism. Here we describe a case of rhabdomyolysis due to severe hypothyroidism in a 56-year-old female hemodialysis patient

Neither a Nitric Oxide Donor Nor Potassium Channel Blockage Inhibit RBC Mechanical Damage Induced by a Roller Pump

Red blood cells (RBC) are exposed to various levels of shear stresses when they are exposed to artificial flow environments, such as extracorporeal flow circuits and hemodialysis equipment. This mechanical trauma affects RBC and the resulting effect is determined by the magnitude of shear forces and exposure time. It has been previously demonstrated that nitric oxide (NO) donors and potassium channel blockers could prevent the sub-hemolytic damage to RBC, when they are exposed to 120 Pa shear stress in a Couette shearing system. This study aimed at testing the effectiveness of NO donor sodium nitroprussid (SNP, 10-4 M) and non-specific potassium channel blocker tetraethylammonium (TEA, 10-7 M) in preventing the mechanical damage to RBC in a simple flow system including a roller pump and a glass capillary of 0.12 cm diameter. RBC suspensions were pumped through the capillary by the roller pump at a flow rate that maintains 200 mmHg hydrostatic pressure at the entrance of the capillary. An aliquot of 10 ml of RBC suspension of 0.4 L/L hematocrit was re-circulated through the capillary for 30 minutes. Plasma hemoglobin concentrations were found to be significantly increased (~7 folds compared to control aliquot which was not pumped through the system) and neither SNP nor TEA prevented this hemolysis. Alternatively, RBC deformability assessed by laser diffraction ektacytometry was not altered after 30 min of pumping and both SNP and TEA had no effect on this parameter. The results of this study indicated that, in contrast with the findings in RBC exposed to a well-defined magnitude of shear stress in a Couette shearing system, the mechanical damage induced by a roller pump could not be prevented by NO donor or potassium channel blocker

Constitutive gene expression profile segregates toxicity in locally advanced breast cancer patients treated with high-dose hyperfractionated radical radiotherapy

Breast cancer patients show a wide variation in normal tissue reactions after radiotherapy. The individual sensitivity to x-rays limits the efficiency of the therapy. Prediction of individual sensitivity to radiotherapy could help to select the radiation protocol and to improve treatment results. The aim of this study was to assess the relationship between gene expression profiles of ex vivo un-irradiated and irradiated lymphocytes and the development of toxicity due to high-dose hyperfractionated radiotherapy in patients with locally advanced breast cancer. Raw data from microarray experiments were uploaded to the Gene Expression Omnibus Database (GEO accession GSE15341). We obtained a small group of 81 genes significantly regulated by radiotherapy, lumped in 50 relevant pathways. Using ANOVA and t-test statistical tools we found 20 and 26 constitutive genes (0 Gy) that segregate patients with and without acute and late toxicity, respectively. Non-supervised hierarchical clustering was used for the visualization of results. Six and 9 pathways were significantly regulated respectively. Concerning to irradiated lymphocytes (2 Gy), we founded 29 genes that separate patients with acute toxicity and without it. Those genes were gathered in 4 significant pathways. We could not identify a set of genes that segregates patients with and without late toxicity. In conclusion, we have found an association between the constitutive gene expression profile of peripheral blood lymphocytes and the development of acute and late toxicity in consecutive, unselected patients. These observations suggest the possibility of predicting normal tissue response to irradiation in high-dose non-conventional radiation therapy regimens. Prospective studies with higher number of patients are needed to validate these preliminary results

Combined low initial DNA damage and high radiation-induced apoptosis confers clinical resistance to long-term toxicity in breast cancer patients treated with high-dose radiotherapy

Journal Article; Research Support, Non-U.S. Gov't;BACKGROUND. Either higher levels of initial DNA damage or lower levels of radiation-induced apoptosis in peripheral blood lymphocytes have been associated to increased risk for develop late radiation-induced toxicity. It has been recently published that these two predictive tests are inversely related. The aim of the present study was to investigate the combined role of both tests in relation to clinical radiation-induced toxicity in a set of breast cancer patients treated with high dose hyperfractionated radical radiotherapy. METHODS. Peripheral blood lymphocytes were taken from 26 consecutive patients with locally advanced breast carcinoma treated with high-dose hyperfractioned radical radiotherapy. Acute and late cutaneous and subcutaneous toxicity was evaluated using the Radiation Therapy Oncology Group morbidity scoring schema. The mean follow-up of survivors (n = 13) was 197.23 months. Radiosensitivity of lymphocytes was quantified as the initial number of DNA double-strand breaks induced per Gy and per DNA unit (200 Mbp). Radiation-induced apoptosis (RIA) at 1, 2 and 8 Gy was measured by flow cytometry using annexin V/propidium iodide. RESULTS. Mean DSB/Gy/DNA unit obtained was 1.70 ± 0.83 (range 0.63-4.08; median, 1.46). Radiation-induced apoptosis increased with radiation dose (median 12.36, 17.79 and 24.83 for 1, 2, and 8 Gy respectively). We observed that those "expected resistant patients" (DSB values lower than 1.78 DSB/Gy per 200 Mbp and RIA values over 9.58, 14.40 or 24.83 for 1, 2 and 8 Gy respectively) were at low risk of suffer severe subcutaneous late toxicity (HR 0.223, 95%CI 0.073-0.678, P = 0.008; HR 0.206, 95%CI 0.063-0.677, P = 0.009; HR 0.239, 95%CI 0.062-0.929, P = 0.039, for RIA at 1, 2 and 8 Gy respectively) in multivariate analysis. CONCLUSIONS. A radiation-resistant profile is proposed, where those patients who presented lower levels of initial DNA damage and higher levels of radiation induced apoptosis were at low risk of suffer severe subcutaneous late toxicity after clinical treatment at high radiation doses in our series. However, due to the small sample size, other prospective studies with higher number of patients are needed to validate these results.This work was subsidized by a grant from the Ministerio de Educación y Ciencia (CICYT: SAF 2004-00889) and Fundación del Instituto Canario de Investigación del Cáncer (FICIC).Yes2011-0

Frequency and Outcomes of Pregnancy on Nocturnal Home Haemodialysis

WOS: 000404651700006OBJECTIVE: Pregnancy in women of reproductive age on dialysis is rare and has a poor outcome. Several studies published in the 1990s revealed pregnancy rates of 0.3 to 0.5 per 100 patient- years, but not all pregnancies resulted in live births. More recent studies suggest that intensive haemodialysis increases fertility and successful pregnancies with live births. Our objectives were to evaluate whether nocturnal home haemodialysis (NHHD) three times a week supports successful pregnancies and live births in addition to the changes in clinical and biochemical parameters. MATER IAL and METHODS: Descriptive cohort study analysing pregnancies and their outcomes in 60 women of reproductive age (14- 44 years) who started NHHD between August 2010 and January 2015. RESULTS: During a mean follow-up of 20 +/- 11 months on NHHD, four pregnancies were identified (4 per 100 patient-years). In these four patients, the mean age was 37.3 +/- 4.8 years and the mean NHHD duration 19 +/- 12 months at the beginning of pregnancy. Duration of the weekly haemodialysis session was increased from 23.8 +/- 1.8 at baseline to 36.6 +/- 0.5 hours at term; serum urea was maintained below 50 mg/dl, and haemoglobin over 10 g/dl with an increase in erythropoietin doses. Blood pressure was within the normal ranges and there was no need for antihypertensive drugs. Three women underwent a caesarean section at 38,35,38 weeks, delivering three healthy newborns without any maternal or fetal complications. Birth weights were 2.750, 2.550 and 3.100 g, respectively. The fourth patient (with a history of secondary amyloidosis and multiple spontaneous abortions) delivered at the 25th week, resulting in neonatal death on the second day. CONCLUSION: We observed that women of reproductive age on NHHD had high rates of conception and live birth

Impact Of Oncotype Dx Recurrence Score On Treatment Decisions: Results Of A Prospective Multicenter Study In Turkey

Introduction: Breast cancer is the most common malignancy among Turkish women and the rate of early stage disease is increasing. The Oncotype DX® 21-gene assay is predictive of distant recurrence in ER-positive, HER2-negative early breast cancer. We aimed to evaluate the impact of the Recurrence Score® (RS) on treatment decisions and physician perceptions in Turkey. We also studied correlations between RS and routine risk factors., Patients and Methods: Ten academic centers across Turkey participated in this prospective trial. Consecutive breast cancer patients with pT1-3, pN0-N1mic, ER-positive, and HER2-negative tumors were identified at multidisciplinary tumor conferences. The initial treatment decision was recorded before tumor blocks were sent to the central laboratory. Each case was brought back to tumor conference after receiving the RS result. Both pre- and post-RS treatment decisions and physician perceptions were recorded on questionnaire forms. Correlations between RS and classical risk factors were evaluated using univariate and multivariate analyses., Results: Ten centers enrolled a total of 165 patients. The median tumor size was 2 cm. Of 165 patients, 57% had low RS, 35% had intermediate RS, and 8% had high RS, respectively. The overall rate of change in treatment decision was 33%. Initially, chemotherapy followed by hormonal therapy (CT+HT) was recommended to 92 (56%) of all patients, which decreased to 61 (37%) patients post-RS assay (p<0.001). Multivariate analysis indicated that progesterone receptor (PR) and Ki-67 scores were significantly related to RS., Conclusion: Oncotype DX testing may provide meaningful additional information in carefully selected patients.PubMe

Impact of Oncotype DX Recurrence Score on Treatment Decisions: Results of a Prospective Multicenter Study in Turkey

Introduction: Breast cancer is the most common malignancy among Turkish women and the rate of early stage disease is increasing. The Oncotype DX (R) 21-gene assay is predictive of distant recurrence in ER-positive, HER2-negative early breast cancer. We aimed to evaluate the impact of the Recurrence Score (R) (RS) on treatment decisions and physician perceptions in Turkey. We also studied correlations between RS and routine risk factors