GFR was calculated using the MDRD4 (Modification of Diet of Renal Disease) formula: 186 x (creatinine) -1,154 x (age) -0,203 x (0.7402 if female) x (1.210 if black) and patients were grouped into stages: GF > 90 ml/min (S1 or normal), 89-60 ml/min (S2), 59-30 ml/min (S3) and < 30 ml/min (S4), according to K/DOQI 2002 of the National Kidney Foundation.
Treatment. The cornerstone in the treatment of IgA nephropathy in the general population is the use of renin-angiotensin-aldosterone system blockers (angiotensin converting enzyme [ACE] inhibitors or aldosterone receptor antagonists [ARA II]), together with salt intake restriction to less than 5 g per day and tight blood pressure control (< 125/75 mm/Hg). Inpatientswith concomitant nephrotic syndrome, adding steroids at a dose of 0.5-1 mg/kg/day for 4-6 weeks is recommended (14, 23). In cases with no nephrotic syndrome or renalfunction decline, 3 to 6 months must be allowed in order to assess responseto ACEi or ARAII treatment; if proteinuria remains above 1 g, prednisolone 0.5-1 mg/kg/day for 6 months must be added. During pregnancy, the use of ACE inhibitors and ARA II is contraindicated and treatment is therefore based on salt intake restriction. Monitoring is based on creatinine and proteinuria in 24-hour urine, and remission is considered to have been achieved when proteinuria comes down to less than 500 mg/24 h (14, 23).
Chronic hypothyroidismin adult rats leads to the loss of coronary arterioles and impaired blood flow; it induces maladaptive changes in the shape of myocytes and the development of HF (19). Important changes in cardiac structure and function have been reported inpatientswith overt and subclinicalhypothyroidism (SHypo) with a severity depending on the degree and the duration of thyroid hormone deficiency (14, 15, 16, 77, 78, 79). Hypothyroidism is characterized by a low cardiac output due to the decreased heart rate and stroke volume (15, 16). Systolic and diastolic functions are reduced at rest and during exercise, thus impairing quality of life (80). Cardiac preload is decreased due to the impaired diastolic function and the decreased blood volume (78). Vascular function may also be deranged in overt and mild thyroid hormone deficiency (78, 79, 81). Renal perfusion is decreased with a consequent reduction in glomerular filtration, impaired free water clearance and hyponatremia (15). The cardiac energetic efficiency of the hypothyroid human heart is impaired despite its reduced cardiac oxygen consumption (15). Moreover, important metabolic effects may develop in long-term untreated hypo- thyroidism (74, 75). An increased cardiovascular risk has been reported inpatientswith various degrees of hypothyroidism (74, 75). This may be linked to the increased risk of coronary artery disease and HF associated withhypothyroidism (11, 82, 83). In parti- cular, an increased risk of coronary heart disease events and mortality has been reported in young patients affected by SHypo with TSH O10 mU/l (83, 84).
present in 33 of 2450 patients who attended our center, with a prevalence of 1.34 %; the other 8 patients did not want to participate in the study. The mean daily dose was 147.19 ± 36.47 µg/day, and the mean body weight 69.43 ± 14.59 kg. None of the patients were taking medication known to interfere with LT4 absorption/metabolism (Table I), nor were they known to have gastrointestinal diseases that could alter LT4 absorption (Table I). Gastrointestinal or liver diseases were excluded by absence of symptoms of impaired gastric acid secretion or intestinal malabsorption and, when possible, through laboratory investigations. All 28 patients had normal liver function tests and antibodies against gliadin and endomysium were negative, and 8/28 had parietal-cell antibodies measured and were negative. Carbon-13-labeled- urea breath test, used to diagnose Helicobacter pylori infection, was performed in 14/28 patients and was negative in all cases. Twenty of the 28 patients had psychiatric evaluation in order to exclude non-compliance. Five patients had been on a lactose-free diet before vitamin C co-administra- tion, with no change in TSH level. Other potential causes of LT4 malabsorption or accelerated LT4 metabolism were not studied.
Some studies have demonstrated that patientswith TSH ≥ 3.5 mIU/L have more frequent hypothy- roidism-related clinical symptoms. In this study, pa- tients with TSH values above 3.5 mIU/L were more symptomatic; however, our results demonstrated that most of the patientswithsubclinical disease did not seek medical attention and did not pay at- tention to subtle clinical symptoms. Thus, further studies are necessary to understand the impact of these symptoms on quality of life, well-being and job performance. Also we included headache and hair loss as symptoms to be asked in the questionnaire due to we have observed that patientswith hypothy- roidism frequently complain of this symptoms, and when we did the statistical analysis we found there was difference between the patientswith hypothy- roidism and those who do not have abnormal thyroid tests, in consequence we think it is neces- sary to explore these symptoms in other clinical studies in order to confirm this finding based on clinical practice experience. Recent controlled trials administering levothyroxine failed to demonstrate any improvement in clinical symptoms and quality of life withlevothyroxine administration inpatientswith sub-hypo and there is insufficient evidence that levothyroxinetreatment improves the lipid profile, cardiac dysfunction or decreases fracture risk. 23,24
Conclusions: Although overall survival rate is the gold standard in cancer therapy, it is not the most often used outcome. Intermediate outcomes, such as disease-free survival or biomarkers are often good predictors, and require smaller samples and less follow-up time. Nevertheless, their predictive capacity for overall survival rate (or, in some cases, quality of life) should also be assessed. The use of the overall survival rate as the routine primary outcome is only justiﬁed in the most aggressive forms of cancer.
In the second phase of EAP, there was no requi- rement for a liver biopsy to enroll patients. The de- cision was left to the usual clinical practice of the participating physician. Any biopsies performed onpatients enrolled in the EAP were read by the presi- ding local pathologist at each study site. For those who underwent liver biopsy, grading of inflamma- tion and staging of fibrosis were analyzed accor- ding to the METAVIR scoring system. Only the most recent biopsy result was recorded on the case report form. For patients who were treated without a liver biopsy, the reason for not perfor- ming a liver biopsy was not collected on the case report forms.
As described earlier, BRAF V600E mutation is the genetic key in HCL. Therefore, it is a therapeutic target which has been studied in recent years. Vemurafenib is a BRAF V600E oral inhibitor. Tiacci et al. conducted a studyto measure Vemurafenib activity and safety inpatientswith HLC who relapsed after treatmentwith purine analogues or who were refractory to the administration of purine analogues. Global response rate was 96% and complete response rate was 35%, with a relapse-free survival mean of 19 months. The adverse effects were rash, arthralgia and arthritis. 63
Material and methods: 70 patients were prospectively evaluated. They were classified into: SH Group: 41 patients (normal T4, TSH> 4.2 and <10 mIU/L), TAI Group: 10 euthyroid patients (TSH <4.2 mUI/L) with positive aTPO and/or aTg and Control Group: 19 euthyroid patients without TAI. Other cardiovascular risk factors were excluded inpatients and controls. Plasma ET1, hsCRP and TRAP were measured basally, and ET1 and hsCRP under LT4 therapy in the HS Group.
In summary, this study suggests that patientswith se- vere fibrosis are more likely to have TD and to require treatment for TD during therapy with Peg IFN than those with mild fibrosis. We postulate that risk for TD may be associated to immune processes allied to the progression of fibrosis inpatientswith HCV. In our opinion, this study is of clinical interest and the first tostudy TD among different stages of fibrosis in HCV. Patientswith more advanced chronic hepatitis C require closer follow up to diagnose and manage TD, including a high level of suspicion for thyroid carcinoma. This is particularly im- portant in sub populations with more rapid liver disease progression as Latinos, HCV/HIV co-infected patients and HCV patientswith concomitant alcohol use.
Patient 5: A 52-year-old female, with a background of hypothyroidism, presented with abdominal distention and a pelvic tumour in a CT scan. She was diagnosed with a stage IIIC infiltrating endometrioid ovarian adenocarcinoma. She received surgery and standard chemo- therapy with a total of three lines of treatments. After progression, she started MCT Cy (50 mg p.o.d) with a minimal hematological toxicity. MCT began in September 2014 with no interruptions and, at present, the patient continues the treatment. The patient’s condition remained stable with good QOL (ECOG 1). The patient is still alive (June 2016) with 21 months of PFS at the moment of manuscript writing. Patient 6: A 54-year-old woman was diagnosed with a stage IIIC papillary ovarian adenocarcinoma. Pre-operative CA125: 1648 U/ml; she underwent optimal cytoreductive surgery and received adjuvant chemotherapy. She received two lines of chemotherapy, a new surgery of the peritoneal masses and hormonal treatment before MCT. She was treated with MCT (Cy 50 mg p.o.d) with good tolerance and stable disease for 12 months. She received MCT from December 2013 to December 2014. After that period, the tumour progressed and she began a scheme with targeted therapy (bevacizumab) plus chemotherapy with partial response, severe toxicity and rapid progression. The patient is still alive and is under liposomal doxorubicin (LSD) chemotherapy at the moment of manuscript writing.
trica en Europa (12, 15), ha madurado la tecnología actual indicada para la terapia de cardioresincronización y cardiodesfib- rilación en el manejo avanzado de la IC. Estas terapias están avaladas por ensayos clínicos con más de 7000 pacientes re- clutados y seguidos hasta por 37 meses (16), y son parte de las guías de manejo basadas en la evidencia a nivel mun- dial (17). La terapia de resincronización cardíaca con cardiodesfibrilador ha dem- ostrado un beneficio significativo en la reducción de la mortalidad: 18 al 23% por IC, 43% en la mortalidad global, 18% en hospitalización por empeoramiento de falla subyacente y otros beneficios como la mejoría en la capacidad funcional, caminata de 6 minutos, difusión de CO 2 , parámetros hemodinámicos y de mecáni- ca cardíaca contemplados como benefi- cios adjuntos a estas terapias (18). A escala global, el impacto de estas in- tervenciones se ha estimado entre los 48.000 y 112.000 euros por año con rel- ación al costo del dispositivo, su implan- te y monitoreo temprano; sin considerar otros gastos directos e indirectos que se derivan (19).
The design and rationale of the IMPACT-AF trial has been described previously.12 Briefly, IMPACT-AF was a two-arm, prospective, international, cluster-randomised, controlled- trial that enrolled patientswith atrial fibril- lation. IMPACT-AF was designed as a cluster-randomised studyto provide a randomised control group, while minimising the presence of contamination that might occur with individual randomisation, given that the implementation of the educational intervention was applied at both the cluster and individual level. The national coordinating centres from five participating middle-income countries (Argentine Clinical Research Group [ACRG], Rosario, Argentina; Brazilian Clinical Research Institute, São Paulo, Brazil; Peking University First Hospital, Beijing, China; St John’s Medical College and Research Institute, Bangalore, India; and University of Medicine and Pharmacy Carol Davila, Bucharest, Romania) were responsible for the conduct of the trial in each respective country. Clusters (sites) were identified by each coordinating centre based on feasibility and patient volume. All clusters demonstrated access to adequate numbers of eligible patients by providing pre-screening lists of 40–90 eligible patients.
The primary endpoint was the reduction in IHTG from baseline to month 6 as measured by proton-magnetic resonance spectroscopy. Seconda- ry endpoints included changes in ALT, aspartate aminotransferase (AST), BMI, fasting glucose, li- pids and liver stiffness measurement by transient elastography. Liver stiffness measurement was per- formed using the Fibroscan machine (Echosens, Paris, France). The procedure was performed according to the manufacturer’s instructions as described previously. 23,24 Liver stiffness measure-
The distribution of variables was analyzed; in case of quantitative variables with a non-normal distribution base, a 10-logarithmic transformation was performed to normalize their distribution. De- scriptive statistics were used, quantitative variables were expressed as the mean and standard deviation (SD), and qualitative variables were expressed as proportions and percentages. Analysis with inten- tion to treat (ITT) was conducted. To compare pri- mary and secondary outcomes between groups, the chi-square test, Fisher’s exact test or Student’s t- test was used, based on the variable type. Survival analysis was performed using Kaplan-Meier curves for up to 30 and 90 days, respectively, and compared with the log-rank test.
It also proved impossible in the present studyto predict acute or late effects from the results of an in vitro assay to measure initial radiation-induced DNA damage. Until recently, it has been generally accepted that the genotoxic consequences of radiation exposure derive from the damage inflicted directly by radiation, producing irreversible changes during DNA replica- tion or cell division or during the processing of DNA damage by enzymatic repair processes . However, there is now considerable evidence that cells that are the progeny of exposed cells but that are not themselves exposed may divide, express delayed gene mutations, and carry chromosomal aberrations. This effect, known as radiation-induced genomic instability, may be expressed via delayed lethal mutations , causing prolonged perturbation of tissue volume within the radiation field . Although the mechanisms of those delayed effects of ionizing radiation are unclear, excessive production of reactive oxygen species has been implicated . Recent experiments showed that macrophage activation and neu- trophil infiltration are consequences of the recognition and clearance of radiation-induced apoptotic cells and that increased phagocytic cell activity persists after removal of apoptotic bodies. It was demonstrated, contrary to expecta- tions, that the recognition and clearance of apoptotic cells after exposure to radiation produces persistent macrophage activation and a genotype-dependent inflammatory-type response . These phenomena and radiation-induced genetic changes may be important determinants of the longer- term consequences of radiation exposure . Moreover, new evidence suggests that cytokine-mediated multicellular inter- actions initiate and sustain the fibrogenic process [29,30] that is a long-term effect of radiotherapy.
spondylopathies (See additional fi les). LDD diagnosis was established in all patientswith defi ned diagnosis by a specialist in Neurosurgery, Orthopedics, as a result of complementary tests or diagnosis described in medical re- cords. Separately, two researchers (TAF, TAA) reviewed the medical records and included patients who received 2 or more continuous sessions of some type of AT for the diagnosis of LDD; any uncertainty about the diagnosis was resolved by a third investigator (PLM). Patients who received only one medical inspection, were not treated or had secondary spinal cord injury to neoplasia were exclu- ded (Figure S1, see supplementary fi les).