Treatment with multiple cycles of (177)Lu-DOTATATE peptide receptor radionuclide therapy is well tolerated. This treatment results in control of the disease in most patients, whereas systemic toxicities are limited and reversible. Quality of life is also improved.

Objective To examine the demographic and clinical characteristics of systemic sclerosis (SSc) patients without antinuclear antibodies (ANA) compared to ANA positive patients. Methods SSc patients enrolled in the Scleroderma Family Registry and DNA Repository were included. Relevant demographic and clinical data were entered by participating sites or obtained by chart review. ANA and SSc related antibodies were determined in all investigated patients using commercially available kits at our laboratories. Results This study included 3249 patients, of whom 208 (6.4%) were ANA negative. The proportion of male patients was higher in the ANA negative group (OR 1.65; p=0.008). ANA negative patients experienced less vasculopathic manifestations of SSc. The percent predicted diffusing capacity of carbon monoxide (DLco) was higher in ANA negative patients (p=0.03). Pulmonary arterial hypertension (PAH) per right heart catheterization was less common in the ANA negative group (OR= 0.28; p=0.03). Furthermore, patients with negative ANA had a lower prevalence of telangiectasias and digital ulcers/pits (OR= 0.59; p=0.03 and OR=0.38; p=0.01, respectively). Although diffuse cutaneous involvement was more common, the modified Rodnan Skin Score (mRSS) was lower in the ANA negative group (2.4 points lower, p=0.05). Furthermore, they experienced more malabsorption (p=0.05). There was no difference in the frequency of pulmonary fibrosis or scleroderma renal crisis. All-cause mortality was not different between the two groups (p=0.28). Conclusions In conclusion, the results of this study suggest that SSc patients who are ANA negative constitute a distinct subset of SSc with less vasculopathy (less PAH, digital ulcers and fewer telangiectasias), a greater proportion of males and possibly, more frequent lower gastrointestinal involvement.

In observational studies, left ventricular mass (LVM) and structure are strong predictors of mortality and cardiovascular events. However, the effect of hypertension treatment on LVM reduction and its relation to subsequent outcomes is unclear, particularly at lower blood pressure (BP) targets. In an ancillary study of SPRINT (Systolic Blood Pressure Intervention Trial), where participants were randomly assigned to intensive BP control (target systolic BP target <120 mm Hg) versus standard BP control (<140 mm Hg), cardiac magnetic resonance imaging was performed at baseline and 18-month follow-up to measure: LVM, volumes, ejection fraction, and native T1 mapping for myocardial fibrosis. At baseline, 337 participants were examined (age: 64±9 years, 45% women); 300 completed the 18-month exam (153 intensive control and 147 standard control). In the intensive versus standard BP control group at 18 months, there was no difference in change in LVM (mean±SE =−2.7±0.5 g versus −2.3±0.7 g; P =0.368), ejection fraction, or native T1 ( P =0.79), but there was a larger decrease in LVM/end-diastolic volume ratio (−0.04±0.01 versus −0.01±0.01; P =0.002) a measure of concentric LV remodeling. There were fewer cardiovascular events in the intensive control group, but no significant association between the reduced events and change in LVM or any other cardiac magnetic resonance imaging measure. In SPRINT-HEART, contrary to our hypothesis, there were no significant between-group differences in LVM, function, or myocardial T1 at 18-month follow-up. These results suggests that mediators other than these LV measures contribute to the improved cardiovascular outcomes with intensive BP control.

Aim: To study the long term benefits, toxicity and survival rate in patients with neuroendocrine tumors receiving multiple cycles of high activity In-111 Pentetreotide therapy. Moreover, our secondary aim was to evaluate the value of F-18 FDG PET-CT scan as prognostic indicator in this group of patients.Background: Neuroendocrine tumors are a heterogeneous group of malignancies which are usually metastatic at diagnosis. Standard chemotherapy in these patients is associated with appreciable adverse events and low effectiveness. Since 1990s, Peptide receptor radionuclide therapy (PRRT) with radio-labeled somatostatin analogues has been introduced as a new method of treatment in patients with unresectable and/or metastatic neuroendocrine tumors expressing high levels of Somatostatin receptors.Methods: 112 patients with progressive disseminated and unresectable neuroendocrine tumor (stage III and stage IV) were enrolled in a non-randomized trial in an out-patient setting. High activity In-111 Pentetreotide (500 mCi (18.5 GBq) per cycle) was administered as an intravenous infusion over 3 hours and repeated therapy cycles every 9-12 weeks in eligible patients up to maximum of 4 cycles. Response to therapy was evaluated by clinical imaging using the RECIST criteria, metabolic criteria and patient's quality of life questionnaire. Dosimetry and biodistribution studies were also performed. Finally, Kaplan-Meier survival analysis was performed for patients followed for greater than 12 months. The relationship between pretreatment F-18 FDG PET-CT scan status and survival was determined by two-tailed Student's t-test in 42 patients who underwent pre-therapy PET scans.Results: For an average of 25 (median 18.65) months following the therapy, patients were evaluated for any evidence of toxicity. No significant acute toxicity was observed in patients. Grade II or III hematological toxicity (7.6% of patients), liver toxicity (18.4%) and also grade I renal toxicity (6.1%) was observed in 92 evaluable patients. Radiological responses were evaluated for an average of 29 months following their last cycle of therapy and results were analyzed by the RECIST criteria. Majority (85%) of patients had stable disease (SD), partial response (PR) rate was 7.5% and progressive disease (PD) was observed in 7.5% of patients. The average survival was 24.67 months after 2 cycles of therapy, 30.53 months after 3 cycles of therapy and 30.19 months after 4 cycles of therapy. Of the 42 patients who had pretreatment PET-CT imaging, 31 patients had positive F-18 FDG scans (SUV > 2.5) with an average survival time of 18.9 months (range 1.4-45.8 months) and 11 patients had negative F-18 FDG scans (SUV ≤ 2.5) with an average survival time of 31.8 months (range 7.4-42.9 months). Survival times for FDG negative patients were significantly longer than those for FDG positive patients (p = 0.001 with 95% confidence).Conclusion: High activity In-111 therapy is a safe and effective therapy for patients with progressive disseminated neuroendocrine tumors. No major ...

Background: Chronic kidney disease (CKD) is increasingly common and disproportionately affects older adults. The contribution of kidney disease to the functional impairment noted in the elderly CKD population is unclear. Methods: This is a cross-sectional analysis of a hypertensive cohort of people aged ≥75 years from the Systolic Blood Pressure Intervention Trial. We evaluated estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR) as predictors of 3 measures of functional status: EuroQol-5 Dimensional (EQ-5D) score, Falls Efficacy Scale (FES) score, and gait speed. Linear regression models were used to evaluate the associations between our independent variables and outcome measures. Results: Our analysis included 2,620 participants, mean age of 79.9 (4.0) years. Unadjusted models showed that lower eGFR level and higher UACR level were associated with lower EQ-5D (p < 0.001 for both) and slower gait speed (p < 0.001 for both) and worse scores on FES (p = 0.032 and p = 0.039). In the fully adjusted models, higher levels of UACR remained significantly associated with lower EQ-5D scores and slower gait speed (p = 0.011 and p = 0.002, respectively). In contrast, level of eGFR was not associated with any functional outcome measures when accounting for covariates. Conclusions: In individuals aged ≥75 years, albuminuria and eGFR were associated with impairments in physical performance and self-reported functional status; however, only the association with albuminuria remained after adjusting for relevant demographics and comorbidities. Evaluation of albuminuria may provide an additional tool for identifying older individuals at risk for functional impairment.

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