The Prevalence of Severely Increased Albuminuria in the Type 2 Diabetes Population with Chronic Kidney Disease of Low Socioeconomic Status in San Juan: A Population in Need of Improved Accessibility to Disease-Modifying Therapy.

OBJECTIVE: The aim of this study was to determine the prevalence of severely increased albuminuria and the percentage of patients with the indication for canagliflozin in the type 2 diabetes population with chronic kidney disease (CKD) and low socioeconomic status in the San Juan City Hospital. METHODS: This cross-sectional study examined the electronic records of 129 Hispanic type 2 diabetes patients. CKD in this population was defined according to the most recent nephrology and endocrinology guidelines. Albuminuria was diagnosed with two positive urine albumin/creatinine ratio results within 3-6 months. Data was obtained from July 2017 to January 2020 and analyzed utilizing descriptive statistics and correlations. RESULTS: The prevalence of moderately and severely increased albuminuria in patients with type 2 diabetes and CKD were 51.2% and 18.6% respectively. The number of patients with type 2 diabetes who filled the FDA indication for canagliflozin were 16.3%. The prevalence of hypertension, coronary artery disease (CAD) and heart failure (HF) was 61.2%, 15.5% and 10.1% respectively. Between albuminuria severity and decreased renal function, a tendency was observed although not statistically significant (r = -0.14, 95% CI: -0.31, 0.03; P = 0.109). While evaluating association between albuminuria groups and CAD, there was a noticeable tendency close to reaching statistical significance (P = 0.060). CONCLUSION: There is a scarcity of studies regarding the prevalence of severely increased albuminuria in type 2 diabetics with CKD and this study contributes to the literature. On analysis of associations, statistical significance not reached likely due to small sample size.

Orodispersible sublingual piribedil to abort OFF episodes: a single dose placebo-controlled, randomized, double-blind, cross-over study.

S90049, a novel sublingual formulation of the non-ergoline D(2)-D(3) agonist piribedil, has a pharmacokinetic profile promising to provide rapid relief on motor signs in Parkinson's disease (PD). We assessed the efficacy and safety of S90049 in aborting OFF episodes responding to subcutaneous apomorphine in PD patients with motor fluctuations. This was a single-dose double-blind double-placebo 3 x 3 cross-over study. Optimal tested doses were determined during a previous open-label titration phase (S90049 median dose: 60 mg, apomorphine: 5 mg). Primary endpoint was the maximal change versus baseline in UPDRS motor score (Delta UPDRS III) assessed after drug administration following an overnight withdrawal of antiparkinsonian medications. Thirty patients (age: 60 +/- 8 years, PD duration: 12 +/- 6 years, UPDRS III OFF: 37 +/- 15) participated. S90049 was superior to placebo on Delta UPDRS III (-13 +/- 12 versus -7 +/- 9 respectively; estimated difference -5.2, 95% Confidence Interval (CI)[-10.4;0.05], P = 0.05). This was also true for secondary outcomes: number of patients switching from OFF to ON (17 on S90049 vs. 8 on placebo, P = 0.03), time to turn ON (P = 0.013) and duration of the ON phase (P = 0.03). In the 17 patients who switched ON on S90049, Delta UPDRS III was similar on S90049 (-21.2 +/- 10.1) and apomorphine (-23.6 +/- 14.1) (estimated difference: 4.0 95% CI [-2.9;10.9]). S90049 was well tolerated: no serious or unexpected adverse event occurred. A single dose of up to 60 mg of S90049 given sublingually was superior to placebo in improving UPDRS III and aborting a practical OFF in patients with advanced PD. Testing greater doses might improve response rate.

Clinical impact of dual-tracer FDOPA and FDG PET/CT for the evaluation of patients with parkinsonian syndromes.

Parkinsonian syndromes include typical cases of idiopathic Parkinson's disease (PD) and atypical parkinsonian syndromes (APS) associated with cognitive and vegetative disorders, which are more challenging to diagnose. The aim of this study was to assess -the value of dual-tracer imaging 6-fluoro-(18F)-L-DOPA (FDOPA) and fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT), performed in routine patients demonstrating extrapyramidal signs and cognitive complains, for the diagnosis and management of parkinsonian syndromes.We retrospectively included 143 consecutive patients who underwent both FDOPA PET/CT (for the evaluation of parkinsonism) and FDG PET/CT (for the evaluation of cognitive complaints) in the same institution. The suspected clinical diagnosis before imaging and the final post-imaging diagnosis were collected by a dedicated questionnaire.FDOPA was pathological in 90.2% of cases, including 74.1% of PD, 3.5% of parkinsonian dementia and 7% of APS. FDG was normal or near normal in 58.7% of patients. A pattern of diffuse cortical hypometabolism was observed in the remaining patients, more frequently in APS than in PD patients (P = .001). Importantly, in 7.7% of cases dual-tracer PET/CT allowed to decide between several diagnostic hypotheses and led to a new diagnosis in 14.0%. Therefore, the management of these patients was modified, with clinical re-evaluation in a specialized unit and a control of neuropsychological tests and imaging.Dual-tracer PET/CT imaging may be a precious help in the diagnosis and management of parkinsonian syndromes.

A Rare Case of Uterine Leiomyosarcoma with Metastasis to the Thyroid Gland.

Uterine leiomyosarcomas are aggressive tumors associated with a poor prognosis. These neoplasms have high metastatic potential, more frequently affecting the lungs, liver, and peritoneum. There are very few cases of metastasis to the thyroid described in the literature. We present the case of a 47-year-old female diagnosed with uterine leiomyosarcoma metastatic to the thyroid gland. In this case report, we want to emphasize the utility of ancillary studies to help differentiate a leiomyosarcoma from anaplastic thyroid carcinoma since cytologic evaluation alone can be challenging.

Can nicotine be used medicinally in Parkinson's disease?

The risk of Parkinson's disease is reduced by cigarette smoking, which raises some unanswered questions. Nicotine, a major component of tobacco smoke, could exert either nonreceptor-mediated biological effects or, more importantly, act on the different subtypes of nicotinic brain receptors, in particular those associated with the nigrostriatal dopaminergic pathway. There is now robust experimental evidence for a neuroprotective effect of nicotine upon dopaminergic neurons. By contrast, in animal models of Parkinson's disease, nicotine alone has slight or no motor effects. However, nicotine may modulate dopamine transmission and has clear motor effects when associated with L-DOPA, reducing L-DOPA-induced dyskinesias. Clinical trials have yielded inconclusive results thus far and are hampered by different designs and small cohorts. Ongoing studies address either symptomatic motor or nonmotor symptoms, or neuroprotection. There is still no agreement on the daily dosage of nicotine or the method of administration. Together, these data suggest that nicotine or nicotinic receptor drugs have therapeutic potential for Parkinson's disease, although the specific treatment regimens remain to be determined.

Dopamine transporter imaging under high-dose transdermal nicotine therapy in Parkinson's disease: an observational study.

OBJECTIVES: Nicotine therapy might improve the course of Parkinson's disease. This observational study evaluated the performance of dopamine transporter imaging in follow-up patients under nicotine therapy. METHODS: Six Hoehn and Yahr stage III patients underwent 123I-FP-CIT imaging prior to, 3 months, and 1 year after the onset of nicotine therapy. Nicotine was administered transdermally with increasing daily doses during 3 months (up to 105 mg/day) and decreased progressively. On co-registered magnetic resonance imaging, striatal regions of interest were drawn and binding potentials of 123I-FP-CIT were calculated.Changes in Unified Parkinson's Disease Rating Scale-III over time were compared with binding potentials using regression analysis. RESULTS: All patients improved motor scores at 3 months (-65 +/- 22% 'off', -89 +/- 12% 'on') and most received fewer dopaminergic drugs (-30% dosage in average). Motor improvement persisted to a lesser extent at 1 year(-39 +/- 31% 'off', -13 +/- 43% 'on'), partly because one patient stopped the treatment. Interestingly, the decrease in binding potentials (-4.0 +/- 10.5%) was slower than that expected in Parkinsonian patients (usually -10% per year) and was inversely correlated with Unified Parkinson's Disease Rating Scale-III improvement, r= 0.83 'off' and 0.91 'on'. CONCLUSION: This observational study emphasizes a potential effect of nicotine therapy on striatal dopamine transporter density, which may be interpreted as direct pharmacological effect or deceleration of neuronal loss.

Decrease of nicotinic receptors in the nigrostriatal system in Parkinson's disease.

Smoking is associated with a lower incidence of Parkinson's disease (PD), which might be related to a neuroprotective action of nicotine. Postmortem studies have shown a decrease of cerebral nicotinic acetylcholine receptors (nAChRs) in PD. In this study, we evaluated the decrease of nAChRs in PD in vivo using positron emission tomography (PET), and we explored the relationship between nAChRs density and PD severity using both clinical scores and the measurement of striatal dopaminergic function. Thirteen nondemented patients with PD underwent two PET scans, one with 6-[(18)F]fluoro-3,4-dihydroxy-L-phenylalanine (6-[(18)F]fluoro-L-DOPA) to measure the dopaminergic function and another with 2-[(18)F]fluoro-3-[2(S)-2-azetidinylmethoxy]pyridine (2-[(18)F]fluoro-A-85380), a radiotracer with high affinity for the nAChRs. Distribution volumes (DVs) of 2-[(18)F]fluoro-A-85380 measured in the PD group were compared with those obtained from six nonsmoking healthy controls, with regions-of-interest and voxel-based approaches. Both analyses showed a significant (P <0.05) decrease of 2-[(18)F]fluoro-A-85380 DV in the striatum (-10%) and substantia nigra (-14.9%) in PD patients. Despite the wide range of PD stages, no correlation was found between DV and the clinical and PET markers of PD severity.

Transplantation in Parkinson's disease: PET changes correlate with the amount of grafted tissue.

We compared the striatal uptake of [(18)F]fluorodopa with [(76)Br]-FE-CBT, a positron emission tomography (PET) ligand of the dopamine transporter (DAT), which estimates the density of dopamine nerve terminals, in 6 patients with Parkinson's disease grafted with fetal mesencephalic cells. There was no change in DAT ligand binding in the grafted putamen, despite a significant increase of [(18)F]fluorodopa uptake. This finding suggests that the clinical benefit induced by the graft is more related to increased dopaminergic activity than improved dopaminergic innervation in the host striatum and, therefore, that [(18)F]fluorodopa remains the optimal tracer to evaluate grafted PD patients. Further analysis showed that the clinical and [(18)F]fluorodopa uptake changes after the grafts were correlated with the number of ventral mesencephalae used for implantation.