Reduced cardiac 123I-metaiodobenzylguanidine uptake in patients with spinocerebellar ataxia type 2: a comparative study with Parkinson’s disease

Purpose

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant neurodegenerative disorder characterized by cerebellar ataxia, supranuclear ophthalmoplegia, and peripheral neuropathy. Autonomic nervous system dysfunction is often present. This study evaluated the cardiac sympathetic function in patients with SCA2 using ¹²³I-metaiodobenzylguanidine (MIBG) in comparison with patients with Parkinson’s disease (PD) and control subjects.

Methods

Nine patients with SCA2, nine patients with PD, and nine control subjects underwent ¹²³I-MIBG imaging studies from which early and late heart-to-mediastinum (H/M) ratios and myocardial washout rates were calculated.

Results

Early (F?=?12.3, p?<?0.0001) and late (F?=?16.8, p?<?0.0001) H/M ratios were significantly different among groups. In controls, early and late H/M ratios (2.2?±?0.12 and 2.1?±?0.20) were significantly higher than in patients with SCA2 (1.9?±?0.23 and 1.8?±?0.20, both p?<?0.05) and with patients with PD (1.7?±?0.29 and 1.4?±?0.35, both p?<?0.001). There was also a significant difference in washout rates among groups (F?=?11.7, p?<?0.0001). In controls the washout rate (19.9?±?9.6 %) was significantly lower (p?<?0.005) than in patients with PD (51.0?±?23.7 %), but not different from that in SCA2 patients (19.5?±?9.4 %). In SCA2 patients, in a multivariable linear regression analysis only the Scale for the Assessment and Rating of Ataxia score was independently associated with early H/M ratio (β?=??0.12, p?<?0.05).

Conclusion

¹²³I-MIBG myocardial scintigraphy demonstrated an impairment of cardiac sympathetic function in patients with SCA2, which was less marked than in PD patients. These results suggest that ¹²³I-MIBG cardiac imaging could become a useful tool for analysing the pathophysiology of SCA2.     

Thromboprophylaxis in carriers of antiphospholipid antibodies (APL) without previous thrombosis: "Pros" and "Cons"

The presence of anti-phospholipid (aPL) is necessary but not sufficient to induce a thrombotic event. The "second hit" hypothesis suggested that an additional trigger may be needed to develop a vascular event in aPL carriers. In this article, pro and con of primary thromboprophylaxis in aPL carriers is deeply discussed, concluding that univocal data are not available, due to conflicting results of available clinical trials. However, in clinical practice the primary thromboprophylaxis is not indicated in all unselected asymptomatic aPL carriers, and the best strategy begin with the assessment of the peculiar risk profile of the subject. Thus, it is mandatory to eliminate modifiable prothrombotic risk factors (i.e. smoking, oral contraceptive), to treat the irreversible risk factors (i.e. hypertension, diabetes) and to introduce an aggressive prophylaxis with subcutaneous LMWH in high-risk situations (i.e. surgical procedures with prolonged immobilization). A different evaluation should be addressed to aPL carriers with a concomitant autoimmune disease that are considered as an additional pro-thrombotic risk factor. Similarly, concomitant positivity for more than one anti-phospholipid test confer a stronger risk of developing the thrombotic manifestations. Specific trials with larger cohorts of patients are needed to better clarify this issue.     

Ultrastructural and Spectrophotometric Study on the Effects of Putative Triggers on Aortic Valve Interstitial Cells in In Vitro Models Simulating Metastatic Calcification

Metastatic calcification of cardiac valves is a common complication in patients affected by chronic renal failure. In this study, primary bovine aortic valve interstitial cells (AVICs) were subjected to pro‐calcific treatments consisting in cell stimulation with (i) elevated inorganic phosphate (Pi = 3 mM), to simulate hyperphosphatemic conditions; (ii) bacterial endotoxin lipopolysaccharide (LPS), simulating direct effects by microbial agents; and (iii) conditioned media (CM) derived from cultures of either LPS‐stimulated heterogenic macrophages (commercial murine RAW264.7 cells) or LPS‐stimulated fresh allogenic monocytes/macrophages (bCM), simulating consequent inflammatory responses, alone or combined. Compared to control cultures, spectrophotometric assays revealed shared treatment‐dependent higher values of both calcium amounts and alkaline phosphatase activity for cultures involving the presence of elevated Pi. Ultrastructurally, shared peculiar pro‐calcific degeneration patterns were exhibited by AVICs from these latter cultures irrespectively of the additional treatments. Disappearance of all cytomembranes and concurrent formation of material showing positivity to Cuprolinic Blue and co‐localizing with silver precipitation were followed by the outcropping of such a material, which transformed in layers outlining the dead cells. Subsequent budding of these layers resulted in the formation of bubbling bodies and concentrically laminated calcospherulae mirroring those in actual soft tissue calcification. In conclusion, the in vitro models employed appear to be reliable tools for simulating metastatic calcification and indicate that hyperphosphatemic‐like conditions could trigger valve calcification per se, with LPS and allogenic macrophage‐derived secretory products acting as possible calcific enhancers via inflammatory responses. Anat Rec, 2012. © 2012 Wiley Periodicals, Inc.     

Respiratory mechanics in COPD patients who failed non-invasive ventilation: Role of intrinsic PEEP

The purpose was to determine if 2 weeks of buspirone suppressed post-hypoxic breathing instability and pauses in the C57BL/6J (B6) mouse. Study groups were vehicle (saline, n=8), low-dose (1.5 mg/kg, n=8), and high-dose buspirone (5.0 mg/kg, n=8). Frequency, measured by plethysmography, was the major metric, and a pause defined by breathing cessation >2.5 times the average frequency. Mice were tested after 16 days of ip injections of vehicle or drug. On day 17, 4 mice in each group were tested after buspirone and the 5-HT(1A) receptor antagonist, 4-iodo-N-{2-[4-(methoxyphenyl)-1-piperazinyl] ethyl}-N-2-pyridinyl-benzamide (p-MPPI, 5 mg/kg). A post-hypoxic pause was present in 6/8 animals given vehicle and 1/16 animals given buspirone at either dose, but always present (8/8) with p-MPPI, regardless of buspirone dose. Post-hypoxic frequency decline was blunted by buspirone (-10% vehicle vs. -5% at both doses) and restored by p-MPPI; ventilatory stability as described by the coefficient of variation which was reduced by buspirone (p<0.04) was increased by p-MPPI (0.01). In conclusion, buspirone administration after 2 weeks acts through the 5-HT(1A) receptor to reduce post-hypoxic ventilatory instability in the B6 strain.     

A comparison of single breath and re-breathe diffusing capacity in emphysema patients and controls

In emphysema patients, gas dilutional alveolar volume is underestimated by a 10s single breath maneuver at total lung capacity (TLC) compared with re-breathing at functional residual capacity (FRC); corresponding underestimation of single breath diffusing capacity (DLCO) in emphysema has not been demonstrated. The purpose of this study was to quantify the degree to which re-breathe DLCO at FRC (DLCO(RB)) differs from single breath DLCO at TLC (DLCO(SB)) in emphysema. In 37 consecutively recruited patients with moderate to severe emphysema (FEV1/FVC 40%±10% predicted), DLCO(RB) as % predicted of 91 controls without cardiopulmonary disease was 79%±24%, significantly greater than % predicted DLCO(SB) (44%±19%; p<0.0001). DLCO(RB)/DLCO(SB) was inversely proportional to FEV1% predicted (R = -0.47, p=0.004), and FEV1/FVC (R = -0.54, p<0.001). These data indicate that a 10s single breath DLCO maneuver progressively under-represents re-breathe lung diffusing capacity in emphysema as airflow obstruction increases.     

Cx26 gene mutations in idiopathic progressive hearing loss

OBJECTIVE: The present study evaluated the frequency and type of mutations throughout the entire GJB2 region in a population of 39 patients affected with sporadic progressive "idiopathic" hearing loss. MATERIAL: A large series of patients suffering from progressive hearing loss underwent a systematic screening program to identify the etiology of the hearing loss. Of these patients, 39 presented with sporadic idiopathic progressive hearing loss and were included in this study. METHOD: We performed molecular analysis of GJB2 in each patient sequencing the genomic deoxyribonucleic acid (DNA) in both directions for detection of GJB2 mutations. Furthermore, in all patients bearing a Cx26 mutation, a search was also conducted for mutations or deletions of GJB6 (Cx30 gene) and for the A1555G mutation of the mitochondrial DNA. A control group was also considered to evaluate the frequency of Cx26 mutations in the normal population. RESULTS: A Cx26 gene mutation was detected in nine cases. One subject was found to bear a homozygous genotype for the 35delG mutation, another subject was compound heterozygous for 35delG and E47X, and the remaining patients showed heterozygous genotypes (35delG, L90P, R127H, M34T, V153I, V37I). No mutation or delection of the Cx30 gene was observed in these nine patients, and none of them presented with the A1555G mutation in the mitochondrial DNA. In the control group (40 individuals), a Cx26 mutation was detected in two cases (5%). CONCLUSIONS: About 23% of our patients (nine subjects) presented with mutations in GJB2, and 18% (seven subjects) were heterozygous. However, most of the described mutations are recessive, so a monogenic model of inheritance cannot explain the deafness phenotype. On the basis of these findings, we can speculate that the heterozygote Cx26 genotype could be a cause of progressive hearing loss, probably in association with mutations in other alleles. Thus, we recommend carefully following all hearing-impaired subjects with GJB2 mutations, even if they present with only mild hearing loss, because the hearing deficit could worsen. Furthermore, molecular analysis of the Cx26 gene should also be performed in adult patients affected with idiopathic progressive hearing loss.     

Postoperative adjuvant chemoradiotherapy in older patients with head and neck cancer

BACKGROUND: In head and neck cancer, the locoregional failure of patients with positive margins, vascular or perineural invasion, and extracapsular spread is high and results in poor survival. OBJECTIVE: To assess the effect of adjuvant chemoradiotherapy in improving treatment outcomes among older patients with head and neck cancer. METHODS: Forty patients undergoing radical surgery (median age, 73.5 years [range, 70-78 years]) were enrolled (35 men and 5 women; Eastern Cooperative Oncology Group performance status, grade 0-2). Disease sites included the oral cavity (10 patients), oropharynx (12 patients), hypopharynx (8 patients), and larynx (10 patients); pathological TNM classifications included T1 N2 (8 patients), T2 N1-2 (12 patients), T3 N0-2 (8 patients), and T4 N0-2 (12 patients), with the following poor prognostic factors: positive margins (6 patients), vascular invasion (14 patients), neural invasion (16 patients), and extracapsular spread (26 patients). All patients were treated with carboplatin (30 mg/m2 on days 1-5 of weeks 1, 3, and 5) concomitant with radiotherapy (54.0 Gy to all risk volumes plus 10.0 Gy to high-risk volumes; 5 daily fractions of 1.8 Gy each per week). RESULTS: No grade 4 toxicity was observed. Grade 3 toxicity included mucositis (10 patients), neutropenia (6 patients), dermatitis (2 patients), and thrombocytopenia (1 patient). The radiotherapy dose administered was 52.0 Gy to all risk volumes plus 10.0 Gy to high-risk volumes. Thirty-two patients (80%) received 3 cycles, 6 (15%) received 2 cycles, and 2 (5%) received 1 cycle. Three-year survival was as follows: disease-free survival, 58%; overall survival, 64%; and local control, 79%. CONCLUSIONS: Adjuvant chemoradiotherapy may be successful in fit older patients. The results of adjuvant chemoradiotherapy were better than those observed in a comparable group treated with radiotherapy alone and were similar to those observed in a younger group with the same poor prognostic factors treated with adjuvant carboplatin plus radiotherapy.     

Should we fear direct oral anticoagulants more than vitamin K antagonists in simple single tooth extraction? A prospective comparative study

Objectives

The aim of this prospective comparative clinical study was to evaluate the effect of oral anticoagulants on peri- and post-operative bleeding during simple single tooth extractions, comparing patients in treatment with vitamin K antagonists (VKAs) and patients assuming direct oral anticoagulants (DOACs).

Materials and methods

Patients under oral anticoagulant therapy needing dental extraction were eligible for entering the study; patients were enrolled following inclusion and exclusion criteria and divided into VKAs and DOAC group according to the anticoagulation therapy. Included patients underwent a simple single dental extraction with elevators and forceps with a maximum surgical time of 15 minutes, without anticoagulation therapy discontinuation. All participants were assessed pre-operatively, during surgery, 30 min minutes and 7 days after surgery. Biological complications were registered and post-extraction bleeding was clinically defined according to Iwabuchi classification. Parametric and non-parametric tests were used to evaluate the variables between the groups.

Results

Sixty-five patients per group were enrolled and 130 teeth were extracted. The two groups were comparable for pre-, peri-, and post-operative variables. Only 1 patient of DOAC group and 2 patients for VKA group needed medical evaluation for post-extractive bleeding. No statistically significant difference resulted in post-operative bleeding events between the groups (p = 0.425).

Conclusions

DOAC and VKA patients showed the same incidence of bleeding complications after simple single tooth extraction. Bleeding events were not statistically significant and not clinically relevant.

Clinical relevance

Patients assuming DOACs can be treated similarly to patients in VKAs therapy with INR index between 2 and 3. Non-ceasing of DOAC therapy seems to be appropriate for simple single dental extractions.