The Parkinson’s Disease-Cognitive Rating Scale (PD-CRS): normative values from 268 healthy Italian individuals

The Parkinson’s Disease-Cognitive Rating Scale (PD-CRS) is a cognitive screening battery that includes subtests to assess cortical and subcortical functions. It is a valid screening tool for mild cognitive impairment (MCI) in Parkinson’s disease (PD) and is recommended for diagnosing PD-MCI-Level I. Until now, no study has provided population-based norms for the Italian population. The aim of the present study was to collect normative values in a sample of Italian healthy subjects. Two hundred and sixty-eight (125 men) participants of different ages (age range 30–79 years) and educational levels (from primary school to university) underwent the PD-CRS. Regression-based norming was used to explore the influence of demographic variables (age, education level, and gender) on PD-CRS total score, frontal-subcortical and instrumental-cortical sub-scores, and score achieved on each task of the PD-CRS. Multiple linear regression analysis revealed that age and education significantly predicted the total score, the two sub-scores and the score on each task of the PD-CRS. No significant effect of gender was found. From the derived linear equations, a correction grid for raw scores was developed. Inferential cut-off scores, estimated using a non-parametric technique, were 71.25 for PD-CRS total score and 46.25 and 20.17 for frontal-subcortical and instrumental-cortical sub-score, respectively. Since the use of adjusted scores is more informative when they are standardized, we have converted adjusted scores into equivalent scores. The present study provides normative data for the PD-CRS, being useful and recommended by Movement Disorders Society task force to identify PD-MCI-Level I, at several stages of the disease.     

The role of anti-CGRP antibodies in the pathophysiology of primary headaches

Calcitonin gene-related peptide (CGRP), a potent vasodilator and pain-signaling neuropeptide, is a validated therapeutic target for migraine and cluster headache. Four anti-CGRP monoclonal antibodies (mAbs) have been developed, representing the first specific, mechanism-based, migraine prophylactic treatment. CGRP mAbs demonstrated good efficacy coupled to excellent tolerability and safety in 5 phase II clinical trials. Notably, CGRP mAbs induced complete migraine remission in a patients’ subset. To date, more than 20 phase III trials using CGRP mAbs for of episodic and chronic migraine and cluster headache prevention are ongoing. Future investigations will shed light on migraine endophenotypes predictive of good CGRP mAbs responsiveness and provide answers on their long-term cardiovascular safety.     

Heteroresistance and fungi

The concept of heteroresistance refers to the heterogeneous susceptibility to an antimicrobial drug in a microorganism population, meaning that some clones may be resistant and others are susceptible. This phenomenon has been widely studied in bacteria, but little attention has been given to its expression in fungi. We review the available literature on heteroresistance in fungi and invite the reader to recognise this phenomenon as a fungal mechanism to adapt to environmental stress, which may interfere both in resistance and virulence. Finally, heteroresistance may explain the treatment failures to eradicate mycosis in some patients treated with a seemingly appropriate antifungal.     

Impact of Radiation Therapy in Surgically Resected Limited-Stage Small Cell Lung Carcinoma

Purpose

To elucidate the role of radiation therapy (RT) in the treatment of surgically resected limited-stage small cell lung carcinoma (LSCLC).

Methods

We queried the SEER database from 1998 to 2012 to identify patients who were diagnosed with LSCLC as their only primary tumor. Kaplan–Meier analysis was utilized to determine disease-specific survival (DSS) and overall survival (OS), while multivariate analysis was used to compare survival in terms of patients and treatment characteristics.

Results

Eight hundred twenty-three LSCLC patients were identified for inclusion within the study. 12-month DSS for patients who did not receive surgery or RT was 31.9% (95% CI 27.7–36.3), 93.3% (95% CI 71.6–90.5) for surgery alone, and 81.0% (95% CI 69.3–88.6) for surgery?+?RT. 12-month OS was 27.2% (95% CI 23.4–31.1), 74.7% (95% CI 62.6–83.4), and 78.3% (95% CI 66.4–86.4) for no surgery or RT, for surgery alone, and for surgery?+?RT, respectively. In terms of multivariate analysis, patients receiving surgery alone and patients receiving surgery?+?RT had a better DSS and OS than those who received neither treatment. However, OS (HR 1.60; 95% CI 0.93–2.75, p?=?0.09) and DSS (HR 1.34; 95% CI 0.72–2.51, p?=?0.37) were not significantly associated with patients receiving surgery alone compared to surgery?+?RT.

Conclusions

Surgery alone and surgery?+?RT were positively associated with DSS and OS compared to patients who did not receive surgery or RT. However, the addition of RT to surgery did not significantly predict DSS or OS compared to surgery alone.

     

Cytomegalovirus infection in patients with haematological diseases and after autologous stem cell transplantation as consolidation: a single-centre study

Because of the widespread use of immunosuppressive drugs, CMV infection is one of the most important causes of morbidity and mortality in patients with haematological malignancies worldwide. The aim of the study was to retrospectively analyse the epidemiology of CMV infection in haematological patients. Between 2008 and 2014, 1238 quantitative CMV DNA detections from plasma specimens were performed. These specimens were collected from 271 patients with haematological malignancy. Patients were grouped on the basis of underlying diseases (lymphoid and myeloid malignancies and other haematological diseases). In the lymphoid and myeloid groups, we distinguished ASCT and non-ASCT groups. During the studied period, the majority of examined patients (82.6 %) were treated with lymphoproliferative disease. A total of 126 (46.5 %) patients underwent ASCT, while 145 (53.5 %) did not have stem cell transplantation. A total of 118 (9.5 %) of 1238 plasma specimens proved to be positive for CMV DNA; these specimens were collected from 66 (24.4 %) patients. Twenty-four (16.6 %) of 145 non-ASCT patients had CMV PCR positive specimens. Among non-ASCT patients with positive CMV PCR results, 10 patients were asymptomatic, 14 had symptomatic reactivation, while 2 had CMV disease. In the ASCT group, 42 (33.3 %) patients had CMV PCR positive samples. CMV reactivation was asymptomatic in 34 (81 %) cases, and 8 (19 %) patients had symptomatic reactivation. In the non-ASCT group, the rate of CMV infection is low. In the ASCT group, the prevalence of CMV infection was higher than in the non-ASCT group, but the majority of CMV infection was asymptomatic and only small number of patients had symptomatic reactivation. Thus, our results also showed that the use of routine CMV DNA monitoring is not necessary in patients with haematological malignancies not receiving fludarabine-containing regimen or alemtuzumab, in spite of this to decrease the mortality we have to consider the use of molecular tests in case of suspected infectious conditions.     

Digital droplet PCR (ddPCR) for the detection and quantification of HPV 16, 18, 33 and 45 - a short report

Purpose

Human papilloma virus (HPV) infection is associated with several anogenital malignancies. Here, we set out to evaluate digital droplet PCR (ddPCR) as a tool for HPV 16, 18, 33 and 45 viral load quantification and, in addition, to compare the efficacy of the ddPCR assay for HPV 16 detection with that of quantitative real-time PCR (qPCR).

Methods

Clinical samples, positive for HPV genotypes 16, 18, 33 and 45 were analyzed for viral load using ddPCR. Sample DNA was cleaved before droplet generation and PCR. Droplets positive for VIC and FAM fluorescence were read in a QX200 Droplet reader? (BIO-RAD) after which the viral load was calculated using Quantasoft software.

Results

We found that DNAs extracted from formalin fixed paraffin embedded (FFPE) tissue samples yielded lower amplification signals compared to those obtained from liquid based cytology (LBC) samples, but they were clearly distinguishable from negative background signals. The viral limit of detection was 1.6 copies of HPV 16, 2.8 copies of HPV 18, 4.6 copies of HPV 33 and 1.6 copies of HPV 45. The mean inter-assay coefficients of variability (CV) for the assays ranged from 3.4 to 7.0%, and the mean intra-assay CV from 2.6 to 8.2%. The viral load in the different cohorts of tumor samples ranged from 154 to 340,200 copies for HPV 16, 244 to 31,300 copies for HPV 18 and 738 to 69,100 copies for HPV 33. One sample positive for HPV 45 contained 1331 viral copies. When comparing qPCR data with ddPCR copy number data, the qPCR values were found to be 1 to 31 times higher.

Conclusions

Separation of fragments in nanodroplets may facilitate the amplification of fragmented human and viral DNA. The method of digital droplet PCR may, thus, provide a new and promising tool for evaluating the HPV viral load in clinical samples.

     

Rituximab therapy for primary glomerulonephritis: Report on two cases

The evidence in the medical literature on the efficacy and safety of rituximab therapy for primary glomerulonephritis is limited and controversial. We describe two male Caucasian patients with rapidly progressive kidney failure due to primary proliferative glomerulonephritis. Both of them received high-dose intravenous corticosteroids and oral cyclophosphamide with limited benefit. The first patient(hepatitis C virus-negative mixed cryoglobulinemia) underwent plasma-exchange with intravenous immunoglobulins; he showed significant benefit on kidney function(he became dialysis independent with serum creatinine going back to 1.6 mg/d L) after one rituximab pulse even if urinary abnormalities were still present. No improvement in renal function or urinary changes occurred in the second patient. Both these individuals developed sepsis over the follow-up, the first patient died two months after rituximab therapy. This report is in keeping with the occurrence of severe infections after rituximab therapy in patients with renal impairment at baseline and concomitant high-dose steroids.     

Effects of 60-Day Saccharomyces boulardii and Superoxide Dismutase Supplementation on Body Composition,Hunger Sensation,Pro/Antioxidant Ratio,Inflammation and Hormonal Lipo-Metabolic Biomarkers in Obese Adults: A Double-Blind,Placebo-Controlled Trial

In animals it has been demonstrated that Saccharomyces boulardii and Superoxide Dismutase (SOD) decrease low-grade inflammation and that S. boulardii can also decrease adiposity. The purpose of this study was to evaluate the effect of a 60-day S. boulardii and SOD supplementation on circulating markers of inflammation, body composition, hunger sensation, pro/antioxidant ratio, hormonal, lipid profile, glucose, insulin and HOMA-IR, in obese adults (BMI 30–35 kg/m²). Twenty-five obese adults were randomly assigned to intervention (8/4 women/men, 57 ± 8 years) or Placebo (9/4 women/men, 50 ± 9 years). Intervention group showed a statistically significant (p < 0.05) decrease of body weight, BMI, fat mass, insulin, HOMA Index and uric acid. Patients in intervention and control groups showed a significant decrease (p < 0.05) of GLP-1. Intervention group showed an increase (p < 0.05) of Vitamin D as well. In conclusion, the 60-day S. boulardii-SOD supplementation in obese subjects determined a significant weight loss with consequent decrease on fat mass, with preservation of fat free mass. The decrease of HOMA index and uric acid, produced additional benefits in obesity management. The observed increase in vitamin D levels in treated group requires further investigation.