Changes in symptom scores as a potential clinical endpoint for studies of cystic fibrosis pulmonary exacerbation treatment

Introduction: Symptom improvement was assessed as changes in the Chronic Respiratory Infection Symptom Score (CRISS) during intravenous antimicrobial exacerbation treatments among subjects from study NCT02109822.Methods: Median daily CRISS reduction (i.e., improvement) and covariates associated with CRISS reduction by Day 14 were assessed by logistic regression.Results: Among 173 subjects, median baseline CRISS was 49 [IQR 41, 56]; 93.6% had a CRISS reduction of ≥11 (minimal clinically important difference); median time to –11 reduction was 2 days [95% CI 2, 3]. The greatest median CRISS difference from baseline, on Day 17, was –26 [–29, –23]. Odds of –26 CRISS change by Day 14 were greater in subjects with higher baseline CRISS (P=.006) and younger ages (P=.041).Conclusions: CRISS response has good dynamic range and may be a useful efficacy endpoint for PEx interventional trials. The optimal use of CRISS change as an endpoint remains uncharacterized.     

A COMPARISON OF NSP-RETICULONS WITH CONVENTIONAL NEUROENDOCRINE MARKERS IN IMMUNOPHENOTYPING OF LUNG CANCERS

Neuroendocrine-specific protein (NSP)-reticulons are endoplasmic reticulum-associated protein complexes, which have been identified as markers for neuroendocrine differentiation. In this study, the expression of two members of the family of NSP-reticulons, NSP-A and NSP-C, have been investigated in different types of lung cancer and compared with the expression patterns of five conventional neuroendocrine markers, the neural cell adhesion molecule (NCAM), synaptophysin, chromogranin A, Leu-7, and neurofilament proteins. NSP-A and NSP-C antibodies were reactive with most carcinoid tumour and small cell lung carcinoma (SCLC) cases, while atypical carcinoid tumours showed a variable expression. In the total group of neuroendocrine tumours, a high concordance of expression was found between NSP-A and NSP-C, while their expression correlated well with NCAM and synaptophysin positivity. Chromogranin A, Leu-7, and neurofilament proteins were shown to be expressed to a limited extent in these neuroendocrine tumours. In a selected group of non-SCLCs known to exhibit neuroendocrine features, NSP-A expression was detected at much higher frequency than NSP-C. In virtually all NSP-A positive cases, this expression was associated with one or more of the other neuroendocine markers. NSP-A expression showed a stronger correlation with conventional neuroendocrine markers than NCAM. In detecting neuroendocrine differentiation in non-SCLC, NSP-A is more sensitive than synaptophysin, chromogranin A, Leu-7, and neurofilament proteins. It is concluded that NSP-reticulons are valuable markers in the diagnosis of neuroendocrine differentiation in non-SCLC and should be used in conjunction with NCAM. © 1997 John Wiley & Sons, Ltd.     

Cerebrospinal fluid progranulin levels in patients with different multiple sclerosis subtypes

Progranulin has recently attracted attention due to the discovery of mutations in its encoding gene (GRN) in several cases of frontotemporal lobar degeneration, but also for a possible role in inflammatory processes. In adult central nervous system, GRN mRNA is expressed in forebrain, olfactory bulbs and spinal cord. Progranulin cerebrospinal fluid (CSF) levels were evaluated in 55 patients with multiple sclerosis (MS) as well as in 35 subjects with non-inflammatory neurological diseases (NIND), 7 individuals with other inflammatory neurological disease (OIND) and 8 controls (CON), matched for ethnic background, gender and age. No statistically significant differences were found in patients compared with either NIND, OIND or CON (P > 0.05), even stratifying according to disease subtype or gender. A positive correlation between progranulin CSF levels and age was observed in patients (ρ = 0.29, P = 0.03). According to these data, progranulin does not likely play a major role in the pathogenesis of MS.     

Antidiarrhoeal activity of leaf methanolic extract of Rauwolfia serpentina

Objective

To evaluate the antidiarrhoeal property of methanol extract of the leaves of Rauwolfia serpentina (R. serpentina) in experimental diarrhoea induced by castor oil in mice.

Methods

Doses of 100, 200 and 400 mg/kg R. serpentina leaf methanol extracts were administered to castor oil induced diarrhoea mice to determine its antidiarrhoeal activity.

Results

All doses of the extract and the reference drug atropine sulphate (3 mg/kg, i.p.) produced a dose-dependent reduction in intestinal weight and fluid volume. The extracts also significantly reduced the intestinal transit in charcoal meal test when compared to diphenoxylate Hcl (5 mg/kg, p.o.).

Conclusions

The results show that the extract of R. serpentina leaves has a significant antidiarrhoeal activity and supports its traditional uses in herbal medicine.     

High tie versus low tie of the inferior mesenteric artery in colorectal cancer: A RCT is needed

Nowadays left colon and rectal cancer treatment has been well standardized in both open and laparoscopy. Nevertheless, the level of the ligation of the inferior mesenteric artery (IMA), at the origin from the aorta (high tie) or below the origin of the left colic artery (low tie), is still debated. The objective of the systematic review is to evaluate the current scientific evidence of high versus low tie of the IMA in colorectal cancer surgery. The outcomes considered were overall 30-days postoperative morbidity, overall 30-days postoperative mortality, anastomotic leakage, 5-years survival rate, and overall recurrence rate. A total of 8.666 patients were included in our analysis, 4.281 forming the group undergoing high tie versus 4.385 patients undergoing low tie. Neither the high tie nor the low tie strategy showed an evidence based success, as no statistically significant differences were identified for all outcomes measured. Future high powered and well designed randomized clinical trials are needed to draw definitive conclusion on this dilemma.     

The beginning of a decline in breast cancer incidence in Italy?

The incidence of invasive breast cancer in Turin, Italy, showed a statistically significant decrease during 1999-2003 overall (estimated annual percent change -2.6; 95% CL -8.52; -0.78) and in women aged over 50, similar to the recently documented trend in American data. This represents the first demonstration of a decline in breast cancer incidence in the early years of this decade outside the United States. In our population, the drop in the usage of hormone replacement therapy which occurred after 2002 is unlikely to be at the origin of this declining incidence trend, which is largely explained by a screening effect. This observation may be relevant to other geographical areas where organized or spontaneous screening reached a plateau after an increase in the preceding years.