A comparative effectiveness study of lipegfilgrastim in multiple myeloma patients after high dose melphalan and autologous stem cell transplant

G-CSF administration after high-dose chemotherapy and autologous stem cell transplantation (ASCT) has been shown to expedite neutrophil recovery. Several studies comparing filgrastim and pegfilgrastim in the post-ASCT setting concluded that the two are at least equally effective. Lipegfilgrastim (LIP) is a new long-acting, once-per-cycle G-CSF. This multicentric, prospective study aimed to describe the use of LIP in multiple myeloma patients receiving high-dose melphalan and autologous stem cell transplantation (ASCT) and compare LIP with historic controls of patients who received short-acting agent (filgrastim [FIL]). Overall, 125 patients with a median age of 60 years received G-CSF after ASCT (80 patients LIP on day 1 post-ASCT and 45 patients FIL on day 5 post-ASCT). The median duration of grade 4 neutropenia (absolute neutrophil count [ANC] < 0.5 × 10 [9]/L) was 5 days in both LIP and FIL groups, whereas the median number of days to reach ANC ≥ 0.5 × 10 [9]/L was 10% lower in the LIP than in the FIL group (10 vs 11 days), respectively. Male sex was significantly associated with a faster ANC ≥ 0.5 × 10 [9] L response (p = 0.015). The incidence of FN was significantly lower in the LIP than in the FIL group (29% vs 49%, respectively, p = 0.024). The days to discharge after ASCT infusion were greater in patients with FN (p < 0.001). The study indicates that LIP had a shorter time to ANC recovery and is more effective than FIL for the prevention of FN in the ASCT setting.     

Do mobile family planning clinics facilitate vasectomy use in Nepal?

Background

Nepal has a distinct topography that makes reproductive health and family planning services difficult to access, particularly in remote mountain and hill regions where over a quarter of modern contraceptive users rely exclusively on vasectomy.

Study design

A three-level random intercept logistic regression analysis was applied on data from the 2011 Nepal Demographic and Health Survey to investigate the extent of influence of mobile family planning clinics on the odds of a male or a female sterilization, adjusting for relevant characteristics including ecological differences and random effects. The analyses included a sample of 2014 sterilization users, considering responses from currently married women of reproductive ages.

Results

The odds of a male sterilization were significantly higher in a mobile clinic than those in a government hospital (odds ratio, 1.65; 95% confidence interval, 1.21–2.25). The effects remained unaltered and statistically significant after adjusting for sociodemographic and clustering effects. Random effects were highly significant, which suggest the extent of heterogeneity in vasectomy use at the community and district levels. The odds of vasectomy use in mobile clinics were significantly higher among couples residing in hill and mountain regions and among those with three or more sons or those with only daughters.

Conclusion

Mobile clinics significantly increase the uptake of vasectomy in hard-to-reach areas of Nepal. Reproductive health interventions should consider mobile clinics as an effective strategy to improve access to male-based modern methods and enhance gender equity in family planning.

Implications

Family planning interventions in hard-to-reach communities could consider mobile clinic as an effective strategy to promote male-based modern methods. Improving access to vasectomy could substantially reduce unmet need for family planning in countries experiencing rapid fertility transition.     

Stage-related differences of mitotic and apoptotic indices,and bcl-2 protein expression in diffusely growing non-Hodgkin's lymphomas

The present study examined whether growth characteristics of diffusely growing non-Hodgkin's lymphomas (NHL) may differ as a function of stage. Among 105 NHL of various types and sub-types (REAL [Revised European-American Lymphoma] classification), localized (Ann Arbor pathologic stages I + II) lymphomas exhibited clearly higher indices for mitotic activity, apoptosis and cell turnover, as well as a significantly lower percentage of cells containing immunohistochemically detectable bcl-2 protein, than disseminated (stages III + IV) NHL. A similar pattern emerged when high-grade (Kiel classification) lymphomas only were evaluated. Low-grade NHL showed analogous, but less marked, stage-dependent characteristics, with the exception of median percentages of bcl-2⁺ cells, which remained comparable in all stages. Our findings are consistent with the notion that dissemination of diffusely growing NHL is usually associated with reduced cell turnover and, in high-grade lymphomas, with the generation of longer-lived cells. © 1996 Wiley-Liss, Inc.     

Tannat Grape Skin: A Feasible Ingredient for the Formulation of Snacks with Potential for Reducing the Risk of Diabetes

In the present work the feasibility of Tannat grape skin (TGS) as a functional ingredient in the formulation of two snacks (yogurt and biscuits) was studied. The research provided novel information on the effects of the food matrix and digestion process, under simulated human oral gastrointestinal conditions, in the bioaccessibility of TGS bioactive compounds composing of the snacks with health promoting properties (antioxidant, anti-inflammatory, and antidiabetic). TGS polyphenolic profile was analyzed by ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) finding mainly flavonoids, phenolic acids, and anthocyanins, which may exert antioxidant, anti-inflammatory, and carbohydrase inhibition capacities. TGS digest showed antioxidant and antidiabetic potential compared to the undigested sample (p < 0.05). Yogurt and biscuits with TGS were developed with the nutrition claims “no-added sugars” and “source of fiber” and were digested in vitro to evaluate the bioaccessibility of compounds with health promoting properties after food processing and digestion. After in vitro simulation of digestion, bioactive properties were enhanced for control and TGS snacks which may be attributed to the formation/release of compounds with health-promoting properties. Biscuits showed significant increase in ABTS antioxidant capacity and yogurt showed increased α-glucosidase inhibition capacity by the addition of TGS (p < 0.05). Polyphenols from TGS and bioactive peptides from snacks which may be released during digestion might be responsible for the observed bioactivities. Consumer’s acceptance of TGS yogurt and biscuits showed scores of 6.3 and 5.1 (scale 1–9), respectively, showing TGS yogurt had higher overall acceptance. Sensory profile assessed by check-all-that-apply + just-about-right (CATA+JAR) showed most of the attributes were evaluated as “just about right”, supporting good food quality. The developed yogurt presented adequate shelf-life parameters for 28 days. TGS yogurt with higher acceptability showed reduced ROS formation (p < 0.05) induced by tert-butyl hydroperoxide (1 mM) in CCD-18Co colon cells and RAW264.7 macrophages when pre-treated with concentrations 500–1000 and 100–500 µg/mL of the digests, respectively. Moreover, TGS yogurt digest pre-treatment reduced nitric oxide (NO) production (p < 0.05) in lipopolysaccharide (LPS)-induced RAW264.7 macrophages, showing anti-inflammatory potential. Bioactive peptides generated during lactic fermentation and digestion process may be contributors to intracellular effects. In conclusion, yogurt and biscuits with Tannat grape skin addition were obtained with nutrition claims “no-added sugars” and “source of fiber” with the potential to modulate key biochemical events associated with diabetes pathogenesis.     

Sporadic hereditary neuropathies misdiagnosed as chronic inflammatory demyelinating polyradiculoneuropathy: Pitfalls and red flags

Hereditary neuropathies may be misdiagnosed with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). A correct diagnosis is crucial for avoiding unnecessary therapies and access genetic counseling. We report on nine patients (seven men, mean age 49.2 ± 16.1) diagnosed with and treated as CIDP, in whom mutations or variants of unknown significance (VUS) in genes associated with hereditary neuropathies were reported. All underwent neurological and neurophysiological examination, eight also cerebrospinal fluid (CSF) analysis. In 4/9, nerve ultrasound and/or MR‐neurography were performed. All the patients complained of progressive upper or lower limbs sensory‐motor symptoms, with heterogeneous disease duration (1‐34 years, mean 8.6 ± 10.8). Neurophysiology showed demyelinating signs in seven patients, mixed findings with predominant axonal damage in two patients. Neuroimaging disclosed diffuse abnormalities at proximal and distal segments. Molecular screening showed PMP22 duplication in two patients, mutations in the MPZ, EGR2, and GJB1 genes were reported in each of the remaining patients. The two patients with mixed neurophysiological findings had p.Val30Met mutation in the transthyretin gene. Two patients had VUS in the MARS and HSPB1 genes. Four patients had partial response to immunomodulant therapies, and CSF and neurophysiological features suggesting an inflammatory condition concomitant with the hereditary neuropathy. Hereditary neuropathy may be misdiagnosed with CIDP. The most common pitfalls are CSF (high protein levels and oligoclonal bands), incorrect interpretation of neurophysiology, and transient benefit from therapies. Neuroimaging may be helpful in cases with atypical presentations or when severe axonal damage complicate the neurophysiological interpretation.     

Daily Exposure to a Cranberry Polyphenol Oral Rinse Alters the Oral Microbiome but Not Taste Perception in PROP Taster Status Classified Individuals

Diet and salivary proteins influence the composition of the oral microbiome, and recent data suggest that TAS2R38 bitter taste genetics may also play a role. We investigated the effects of daily exposure to a cranberry polyphenol oral rinse on taste perception, salivary proteins, and oral microbiota. 6-n-Propylthiouracil (PROP) super-tasters (ST, n = 10) and non-tasters (NT, n = 10) rinsed with 30 mL of 0.75 g/L cranberry polyphenol extract (CPE) in spring water, twice daily for 11 days while consuming their habitual diets. The 16S rRNA gene sequencing showed that the NT oral microbiome composition was different than that of STs at baseline (p = 0.012) but not after the intervention (p = 0.525). Principal coordinates analysis using unweighted UniFrac distance showed that CPE modified microbiome composition in NTs (p = 0.023) but not in STs (p = 0.096). The intervention also altered specific salivary protein levels (α-amylase, MUC-5B, and selected S-type Cystatins) with no changes in sensory perception. Correlation networks between oral microbiota, salivary proteins, and sensory ratings showed that the ST microbiome had a more complex relationship with salivary proteins, particularly proline-rich proteins, than that in NTs. These findings show that CPE modulated the oral microbiome of NTs to be similar to that of STs, which could have implications for oral health.