Second cancers in MPN: Survival analysis from an international study

One out of ten patients with Philadelphia-negative myeloproliferative neoplasms (MPN) develop a second cancer (SC): in such patients we aimed at assessing the survival impact of SC itself and of MPN-specific therapies. Data were therefore extracted from an international nested case-control study, recruiting 798 patients with SC diagnosed concurrently or after the MPN. Overall, 2995 person-years (PYs) were accumulated and mortality rate (MR) since SC diagnosis was 5.9 (5.1-6.9) deaths for every 100 PYs. A “poor prognosis” SC (stomach, esophagus, liver, pancreas, lung, ovary, head-and-neck or nervous system, osteosarcomas, multiple myeloma, aggressive lymphoma, acute leukemia) was reported in 26.3% of the patients and was the cause of death in 65% of them (MR 11.0/100 PYs). In contrast, patients with a “non-poor prognosis” SC (NPPSC) incurred a MR of 4.6/100 PYs: 31% of the deaths were attributed to SC and 15% to MPN evolution. At multivariable analysis, death after SC diagnosis was independently predicted (HR and 95% CI) by patient age greater than 70 years (2.68; 1.88-3.81), the SC prognostic group (2.57; 1.86-3.55), SC relapse (1.53; 10.6-2.21), MPN evolution (2.72; 1.84-4.02), anemia at SC diagnosis (2.32; 1.49-3.59), exposure to hydroxyurea (1.89; 1.26-2.85) and to ruxolitinib (3.63; 1.97-6.71). Aspirin was protective for patients with a NPPSC (0.60; 0.38-0.95). In conclusion, SC is a relevant cause of death competing with MPN evolution. Prospective data are awaited to confirm the role of cytoreductive and anti-platelet drugs in modulating patient survival after the occurrence of a SC.     

Memories of attachment hamper EEG cortical connectivity in dissociative patients

In this study, we evaluated cortical connectivity modifications by electroencephalography (EEG) lagged coherence analysis, in subjects with dissociative disorders and in controls, after retrieval of attachment memories. We asked thirteen patients with dissociative disorders and thirteen age- and sex-matched healthy controls to retrieve personal attachment-related autobiographical memories through adult attachment interviews (AAI). EEG was recorded in the closed eyes resting state before and after the AAI. EEG lagged coherence before and after AAI was compared in all subjects. In the control group, memories of attachment promoted a widespread increase in EEG connectivity, in particular in the high-frequency EEG bands. Compared to controls, dissociative patients did not show an increase in EEG connectivity after the AAI. Conclusions: These results shed light on the neurophysiology of the disintegrative effect of retrieval of traumatic attachment memories in dissociative patients.     

Fatty acid ethanolamide levels are altered in borderline personality and complex posttraumatic stress disorders

Borderline personality (BPD) and complex posttraumatic stress disorders (PTSD) are both powerfully associated with the experience of interpersonal violence during childhood and adolescence. The disorders frequently co-occur and often result in pervasive problems in, e.g., emotion regulation and altered pain perception, where the endocannabinoid system is deeply involved. We hypothesize an endocannabinoid role in both disorders. We investigated serum levels of the endocannabinoids anandamide and 2-arachidonoylglycerol and related fatty acid ethanolamides (FAEs) in BPD, PTSD, and controls. Significant alterations were found for both endocannabinoids in BPD and for the FAE oleoylethanolamide in PTSD suggesting a respective link to both disorders.     

Membranous nephropathy associated with angiomatoid fibrous histiocytoma in a pediatric patient

Background

Though membranous nephropathy is a much more common cause of nephrotic syndrome in the adult population, it accounts for only a small fraction of cases in pediatrics.

Case-Diagnosis/Treatment

We report a case of a 16-year-old boy with nephrotic syndrome due to membranous nephropathy in the setting of a rare tumor, angiomatoid fibrous histiocytoma. This patient’s nephrotic-range proteinuria completely resolved following resection of this tumor. Angiomatoid fibrous histiocytoma, while known to cause other paraneoplastic syndromes such as anemia, has never been reported to cause membranous nephropathy.

Conclusions

This case highlights a novel and treatable secondary cause of membranous nephropathy. Because secondary causes are more common in children than in adults, a high index of suspicion for other underlying pathology including malignancy should be considered. It also suggests that urinalysis may be a helpful screening tool in cases of angiomatoid fibrous histiocytoma.     

Costly teeth? Gestation length in primates suggests that neonate dentition is not expensive to produce

Variation in the relationship between gestation length and body mass can arise because different types of tissue require varying amounts of energy to build, and not all species build such tissues in the same proportions. Given that a pregnant female has a finite amount of energy, trade-offs between investment in different tissues may occur. Here we examine if dental precocity accounts for variation in primate gestation length. If true, this could explain why folivorous species with precocial dentition have longer gestation lengths than predicted by neonatal brain and body mass. We compiled data on gestation length, neonate and adult female body and brain mass from the literature. We used published postcanine eruption schedules at 4 months of age and measured the total occlusal area as dental endowment to approximate dental precocity at birth. Species with embryonic delay in growth or altricial neonates were not considered because they represent grade shifts regarding gestation length. Consequently, our data were biased toward Simiiformes and Old World monkeys, specifically. We performed a phylogenetic generalized least squares regression (pGLS) of neonate brain mass in relation to neonate body mass, and a second pGLS with dental endowment as an additional predictor variable. Including dental endowment in the pGLS did not improve the model. Dental endowment did not systematically impact primate gestation length. Concordant with results from previous studies, this indicates that the energetically expensive period of tooth mineralization may occur postnatally. More data are required to examine if the results are typical across primates.     

Neonatal blue light phototherapy increases café-au-lait macules in preschool children

Neonatal blue light phototherapy (NBLP) is an effective treatment for hyperbilirubinaemia. Concerning the influence on melanocytic nevi, conflicting studies have been published. To assess the role of NBLP according to the incidence of melanocytic nevi in preschool children, a cohort of 104 5- to 6-year-old children were included. The case group consisted of 52 NBLP-exposed children, while the control group (n?=?52) never had NBLP and was matched regarding age, gender, gestational age and skin phototype. Six dizygotic twins were included with one twin having received NBLP, respectively. The following parameters were recorded: nevi count, presence of freckles, café-au-lait macules, skin phototype and previous history of sun exposure. There was no significant association between nevi count and exposure to NBLP (median nevi count 17.0 compared to 18.5 in controls). No significant difference was also found in the dizygotic twin pairs with a median nevi count of 10.0 (with NBLP) compared to 14.5 (without NBLP). However, a significantly higher prevalence of café-au-lait macules was found in children with NBLP (mean count 0.5) than in children without NBLP (mean count 0.2; p?=?0.001). Significant predictors for the number of melanocytic nevi included skin phototype, sun exposure and vacations in the South. Conclusion: In this study, NBLP had no significant influence on the development of melanocytic nevi, but on café-au-lait macules which was a new finding. Differences with comparable studies regarding age, differentiation between nevi and other pigmented lesions as well as dose and type of NBLP need to be taken into account for further investigations.     

Risk factors for septic arthritis in patients with joint disease

Objective. To quantify potential risk factors for septic arthritis, in order to identify a basis for prevention. Methods. The occurrence of potential risk factors for septic arthritis in patients with joint diseases attending a rheumatic disease clinic was prospectively monitored at 3-m onth intervals over a period of 3 years. Potential risk factors investigated were type of joint disease, comorbidity, medication, joint prosthesis, infections, and invasive procedures. The frequencies of risk factors in patients with and those without septic arthritis were compared using multiple logistic regression analysis. Results. There were 37 patients with and 4,870 without septic arthritis. Risk factors for developing septic arthritis were age ≥80 years (odds ratio [OR] = 3.5, 95% confidence interval [95% CI] 1.4–8.6), diabetes mellitus (OR = 3.3, 95% CI 1.1–10.1), rheumatoid arthritis (OR = 4.0, 95% CI 1.9–8.3), hip and/or knee prosthesis (OR = 15, 95% CI 4.1–54.3), joint surgery (OR = 5.1, 95% CI 2.2–11.9), and skin infection (OR = 27.2, 95% CI 7.6–97.1) Conclusion. These findings indicate that preventive measures against septic arthritis in patients with joint diseases should mainly be directed at those with joint prostheses and/or skin infection.     

A Synbiotic Formulation Comprising Bacillus subtilis DSM 32315 and L-Alanyl-L-Glutamine Improves Intestinal Butyrate Levels and Lipid Metabolism in Healthy Humans

The gut microbiota is a crucial modulator of health effects elicited by food components, with SCFA (short chain fatty acids), especially butyrate, acting as important mediators thereof. We therefore developed a nutritional synbiotic composition targeted at shifting microbiome composition and activity towards butyrate production. An intestinal screening model was applied to identify probiotic Bacillus strains plus various amino acids and peptides with suitable effects on microbial butyrate producers and levels. A pilot study was performed to test if the synbiotic formulation could improve fecal butyrate levels in healthy humans. A combination of Bacillus subtilis DSM (Number of German Collection of Microorganisms and Cell Cultures) 32315 plus L-alanyl-L-glutamine resulted in distinctly increased levels of butyrate and butyrate-producing taxa (Clostridium group XIVa, e.g., Faecalibacterium prausnitzii), both in vitro and in humans. Moreover, circulating lipid parameters (LDL-, and total cholesterol and LDL/HDL cholesterol ratio) were significantly decreased and further metabolic effects such as glucose-modulation were observed. Fasting levels of PYY (Peptide YY) and GLP-1 (Glucagon-like Peptide 1) were significantly reduced. In conclusion, our study indicates that this synbiotic composition may provide an effective and safe tool for stimulation of intestinal butyrate production with effects on e.g., lipid and glucose homeostasis. Further investigations in larger cohorts are warranted to confirm and expand these findings.