Use of Single-Item Self-Rated Health Measure to Identify Frailty and Geriatric Assessment-Identified Impairments Among Older Adults with Cancer

BackgroundPoor self-rated health (SRH) is a known predictor of frailty and mortality in the general population; however, its role among older adults with cancer is unknown. We evaluated the role of SRH as a potential screening tool to identify frailty and geriatric assessment (GA)-identified impairments.Materials and MethodsAdults ≥60 years diagnosed with cancer in the UAB Cancer & Aging Resilience Evaluation (CARE) registry underwent a GA at the time of initial consultation. We measured SRH using a single-item from the Patient-Reported Outcomes Measurement Information System global health scale and dichotomized responses as poor (poor, fair) and good (good, very good, and excellent). We evaluated the diagnostic performance of SRH in measuring frailty, and GA impairment (≥2 deficits among a set of seven GA domains). We examined the impact of SRH with survival using a Cox model adjusting for confounders, exploring the mediating role of frailty.ResultsSix hundred and three older adults with cancer were included, with a median age of 69 years. Overall, 45% (n = 274) reported poor SRH. Poor SRH demonstrated high sensitivity and specificity for identifying frailty (85% and 78%, respectively) and GA impairment (75% and 78%, respectively). In a Cox regression model, poor SRH was associated with inferior survival (HR = 2.26; 95% CI 1.60-3.18) after adjusting for confounders; frailty mediated 69% of this observed relationship.ConclusionSelf-rated health may be used as a screening tool to identify older adults with cancer with frailty and GA impairments. Poor SRH is associated with inferior survival, which is mediated by frailty.     

Synchronous water-clear cell double parathyroid adenomas a hitherto uncharacterized entity?

Water-clear cell hyperplasia is a rare but well-documented cause of primary hyperparathyroidism. Parathyroid adenomas of the water-clear cell type are exceptionally rare, and only 2 cases have been reported. We describe a patient with synchronous water-clear cell double parathyroid adenomas, an entity that has not previously been reported. In our case, the enlarged superior parathyroid glands were completely replaced by water-clear cells, with only a minute rim of extracapsular, histologically unremarkable parathyroid tissue. The inferior parathyroid glands were grossly unremarkable, and incisional biopsy specimens were histologically normal (no foci of water-clear cells were identified). The findings in this case are most consistent with the diagnosis of double adenomas of the water-clear cell type. We acknowledge that despite molecular proof of monoclonality of the 2 lesions, it is not possible to entirely exclude the possibility that this unusual case could be due to asymmetric hyperplasia.     

Nitro‐Group Functionalization of Dopamine and its Contribution to the Viscoelastic Properties of Catechol‐Containing Nanocomposite Hydrogels

Linear polyacrylamide (PAAm) is modified with dopamine or nitrodopamine (PAAm‐D and PAAm‐ND, respectively) to evaluate the effect of nitro‐group modification on the interfacial binding properties of polymer‐bound catechol. Nanocomposite hydrogels are prepared by mixing PAAm‐based polymers with Laponite and the viscoelastic properties of these materials are determined using oscillatory rheometry. The incorporation of a small amount of catechol (≈0.1 wt% in swollen hydrogel) drastically increases the shear moduli by 1–2 orders of magnitude over those of the catechol‐free control. Additionally, PAAm‐ND exhibits higher shear moduli values than PAAm‐D across the whole pH range tested (pH 3.0–9.0). Based on the calculated effective crosslinking density, effective functionality, and molecular weight between crosslinks, nitro‐group functionalization of dopamine results in a polymer network with increased crosslinking density and crosslinking points with higher functionality. Nitro‐functionalization enhances the interfacial binding property of dopamine and increases its resistant to oxidation, which results in nanocomposite hydrogels with enhanced stiffness and a viscous dissipation property.

     

Treatment of submassive and massive pulmonary embolism: a clinical practice survey from the second annual meeting of the Pulmonary Embolism Response Team Consortium

There is a paucity of robust clinical trial data to guide the treatment of acute pulmonary embolism (PE) thus the clinical guidelines rely heavily on expert opinion. Pulmonary Embolism Response Teams (PERT) have been developed to streamline the care of patients with acute PE. We conducted a survey among 100 experts in the field of PE during the second annual meeting of the PERT Consortium. Respondents were queried with respect to their demographic information, clinical practice questions and clinical vignettes. Clinical practice questions were focused questions about the risk stratification and treatment of patients with acute submassive PE, anticoagulation strategies for patients receiving thrombolysis and the use of inferior vena cava filters. Clinical vignettes were designed to assess participants’ preferred choice of treatment for a variety of commonly encountered clinical scenarios. Among physicians affiliated with a PERT, there is overall agreement with regards to the criteria used for risk classification of patients with PE and its application to patients in the provided clinical vignettes. In contrast, there is substantial variability in the treatment strategies of patients presenting with commonly encountered clinical scenarios. The results of this survey highlight the need for more clinical trial data along with accepted algorithms for treatment of acute PE. In the absence of this, PERTs can facilitate multidisciplinary discussions in order to standardize treatment and provide evidence-based therapies to patients with acute PE.     

Longitudinal assessment of pigtailed macaque lower genital tract microbiota by pyrosequencing reveals dissimilarity to the genital microbiota of healthy humans

Abstract Vaginal bacterial communities play an important role in human health and have been shown to influence HIV infection. Pigtailed macaques (Macaca nemestrina) are used as an animal model of HIV vaginal infection of women. Since the bacterial microbiota could influence retrovirus infection of pigtailed macaques, the genital microbiota in 10 cycling macaques was determined by pyrosequencing. The microbiota of all macaques was polymicrobial with a median of 13 distinct genera. Strikingly, the genera Sneathia and Fusobacterium, both in the phylum Fusobacteria, accounted for 18.9% and 13.3% of sequences while the next most frequent were Prevotella (5.6%), Porphyromonas (4.1%), Atopobium (3.6%), and Parvimonas (2.6%). Sequences corresponding to Lactobacillus comprised only 2.2% of sequences on average and were essentially all L. amylovorus. Longitudinal sampling of the 10 macaques over an 8-week period, which spanned at least one full ovulatory cycle, showed a generally stable presence of the major types of bacteria with some exceptions. These studies show that the microbiota of the pigtailed macaques is substantially dissimilar to that found in most healthy humans, where the genital microbiota is usually dominated by Lactobacillus sp. The polymicrobial makeup of the macaque bacterial populations, the paucity of lactobacilli, and the specific types of bacteria present suggest that the pigtailed macaque microbiota could influence vaginal retrovirus infection.     

Dilated cardiomyopathy: a new insight into the rare but common cause of heart failure

Heart Failure Reviews - Heart failure is a global health burden responsible for high morbidity and mortality with a prevalence of greater than 60 million individuals worldwide. One of the major...     

In vitro characterisation of two naturally occurring mutations in the thrombin-sensitive region of anticoagulant protein S

The molecular consequences of two naturally occurring mutations in the thrombin-sensitive region of protein S were investigated using a combination of recombinant protein expression, functional analysis and molecular modelling. Both mutations (R49H and R70S) have been found in thrombosis patients diagnosed as having type I protein S deficiency. Molecular modelling analysis suggested the R49H substitution not to disrupt the structure of thrombin-sensitive region, whereas the R70S substitution could affect the 3D structure mildly. To elucidate the molecular consequences of these substitutions experimentally, site directed mutagenesis of protein S cDNA and expression in mammalian cells created the two mutants. The secretion profiles and functional anticoagulant activities of the protein S mutants were characterised. Secretion of the R49H mutant was similar to that of wild type protein S, whereas the R70S mutant showed moderately decreased expression. Neither of the mutants showed any major functional defects as cofactors to activated protein C (APC) in an APTT-based assay or in degradation of factor Va. However, both mutants demonstrated decreased activity in a factor VIIIa degradation assay, which in addition to APC and protein S also included factor V as synergistic APC cofactor. In conclusion, the R49H substitution did not produce a quantitative abnormality in vitro, raising doubts as to whether it caused the type I deficiency. In contrast, the experimental data obtained for the R70S mutant agrees well with the observed type I deficiency. Our study illustrates that in vitro experimental characterisation together with computer-based structural analysis are useful tools in the analysis of the relationship between naturally occurring mutations and clinical phenotypes.