Improving HIV medical care engagement by attending to status disclosure and social support

ABSTRACT

Expeditious linkage and consistent engagement in medical care is important for people with HIV’s (PWH) health. One theory on fostering linkage and engagement involves HIV status disclosure to mobilize social support. To assess disclosure and social support’s association with linkage and engagement, we conducted a qualitative study sampling black and Latino men who have sex with men (MSM of color) in the U.S. Participants' narratives presented mixed results. For instance, several participants who reported delaying, inconsistent access, or detachment from care also reported disclosing for support purposes, yet sporadic engagement suggests that their disclosure or any subsequent social support have not assisted. The findings contribute to the literature that questions disclosure and social support’s influence on care engagement, especially when decontextualized from circumstances and intentions. Our findings suggest the mechanics of disclosure and social support require planned implementation if intending to affect outcomes, especially among MSM of color. From the findings, we explore steps that may bolster interventions seeking to anchor medical care engagement.     

Homologous recombination deficiency and host anti-tumor immunity in triple-negative breast cancer

Purpose

Triple-negative breast cancer (TNBC) is associated with worse outcomes relative to other breast cancer subtypes. Chemotherapy remains the standard-of-care systemic therapy for patients with localized or metastatic disease, with few biomarkers to guide benefit.

Methods

We will discuss recent advances in our understanding of two key biological processes in TNBC, homologous recombination (HR) DNA repair deficiency and host anti-tumor immunity, and their intersection.

Results

Recent advances in our understanding of homologous recombination (HR) deficiency, including FDA approval of PARP inhibitor olaparib for BRCA1 or BRCA2 mutation carriers, and host anti-tumor immunity in TNBC offer potential for new and biomarker-driven approaches to treat TNBC. Assays interrogating HR DNA repair capacity may guide treatment with agents inducing or targeting DNA damage repair. Tumor infiltrating lymphocytes (TILs) are associated with improved prognosis in TNBC and recent efforts to characterize infiltrating immune cell subsets and activate host anti-tumor immunity offer promise, yet challenges remain particularly in tumors lacking pre-existing immune infiltrates. Advances in these fields provide potential biomarkers to stratify patients with TNBC and guide therapy: induction of DNA damage in HR-deficient tumors and activation of existing or recruitment of host anti-tumor immune cells. Importantly, these advances provide an opportunity to guide use of existing therapies and development of novel therapies for TNBC. Efforts to combine therapies that exploit HR deficiency to enhance the activity of immune-directed therapies offer promise.

Conclusions

HR deficiency remains an important biomarker target and potentially effective adjunct to enhance immunogenicity of ‘immune cold’ TNBCs.

     

Abdominal Adiposity and Coronary Heart Disease in Women

Context.— Obesity is a well-established risk factor for coronary heart disease (CHD), but whether regional fat distribution contributes independently to risk remains unclear. Objective.— To compare waist-hip ratio (WHR) and waist circumference in determining risk of CHD in women. Design and Setting.— Prospective cohort study among US female registered nurses participating in the Nurses' Health Study conducted between 1986, when the nurses completed a questionnaire, and follow-up in June 1994. Participants.— A total of 44,702 women aged 40 to 65 years who provided waist and hip circumferences and were free of prior CHD, stroke, or cancer in 1986. Main Outcome Measures.— Incidence of CHD (nonfatal myocardial infarction or CHD death). Results.— During 8 years of follow-up 320 CHD events (251 myocardial infarctions and 69 CHD deaths) were documented. Higher WHR and greater waist circumference were independently associated with a significantly increased age-adjusted risk of CHD. After adjusting for body mass index (BMI) (defined as weight in kilograms divided by the square of height in meters) and other cardiac risk factors, women with a WHR of 0.88 or higher had a relative risk (RR) of 3.25 (95% confidence interval [CI], 1.78-5.95) for CHD compared with women with a WHR of less than 0.72. A waist circumference of 96.5 cm (38 in) or more was associated with an RR of 3.06 (95% CI, 1.54-6.10). The WHR and waist circumference were independently strongly associated with increased risk of CHD also among women with a BMI of 25 kg/m² or less. After adjustment for reported hypertension, diabetes, and high cholesterol level, a WHR of 0.76 or higher or waist circumference of 76.2 cm (30 in) or more was associated with more than a 2-fold higher risk of CHD. Conclusions.— The WHR and waist circumference are independently associated with risk of CHD in women.      

Prognostic indicators for gastrointestinal stromal tumours: a clinicopathological and immunohistochemical study of 108 resected cases of the stomach

AIMS: Whether immunohistochemical markers increase accuracy in predicting prognosis for gastrointestinal stromal tumours (GISTs) remains uncertain. However, past studies have used only small, heterogeneous patient groups. Our aim was to test previously studied and more novel morphological features as well as four immunohistochemical markers as prognostic indicators amongst a large cohort of surgically resected, gastric GISTs. METHODS AND RESULTS: Tissues from 127 gastric mesenchymal tumours were collected retrospectively and subjected to repeat histological assessment and immunophenotyping. Further immunohistochemistry was performed for Ki67, p53, Bcl-2 and cyclin D1. Complete follow-up data were collected for 108 patients with immunophenotyped diagnoses of GIST (i.e. c-kit+ tumours). At the census point, 52 patients were alive, 24 had died from their GISTs and the remainder of other causes. Univariate analysis showed the following predicted for shorter disease-specific survival: size > or =50 mm; necrosis, no intratumoral lymphocytes; mitotic count > or =5/50 high power fields; Ki67 labelling index > or =5%; p53 immunopositivity. Of these variables, multivariate analyses showed only mitotic count and, to a lesser extent, Ki67 labelling to be independent prognostic indicators. CONCLUSIONS: Mitotic count remains the best predictor of outcome following surgical resection of gastric GISTs. Ki67 immunohistochemistry does not provide better prognostication and p53, Bcl-2 and cyclin D1 immunohistochemistry provide no additional prognostication.     

Reaching to ipsilateral or contralateral targets: within-hemisphere visuomotor processing cannot explain hemispatial differences in motor control

Aiming movements made to visual targets on the same side of the body as the reaching hand typically show advantages as compared to aiming movements made to targets on the opposite side of the body midline in the contralateral visual field. These advantages for ipsilateral reaches include shorter reaction time, higher peak velocity, shorter duration and greater endpoint accuracy. It is commonly hypothesized that such advantages are related to the efficiency of intrahemispheric processing, since, for example, a left-sided target would be initially processed in the visual cortex of the right hemisphere and that same hemisphere controls the motor output to the left hand. We tested this hypothesis by examining the kinematics of aiming movements made by 26 right-handed subjects to visual targets briefly presented in either the left or the right visual field. In one block of trials, the subjects aimed their finger directly towards the target; in the other block, subjects were required to aim their movement to the mirror symmetrical position on the opposite side of the fixation light from the target. For the three kinematic measures in which hemispatial differences were obtained (peak velocity, duration and percentage of movement time spent in deceleration), the advantages were related to the side to which the motor response was directed and not to the side where the target was presented. In addition, these effects tended to be larger in the right hand than in the left, particularly for the percentage of the movement time spent in deceleration. The results are interpreted in terms of models of biomechanical constraints on contralateral movements, which are independent of the hemispace of target presentation.     

Premixed rapid-setting calcium phosphate composites for bone repair

Although calcium phosphate cement (CPC) is promising for bone repair, its clinical use requires on site powder-liquid mixing. To shorten surgical time and improve graft properties, it is desirable to develop premixed CPC in which the paste remains stable during storage and hardens only after placement into the defect. The objective of this study was to develop premixed CPC with rapid setting when immersed in a physiological solution. Premixed CPCs were formulated using the following approach: Premixed CPC = CPC powder + nonaqueous liquid + gelling agent + hardening accelerator. Three premixed CPCs were developed: CPC-monocalcium phosphate monohydrate (MCPM), CPC-chitosan, and CPC-tartaric. Setting time for these new premixed CPCs ranged from 5.3 to 7.9 min, significantly faster than 61.7 min for a premixed control CPC reported previously (p < 0.05). SEM revealed the formation of nano-sized needle-like hydroxyapatite crystals after 1 d immersion and crystal growth after 7 d. Diametral tensile strength for premixed CPCs at 7 d ranged from 2.8 to 6.4 MPa, comparable to reported strengths for cancellous bone and sintered porous hydroxyapatite implants. Osteoblast cells attained a normal polygonal morphology on CPC-MCPM and CPC-chitosan with cytoplasmic extensions adhering to the nano-hydroxyapatite crystals. In summary, fast-setting premixed CPCs were developed to avoid the powder-liquid mixing in surgery. The pastes hardened rapidly once immersed in physiological solution and formed hydroxyapatite. The cements had strengths matching those of cancellous bone and sintered porous hydroxyapatite and non-cytotoxicity similar to conventional non-premixed CPC.     

Tuberculous tenosynovitis

Tuberculous tenosynovitis is rare and may be overlooked as a cause of chronic tenosynovitis. This report presents a case of a young woman with tuberculosis tenosynovitis of the wrist, and highlights the clinical, imaging, histological, and laboratory features most commonly seen in this disease.     

Dominantly inherited renal adysplasia

We are reporting on 7 families with both unilateral and bilateral renal agenesis (or severe dysplasia). This condition, termed hereditary renal adysplasia (HRA) [Buchta et al, 1973], is an autosomal dominant trait with incomplete penetrance and variable expression. Review of the literature on familial renal agenesis suggests that HRA is more common than previously supposed and may account for most recurrences of bilateral renal agenesis (BRA), even when the parents are normal. There are no consistent phenotypic differences between sporadic and familial renal agenesis. Associated non-urogenital anomalies, although more frequent in sporadic cases, have been reported in HRA. Use of several approaches, including the Weinberg Proband Method, segregation analysis, and empiric risk estimation, leads to the conclusion that autosomal dominant inheritance is the most likely pattern of transmission for most cases of renal agenesis. Penetrance is between 50% and 90%. Ultrasound study of the kidneys of parents, sibs, and other relatives is recommended in all families in which there is an individual with unilateral or bilateral renal agenesis. The empiric risk for recurrence of BRA in sibs has been estimated at 3.5% [Carter, et al, 1979] but in the offspring of affected or obligate heterozygotes for HRA, the empiric risk of bilateral severe renal adysplasia is 15-20%.