Publications

PURPOSE

Reports have suggested that metastatic site is an important predictor of overall survival (OS) in men with metastatic castration-resistant prostate cancer (mCRPC), but these were based on a limited number of patients. We investigate the impact of site of metastases on OS of a substantial sample of men with mCRPC who received docetaxel chemotherapy in nine phase III trials.

PATIENTS AND METHODS

Individual patient data from 8,820 men with mCRPC enrolled onto nine phase III trials were combined. Site of metastases was categorized as lymph node (LN) only, bone with or without LN (with no visceral metastases), any lung metastases (but no liver), and any liver metastases.

RESULTS

Most patients had bone with or without LN metastases (72.8%), followed by visceral disease (20.8%) and LN-only disease (6.4%). Men with liver metastases had the worst median OS (13.5 months). Although men with lung metastases had better median OS (19.4 months) compared with men with liver metastases, they had significantly worse median survival duration than men with nonvisceral bone metastases (21.3 months). Men with LN-only disease had a median OS of 31.6 months. The pooled hazard ratios for death in men with lung metastases compared with men with bone with or without LN metastases and in men with any liver metastases compared with men with lung metastases were 1.14 (95% CI, 1.04 to 1.25; P = .007) and 1.52 (95% CI, 1.35 to 1.73; P < .0001), respectively.

CONCLUSION

Specific sites of metastases in men with mCRPC are associated with differential OS, with successive increased lethality for lung and liver metastases compared with bone and nonvisceral involvement. These data may help in treatment decisions, the design of future clinical trials, and understanding the variation in biology of different sites of metastases in men with mCRPC.

BACKGROUND

Sentinel surveillance for HIV among women attending antenatal clinics using unlinked anonymous testing is a cornerstone of HIV surveillance in sub-Saharan Africa. Increased use of routine antenatal HIV testing allows consideration of using these programmatic data rather than sentinel surveillance data for HIV surveillance.

METHODS

To gauge Kenya's readiness to discontinue sentinel surveillance, we evaluated whether recommended World Health Organization standards were fulfilled by conducting data and administrative reviews of antenatal clinics that offered both routine testing and sentinel surveillance in 2010.

RESULTS

The proportion of tests that were HIV-positive among women aged 15-49 years was 6.2% (95% confidence interval [CI] 4.6-7.7%] in sentinel surveillance and 6.5% (95% CI 5.1-8.0%) in routine testing. The agreement of HIV test results between sentinel surveillance and routine testing was 98.0%, but 24.1% of specimens that tested positive in sentinel surveillance were recorded as negative in routine testing. Data completeness was moderate, with HIV test results recorded for 87.8% of women who received routine testing.

CONCLUSIONS

Additional preparation is required before routine antenatal HIV testing data can supplant sentinel surveillance in Kenya. As the quality of program data has markedly improved since 2010 a repeat evaluation of the use of routine antenatal HIV testing data in lieu of ANC sentinel surveillance is recommended.

CONTEXT

Understanding the etiology, diagnosis, and symptoms of hypoparathyroidism may help to improve quality of life and long-term disease outcomes. This paper summarizes the results of the findings and recommendations of the Working Group on Presentation of Hypoparathyroidism.

EVIDENCE ACQUISITION

Experts convened in Florence, Italy, in May 2015 and evaluated the literature and recent data on the presentation and long-term outcomes of patients with hypoparathyroidism.

EVIDENCE SYNTHESIS

The most frequent etiology is surgical removal or loss of viability of parathyroid glands. Despite precautions and expertise, about 20-30% of patients develop transient and 1-7% develop permanent postsurgical hypoparathyroidism after total thyroidectomy. Autoimmune destruction is the main reason for nonsurgical hypoparathyroidism. Severe magnesium deficiency is an uncommon but correctable cause of hypoparathyroidism. Several genetic etiologies can result in the loss of parathyroid function or action causing isolated hypoparathyroidism or a complex syndrome with other symptoms apart from those of hypoparathyroidism or pseudohypoparathyroidism. Neuromuscular signs or symptoms due to hypocalcemia are the main characteristics of the disease. Hyperphosphatemia can contribute to major long-term complications such as ectopic calcifications in the kidney, brain, eye, or vasculature. Bone turnover is decreased, and bone mass is increased. Reduced quality of life and higher risk of renal stones, renal calcifications, and renal failure are seen. The risk of seizures and silent or symptomatic calcifications of basal ganglia is also increased.

CONCLUSIONS

Increased awareness of the etiology and presentation of the disease and new research efforts addressing specific questions formulated during the meeting should improve the diagnosis, care, and long-term outcome for patients.

OBJECTIVE

Hypoparathyroidism is a rare disorder characterized by hypocalcemia and absent or deficient PTH. This report presents a summary of current information about epidemiology, presentation, diagnosis, clinical features, and management and proposes guidelines to help clinicians diagnose, evaluate, and manage this disorder.

PARTICIPANTS

Participants in the First International Conference on the Management of Hypoparathyroidism represented a worldwide constituency with acknowledged interest and expertise in key basic, translational, and clinical aspects of hypoparathyroidism. Three Workshop Panels were constituted to address questions for presentation and discussion at the Conference held in Florence, Italy, May 7-9, 2015. At that time, a series of presentations were made, followed by in-depth discussions in an open forum. Each Workshop Panel also met in closed sessions to formulate the three evidence-based reports that accompany this summary statement. An Expert Panel then considered this information, developed summaries, guidelines, and a research agenda that constitutes this summary statement.

EVIDENCE

Preceding the conference, each Workshop Panel conducted an extensive literature search as noted in the individual manuscripts accompanying this report. All presentations were based upon the best peer-reviewed information taking into account the historical and current literature.

CONSENSUS PROCESS

This report represents the Expert Panel's synthesis of the conference material placed in a context designed to be relevant to clinicians and those engaged in cutting-edge studies of hypoparathyroidism.

CONCLUSIONS

This document not only provides a summary of our current knowledge but also places recent advances in its management into a context that should enhance future advances in our understanding of hypoparathyroidism.

Fibrosis is a common pathological sequela of tissue injury or inflammation, and is a major cause of organ failure. Subsets of fibroblasts contribute to tissue fibrosis in multiple ways, including generating contractile force to activate integrin-bound, latent TGFβ and secreting excess amounts of collagens and other extracellular matrix proteins (ECM) that make up pathologic scar. However, the precise fibroblast subsets that drive fibrosis have been poorly understood. In the absence of well-characterized markers, α-smooth muscle actin (αSMA) is often used to identify pathologic fibroblasts, and some authors have equated αSMA(+) cells with contractile myofibroblasts and proposed that these cells are the major source of ECM. Here, we investigated how well αSMA expression describes fibroblast subsets responsible for TGFβ activation and collagen production in three commonly used models of organ fibrosis that we previously reported could be inhibited by loss of αv integrins on all fibroblasts (using PDGFRβ-Cre). Interestingly, αSMA-directed deletion of αv integrins protected mice from CCl4-induced hepatic fibrosis, but not bleomycin-induced pulmonary or unilateral ureteral obstruction-induced renal fibrosis. Using Col-EGFP/αSMA-RFP dual reporter mice, we found that only a minority of collagen-producing cells coexpress αSMA in the fibrotic lung and kidney. Notably, Col-EGFP(+)αSMA-RFP(-) cells isolated from the fibrotic lung and kidney were equally capable of activating TGFβ as were Col-EGFP(+)αSMA-RFP(+) cells from the same organ, and this TGFβ activation was blocked by a TGFβ-blocking antibody and an inhibitor of nonmuscle myosin, respectively. Taken together, our results suggest that αSMA is an inconsistent marker of contractile and collagen-producing fibroblasts in murine experimental models of organ fibrosis.

BACKGROUND

Although involvement of geriatricians in the care of older trauma patients is associated with changes in processes of care and improved outcomes, few geriatrician consultations were ordered on our service.

STUDY DESIGN

Mandatory geriatric consults were initiated in September 2013 for all trauma patients 70 years and older admitted to our hospital. We prospectively collected data on patients admitted from October 2013 through September 2014 (postintervention) and compared their data with those of patients admitted from June 2011 through June 2012 (preintervention). We collected data on processes of care (DNR and do not intubate status, delirium, and referral for cognitive evaluation) and patient outcomes (mortality, readmission, and length of stay). Descriptive statistics and post-hoc power analyses were performed.

RESULTS

There were 215 and 191 patients included in the preintervention and postintervention cohorts, respectively. After the intervention, geriatric consults increased from 3.26% to 100%. Patients with DNR and do not intubate status increased from 10.23% to 38.22% (p < 0.01). Referral for formal cognitive evaluation increased from 2.33% to 14.21% (p < 0.01) and delirium documentation increased from 31.16% to 38.22% (p = 0.14). In-hospital mortality and 30-day mortality in the pre- and postintervention periods were 9.30% vs 5.24% (p = 0.12) and 11.63% vs 6.81% (p = 0.10), respectively. Intensive care unit readmission rate was 8.26% preintervention and 1.96% postintervention (p = 0.06). There were no changes in 30-day hospital readmission and length of stay. Power analyses showed more patients were needed to show statistically significant outcomes.

CONCLUSIONS

The initiation of mandatory geriatric consults on our trauma service was associated with improved advance care planning and increased multidisciplinary care. Ensuring involvement of geriatricians can aid in reducing adverse outcomes among geriatric trauma patients.