Ten-year Outcomes of Sexual Function After Radical Prostatectomy: Results of a Prospective Longitudinal Study

Background

The long-term impact of radical prostatectomy (RP) on sexual function (SF) and erectile function (EF) has important implications related to the risk-to-benefit ratio of this treatment.

Objective

To determine the long-term effect of RP on male SF and EF over 10 yr of follow-up.

Design, setting, and participants

This was a prospective, longitudinal outcomes study in 1836 men following RP at a university hospital. Men were invited to complete the University of California, Los Angeles, Prostate Cancer Index SF survey at baseline, 3, 6, 12, 24, 96, and 120 mo postoperatively and a survey at 4 and 7 yr postoperatively assessing global changes in their EF over the preceding 2 yr.

Intervention

All men underwent open RP.

Outcome measurements and statistical analysis

Multiple, generalized linear regression models were used to evaluate the association between time following RP and SF and EF scores controlling for age, prostate-specific antigen, Gleason scores, stage, nerve sparing, race, and marital status.

Results and limitations

After an expected initial decline, time-dependent improvements in SF and EF were observed through 2 yr postoperatively. Overall, SF and EF were both generally stable between 2 and 10 yr following RP. The subgroups of younger men and men with better preoperative function were more likely to maintain their EF and SF through 10 yr following RP. The primary limitation is the potential bias attributable to nonresponders.

Conclusions

The recovery of EF can extend well beyond 2 yr. There is a significant association between younger age and better preoperative function and the likelihood of experiencing improvements beyond 2 yr. Assessing the comparative effectiveness of treatment options for localized prostate cancer must examine SF beyond 2 yr to account for delayed treatment effects and the natural history of SF in the aging male population.     

Toll‐like receptor 4 deficiency impairs microglial phagocytosis of degenerating axons

Microglia are rapidly activated in the central nervous system (CNS) in response to a variety of injuries, including inflammation, trauma, and stroke. In addition to modulation of the innate immune response, a key function of microglia is the phagocytosis of dying cells and cellular debris, which can facilitate recovery. Despite emerging evidence that axonal debris can pose a barrier to regeneration of new axons in the CNS, little is known of the cellular and molecular mechanisms that underlie clearance of degenerating CNS axons. We utilize a custom micropatterned microfluidic system that enables robust microglial‐axon co‐culture to explore the role of Toll‐like receptors (TLRs) in microglial phagocytosis of degenerating axons. We find that pharmacologic and genetic disruption of TLR4 blocks induction of the Type‐1 interferon response and inhibits phagocytosis of axon debris in vitro. Moreover, TLR4‐dependent microglial clearance of unmyelinated axon debris facilitates axon outgrowth. In vivo, microglial phagocytosis of CNS axons undergoing Wallerian degeneration in a dorsal root axotomy model is impaired in adult mice in which TLR4 has been deleted. Since purinergic receptors can influence TLR4‐mediated signaling, we also explored a role for the microglia P2 receptors and found that the P2X7R contributes to microglial clearance of degenerating axons. Overall, we identify TLR4 as a key player in axonal debris clearance by microglia, thus creating a more permissive environment for axonal outgrowth. Our findings have significant implications for the development of protective and regenerative strategies for the many inflammatory, traumatic, and neurodegenerative conditions characterized by CNS axon degeneration. GLIA 2014;62:1982–1991     

A modified collagen gel dressing promotes angiogenesis in a preclinical swine model of chronic ischemic wounds

We recently performed proteomic characterization of a modified collagen gel (MCG) dressing and reported promising effects of the gel in healing full‐thickness excisional wounds. In this work, we test the translational relevance of our aforesaid findings by testing the dressing in a swine model of chronic ischemic wounds recently reported by our laboratory. Full‐thickness excisional wounds were established in the center of bipedicle ischemic skin flaps on the backs of animals. Ischemia was verified by laser Doppler imaging, and MCG was applied to the test group of wounds. Seven days post wounding, macrophage recruitment to the wound was significantly higher in MCG‐treated ischemic wounds. In vitro, MCG up‐regulated expression of Mrc‐1 (a reparative M2 macrophage marker) and induced the expression of anti‐inflammatory cytokine interleukin (IL)‐10 and of fibroblast growth factor‐basic (β‐FGF). An increased expression of CCR2, an M2 macrophage marker, was noted in the macrophages from MCG treated wounds. Furthermore, analyses of wound tissues 7 days post wounding showed up‐regulation of transforming growth factor‐β, vascular endothelial growth factor, von Willebrand's factor, and collagen type I expression in MCG‐treated ischemic wounds. At 21 days post wounding, MCG‐treated ischemic wounds displayed higher abundance of proliferating endothelial cells that formed mature vascular structures and increased blood flow to the wound. Fibroblast count was markedly higher in MCG‐treated ischemic wound‐edge tissue. In addition, MCG‐treated wound‐edge tissues displayed higher abundance of mature collagen with increased collagen type I : III deposition. Taken together, MCG helped mount a more robust inflammatory response that resolved in a timely manner, followed by an enhanced proliferative phase, angiogenic outcome, and postwound tissue remodeling. Findings of the current study warrant clinical testing of MCG in a setting of ischemic chronic wounds.     

System dynamics model of cervical cancer vaccination and screening interventions in Kenya

Objectives

This paper presents a simulation model for evaluating the possible effects of a screening and vaccination campaign against Human Papillomavirus [HPV] in Kenya.

Method

A System Dynamics model was developed using the iThink? computer simulation package. The model was based on data extracted from epidemiological, demographic and published research and where data was not available, expert opinion was sought. The deterministic model stratified the population by vaccination status, screening status and HPV infection status. The model was simulated to estimate outputs for the next 50 years from 2011. Cost Utility indicators of Disability Adjusted Life Years (DALYs) and cost per averted DALY were used for economic evaluation.

Results

The model predicted that catch up vaccination had the greatest impact in reducing the prevalence of cervical cancer. This was followed by Primary vaccination, with early detection through Screening having the lowest impact of the three choices of interventions in respect of averted cases of cervical cancer and DALY estimates.

Conclusion

Kenya as a country should consider adoption of secondary /catch up vaccination as an immediate measure to curb cervical cancer followed by primary vaccination of pre-adolescent girls. Screening should be a complementary measure(s). This model provides a policy decision support vehicle that can allow for choice between different interventions based on their expected outcomes. It also allows modification to accommodate new research results and information to assess the clinical impact of different policies and interventions in cervical cancer management in Kenya.

     

Macrophage mediation in normal and diabetic wound healing responses

Inflammation Research - The failure in timely healing of wounds is a central feature in chronic wounds that leads to physiological, psychological and economic burdens. Macrophages have been...     

Emerging trends in the epidemiology of human astrovirus infection among infants,children and adults hospitalized with acute watery diarrhea in Kolkata,India

Human astroviruses (HAstVs) have now emerged as another common cause of non-bacterial acute gastroenteritis (AGE) in humans worldwide. This study investigated the epidemiology and genetic diversity of human astrovirus strains circulating among infants, younger children (up to 6 years), older children and adolescents (>6–17 years) and adults (18 years and above) hospitalized for diarrhea and their role in AGE in Kolkata, India. A total of 2535 fecal samples were screened for the presence of known enteric viral, bacterial and parasitic etiologies by conventional microbiological assays and molecular methods. The overall incidences of sole or mixed infection of HAstV with known enteric viral, bacterial and parasitic pathogens were detected in 60 cases (2.4%) among all age groups. The clinical symptoms of astrovirus-associated acute watery diarrhea cases were recorded for all sole and mixed infection cases. A high number of sole (n = 13/60 [21.7%]) and mixed infection cases (n = 22/60 [36.7%]) were observed in adults (18 years old or more). Considering all age groups, 18 sole infection cases (n = 18/60 [30%]) and 42 mixed infection cases (n = 42/60 [70%]) with Rotavirus (n = 11/25 [44%]), Vibrio cholerae O1 (n = 6/24 [25%]) Cryptosporidium spp and Giardia lamblia (n = 5/13 [38.4%]) were observed. Further, eleven HAstV samples from infants and children (up to 6 years), children and adolescents (>6–17 years) and adults (18 years and above) were analyzed for their sequences of overlap region between ORF1b (RdRp) and ORF2 (capsid). Among these, ten strains were found to have close genetic relatedness to the Japanese strain HAstV_G1 [AB009985]. Additionally, the IDH2211 Kolkata strain showed a close genetic match with the Thai HAstV_G3 strain [EU363889]. Our study reports show that HAstVs as the sole agent and as mixed infection with other known enteric viral, bacterial, parasitic pathogens are also responsible for AGE among infants, children, adolescents and adults in Kolkata, India.