Pannexin 1 (Panx1) represents a class of vertebrate membrane channels, bearing significant sequence homology with the invertebrate gap junction proteins, the innexins and more distant similarities in the membrane topologies and pharmacological sensitivities with gap junction proteins of the connexin family. In the nervous system, cooperation among pannexin channels, adenosine receptors, and KATP channels modulating neuronal excitability via ATP and adenosine has been recognized, but little is known about the significance in vivo. However, the localization of Panx1 at postsynaptic sites in hippocampal neurons and astrocytes in close proximity together with the fundamental role of ATP and adenosine for CNS metabolism and cell signaling underscore the potential relevance of this channel to synaptic plasticity and higher brain functions. Here, we report increased excitability and potently enhanced early and persistent LTP responses in the CA1 region of acute slice preparations from adult Panx1−/− mice. Adenosine application and N-methyl-D-aspartate receptor (NMDAR)-blocking normalized this phenotype, suggesting that absence of Panx1 causes chronic extracellular ATP/adenosine depletion, thus facilitating postsynaptic NMDAR activation. Compensatory transcriptional up-regulation of metabotropic glutamate receptor 4 (grm4) accompanies these adaptive changes. The physiological modification, promoted by loss of Panx1, led to distinct behavioral alterations, enhancing anxiety and impairing object recognition and spatial learning in Panx1−/− mice. We conclude that ATP release through Panx1 channels plays a critical role in maintaining synaptic strength and plasticity in CA1 neurons of the adult hippocampus. This result provides the rationale for in-depth analysis of Panx1 function and adenosine based therapies in CNS disorders.

In this large study of men with prostate cancer who underwent either open or robotic radical prostatectomy, we found that robotic surgery has a better morbidity profile but costs more.

Importance There is extensive evidence suggesting that Black men with localized prostate cancer (PCa) have worse cancer-specific mortality compared to their non-Hispanic White (nHW) counterparts. Objective To evaluate racial disparities in the use, quality of care, and outcomes of radical prostatectomy (RP) in elderly men with non-metastatic PCa. Design Inclusion of patients with localized PCa who underwent RP within the first year of PCa diagnosis in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database between 1991 and 2009. Setting Retrospective analysis of outcomes stratified according to race (Black vs. nHW). Participants 2,020 (7.6%) Black and 24,462 (92.4%) nHW elderly men with localized PCa who underwent RP. Main Outcomes and Measures Process of care (i.e. time to treatment, lymph node dissection), as well as outcome measures (i.e. complications, emergency department visits, readmissions, PCa-specific and all-cause mortality, costs) were evaluated using Cox proportional hazards regression. Multivariable conditional logistic regression and quantile regression were used to study the association of racial disparities with process of care and outcome measures. Results 59.4% of Blacks vs. 69.5% of nHWs underwent RP within 90 days (p<.001); the top 50% of Blacks had an 8-day treatment delay compared to nHW (p<.001). Blacks were less likely to undergo lymph node dissection and to receive blood transfusions, but more likely to experience postoperative complications, subsequent emergency department visits, and readmissions (all p<.05). The surgical treatment of Black patients was associated with a higher incremental annual cost (top 50% spent $1185.5 more). There was no difference in PCa-specific mortality (p=.16) or all-cause mortality (p=.64) between Black and nHW men. Conclusions and Relevance Blacks treated with RP for localized PCa are more likely to experience adverse events and incur higher costs compared to nHW men, however this does not translate into a difference in PCa-specific or all-cause mortality.

Rationale. Pneumonia is a leading cause of postoperative complication. Objective. To examine trends, factors, and mortality of postoperative pneumonia following major cancer surgery (MCS). Methods. From 1999 to 2009, patients undergoing major forms of MCS were identified using the Nationwide Inpatient Sample (NIS), a Healthcare Cost and Utilization Project (HCUP) subset, resulting in weighted 2,508,916 patients. Measurements. Determinants were examined using logistic regression analysis adjusted for clustering using generalized estimating equations. Results. From 1999 to 2009, 87,867 patients experienced pneumonia following MCS and prevalence increased by 29.7%. The estimated annual percent change (EAPC) of mortality after MCS was −2.4% (95% CI: −2.9 to −2.0, P < 0.001); the EAPC of mortality associated with pneumonia after MCS was −2.2% (95% CI: −3.6 to 0.9, P = 0.01). Characteristics associated with higher odds of pneumonia included older age, male, comorbidities, nonprivate insurance, lower income, hospital volume, urban, Northeast region, and nonteaching status. Pneumonia conferred a 6.3-fold higher odd of mortality. Conclusions. Increasing prevalence of pneumonia after MCS, associated with stable mortality rates, may result from either increased diagnosis or more stringent coding. We identified characteristics associated with pneumonia after MCS which could help identify at-risk patients in order to reduce pneumonia after MCS, as it greatly increases the odds of mortality.

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