Characteristics Associated With Postoperative Catheterization at Discharge in Women Undergoing Colpocleisis.

IMPORTANCE: Although transient voiding dysfunction is common after surgical correction of pelvic organ prolapse, it has not been well studied in women undergoing colpocleisis. OBJECTIVE: This study aimed to identify characteristics associated with discharge home with a urinary catheter in women undergoing colpocleisis. STUDY DESIGN: This is a secondary analysis of a multicenter prospective study examining the effect of pelvic support, symptoms, and satisfaction in women undergoing colpocleisis. Publicly accessible deidentified data sets of the index study were analyzed. Primary outcome was discharge with a urinary catheter postoperatively. Characteristics associated with discharge with catheter after colpocleisis were assessed via logistic regression. Covariates were selected based on statistical significance at 0.05 and clinical relevance on bivariate analysis. RESULTS: Of the 136 women (mean age, 77.8 ± 5.5 years) undergoing colpocleisis in the index study, 68 (50.0%) were discharged with catheter. Baseline characteristics did not differ, except that the catheter group had lower prior incontinence surgery (7.4% vs 22.1%, P = 0.02) and higher preoperative postvoid residual volume (PVR; 189.8 ± 187.6 vs 91.3 ± 124.2 mL, P < 0.01). Those discharged with catheter had greater estimated blood loss (128.7 ± 88.5 vs 95.3 ± 74.5 mL, P = 0.02), operative time (125.2 ± 56.3 vs 100.8 ± 45.4 minutes, P < 0.01), and concomitant levator myorrhaphy (82.4% vs 58.8%, P < 0.01). Multivariable analysis revealed preoperative PVR (adjusted odds ratio, 1.2; 95% confidence interval, 1.0-1.4 for every 50-mL increase in PVR) and levator myorrhaphy (adjusted odds ratio, 4.3; 95% confidence interval, 1.6-11.3) were associated with postoperative catheterization. CONCLUSIONS: In women undergoing colpocleisis, higher preoperative PVR and levator myorrhaphy were associated with discharge with catheter.

Moderate to severe distress in half of ovarian cancer patients undergoing treatment highlights a need for more proactive symptom and psychosocial management.

OBJECTIVE: Distress screening and management is a recommended component of oncology care. Our objective was to evaluate distress rate, sources, and compliance with psychosocial follow-up among ovarian cancer patients receiving chemotherapy. METHODS: We reviewed patient distress surveys completed by ovarian cancer patients receiving chemotherapy from 10/2017-6/2019. Lay or nurse navigators conducted screening with the NCCN Distress Thermometer from 0 (none) to 10 (highest distress). A distress score ≥ 4 (moderate/severe) was considered a positive screen. A recommendation for psychosocial follow-up was automatically generated in the treatment care plan based upon a yes response to any depression-related concern, independent of distress score. Documentation of referral to a mental health professional or social worker for counseling was considered compliant with psychosocial follow-up. We performed descriptive statistics and bivariate analyses. RESULTS: 97/211 (46%) ovarian cancer patients screened positive for distress. Average score was 6.1 for those who screened positive and 3.3 for the entire cohort (range 0-10). Unmarried status (p < 0.01) was associated with positive screen, whereas non-white race (p = 0.26) and recurrent disease (p = 0.21) were not. Median age was older for patients with a positive distress screen (p < 0.01). Among screened patients, the most frequent sources of distress were: cognitive/physical (87%), psychosocial (62%), practical (84%), and family concerns (40%). Of 50 patients recommended to have psychosocial referral, 4 (8%) patients had documented psychiatric follow-up and 19 (38%) patients had documented psychosocial counseling by a social worker. CONCLUSIONS: Nearly half of ovarian cancer patients screened positive for moderate/severe distress. Cancer/treatment-related cognitive/physical symptoms were the most frequent sources. Improved methods of symptom monitoring and management during treatment and resources to address psychosocial concerns are needed to improve distress management of ovarian cancer patients.

Timing and Success of Postoperative Voiding Trial After Colpocleisis With and Without Concomitant Midurethral Sling.

OBJECTIVE: The aim of this study was to compare failure rates of first voiding trial (VT) within 7 days and on postoperative day (POD) 1 after colpocleisis with versus without concomitant midurethral sling (MUS). Predictors of POD 1 VT failure were also examined. METHODS: This was a retrospective cohort study of women undergoing colpocleisis from January 2012 to October 2019 comparing VT outcomes with versus without MUS. Primary outcome was first VT failure within 7 days; outcomes of VTs performed on POD 1 were also assessed. Association between MUS and VT failure and predictors of POD 1 VT failure were assessed via logistic regression. RESULTS: Of 119 women, 45.4% had concomitant MUS. First VT was performed on mean POD 3.1 ± 2.2 in the MUS group versus POD 1.8 ± 1.8 in the no MUS group (P < 0.01). The MUS group was less likely to undergo POD 1 VT (50% vs 83%, P < 0.01). Failure of the first VT did not differ (22.2% with MUS vs 32.8% without MUS, P = 0.20); no association between VT failure and MUS was noted (adjusted odds ratio [aOR], 0.6; 95% confidence interval [CI], 0.18-2.1). There were 68.1% (81/119) of participants who underwent POD 1 VT, MUS was performed in 33.3% (27/81). The POD 1 failure did not differ between those with 33.3% versus 40.7% without MUS (P = 0.52). Midurethral sling was not associated with POD 1 VT failure (aOR, 0.93; 95% CI, 0.27-3.23). In women undergoing POD 1 VT, preoperative postvoid residual was associated with VT failure (aOR, 1.39; 95% CI, 1.01-1.92). CONCLUSIONS: In women undergoing colpocleisis, MUS was not associated with VT failure within 7 days or on POD 1. Increased preoperative postvoid residual was associated with POD 1 VT failure.

Hypoxia-Inducible Factor-1α Regulates CD55 in Airway Epithelium.

Airway epithelial CD55 down-regulation occurs in several hypoxia-associated pulmonary diseases, but the mechanism is unknown. Using in vivo and in vitro assays of pharmacologic inhibition and gene silencing, the current study investigated the role of hypoxia-inducible factor (HIF)-1α in regulating airway epithelial CD55 expression. Hypoxia down-regulated CD55 expression on small-airway epithelial cells in vitro, and in murine lungs in vivo; the latter was associated with local complement activation. Treatment with pharmacologic inhibition or silencing of HIF-1α during hypoxia-recovered CD55 expression in small-airway epithelial cells. HIF-1α overexpression or blockade, in vitro or in vivo, down-regulated CD55 expression. Collectively, these data show a key role for HIF-1α in regulating the expression of CD55 on airway epithelium.

Apurinic/apyrimidinic endonuclease/redox factor-1 (APE1/Ref-1) redox function negatively regulates NRF2.

Apurinic/apyrimidinic endonuclease/redox factor-1 (APE1/Ref-1) (henceforth referred to as Ref-1) is a multifunctional protein that in addition to its base excision DNA repair activity exerts redox control of multiple transcription factors, including nuclear factor κ-light chain enhancer of activated B cells (NF-κB), STAT3, activator protein-1 (AP-1), hypoxia-inducible factor-1 (HIF-1), and tumor protein 53 (p53). In recent years, Ref-1 has emerged as a promising therapeutic target in cancer, particularly in pancreatic ductal carcinoma. Although a significant amount of research has centered on Ref-1, no wide-ranging approach had been performed on the effects of Ref-1 inhibition and transcription factor activity perturbation. Starting with a broader approach, we identified a previously unsuspected effect on the nuclear factor erythroid-related factor 2 (NRF2), a critical regulator of cellular defenses against oxidative stress. Based on genetic and small molecule inhibitor-based methodologies, we demonstrated that repression of Ref-1 potently activates NRF2 and its downstream targets in a dose-dependent fashion, and that the redox, rather than the DNA repair function of Ref-1 is critical for this effect. Intriguingly, our results also indicate that this pathway does not involve reactive oxygen species. The link between Ref-1 and NRF2 appears to be present in all cells tested in vitro, noncancerous and cancerous, including patient-derived tumor samples. In particular, we focused on understanding the implications of the novel interaction between these two pathways in primary pancreatic ductal adenocarcinoma tumor cells and provide the first evidence that this mechanism has implications for overcoming the resistance against experimental drugs targeting Ref-1 activity, with clear translational implications.

Role of complement activation in obliterative bronchiolitis post-lung transplantation.

Obliterative bronchiolitis (OB) post-lung transplantation involves IL-17-regulated autoimmunity to type V collagen and alloimmunity, which could be enhanced by complement activation. However, the specific role of complement activation in lung allograft pathology, IL-17 production, and OB is unknown. The current study examines the role of complement activation in OB. Complement-regulatory protein (CRP) (CD55, CD46, complement receptor 1-related protein y/CD46) expression was downregulated in human and murine OB; and C3a, a marker of complement activation, was upregulated locally. IL-17 differentially suppressed complement receptor 1-related protein y expression in airway epithelial cells in vitro. Neutralizing IL-17 recovered CRP expression in murine lung allografts and decreased local C3a production. Exogenous C3a enhanced IL-17 production from alloantigen- or autoantigen (type V collagen)-reactive lymphocytes. Systemically neutralizing C5 abrogated the development of OB, reduced acute rejection severity, lowered systemic and local levels of C3a and C5a, recovered CRP expression, and diminished systemic IL-17 and IL-6 levels. These data indicated that OB induction is in part complement dependent due to IL-17-mediated downregulation of CRPs on airway epithelium. C3a and IL-17 are part of a feed-forward loop that may enhance CRP downregulation, suggesting that complement blockade could be a therapeutic strategy for OB.

Allergic airway disease in mice alters T and B cell responses during an acute respiratory poxvirus infection.

Pulmonary viral infections can exacerbate or trigger the development of allergic airway diseases via multiple mechanisms depending upon the infectious agent. Respiratory vaccinia virus transmission is well established, yet the effects of allergic airway disease on the host response to intra-pulmonary vaccinia virus infection remain poorly defined. As shown here BALB/c mice with preexisting airway disease infected with vaccinia virus developed more severe pulmonary inflammation, higher lung virus titers and greater weight loss compared with mice inoculated with virus alone. This enhanced viremia was observed despite increased pulmonary recruitment of CD8(+) T effectors, greater IFNγ production in the lung, and high serum levels of anti-viral antibodies. Notably, flow cytometric analyses of lung CD8(+) T cells revealed a shift in the hierarchy of immunodominant viral epitopes in virus inoculated mice with allergic airway disease compared to mice treated with virus only. Pulmonary IL-10 production by T cells and antigen presenting cells was detected following virus inoculation of animals and increased dramatically in allergic mice exposed to virus. IL-10 modulation of host responses to this respiratory virus infection was greatly influenced by the localized pulmonary microenvironment. Thus, blocking IL-10 signaling in virus-infected mice with allergic airway disease enhanced pulmonary CD4(+) T cell production of IFNγ and increased serum anti-viral IgG1 levels. In contrast, pulmonary IFNγ and virus-specific IgG1 levels were reduced in vaccinia virus-treated mice with IL-10 receptor blockade. These observations demonstrate that pre-existing allergic lung disease alters the quality and magnitude of immune responses to respiratory poxviruses through an IL-10-dependent mechanism.