Effect of BMI on clinical outcomes following minimally invasive sacrocolpopexy.

Our objective was to compare success and complication rates following minimally invasive sacrocolpopexy (SCP) based on body mass index (BMI). This is a retrospective cohort study of women who underwent laparoscopic or robotic SCP at one academic center from 2006 to 2016. Women were included if they had a postoperative pelvic organ prolapse quantification (POPQ) exam and subjective success documented. For our primary outcome, we compared composite success (POPQ stage ≤ I and report of no bulge symptoms) amongst three groups: normal weight (BMI ≤ 25), overweight (BMI 25-30) and obese (BMI ≥ 30) women. Secondary outcomes included intraoperative complications, 6 week postoperative complications, and sacrocolpopexy mesh exposure. Of the 431 women who met inclusion criteria, 140 (32%) had normal BMI (23 kg/m2; IQR 22, 24), 177 (41%) were overweight (27 kg/m2; IQR 26, 28), and 114 (26%) were obese (32 kg/m2; IQR 31, 36). Mean age was 60 ± 11 years, and most were Caucasian, with no differences in demographics or Charlson Comorbidity Index (CCI). Median length of follow-up was 49 weeks (IQR 9, 104), with similar follow-up for all groups. For our primary outcome, composite success was 72% overall, with no significant differences in composite success rates between groups. For secondary outcomes, there were no differences in the rates of perioperative complications but obese women had a 2.8 increased risk of mesh exposure (p = 0.02). Obesity was not associated with differences in the success or peri-operative complication rates for SCP in our population, but was associated with mesh exposure.

The Impact of Age on Perioperative Complications After Minimally Invasive Sacrocolpopexy.

OBJECTIVE: Our aim was to compare perioperative complications between older (≥65 years), middle-age (55-64 years), and younger (<55 years) women after minimally invasive sacrocolpopexy (SCP). METHODS: This retrospective cohort study included women undergoing SCP from 2006 to 2016 at a single academic center. Our primary outcome was the rate of perioperative complications (intraoperative and postoperative within 6 weeks of surgery), between groups. Secondary outcomes included readmission and reoperation rates. RESULTS: There were 440 consecutive participants: 159 (36.1%) older, 160 (36.4%) middle-age, and 121 (27.5%) younger women. The overall intraoperative complication rate from SCP was 9.1%, with the most common being cystotomy (5.0%) and vaginotomy (1.8%). There were no differences in intraoperative complications between groups. Urinary tract infection (10.9%) and port-site cellulitis (3.4%) were the most common postoperative complications. For our primary outcome, younger women had a higher rate of postoperative complications compared with middle-age and older women (P < 0.001). There was no difference in postoperative complications between older and middle-aged women. In a multivariate regression controlling for comorbidity, body mass index, diabetes, smoking status, concomitant hysterectomy, and/or sling, younger women retained a higher rate of postoperative complications (odds ratio, 1.7 [1.2,2.2]). Rates of readmission (3.2%) and reoperation (0.7%) were also similar between groups. CONCLUSIONS: The rate of perioperative complications was low with no difference in intraoperative complications. Women under 55 had a higher rate of postoperative complications compared to women age 55 to 65 years and those older than 65 years. Our results suggest that it is reasonable to offer SCP to women older than 65 years.

Prevalence of positive screening test for cognitive impairment among elderly urogynecologic patients.

BACKGROUND: Impaired cognition has been correlated with adverse postoperative outcomes, such as an increased incidence of delirium, a longer length of hospital stay, and higher 6 month mortality. The incidence of cognitive impairment in the elderly is high. Per the Centers for Disease Control and Prevention, 1 in 8 adults aged 60 years and older deal with memory loss and confusion, and less than 20% inform their health care providers. Most studies in the elderly or cognitively impaired have been conducted at Veterans Administration hospitals, in which the majority of patients are male. As the female patient population ages, it is increasingly important to describe the prevalence of cognitive impairment in this specific population as well as identify and manage risk factors for cognitive decline in the ambulatory and perioperative setting. OBJECTIVE: The objective of the study was to determine the prevalence of positive screening for cognitive impairment in a urogynecology ambulatory population and to establish the feasibility of using standardized, validated screening questionnaires in a tertiary care setting. STUDY DESIGN: After institutional review board approval, all English-speaking patients 65 years old or older presenting to our ambulatory urogynecology clinic were invited to participate. Cognitive impairment was assessed using both the validated Mini-Cog test and the Eight-Item Interview to Differentiate Aging and Dementia screen for mild dementia. A Mini-Cog score <3 suggests cognitive impairment, whereas an Eight-Item Interview to Differentiate Aging and Dementia score of ≥2 discriminates dementia from normal cognition. Because of the association of depression and cognition in the elderly, the Geriatric Depression Scale (short form of 15 items) was administered, with a score >5 suggesting depression. Demographic and medical history were abstracted from the medical record. RESULTS: A total of 371 subjects were asked to participate (39 were excluded and 37 declined); 295 subjects (79.5%) were included in the study. Mean subject age was 74.5 years, and 96.6% were white, with an average of 4.1 chronic medical comorbidities. Cognitive impairment was identified in all age groups per the Mini-Cog as follows: 65-74 years, 5.3%; 75-84 years, 13.7%; and 85 years and older, 30%. There was a significant difference in the positive screen for cognitive impairment between ages 65-74 vs >75 (P ≤ .001). According to the Eight-Item Interview to Differentiate Aging and Dementia, all 3 age groups perceived themselves to have early cognitive changes: 65-74 years, 25.9%; 75-84 years, 31.9%; and 85 years and older, 40% (P = .231). The most commonly identified areas of impairment were having daily problems with thinking and memory (62%), problems with judgment (52%), and trouble learning new tools or gadgets (44%). There was no difference in the number of patients who screened positive for depression across age groups: 65-74 years, 5.9%; 75-84 years, 6.3%; and 85 years and older, 10% (P = .697). CONCLUSION: In our study population positive screening for cognitive impairment, as measured by validated questionnaires, was prevalent among women aged >75 years. Screening for potential cognitive impairment in an ambulatory urogynecology population is feasible and useful in clinical practice. Our subjects were interested in cognitive screening because a third of them self-reported early cognitive changes. These tools are effective in screening for previously unrecognized impaired cognition, a definitive diagnosis, and hence treatment requires additional evaluation. Future studies could evaluate which screening tools for cognitive impairment would be most helpful in assessing patients prior to surgery in an effort to further decrease perioperative morbidity in elderly woman.

Heterogeneity of lung mononuclear phagocytes during pneumonia: contribution of chemokine receptors.

Bacterial pneumonia is a common and dangerous illness. Mononuclear phagocytes, which comprise monocyte, resident and recruited macrophage, and dendritic cell subsets, are critical to antimicrobial defenses, but the dynamics of their recruitment to the lungs in pneumonia is not established. We hypothesized that chemokine-mediated traffic of mononuclear phagocytes is important in defense against bacterial pneumonia. In a mouse model of Klebsiella pneumonia, circulating Ly6C(hi) and, to a lesser extent, Ly6C(lo) monocytes expanded in parallel with accumulation of inflammatory macrophages and CD11b(hi) dendritic cells and plasmacytoid dendritic cells in the lungs, whereas numbers of alveolar macrophages remained constant. CCR2 was expressed by Ly6C(hi) monocytes, recruited macrophages, and airway dendritic cells; CCR6 was prominently expressed by airway dendritic cells; and CX3CR1 was ubiquitously expressed by blood monocytes and lung CD11b(hi) dendritic cells during infection. CCR2-deficient, but not CCL2-, CX3CR1-, or CCR6-deficient animals exhibited worse outcomes of infection. The absence of CCR2 had no detectable effect on neutrophils but resulted in reduction of all subsets of lung mononuclear phagocytes in the lungs, including alveolar macrophages and airway and plasmacytoid dendritic cells. In addition, absence of CCR2 skewed the phenotype of lung mononuclear phagocytes, abrogating the appearance of M1 macrophages and TNF-producing dendritic cells in the lungs. Taken together, these data define the dynamics of mononuclear phagocytes during pneumonia.

Adenosine A(2B) receptor deficiency promotes host defenses against gram-negative bacterial pneumonia.

RATIONALE: Activation of the adenosine A(2B) receptor (A(2B)R) promotes antiinflammatory effects in diverse biological settings, but the role of this receptor in antimicrobial host defense in the lung has not been established. Gram-negative bacillary pneumonia is a common and serious illness associated with high morbidity and mortality, the treatment of which is complicated by increasing rates of antibiotic resistance. OBJECTIVES: To test the hypothesis that absence of adenosine A(2B) receptor signaling promotes host defense against bacterial pneumonia. METHODS: We used a model of Klebsiella pneumoniae pneumonia in wild-type mice and mice with targeted deletion of the A(2B)R. Host responses were compared in vivo and leukocyte responses to the bacteria were examined in vitro. MEASUREMENTS AND MAIN RESULTS: A(2B)R(-/-) mice demonstrated enhanced bacterial clearance from the lung and improved survival after infection with K. pneumoniae compared with wild-type controls, an effect that was mediated by bone marrow-derived cells. Leukocyte recruitment to the lungs and expression of inflammatory cytokines did not differ between A(2B)R(-/-) and wild-type mice, but A(2B)R(-/-) neutrophils exhibited sixfold greater bactericidal activity and enhanced production of neutrophil extracellular traps compared with wild-type neutrophils when incubated with K. pneumoniae. Consistent with this finding, bronchoalveolar lavage fluid from A(2B)R(-/-) mice with Klebsiella pneumonia contained more extracellular DNA compared with wild-type mice with pneumonia. CONCLUSIONS: These data suggest that the absence of A(2B)R signaling enhances antimicrobial activity in gram-negative bacterial pneumonia.

Regulation of neutrophil function by adenosine.

Adenosine is an endogenously released purine nucleoside that signals via 4 widely expressed G protein-coupled receptors: A(1), A(2A), A(2B), and A(3). In the setting of inflammation, the generation and release of adenosine is greatly enhanced. Neutrophils play an important role in host defense against invading pathogens and are the cellular hallmark of acute inflammation. Neutrophils both release adenosine and can respond to it via expression of all 4 adenosine receptor subtypes. At low concentrations, adenosine can act via the A(1) and A(3) adenosine receptor subtypes to promote neutrophil chemotaxis and phagocytosis. At higher concentrations, adenosine acts at the lower-affinity A(2A) and A(2B) receptors to inhibit neutrophil trafficking and effector functions such as oxidative burst, inflammatory mediator production, and granule release. Modulation of neutrophil function by adenosine is relevant in a broad array of disease models, including ischemia reperfusion injury, sepsis, and noninfectious acute lung injury. This review will summarize relevant research in order to provide a framework for understanding how adenosine directly regulates various elements of neutrophil function.

Leukocyte compartments in the mouse lung: distinguishing between marginated, interstitial, and alveolar cells in response to injury.

We developed a flow cytometry-based assay to simultaneously quantify multiple leukocyte populations in the marginated vascular, interstitial, and alveolar compartments of the mouse lung. An intravenous injection of a fluorescently labeled anti-CD45 antibody was used to label circulating and marginated vascular leukocytes. Following vascular flushing to remove non-adherent cells and collection of broncho-alveolar lavage (BAL) fluid, lungs were digested and a second fluorescent anti-CD45 antibody was added ex vivo to identify cells not located in the vascular space. In the naïve mouse lung, we found about 11 million CD45+ leukocytes, of which 87% (9.5 million) were in the vascular marginated compartment, consisting of 17% NK cells, 17% neutrophils, 57% mononuclear myeloid cells (monocytes, macrophage precursors and dendritic cells), and 10% T cells (CD4+, CD8+, and invariant NKT cells). Non-vascular compartments including the interstitial compartment contained 7.7×10(5)cells, consisting of 49% NK cells, 25% dendritic cells, and 16% other mononuclear myeloid cells. The alveolar compartment was overwhelmingly populated by macrophages (5.63×10(5)cells, or 93%). We next studied leukocyte margination and extravasation into the lung following acid injury, a model of gastric aspiration. At 1 h after injury, neutrophils were markedly elevated in the blood while all other circulating leukocytes declined by an average of 79%. At 4 h after injury, there was a peak in the numbers of marginated neutrophils, NK cells, CD4+ and CD8+ T cells and a peak in the number of alveolar NK cells. Most interstitial cells consisted of DCs, neutrophils, and CD4+ T cells, and most alveolar compartment cells consisted of macrophages, neutrophils, and NK cells. At 24 h after injury, there was a decline in the number of all marginated and interstitial leukocytes and a peak in alveolar neutrophils. In sum, we have developed a novel assay to study leukocyte margination and trafficking following pulmonary inflammation and show that marginated cells comprise a large fraction of lung leukocytes that increases shortly after lung injury. This assay may be of interest in future studies to determine if leukocytes become activated upon adherence to the endothelium, and have properties that distinguish them from interstitial and circulating cells.