Human serous cavity macrophages and dendritic cells possess counterparts in the mouse with a distinct distribution between species.

In mouse peritoneal and other serous cavities, the transcription factor GATA6 drives the identity of the major cavity resident population of macrophages, with a smaller subset of cavity-resident macrophages dependent on the transcription factor IRF4. Here we showed that GATA6+ macrophages in the human peritoneum were rare, regardless of age. Instead, more human peritoneal macrophages aligned with mouse CD206+ LYVE1+ cavity macrophages that represent a differentiation stage just preceding expression of GATA6. A low abundance of CD206+ macrophages was retained in C57BL/6J mice fed a high-fat diet and in wild-captured mice, suggesting that differences between serous cavity-resident macrophages in humans and mice were not environmental. IRF4-dependent mouse serous cavity macrophages aligned closely with human CD1c+CD14+CD64+ peritoneal cells, which, in turn, resembled human peritoneal CD1c+CD14-CD64- cDC2. Thus, major populations of serous cavity-resident mononuclear phagocytes in humans and mice shared common features, but the proportions of different macrophage differentiation stages greatly differ between the two species, and dendritic cell (DC2)-like cells were especially prominent in humans.

Grafts in Endonasal Rhinoplasty.

Rhinoplasty is arguably one of the most challenging but rewarding procedures for the facial plastic surgeon. To adequately improve facial aesthetic parameters and preserve nasal function, the appropriate utilization of grafts is of utmost importance. While there is no best method, I found that in my hands, the endonasal approach allowed me to achieve greater control over my results by limiting dissection, utilizing less cartilage, and minimizing variables. In this manuscript, I outline the surgical pearls I have developed throughout my career that have helped me execute these grafts efficiently and effectively.

Orbital cellulitis secondary to sinusitis in upstate New York: current incidence, seasonality, severity, management and outcomes.

PURPOSE: While sinusitis carries a seasonal variation, the temporal features of sinusitis-related orbital cellulitis (SRC) are unclear. This study analyzes the incidence, seasonality, management, and outcomes of SRC in northeastern New York. METHODS: A retrospective review of 79 patients was performed from January 2008 - December 2018. Cases of orbital cellulitis without comitant sinusitis were excluded. Demographic, radiographic, clinical features, month at presentation, interventions (surgical and nonsurgical), microbiology, and hospitalization duration were recorded. Fisher-exact test, Mann-Whitney test, and Kruskal Wallis test statistical analyses were performed in consultation with our institution's statistician via a dedicated software package (vassarstats.net). RESULTS: 79 patients were admitted for SRC. 25 patients were treated with antibiotics only, 31 underwent orbitotomy exclusively and 23 received combined orbitotomy and functional endoscopic sinus surgery (FESS). Of the 31 patients who underwent orbitotomy only, 8 (26%) returned to the operating room. In contrast, of those who underwent concomitant orbitotomy and FESS, only one patient (4.3%) required re-operation (fisher exact test, p = .021). The median length of stay for the antibiotic-only group (4 days), orbitotomy-only group (6 days), and combined surgery group (5 days) were statistically different (Kruskal Wallis, p = .004, Figure 3). Interestingly, there was no significant relationship of incidence or severity of SRC related to seasonality (fisher-exact test, p = .76). CONCLUSION: Our findings suggest that cases requiring surgical management for SRC should undergo coinitial orbitotomy with FESS to reduce re-operation rates. Additionally, SRC incidence and severity did not correlate with season.

A shift from glycolytic and fatty acid derivatives toward one-carbon metabolites in the developing lung during transitions of the early postnatal period.

During postnatal lung development, metabolic changes that coincide with stages of alveolar formation are poorly understood. Responding to developmental and environmental factors, metabolic changes can be rapidly and adaptively altered. The objective of the present study was to determine biological and technical determinants of metabolic changes during postnatal lung development. Over 118 metabolic features were identified by liquid chromatography with tandem mass spectrometry (LC-MS/MS, Sciex QTRAP 5500 Triple Quadrupole). Biological determinants of metabolic changes were the transition from the postnatal saccular to alveolar stages and exposure to 85% hyperoxia, an environmental insult. Technical determinants of metabolic identification were brevity and temperature of harvesting, both of which improved metabolic preservation within samples. Multivariate statistical analyses revealed the transition between stages of lung development as the period of major metabolic alteration. Of three distinctive groups that clustered by age, the saccular stage was identified by its enrichment of both glycolytic and fatty acid derivatives. The critical transition between stages of development were denoted by changes in amino acid derivatives. Of the amino acid derivatives that significantly changed, a majority were linked to metabolites of the one-carbon metabolic pathway. The enrichment of one-carbon metabolites was independent of age and environmental insult. Temperature was also found to significantly influence the metabolic levels within the postmortem sampled lung, which underscored the importance of methodology. Collectively, these data support not only distinctive stages of metabolic change but also highlight amino acid metabolism, in particular one-carbon metabolites as metabolic signatures of the early postnatal lung.

A Comprehensive Approach to Midface Rejuvenation: Our Philosophy, Algorithm, and Surgical Technique.

With a greater understanding of the aging process and relevant anatomy, the facial plastic surgeon has an expansive armamentarium of options for midface rejuvenation. Upon reflection, our practice has evolved over the years and only recently found a select number of interventions that have consistently produced excellent results. In this article, we discuss the steps needed to establish an effective patient relationship, present an algorithm on how to approach midface rejuvenation, describe our surgical technique, and review the attributes and liabilities of each procedure.

Influence of aminoacyl-tRNA synthetase complex-interacting multifunctional protein 1 on epithelial differentiation and organization during lung development.

Proper development of the respiratory bronchiole and alveolar epithelium proceeds through coordinated cross talk between the interface of epithelium and neighboring mesenchyme. Signals that facilitate and coordinate the cross talk as the bronchial forming canalicular stage transitions to construction of air-exchanging capillary-alveoli niche in the alveolar stage are poorly understood. Expressed within this decisive region, levels of aminoacyl-tRNA synthetase complex-interacting multifunctional protein 1 (AIMP1) inversely correlate with the maturation of the lung. The present study addresses the role of AIMP1 in lung development through the generation and characterization of Aimp1-/- mutant mice. Mating of Aimp1+/- produced offspring in expected Mendelian ratios throughout embryonic development. However, newborn Aimp1-/- pups exhibited neonatal lethality with mild cyanosis. Imaging both structure and ultrastructure of Aimp1-/- lungs showed disorganized bronchial epithelium, decreased type I but not type II cell differentiation, increased distal vessels, and disruption of E-cadherin deposition in cell-cell junctions. Supporting the in vivo findings of disrupted epithelial cell-cell junctions, in vitro biochemical experiments show that a portion of AIMP1 binds to phosphoinositides, the lipid anchor of proteins that have a fundamental role in both cellular membrane and actin cytoskeleton organization; a dramatic disruption in F-actin cytoskeleton was observed in Aimp1-/- mouse embryonic fibroblasts. Such observed structural defects may lead to disrupted cell-cell boundaries. Together, these results suggest a requirement of AIMP1 in epithelial cell differentiation in proper lung development.

A distinct transcriptional profile in response to endothelial monocyte activating polypeptide II is partially mediated by JAK-STAT3 in murine macrophages.

Macrophages are important responders to environmental changes such as secreted factors. Among the secreted factors in injured tissues, the highly conserved endothelial monocyte activating polypeptide II (EMAP II) has been characterized to limit vessel formation, to be locally expressed near sites of injury labeling it a "find-me" signal, and to recruit macrophages and neutrophils. The molecular mechanisms mediated by EMAP II within macrophages once they are recruited are unknown. In this study, using a model of partially activated, recruited thioglycollate-elicited peritoneal macrophages, a transient, transcription profile of key functional genes in macrophages exposed to EMAP II was characterized. We found that EMAP II-mediated changes were elicited mainly through signal transducer and activator of transcription 3 (STAT3) as evidenced by increased Y705 phosphorylation and changes in activity and upstream of it, Janus associated kinase (JAK)1/2 upstream. Both inhibition of JAK1/2 and knockdown of Stat3 abrogated a subset of genes that are upregulated by EMAP II. Our results identify a rapid EMAP II-mediated STAT3 activation that coincides with altered pro- and anti-inflammatory gene expression in macrophages.

Learning Data Manifolds with a Cutting Plane Method.

We consider the problem of classifying data manifolds where each manifold represents invariances that are parameterized by continuous degrees of freedom. Conventional data augmentation methods rely on sampling large numbers of training examples from these manifolds. Instead, we propose an iterative algorithm, [Formula: see text], based on a cutting plane approach that efficiently solves a quadratic semi-infinite programming problem to find the maximum margin solution. We provide a proof of convergence as well as a polynomial bound on the number of iterations required for a desired tolerance in the objective function. The efficiency and performance of [Formula: see text] are demonstrated in high-dimensional simulations and on image manifolds generated from the ImageNet data set. Our results indicate that [Formula: see text] is able to rapidly learn good classifiers and shows superior generalization performance compared with conventional maximum margin methods using data augmentation methods.

Bias Reduction and Metric Learning for Nearest-Neighbor Estimation of Kullback-Leibler Divergence.

Nearest-neighbor estimators for the Kullback-Leiber (KL) divergence that are asymptotically unbiased have recently been proposed and demonstrated in a number of applications. However, with a small number of samples, nonparametric methods typically suffer from large estimation bias due to the nonlocality of information derived from nearest-neighbor statistics. In this letter, we show that this estimation bias can be mitigated by modifying the metric function, and we propose a novel method for learning a locally optimal Mahalanobis distance function from parametric generative models of the underlying density distributions. Using both simulations and experiments on a variety of data sets, we demonstrate that this interplay between approximate generative models and nonparametric techniques can significantly improve the accuracy of nearest-neighbor-based estimation of the KL divergence.

Validity of utility measures for women with pelvic organ prolapse.

BACKGROUND: Pelvic organ prolapse is a common condition that frequently coexists with urinary and fecal incontinence. The impact of prolapse on quality of life is typically measured through condition-specific quality-of-life instruments. Utility preference scores are a standardized generic health-related quality-of-life measure that summarizes morbidity on a scale from 0 (death) to 1 (optimum health). Utility preference scores quantify disease severity and burden and are widely used in cost-effectiveness research. The validity of utility preference instruments in women with pelvic organ prolapse has not been established. OBJECTIVE: The objective of this study was to evaluate the construct validity of generic quality-of-life instruments for measuring utility scores in women with pelvic organ prolapse. Our hypothesis was that women with multiple pelvic floor disorders would have worse (lower) utility scores than women with pelvic organ prolapse only and that women with all 3 pelvic floor disorders would have the worst (lowest) utility scores. STUDY DESIGN: This was a prospective observational study of 286 women with pelvic floor disorders from a referral female pelvic medicine and reconstructive surgery practice. All women completed the following general health-related quality-of-life questionnaires: Health Utilities Index Mark 3, EuroQol, and Short Form 6D, as well as a visual analog scale. Pelvic floor symptom severity and condition-specific quality of life were measured using the Pelvic Floor Distress Inventory and Pelvic Floor Impact Questionnaire, respectively. We measured the relationship between utility scores and condition-specific quality-of-life scores and compared utility scores among 4 groups of women: (1) pelvic organ prolapse only, (2) pelvic organ prolapse and stress urinary incontinence, (3) pelvic organ prolapse and urgency urinary incontinence, and (4) pelvic organ prolapse, urinary incontinence, and fecal incontinence. RESULTS: Of 286 women enrolled, 191 (67%) had pelvic organ prolapse; mean age was 59 years and 73% were Caucasian. Among women with prolapse, 30 (16%) also had stress urinary incontinence, 39 (20%) had urgency urinary incontinence, and 42 (22%) had fecal incontinence. For the Health Utilities Index Mark 3, EuroQol, and Short Form 6D, the pattern in utility scores was noted to be lowest (worst) in the prolapse + urinary incontinence + fecal incontinence group (0.73-0.76), followed by the prolapse + urgency urinary incontinence group (0.77-0.85) and utility scores were the highest (best) for the prolapse only group (0.80-0.86). Utility scores from all generic instruments except the visual analog scale were significantly correlated with the Pelvic Floor Distress Inventory and Pelvic Floor Impact Questionnaire total scores (r values -0.26 to -0.57), and prolapse, bladder, and bowel subscales (r values -0.16 to -0.50). Utility scores from all instruments except the visual analog scale were highly correlated with each other (r = 0.53-0.69, P < .0001). CONCLUSION: The Health Utilities Index Mark 3, EuroQol, and Short Form 6D, but not the visual analog scale, provide valid measurements for utility scores in women with pelvic organ prolapse and associated pelvic floor disorders and could potentially be used for cost-effectiveness research.

α5ß1 integrin mediates pulmonary epithelial cyst formation.

BACKGROUND: Formation of the epithelial cyst involves the establishment of apical-basolateral polarity through a series of cellular interactions that are in part mediated by the extracellular matrix (ECM). We report that in a three-dimensional multi-cellular self-assembly model of lung development, α5 integrin regulates epithelial cyst formation through organization of soluble fibronectin matrix into insoluble fibrils through a process called fibrillogenesis. RESULTS: Dissociated murine embryonic lung cells self-assemble into three-dimensional pulmonary bodies that are dependent on α5ß1 integrin mediated fibrillogenesis for cell-cell mediated self-assembly: compaction and epithelial cyst formation. Knockdown of α5 integrin resulted in a significant increase in another mediator of fibrillogenesis, αV integrin. Compensatory increased expression of another mediator of fibrillogenesis, αV integrin, was not sufficient to normalize epithelial cyst formation. Loss of α5 integrin-mediated fibrillogenesis perturbed the ability of clustered epithelial cells to establish clear polarity, loss of epithelial cell pyramidal shape, and disrupted apical F-actin-rich deposition. Lack of rich central epithelial localization of F-actin cytoskeleton and Podocalyxin suggests that loss of α5 integrin-mediated fibrillogenesis interferes with the normal cytoskeleton organization that facilitates epithelial cysts polarization. CONCLUSIONS: We conclude that lung epithelial cyst formation in development is mediated in part by α5ß1 integrin dependent fibrillogenesis. Developmental Dynamics 246:475-484, 2016. © 2017 Wiley Periodicals, Inc.

Endothelial Monocyte-Activating Polypeptide II Mediates Macrophage Migration in the Development of Hyperoxia-Induced Lung Disease of Prematurity.

Myeloid cells are key factors in the progression of bronchopulmonary dysplasia (BPD) pathogenesis. Endothelial monocyte-activating polypeptide II (EMAP II) mediates myeloid cell trafficking. The origin and physiological mechanism by which EMAP II affects pathogenesis in BPD is unknown. The objective was to determine the functional consequences of elevated EMAP II levels in the pathogenesis of murine BPD and to investigate EMAP II neutralization as a therapeutic strategy. Three neonatal mouse models were used: (1) BPD (hyperoxia), (2) EMAP II delivery, and (3) BPD with neutralizing EMAP II antibody treatments. Chemokinic function of EMAP II and its neutralization were assessed by migration in vitro and in vivo. We determined the location of EMAP II by immunohistochemistry, pulmonary proinflammatory and chemotactic gene expression by quantitative polymerase chain reaction and immunoblotting, lung outcome by pulmonary function testing and histological analysis, and right ventricular hypertrophy by Fulton's Index. In BPD, EMAP II initially is a bronchial club-cell-specific protein-derived factor that later is expressed in galectin-3+ macrophages as BPD progresses. Continuous elevated expression corroborates with baboon and human BPD. Prolonged elevation of EMAP II levels recruits galectin-3+ macrophages, which is followed by an inflammatory state that resembles a severe BPD phenotype characterized by decreased pulmonary compliance, arrested alveolar development, and signs of pulmonary hypertension. In vivo pharmacological EMAP II inhibition suppressed proinflammatory genes Tnfa, Il6, and Il1b and chemotactic genes Ccl2 and Ccl9 and reversed the severe BPD phenotype. EMAP II is sufficient to induce macrophage recruitment, worsens BPD progression, and represents a targetable mechanism of BPD development.

Efficient Neural Codes That Minimize Lp Reconstruction Error.

The efficient coding hypothesis assumes that biological sensory systems use neural codes that are optimized to best possibly represent the stimuli that occur in their environment. Most common models use information-theoretic measures, whereas alternative formulations propose incorporating downstream decoding performance. Here we provide a systematic evaluation of different optimality criteria using a parametric formulation of the efficient coding problem based on the [Formula: see text] reconstruction error of the maximum likelihood decoder. This parametric family includes both the information maximization criterion and squared decoding error as special cases. We analytically derived the optimal tuning curve of a single neuron encoding a one-dimensional stimulus with an arbitrary input distribution. We show how the result can be generalized to a class of neural populations by introducing the concept of a meta-tuning curve. The predictions of our framework are tested against previously measured characteristics of some early visual systems found in biology. We find solutions that correspond to low values of [Formula: see text], suggesting that across different animal models, neural representations in the early visual pathways optimize similar criteria about natural stimuli that are relatively close to the information maximization criterion.

Adapted approach to profile genes while reconciling Vegf-a mRNA expression in the developing and injured lung.

During lung development and injury, messenger RNA (mRNA) transcript levels of genes fluctuate over both space and time. Quantitative PCR (qPCR) is a highly sensitive, widely used technique to measure the mRNA levels. The sensitivity of this technique can be disadvantageous and errors amplified when each qPCR assay is not validated. In contrast to other organs, lungs have high RNase activity, resulting in less than optimal RNA integrity. We implemented a strategy to address these limitations in developing and injured lungs. Parameters were established and a filter designed that optimized amplicon length and included or excluded samples based on RNA integrity. This approach was illustrated and validated by measuring mRNA levels including Vegf-a in newborn mouse lungs that were injured by 85% oxygen (hyperoxia) for 12 days and compared with control (normoxia). We demonstrate that, in contrast to contradictory Vegf-a expression when normalized to the least suitable housekeeping genes, application of this filter and normalization to most suitable three housekeeping genes, Hprt, Eef2, and Rpl13a, gave reproducible Vegf-a expression, thus corroborating the sample filter. Accordingly, both short amplicon length and proper normalization to ranked, evaluated genes minimized erroneous fluctuation and qPCR amplification issues associated with nonideal RNA integrity in injured and developing lungs. Furthermore, our work uncovers how RNA integrity, purity, amplicon length, and discovery of stable candidate reference genes enhance precision of qPCR results and utilizes the advantages of qPCR in developmental studies.

Hypertrophic cardiomyopathy: a new mutation illustrates the need for family-centered care.

This is a case series of a family positive for a previously undescribed mutation in the myofilament gene MYH7, causing hypertrophic cardiomyopathy (HCM), a potentially lethal cardiac disease with strong hereditability. The family's significant disease became strikingly apparent with the unanticipated diagnosis of their newborn infant shortly after her birth. This led to the discovery of the MYH7 mutation in the infant, as well as her father and two siblings, all of whom had varying degrees of disease severity. Despite prior diagnosis of HCM for the paternal grandmother and great uncles, this family's situation points to the need for continued education of healthcare providers, when heritable diseases are encountered. Genetics consult should occur early and has been shown to be helpful in making an accurate diagnosis and identifying relatives at risk of developing the condition. It may, as in this case series, lead to the discovery of a novel mutation and contribute to the growing genetic database for familial HCM.

Facial Implants in Male Rejuvenation.

Many different methods achieve male facial augmentation. Arranged from shorter- to longer-term results, these methods include filler, fat/tissue grafting, fat/tissue transposition, and alloplastic implants. This study solely reviews allografts, which provide the most predictable hard-tissue augmentation. An array of alloplasts will be discussed in this study including chin, cheek, mandibular angle, frontal, and temporal implants. The most common and severe complications will also be explored with preventative and treatment algorithms.

Experiences of healthcare providers with a novel emergency response intubation team during COVID-19.

OBJECTIVES: In the early stages of the COVID-19 pandemic, there were significant concerns about the infectious risks of intubation to healthcare providers. In response, a dedicated emergency response intubation team (ERIT) consisting of anesthesiologists and allied health providers was instituted for our emergency department (ED). Given the high-risk nature of intubations and the new interprofessional team dynamics, we sought to assess health-care provider experiences and potential areas of improvement. METHODS: Surveys were distributed to healthcare providers at the University Health Network, a quaternary healthcare centre in Toronto, Canada, which includes two urban EDs seeing over 128,000 patients per year. Participants included ED physicians and nurses, anesthesiologists, anesthesia assistants, and operating room nurses. The survey included free-text questions. Responses underwent thematic analysis using grounded theory and were independently coded by two authors to generate descriptive themes. Discrepancies were resolved with a third author. Descriptive themes were distilled through an inductive, iterative process until fewer main themes emerged. RESULTS: A total of 178 surveys were collected (68.2% response rate). Of these, 123 (69%) participated in one or more ERIT activations. Positive aspects included increased numbers of staff to assist, increased intubation expertise, improved safety, and good team dynamics within the ERIT team. Challenges included a loss of scope (primarily ED physicians and nurses) and unfamiliar workflows, perceived delays to ERIT team arrival or patient intubation, role confusion, handover concerns, and communication challenges between ED and ERIT teams. Perceived opportunities for improvement included interprofessional training, developing clear guidelines on activation, inter-team role clarification, and guidelines on handover processes post-intubation. CONCLUSIONS: Healthcare providers perceived that a novel interprofessional collaboration for intubations of COVID-19 patients presented both benefits and challenges. Opportunities for improvement centred around interprofessional training, shared decision making between teams, and structured handoff processes.

RéSUMé: OBJECTIFS: Aux premiers stades de la pandémie de COVID-19, les risques infectieux de l'intubation pour les prestataires de soins de santé ont suscité de vives inquiétudes. En réponse, une équipe d'intervention d'urgence en intubation (emergency response intubation team ERIT), composée d'anesthésistes et de prestataires de services paramédicaux, a été mise en place dans notre service d'urgence. Compte tenu de la nature à haut risque des intubations et de la nouvelle dynamique d'équipe interprofessionnelle, nous avons cherché à évaluer les expériences des prestataires de soins et les domaines d'amélioration potentiels. MéTHODES: Les questionnaires ont été distribués aux prestataires de soins de santé du University Health Network, un centre de soins de santé quaternaire de Toronto, au Canada, qui comprend deux urgences urbaines accueillant plus de 128 000 patients par an. Les participants comprenaient des médecins et des infirmiers des urgences, des anesthésistes, des assistants en anesthésie et des infirmiers de salle d'opération. Les réponses ont fait l'objet d'une analyse thématique fondée sur la théorie de la base et ont été codées indépendamment par deux auteurs afin de générer des thèmes descriptifs. Les divergences ont été résolues avec un troisième auteur. Les thèmes descriptifs ont été distillés par un processus inductif et itératif jusqu'à ce qu'un nombre réduit de thèmes principaux émerge. RéSULTATS: Au total, 178 sondages ont été recueillis (taux de réponse de 68,2 %). Parmi ceux-ci, 123 (69 %) ont participé à une ou plusieurs activations d'ERIT. Les aspects positifs comprenaient un nombre accru de personnel pour aider, une expertise accrue en matière d'intubation, une sécurité améliorée et une bonne dynamique d'équipe au sein de l'équipe ERIT. Parmi les difficultés rencontrées, citons la perte du champ d'action (principalement les médecins et les infirmières des services d'urgence) et les flux de travail non familiers, les retards perçus dans l'arrivée de l'équipe d'ERIT ou l'intubation du patient, la confusion des rôles, les problèmes de transfert et les difficultés de communication entre les équipes des services d'urgence et d'ERIT. Les possibilités d'amélioration perçues comprennent la formation interprofessionnelle, l'élaboration de directives claires sur l'activation, la clarification des rôles entre les équipes et les directives sur les processus de transfert après l'intubation. CONCLUSIONS: Les prestataires de soins de santé ont perçu qu'une nouvelle collaboration interprofessionnelle pour les intubations des patients COVID-19 présentait à la fois des avantages et des défis.

Video Virtual Clinical Encounters Versus Office Visits for Postoperative Care After Pelvic Organ Prolapse Surgery: A Randomized Clinical Trial.

OBJECTIVES: To determine if patient satisfaction of virtual clinical encounters is noninferior to traditional in-office clinical encounters for postoperative follow-up after reconstructive surgery for pelvic organ prolapse. METHODS: This was a randomized controlled noninferiority trial of women undergoing surgery for pelvic organ prolapse. Women were recruited and randomized during their preoperative counseling visit to virtual clinical encounters via video conference technology or in-office clinical encounters for their 30-day postoperative follow-up visits. The primary outcome was patient satisfaction measured by the validated Patient Satisfaction Questionnaire-18 (score range, 18-90, with higher scores indicating greater satisfaction) administered by telephone following the 30-day visit. Additional information regarding demographics, postoperative health care utilization, and complications was collected via chart review and compared between groups. RESULTS: A total of 52 women were randomly assigned to virtual clinical encounters via videoconference technology or traditional in-office clinical encounters (26 per group). The mean patient satisfaction score was 80.7 ± 2.6 in the virtual group and 81.2 ± 2.8 in the office group (difference, -0.46 points; 95% confidence interval, -1.95 to 1.03), which was consistent with noninferiority. Postoperative complication rates were 31% in the virtual group and 46% in the office group (P = 0.3). There were no significant between-group differences in secondary measures of unscheduled telephone calls (88% versus 77%, P = 0.5) and office visits (35% versus 38%, P = 0.8), emergency room visits (15% versus 19%, P = 1.0), and hospital readmissions (4% versus 12%, P = 0.6) within 90 days of surgery. CONCLUSIONS: For patients with pelvic organ prolapse undergoing reconstructive surgery, postoperative virtual clinical encounters via video conference technology are noninferior to traditional in-office clinical encounters with high levels of short-term patient satisfaction and no differences in postoperative health care utilization and complications rates.

Return to Baseline Functional Status in Older Women Undergoing Surgery for Pelvic Organ Prolapse.

OBJECTIVE: The aim of the study was to determine the rate of return to baseline functional status 3 months after surgery for pelvic organ prolapse (POP) in women 65 years or older. METHODS: This is a multicenter prospective cohort study of women older than 65 years undergoing POP surgery. Functional status was determined by the Activities Assessment Scale at the preoperative visit and 3 months after surgery. We compared a variety of clinical variables and preoperative functional status scores for women who worsened, improved, or returned to baseline functional status after surgery using univariable and multivariable analysis. RESULTS: A total of 192 women were enrolled in the study. Of 176 women who completed both sets of questionnaires, 59% improved, 35% returned, and 6% worsened from their baseline functional status. Variables significantly associated with postoperative functional status score were depression (P < 0.002) and preoperative functional status score (P < 0.001). The group that improved from baseline had the lowest (worst) preoperative functional status score (78.7 ± 16.4), whereas the group that worsened after surgery had the highest (best) preoperative functional status score (98.6 ± 2.2). After adjusting for age and depression, higher preoperative functional status score was predictive of failure to return to baseline functional status. CONCLUSIONS: Most older women undergoing surgery for POP, including those with low preoperative functional status, return to or improve from their baseline functional status within 3 months of surgery. Women with higher functional status before surgery are less likely to report improvement in physical functioning after surgery.

Targeted FGFR/VEGFR/PDGFR inhibition with dovitinib enhances the effects of nab-paclitaxel in preclinical gastric cancer models.

Standard chemotherapy regimens for gastric adenocarcinoma (GAC) have limited efficacy and considerable toxicity profiles. Nab-paclitaxel has shown promising antitumor benefits in previous GAC preclinical studies. Dovitinib inhibits members of the receptor tyrosine kinase family including FGFR, VEGFR and PDGFR, and has exhibited antitumor effects in many solid tumors including GAC. Based on the antimitotic, antistromal and EPR effects of nab-paclitaxel, we investigated augmentation of nab-paclitaxel response by dovitinib in multiple GAC preclinical models. In MKN-45 subcutaneous xenografts, inhibition in tumor growth by nab-paclitaxel and dovitinib was 75% and 76%, respectively. Dovitinib plus nab-paclitaxel had an additive effect on tumor growth inhibition and resulted in tumor regression (85% of its original value). Dovitinib monotherapy resulted in minimal improvement in animal survival (25 days) compared to control (23 days), while nab-paclitaxel monotherapy or dovitinib plus nab-paclitaxel combination therapy led to a clinically significant lifespan extension of 83% (42 days) and 187% (66 days), respectively. IHC analysis of subcutaneous tumors exhibited reduced tumor cell proliferation and tumor vasculature by dovitinib. In vitro studies demonstrated that dovitinib and nab-paclitaxel individually reduced tumor cell proliferation, with an additive effect from combination therapy. Immunoblot analyses of MKN-45 and KATO-III cells revealed that dovitinib decreased phospho-FGFR, phospho-AKT, phospho-ERK, phospho-p70S6K, phospho-4EBP1, Bcl-2 and increased cleaved PARP-1, cleaved-caspase-3, p27, Bax, Bim, with an additive effect from combination therapy. These results demonstrate that the FGFR/VEGFR/PDGFR inhibitor, dovitinib, has the potential to augment the antitumor effects of nab-paclitaxel, with implications for use in the advancement of clinical GAC therapy.