An AI-powered patient triage platform for future viral outbreaks using COVID-19 as a disease model.

Over the last century, outbreaks and pandemics have occurred with disturbing regularity, necessitating advance preparation and large-scale, coordinated response. Here, we developed a machine learning predictive model of disease severity and length of hospitalization for COVID-19, which can be utilized as a platform for future unknown viral outbreaks. We combined untargeted metabolomics on plasma data obtained from COVID-19 patients (n = 111) during hospitalization and healthy controls (n = 342), clinical and comorbidity data (n = 508) to build this patient triage platform, which consists of three parts: (i) the clinical decision tree, which amongst other biomarkers showed that patients with increased eosinophils have worse disease prognosis and can serve as a new potential biomarker with high accuracy (AUC = 0.974), (ii) the estimation of patient hospitalization length with ± 5 days error (R2 = 0.9765) and (iii) the prediction of the disease severity and the need of patient transfer to the intensive care unit. We report a significant decrease in serotonin levels in patients who needed positive airway pressure oxygen and/or were intubated. Furthermore, 5-hydroxy tryptophan, allantoin, and glucuronic acid metabolites were increased in COVID-19 patients and collectively they can serve as biomarkers to predict disease progression. The ability to quickly identify which patients will develop life-threatening illness would allow the efficient allocation of medical resources and implementation of the most effective medical interventions. We would advocate that the same approach could be utilized in future viral outbreaks to help hospitals triage patients more effectively and improve patient outcomes while optimizing healthcare resources.

Co-occurring conditions in Down syndrome: Findings from a clinical database.

Individuals with Down syndrome (DS) experience a range of medical and neurodevelopmental conditions, necessitating systematic study of their occurrence and impact on neurodevelopmental outcomes. We describe the prevalence and relationships of medical, neurodevelopmental (ND), and mental health (MH) conditions in children with DS. We created a prospective clinical database of individuals with DS, integrated into the workflow of a specialty Down Syndrome Program at a specialty pediatric referral hospital. Conditions were collected through caregiver- and clinician report at clinical visits (N = 599). We calculated frequencies of medical, ND, and MH conditions and then assessed the relationship between medical, ND, and MH conditions using frequencies and comparative statistics. The most frequent co-occurring conditions were vision (72.5%), ear/hearing (71.0%), gastrointestinal (61.3%), respiratory (45.6%), and feeding (33.6%) problems, with variation in frequency by age. ND and MH conditions were reported in one quarter, most commonly autism spectrum disorder and attention-deficit/hyperactivity disorder. Those with ND and MH conditions had greater frequency of medical conditions, with highest rates of vision, ear/hearing, and gastrointestinal issues, and CHD. Systematically collected clinical data in a large cohort of children with DS reveals high prevalence of several co-occurring medical, ND, and MH conditions. Clinical care requires an understanding of the complex relationship between medical conditions and neurodevelopment.

Discovery of a potent and selective human AC2 inhibitor based on 7-deazapurine analogues of adefovir.

Adefovir based acyclic nucleoside phosphonates were previously shown to modulate bacterial and, to a certain extent, human adenylate cyclases (mACs). In this work, a series of 24 novel 7-substituted 7-deazaadefovir analogues were synthesized in the form of prodrugs. Twelve analogues were single-digit micromolar inhibitors of Bordetella pertussis adenylate cyclase toxin with no cytotoxicity to J774A.1 macrophages. In HEK293 cell-based assays, compound 14 was identified as a potent (IC50 = 4.45 µM), non-toxic, and selective mAC2 inhibitor (vs. mAC1 and mAC5). Such a compound represents a valuable addition to a limited number of small-molecule probes to study the biological functions of individual endogenous mAC isoforms.

Comparison between Perianal Swab and Stool Specimens for Detecting Colonization with Extended-Spectrum Beta-Lactamase-Producing and Fluoroquinolone-Resistant Enterobacterales.

Stool specimens are frequently used to detect gastrointestinal tract colonization with antimicrobial-resistant enteric bacteria, but they cannot be rapidly collected. Perianal swab specimens can be collected more quickly and efficiently, but data evaluating their suitability as a specimen type for this purpose are sparse. We performed selective culture for extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-E) and fluoroquinolone-resistant Enterobacterales (FQRE) using paired perianal swab and stool specimens that were collected within 1 day of each other from hematopoietic cell transplant recipients and patients with acute leukemia. Nineteen (7.6%) of 251 stool specimens yielded ESBL-E and 64 (26%) of 246 stool specimens yielded FQRE. The positive percent agreement of perianal swab specimens compared to stool specimens was 95% (18/19; 95% confidence interval [CI], 74% to 100%) for detecting ESBL-E and 95% (61/64; 95% CI, 87% to 99%) for detecting FQRE. The concordance between specimen types was 98% (95% CI, 97% to 100%). Perianal swabs are a reliable specimen type for surveillance of the gastrointestinal tract for ESBL-E and FQRE.

Quantitative analysis of short-chain fatty acids in human plasma and serum by GC-MS.

Short-chain fatty acids (SCFAs) are volatile fatty acids produced by gut microbial fermentation of dietary nondigestible carbohydrates. Acetate, propionate, and butyrate SCFA measures are important to clinical and nutritional studies for their established roles in promoting healthy immune and gut function. Additionally, circulating SCFAs may influence the metabolism and allied function of additional tissues and organs. The accurate quantification of SCFAs in plasma/serum is critical to understanding the biological role of SCFAs. The low concentrations of circulating SCFAs and their volatile nature present challenges for quantitative analysis. Herein, we report a sensitive method for SCFA quantification via extraction with methyl tert-butyl ether after plasma/serum acidification. The organic extract of SCFAs is injected directly with separation and detection using a polar GC column coupled to mass spectrometry. The solvent-to-sample ratio, plasma volume, and amount of HCl needed for SCFA protonation were optimized. Method validation shows good within-day and inter-day repeatability. The limit of detection was 0.3-0.6 µg/mL for acetate and 0.03-0.12 µg/mL for propionate and butyrate. Successful application of this method on clinical plasma and serum samples was demonstrated in six datasets. By simplifying the sample preparation procedure, the present method reduces the risk of contamination, lowers the cost of analysis, increases throughput, and offers the potential for automated sample preparation.

Development and implementation of a longitudinal clinical database for down syndrome in a large pediatric specialty clinic: Methodology and feasibility.

Down syndrome (DS) is a complex condition associated with multiple medical, developmental, and behavioral concerns. A prospective, longitudinal clinical database was integrated into a specialty Down Syndrome Program, with the goals of better understanding the incidence, course, and impact of co-occurring medical, neurodevelopmental, and mental health conditions in DS. We describe the process of developing the database, including a systematic approach to data collection and database infrastructure, and report on feasibility, challenges, and solutions of initial implementation. Between March 2018 and November 2021, data from 842 patients (ages 4.8 months to 26 years) was collected. Challenges included caregiver form completion as well as time and personnel required for successful implementation. With full integration into clinical visit flow, the database proved to be feasible. The database enables identification of patterns of development and health throughout the lifespan and it facilitates future data sharing and collaborative research to advance care.

Colonization With Fluoroquinolone-Resistant Enterobacterales Decreases the Effectiveness of Fluoroquinolone Prophylaxis in Hematopoietic Cell Transplant Recipients.

BACKGROUND: Levofloxacin prophylaxis is recommended to prevent gram-negative bloodstream infections (BSIs) in patients with prolonged chemotherapy-induced neutropenia. However, increasing fluoroquinolone resistance may decrease the effectiveness of this approach. METHODS: We assessed the prevalence of colonization with fluoroquinolone-resistant Enterobacterales (FQRE) among patients admitted for hematopoietic cell transplantation (HCT) from November 2016 to August 2019 and compared the risk of gram-negative BSI between FQRE-colonized and noncolonized patients. All patients received levofloxacin prophylaxis during neutropenia. Stool samples were collected upon admission for HCT and weekly thereafter until recovery from neutropenia, and underwent selective culture for FQRE. All isolates were identified and underwent antimicrobial susceptibility testing by broth microdilution. FQRE isolates also underwent whole-genome sequencing. RESULTS: Fifty-four of 234 (23%) patients were colonized with FQRE prior to HCT, including 30 of 119 (25%) allogeneic and 24 of 115 (21%) autologous HCT recipients. Recent antibacterial use was associated with FQRE colonization (P = .048). Ninety-one percent of colonizing FQRE isolates were Escherichia coli and 29% produced extended-spectrum ß-lactamases. Seventeen (31%) FQRE-colonized patients developed gram-negative BSI despite levofloxacin prophylaxis, compared to only 2 of 180 (1.1%) patients who were not colonized with FQRE on admission (P < .001). Of the 17 gram-negative BSIs in FQRE-colonized patients, 15 (88%) were caused by FQRE isolates that were genetically identical to the colonizing strain. CONCLUSIONS: Nearly one-third of HCT recipients with pretransplant FQRE colonization developed gram-negative BSI while receiving levofloxacin prophylaxis, and infections were typically caused by their colonizing strains. In contrast, levofloxacin prophylaxis was highly effective in patients not initially colonized with FQRE.

Overview of PAX gene family: analysis of human tissue-specific variant expression and involvement in human disease.

Paired-box (PAX) genes encode a family of highly conserved transcription factors found in vertebrates and invertebrates. PAX proteins are defined by the presence of a paired domain that is evolutionarily conserved across phylogenies. Inclusion of a homeodomain and/or an octapeptide linker subdivides PAX proteins into four groups. Often termed "master regulators", PAX proteins orchestrate tissue and organ development throughout cell differentiation and lineage determination, and are essential for tissue structure and function through maintenance of cell identity. Mutations in PAX genes are associated with myriad human diseases (e.g., microphthalmia, anophthalmia, coloboma, hypothyroidism, acute lymphoblastic leukemia). Transcriptional regulation by PAX proteins is, in part, modulated by expression of alternatively spliced transcripts. Herein, we provide a genomics update on the nine human PAX family members and PAX homologs in 16 additional species. We also present a comprehensive summary of human tissue-specific PAX transcript variant expression and describe potential functional significance of PAX isoforms. While the functional roles of PAX proteins in developmental diseases and cancer are well characterized, much remains to be understood regarding the functional roles of PAX isoforms in human health. We anticipate the analysis of tissue-specific PAX transcript variant expression presented herein can serve as a starting point for such research endeavors.

Perioperative outcomes following pelvic floor reconstruction in women with hereditary disorders of connective tissue: a retrospective cohort study.

INTRODUCTION AND HYPOTHESIS: Women with hereditary disorders of connective tissue (HDCT) are at increased risk of pelvic organ prolapse (POP) and stress urinary incontinence (SUI). We hypothesized that patients would have increased incidence and severity of perioperative complications up to 6 weeks after surgeries for POP/SUI. Secondary objectives were to compare pre- and post-operative pelvic floor symptoms and anatomical support as well as pelvic floor disorder recurrence. METHODS: In this multi-center retrospective cohort study, we identified patients with HDCTs by patient history and ICD-9 codes over an 11-year period. Controls without HDCTs were matched 2:1 to the primary POP or SUI procedure and surgeon. Demographic characteristics, perioperative pelvic floor information and complications were collected. A sample size of 65 HDCT patients and 130 controls was calculated to detect a 20% difference in complications with 80% power and alpha of 0.05. RESULTS: We identified 59 HDCT patients and 118 controls. Of the women with HDCTs, 49% had Ehlers-Danlos, 22% joint hypermobility syndrome, 15% Marfan syndrome, and 14% had others. Compared with controls, HDCT patients had more total perioperative complications (46% vs 22%, p = 0.002); an age-adjusted relative risk of complications was 1.4 (CI 0.7-2.6). HDCT patients had more Clavien-Dindo grades I and II complications (p = 0.02, 0.03) and more hospital readmissions (14% vs 3%, p = 0.01) than controls. There was no difference in the incidence of specific complications nor was there a difference in recurrence of POP (10%) or SUI (11%) between groups. CONCLUSIONS: Patients with HDCTs had more Clavien-Dindo grade I and II complications following pelvic floor reconstructive surgery and more readmissions.

Double dissociation between perception and action in children.

Previous research has demonstrated a functional dissociation between vision for perception and vision for action. However, the developmental trajectory of this functional dissociation is not well understood. We directly compared the sensitivity of grasping and perceptual estimations within the same experimental design to the real and illusory sizes of objects positioned in the Ponzo illusion display. Two different-sized objects were placed such that the differences between their real sizes and their perceived sizes were pitted against each other. Children aged 5-8 years and adults made perceptual size discriminations and then grasped (action) or estimated (perception) one of the objects based on its perceived size. Consistent with previous results, for the action task, grasping apertures of adults were scaled with the physical differences in the objects' sizes, even in trials where their overt perceptual decisions were deceived by the illusion. In contrast, perceptual estimations were robustly modulated by the illusion. Interestingly, children outperformed adults in their perceptual discriminations but exhibited adult-like behavior in grasping and in perceptual estimations of the objects, demonstrating a dissociation between perception and action. These results suggest that although the two visual functions are not operating at fully mature levels during childhood, some key mechanisms that support a dissociation between these functions are already in place.

Multi-centre randomised controlled trial comparing arthroscopic hip surgery to physiotherapist-led care for femoroacetabular impingement (FAI) syndrome on hip cartilage metabolism: the Australian FASHIoN trial.

BACKGROUND: Arthroscopic surgery for femoroacetabular impingement syndrome (FAI) is known to lead to self-reported symptom improvement. In the context of surgical interventions with known contextual effects and no true sham comparator trials, it is important to ascertain outcomes that are less susceptible to placebo effects. The primary aim of this trial was to determine if study participants with FAI who have hip arthroscopy demonstrate greater improvements in delayed gadolinium-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) index between baseline and 12 months, compared to participants who undergo physiotherapist-led management. METHODS: Multi-centre, pragmatic, two-arm superiority randomised controlled trial comparing physiotherapist-led management to hip arthroscopy for FAI. FAI participants were recruited from participating orthopaedic surgeons clinics, and randomly allocated to receive either physiotherapist-led conservative care or surgery. The surgical intervention was arthroscopic FAI surgery. The physiotherapist-led conservative management was an individualised physiotherapy program, named Personalised Hip Therapy (PHT). The primary outcome measure was change in dGEMRIC score between baseline and 12 months. Secondary outcomes included a range of patient-reported outcomes and structural measures relevant to FAI pathoanatomy and hip osteoarthritis development. Interventions were compared by intention-to-treat analysis. RESULTS: Ninety-nine participants were recruited, of mean age 33 years and 58% male. Primary outcome data were available for 53 participants (27 in surgical group, 26 in PHT). The adjusted group difference in change at 12 months in dGEMRIC was -59 ms (95%CI - 137.9 to - 19.6) (p = 0.14) favouring PHT. Hip-related quality of life (iHOT-33) showed improvements in both groups with the adjusted between-group difference at 12 months showing a statistically and clinically important improvement in arthroscopy of 14 units (95% CI 5.6 to 23.9) (p = 0.003). CONCLUSION: The primary outcome of dGEMRIC showed no statistically significant difference between PHT and arthroscopic hip surgery at 12 months of follow-up. Patients treated with surgery reported greater benefits in symptoms at 12 months compared to PHT, but these benefits are not explained by better hip cartilage metabolism. TRIAL REGISTRATION DETAILS: Australia New Zealand Clinical Trials Registry reference: ACTRN12615001177549 . Trial registered 2/11/2015.

Absent Diurnal Variation in Serum Testosterone in Young Men with Testosterone Deficiency.

PURPOSE: Although healthy young men demonstrate a diurnal pattern of serum testosterone, minimal information is available on diurnal variation in young men with testosterone deficiency. MATERIALS AND METHODS: Blood samples were obtained during a 24-hour period at 8 and 11 a.m., 2, 5 and 8 p.m., and 8 a.m. the following morning. Men were categorized with normal or low testosterone if serum testosterone was greater than 300 ng/dl or less than 300 ng/dl at 8 a.m., respectively. RESULTS: We studied 21 volunteers with a mean age of 31.7 years (range 18 to 49). Testosterone was normal in 11 men and low in 10 and all had a normal luteinizing hormone concentration. The low testosterone group was older (mean age 33.4 vs 30.1 years) with a higher body mass index (mean 32.6 vs 27.5 kg/m2) but the differences were not significant. The highest and lowest overall mean testosterone concentrations were observed at 8 a.m. and 2 p.m., respectively. Mean testosterone levels in the normal group declined between 8 a.m. and 2 p.m. from 423 to 358 ng/dl, representing a 15% decrease (p=0.0003). Mean testosterone in the low testosterone group was 228 ng/dl at 8 a.m. and 218 ng/dl at 2 p.m., representing a 4% decline (p=0.54). Calculated free testosterone paralleled total testosterone with a 14% decrease in the normal testosterone group (p <0.001) and a 5% decrease in the low testosterone group (p=0.52). Two of 11 men in the normal group showed no diurnal variation. No subject with baseline testosterone greater than 400 ng/dl had testosterone less than 300 ng/dl at any time point. CONCLUSIONS: Men with low testosterone failed to show diurnal variation on 24-hour blood sampling. We speculate that similar central mechanisms may be involved in the pathophysiology leading to secondary testosterone deficiency as well as the loss of circadian rhythms.

A randomized controlled noninferiority trial of reduced vs routine opioid prescription after prolapse repair.

BACKGROUND: Given the accelerating opioid crisis in the United States and evidence that patients use fewer opioid tablets than prescribed, surgeons may choose to decrease prescribed quantities. The effect this may have on patient satisfaction with pain control after hospital discharge is unknown. OBJECTIVE: The primary objective of this study was to compare patient satisfaction with postoperative pain control between patients receiving a routine or reduced quantity opioid prescription after prolapse repair. Secondary objectives included a comparison of opioid-related side-effects, the number of opioid tablets used, and the number of excess tablets prescribed between these groups. STUDY DESIGN: This was a single-center, unmasked, 2-arm, randomized controlled noninferiority trial of women who underwent a prolapse repair with a planned overnight hospitalization. Patients were assigned randomly to 1 of 2 study arms: routine (28 tablets of oxycodone 5 mg) or reduced (5 tablets) prescription of opioid tablets. Patients were eligible if they were at least 18 years of age and undergoing a prolapse repair with an anticipated overnight hospital stay. Exclusion criteria included a history of chronic pain, preoperative opioid use, intolerance to study medication, or a score of ≥30 on the Pain Catastrophizing Scale. In addition to their opioid prescription, all patients received multimodal pain medications at discharge. Patients were asked to complete 6 weeks of diaries to record pain and medication use. The primary outcome (patient satisfaction) was collected as part of a postoperative survey completed at patients' routine postoperative visit 6 weeks after surgery. The sample size for noninferiority was calculated at 59 patients per group for a total of 118 patients. RESULTS: One hundred eighteen patients were assigned randomly; the primary outcome was available for 116. The majority of patients were white, postmenopausal, and nonsmokers; the mean age was 62±10.4 years. The most common surgery was a hysterectomy with native tissue repair (n=71; 60%). One hundred ten patients (93%) were satisfied with postoperative pain control. Statistical analysis constructed for noninferiority showed that the difference between the groups was <15% (93% vs 93%; P=.005). Subjects in the reduced arm reported requiring an additional opioid prescription more frequently than in the routine arm (15% vs 2%; P=.01). Patients in the routine arm used more opioid tablets than the reduced arm (median, 3 [interquartile range, 0-14] vs 1 [interquartile range, 0-3]), but overall opioid utilization was low. As such, patients in the routine arm had significantly more unused opioid tablets (median, 26 [interquartile range, 15-28] vs 4 [interquartile range, 2-5]). CONCLUSION: Patient satisfaction with pain control was noninferior in patients who received a reduced quantity of opioid tablets after prolapse repair compared with those who received a routine prescription. A large quantity of excess opioid tablets was seen in both groups. Surgeons should consider prescribing 5-10 opioid tablets after prolapse repair surgery and consider applying these findings to postoperative prescribing after other gynecologic procedures.

Pelvic organ prolapse recurrence in young women undergoing vaginal and abdominal colpopexy.

INTRODUCTION AND HYPOTHESIS: While pelvic organ prolapse (POP) recurrence is believed to increase over time, outcomes of young women who undergo POP surgery are unclear. We hypothesized POP recurrence incidence among women <49 years would be higher after vaginal versus abdominal colpopexy. METHODS: This is a retrospective cohort study with a cross-sectional survey of women 18-49 years who underwent primary POP surgery from January 2003 to September 2013. Patients were identified by CPT codes for vaginal and abdominal colpopexy. POP recurrence was defined as vaginal bulge symptoms, POP retreatment (pessary or surgery) or both. Validated questionnaires were used to assess pelvic floor symptoms, patient satisfaction and improvement. RESULTS: Three hundred thirty-three women met the criteria. Mean age was 43 (+ 5.3) years; 29.1% (97) had an abdominal colpopexy and 70.9% (236) had a vaginal colpopexy. The recurrence incidence overall was 32.0% (31) in the abdominal group and 24.2% (57) in the vaginal group (p = 0.15), with a 10.3% (10) retreatment incidence in the abdominal group and 5.9% (14) in the vaginal group (p = 0.16). Forty-five percent (149) responded to the survey at a median time of 7.9 (3.1-15.2) years since surgery. The overall recurrence incidence in respondents was 13.7% (7) in the abdominal group and 15.3% (15) in the vaginal group (p = 0.80), with a retreatment incidence of 5.9% (3) in the abdominal and 5.2% (5) in the vaginal group (p = 0.85). CONCLUSIONS: One in four young women experienced subjective POP recurrence and/or retreatment, but only 5-10% underwent retreatment. There does not appear to be a difference in the incidence of recurrence between vaginal and abdominal colpopexy.

Long-term pelvic organ prolapse recurrence and mesh exposure following sacrocolpopexy.

INTRODUCTION AND HYPOTHESIS: Large, long-term studies are needed to compare pelvic organ prolapse (POP) recurrence and mesh exposure following all modes of sacrocolpopexy (open, robotic, and laparoscopic). We hypothesized that the prevalence of recurrent POP and mesh exposure does not differ between modes of sacrocolpopexy. METHODS: This is a retrospective cohort study with a cross-sectional, prospective survey. Participants were surveyed regarding complications, retreatments, and symptoms following sacrocolpopexy. Baseline characteristics, POP recurrence, mesh exposure, and survey responses were compared. RESULTS: A total of 709 participants met the criteria. Median time from sacrocolpopexy to last follow-up for all participants was 0.5 years (2 days to 13.4 years). 15.0% experienced recurrent stage 2 or greater POP or underwent retreatment (open 11.7% [95% CI 7.8-17.2%]; robotic 21.1% [95% CI 15.6-27.9%]; laparoscopic 13.8% [95% CI 10.6-17.9%]; p = 0.03). After adjusting for baseline differences there was no significant difference among groups (p = 0.30). 5.3% experienced mesh and/or suture exposure (mesh n = 19, suture n = 10, mesh and suture n = 8) with no significant difference among groups (open 7.7% [95% CI 4.6-12.5%]; robotic 3.6% [95% CI 1.7-7.6%]; laparoscopic 4.9% [95% CI 3.1-7.7%]; p = 0.20). Median time from sacrocolpopexy to survey completion was 6.5 (1.6-13.4) years. 9.2% reported evaluation or treatment for recurrent POP (open 6.3% [95% CI 2.1-16.8%]; robotic 12.5% [95% CI 6.9-21.5%]; laparoscopic 8.5% [5.1-13.8%]; p = 0.44). 6.9% reported evaluation or treatment for mesh exposure (open 6.0% [95% CI 2.1-16.2%]; robotic 3.9% [95% CI 1.3-10.7%]; laparoscopic 8.6% [5.2-13.9%]; p = 0.38). CONCLUSIONS: Objective and patient-reported long-term prevalence of POP recurrence and mesh exposure are low following all modes of sacrocolpopexy.

Does concurrent posterior repair for an asymptomatic rectocele reduce the risk of surgical failure in patients undergoing sacrocolpopexy?

PURPOSE: To determine if a concurrent posterior repair for an asymptomatic rectocele at the time of sacrocolpopexy reduces the incidence of surgical failure. METHODS: This is a retrospective chart review with a cross-sectional follow-up survey of all patients who underwent sacrocolpopexy from 2004 to 2014. Demographic and operative data were collected from the medical record. For the cross-sectional portion, patients were contacted to obtain information on symptoms and retreatment after surgery. In this study, we included patients with an asymptomatic rectocele on examination, defined as Ap or Bp ≥ -1 on POP-Q without defecatory dysfunction, which was defined as constipation based on the Rome III criteria, dyschezia, excessive straining and/or splinting to have a bowel movement. The primary outcome was a composite score of subjective bulge symptoms or retreatment for prolapse. RESULTS: Three hundred forty-four patients met the inclusion criteria: 185 (53.8%) had a sacrocolpopexy only (SCP) and 159 (46.2%) had a concurrent posterior repair (SCP + PR). The composite failure rate was 10.2% (95% CI = 7.4-13.8%), with a 13.5% (25) failure rate in the SCP group compared with 6.3% (10) in the SCP + PR group (p = 0.03). On multivariable logistic regression, the adjusted odds of failure was 2.79 in the SCP compared with the SCP + PR group (CI 1.25-6.23; P = 0.01). The rates of de novo defecatory dysfunction following surgery were low (SCP = 5.6% vs. SCP + PR = 7.5%, p = 0.55). CONCLUSIONS: For patients with asymptomatic rectoceles, a concurrent posterior repair at the time of sacrocolpopexy reduces the odds of composite patient-centered failure without an increased rate of dyspareunia or de novo defecatory dysfunction.

Perioperative adverse events in women undergoing concurrent urogynecologic and gynecologic oncology surgeries for suspected malignancy.

INTRODUCTION AND HYPOTHESIS: This study's objectives were to compare the incidence of adverse events after concurrent urogynecologic and gynecologic oncology surgery to gynecologic oncology surgery alone and to describe the frequency of modification in planned urogynecologic procedures. The authors hypothesized there would be no difference in major complications. METHODS: This was a retrospective matched cohort study of women who underwent concurrent surgery at a large tertiary care center between January 2004 and June 2017. Cohorts were matched by surgeon, surgery route, date, and final pathologic diagnosis. Perioperative data and postoperative adverse events classified by Clavien-Dindo grade were compared. RESULTS: One hundred and eight patients underwent concurrent surgeries, with 216 matched cohorts. Concurrent-case patients were more likely to be older, postmenopausal, have greater vaginal parity, have had preoperative chemotherapy, and have preoperative cardiac or pulmonary disease. There were no differences in intraoperative complications or Dindo grade ≥ 3 adverse events between groups, but there were more grade 2 adverse events in the concurrent cohort (44 vs 19%, p < 0.0001) including postoperative urinary tract infection (UTI) (26 vs 7%, p < 0.0001). Concurrent surgery remained associated with a higher incidence of grade ≥ 2 events on multivariate analysis [odds ratio (OR) 2.5, 95% confidence interval (CI) 1.5-4.2, p = 0.0004). Discharge with a urinary catheter was more frequent after concurrent cases (35 vs 2%, p < 0.0001). Planned urogynecologic procedures were modified in 10% (n = 11) of cases. CONCLUSIONS: Concurrent surgeries have an increased incidence of minor but not serious perioperative adverse events. One in ten planned urogynecologic procedures is either modified or abandoned during combined surgeries.

Route of hysterectomy during minimally invasive sacrocolpopexy does not affect postoperative outcomes.

INTRODUCTION AND HYPOTHESIS: Hysterectomy can be performed during sacrocolpopexy, but there are limited studies comparing the effect of route of hysterectomy on adverse events. We hypothesized there would be no difference in adverse events or patient-reported outcomes in women who underwent minimally invasive sacrocolpopexy with either vaginal or supracervical hysterectomy. METHODS: This was a retrospective chart review with a cross-sectional survey component sent to all consenting patients. Patients were identified by procedure code for sacrocolpopexy and hysterectomy from January 2005 to June 2016. RESULTS: Of the 161 subjects meeting the inclusion criteria, 116 underwent supracervical and 45 vaginal hysterectomy. Overall incidence of perioperative adverse events was low. Vaginal hysterectomy cases were faster (276 vs. 324 min, p < 0.001) and had higher rates of postoperative stress incontinence (22 vs. 9%, p = 0.03). Thirty-one (19%) of all subjects had recurrent prolapse; 10 (6%) underwent repeat surgery. Three (1%) subjects had a mesh exposure (no difference between groups), all treated conservatively. Ninety-six (60%) subjects responded to the survey with a median follow-up of 56 (9-134) months. Ninety-one percent (87) of respondents reported being better since surgery, and 91% (87) reported they would choose the surgery again. Twenty-eight percent (27) reported a surgery-related complication including pain, urinary and bowel symptoms; 8% (8) reported evaluation for recurrent prolapse symptoms, all treated conservatively; 4% (4) of respondents reported a mesh exposure. CONCLUSIONS: Incidence of adverse events is low and not different between patients undergoing minimally invasive sacrocolpopexy with concurrent supracervical or vaginal hysterectomy. One in three patients report pelvic floor symptoms postoperatively, but long-term satisfaction is high.

Use of Vessel-Sealing Devices during Vaginal Hysterectomy.

STUDY OBJECTIVE: To demonstrate the proper use of vessel-sealing devices during vaginal hysterectomy. DESIGN: Educational video (Canadian Task Force classification level III). SETTING: University hospital. INTERVENTION: The video reviews the principles on the use of energy in minimally invasive surgery. We focus on how vessel-sealing devices function and the benefits of their use in difficult vaginal hysterectomy. The video explains the 2 major types of complications, inadequate vessel sealing and undesired thermal injury, and demonstrates techniques to avoid these complications. MEASUREMENTS AND MAIN RESULTS: Laboratory, intraoperative, and cadaveric recordings demonstrate proper use and the complications that may arise in the setting of improper use. CONCLUSION: Vessel-sealing devices may be a useful tool for surgeons performing vaginal hysterectomy. This video demonstrates their use and underlines the importance of understanding the principles of energy devices and their proper usage in surgery.

Increasing dietary EPA and DHA influence estimated fatty acid desaturase activity in systemic organs which is reflected in the red blood cell in mice.

Delta-5 (D5D) and delta-6 (D6D) desaturase are key enzymes in fatty acid (FA) metabolism. Dietary eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may alter tissue FA composition via D5D and D6D. The purpose was to determine the relationship between dietary EPA + DHA, estimated desaturase activities of various tissues and the reflection of desaturase activity in the red blood cell (RBC). Mice were fed diets with increasing percent of energy from EPA + DHA. Phospholipid FA composition of heart, muscle, spleen, lung, adipose tissues and RBC were analysed. D5D and D6D enzyme activity estimates (EAE) were calculated as the ratio of 20:4/20:3 and 20:3/18:2, respectively. D5D EAE decreased in all tissues, except muscle, with increasing dietary EPA + DHA. RBC D5D EAE positively correlated with D5D EAE in all tissues. RBC D6D EAE positively correlated with muscle and inversely correlated with adipose D6D EAE. Our findings suggest differential influence of dietary EPA + DHA upon tissue desaturase activities.