Risk Factors Associated With Postoperative Mortality Among COVID-19 Positive Patients: Results of 3027 Operations and Procedures.

OBJECTIVE: To investigate the predictors of postoperative mortality in coronavirus disease 2019 (COVID-19)-positive patients. BACKGROUND: COVID-19-positive patients have more postoperative complications. Studies investigating the risk factors for postoperative mortality in COVID-19-positive patients are limited. METHODS: COVID-19-positive patients who underwent surgeries/procedures in Cleveland Clinic between January 2020 and March 2021 were identified retrospectively. The primary outcome was postoperative/procedural 30-day mortality. Secondary outcomes were length of stay, intensive care unit admission, and 30-day readmission. RESULTS: A total of 2543 patients who underwent 3027 surgeries/procedures were included. Total 48.5% of the patients were male. The mean age was 57.8 (18.3) years. A total of 71.2% had at least 1 comorbidity. Total 78.7% of the cases were elective. The median operative time was 94 (47.0-162) minutes and mean length of stay was 6.43 (13.4) days. Postoperative/procedural mortality rate was 4.01%. Increased age [odds ratio (OR): 1.66, 95% CI, 1.4-1.98; P <0.001], being a current smoker [2.76, (1.3-5.82); P =0.008], presence of comorbidity [3.22, (1.03-10.03); P =0.043], emergency [6.35, (3.39-11.89); P <0.001] and urgent versus [1.78, (1.12-2.84); P =0.015] elective surgery, admission through the emergency department [15.97, (2.00-127.31); P =0.009], or inpatient service [32.28, (7.75-134.46); P <0.001] versus outpatients were associated with mortality in the multivariable analysis. Among all specialties, thoracic surgery [3.76, (1.66-8.53); P =0.002] had the highest association with mortality. Total 17.5% of the patients required intensive care unit admission with increased body mass index being a predictor [1.03, (1.01-1.05); P =0.005]. CONCLUSIONS: COVID-19-positive patients have higher risk of postintervention mortality. Risk factors should be carefully evaluated before intervention. Further studies are needed to understand the impact of pandemic on long-term surgical/procedural outcomes.

Methods for the defining mechanisms of anterior vaginal wall descent (DEMAND) study.

INTRODUCTION AND HYPOTHESIS: The protocol and analysis methods for the Defining Mechanisms of Anterior Vaginal Wall Descent (DEMAND) study are presented. DEMAND was designed to identify mechanisms and contributors of prolapse recurrence after two transvaginal apical suspension procedures for uterovaginal prolapse. METHODS: DEMAND is a supplementary cohort study of a clinical trial in which women with uterovaginal prolapse randomized to (1) vaginal hysterectomy with uterosacral ligament suspension or (2) vaginal mesh hysteropexy underwent pelvic magnetic resonance imaging (MRI) at 30-42 months post-surgery. Standardized protocols have been developed to systematize MRI examinations across multiple sites and to improve reliability of MRI measurements. Anatomical failure, based on MRI, is defined as prolapse beyond the hymen. Anatomic measures from co-registered rest, maximal strain, and post-strain rest (recovery) sequences are obtained from the "true mid-sagittal" plane defined by a 3D pelvic coordinate system. The primary outcome is the mechanism of failure (apical descent versus anterior vaginal wall elongation). Secondary outcomes include displacement of the vaginal apex and perineal body and elongation of the anterior wall, posterior wall, perimeter, and introitus of the vagina between (1) rest and strain and (2) rest and recovery. RESULTS: Recruitment and MRI trials of 94 participants were completed by May 2018. CONCLUSIONS: Methods papers which detail studies designed to evaluate anatomic outcomes of prolapse surgeries are few. We describe a systematic, standardized approach to define and quantitatively assess mechanisms of anatomic failure following prolapse repair. This study will provide a better understanding of how apical prolapse repairs fail anatomically.

Cystoscopy at the time of benign hysterectomy: a decision analysis.

BACKGROUND: Gynecologists debate the optimal use for intraoperative cystoscopy at the time of benign hysterectomy. Although adding cystoscopy leads to additional up-front cost, it may also enable intraoperative detection of a urinary tract injury that may otherwise go unnoticed. Prompt injury detection and intraoperative repair decreases morbidity and is less costly than postoperative diagnosis and treatment. Because urinary tract injury is rare and not easily studied in a prospective fashion, decision analysis provides a method for evaluating the cost associated with varying strategies for use of cystoscopy. OBJECTIVE: The objective of the study was to quantify costs of routine cystoscopy, selective cystoscopy, or no cystoscopy with benign hysterectomy. STUDY DESIGN: We created a decision analysis model using TreeAge Pro. Separate models evaluated cystoscopy following abdominal, laparoscopic/robotic, and vaginal hysterectomy from the perspective of a third-party payer. We modeled bladder and ureteral injuries detected intraoperatively and postoperatively. Ureteral injury detection included false-positive and false-negative results. Potential costs included diagnostics (imaging, repeat cystoscopy) and treatment (office/emergency room visits, readmission, ureteral stenting, cystotomy closure, ureteral reimplantation). Our model included costs of peritonitis, urinoma, and vesicovaginal/ureterovaginal fistula. Complication rates were determined from published literature. Costs were gathered from Medicare reimbursement as well as published literature when procedure codes could not accurately capture additional length of stay or work-up related to complications. RESULTS: From prior studies, bladder injury incidence was 1.75%, 0.93%, and 2.91% for abdominal, laparoscopic/robotic, and vaginal hysterectomy, respectively. Ureteral injury incidence was 1.61%, 0.46%, and 0.46%, respectively. Hysterectomy costs without cystoscopy varied from $884.89 to $1121.91. Selective cystoscopy added $13.20-26.13 compared with no cystoscopy. Routine cystoscopy added $51.39-57.86 compared with selective cystoscopy. With the increasing risk of injury, selective cystoscopy becomes cost saving. When bladder injury exceeds 4.48-11.44% (based on surgical route) or ureteral injury exceeds 3.96-8.95%, selective cystoscopy costs less than no cystoscopy. Therefore, if surgeons estimate the risk of injury has exceeded these thresholds, cystoscopy may be cost saving. However, for routine cystoscopy to be cost saving, the risk of bladder injury would need to exceed 20.59-47.24% and ureteral injury 27.22-37.72%. Model robustness was checked with multiple 1-way sensitivity analyses, and no relevant thresholds for model variables other than injury rates were identified. CONCLUSION: While routine cystoscopy increased the cost $64.59-83.99, selective cystoscopy had lower increases ($13.20-26.13). These costs are reduced/eliminated with increasing risk of injury. Even a modest increase in suspicion for injury should prompt selective cystoscopy with benign hysterectomy.

Hysteropexy: Evidence and Insights.

Uterovaginal prolapse may be treated with or without concomitant hysterectomy. Many patients express interest in uterine-sparing prolapse procedures, for which there are increasing evidence available regarding techniques and outcomes. Uterine-sparing procedures to treat uterovaginal prolapse require a unique set of surgical considerations including uterine abnormalities, possibility of occult malignancy, and future pregnancy. Data, including randomized controlled trials, support the use of sacrospinous hysteropexy. Other prospective trials detailing outcomes following uterosacral hysteropexy, mesh augmented sacrospinous hysteropexy, and sacrohysteropexy are also encouraging.

Increasing Utilization of Minimally Invasive Hysterectomy.

Once the decision to perform a hysterectomy has been made, the type and route of hysterectomy must be chosen, and efforts made to accomplish the surgery as safely as possible. Hysterectomy can be performed vaginally, abdominally with laparoscopic or robotic assistance, or open. The main goal of gynecologic surgeons should be to lower the rate of open abdominal hysterectomy and increase use of both vaginal and laparoscopic hysterectomy in their patients. We discuss efforts to accomplish a greater use of minimally invasive hysterectomy.

Assessing ureteral patency using 10% dextrose cystoscopy fluid: evaluation of urinary tract infection rates.

BACKGROUND: Intravenous indigo carmine has routinely been used to confirm ureteral patency after urogynecologic surgery. Recent discontinuation of the dye has altered clinical practice. In the absence of indigo carmine, we have used 10% dextrose in sterile water (D10) as cystoscopic fluid to evaluate ureteral patency. Glucosuria has been associated with urinary tract infection (UTI) in vivo and significantly enhanced bacterial growth in vitro. The concern is that the use of D10 would mimic a state of glucosuria albeit transient and increase the risk of postoperative UTI. OBJECTIVES: The objectives of this study were to compare the rates of postoperative UTI and lower urinary tract (LUT) injuries between patients who underwent instillation of D10 vs normal saline at the time of intraoperative cystoscopy after urogynecological surgery. STUDY DESIGN: This was a retrospective cohort study of all women who underwent cystoscopic evaluation of ureteral patency at the time of urogynecological surgery from May through December 2014 at a tertiary care referral center. We compared patients who received D10 cystoscopy fluid vs those who used normal saline. Outcomes included UTI and diagnosis of ureteral or LUT injuries. UTI was diagnosed according to Centers for Disease Control and Prevention guidelines by symptoms alone, urine dipstick, urinalysis, or urine culture. Descriptive statistics compared the rates of UTI between the 2 groups, and a multivariable model was fit to the data to control for potential confounders and significant baseline differences between the groups. RESULTS: A total of 303 women were included. D10 was used in 113 cases and normal saline (NS) was used in 190. The rate of UTI was higher in the D10 group than the NS group: 47.8% (95% confidence interval [CI], 38.3-57.4) vs 25.9% (95% CI, 19.8-32.8, P < .001). After adjusting for age, pelvic organ prolapse stage, use of perioperative estrogen, days of postoperative catheterization, menopausal status, diabetes mellitus, and history of recurrent UTI, the UTI rate remained significantly higher with the use of D10 (adjusted odds ratio, 3.4 [95% CI, 1.6-7.5], P = .002) compared with NS. Overall, 3 cases of transient ureteral kinking (1.0%) and one cystotomy (0.3%) were identified intraoperatively. However, ureteral and LUT injuries were not different between groups. No unidentified injuries presented postoperatively. CONCLUSION: Although the use of D10 cystoscopy fluid has been successful in identifying ureteral patency in the absence of indigo carmine, it is associated with an increased rate of postoperative UTI compared with NS.

Does prolapse equal hysterectomy? The role of uterine conservation in women with uterovaginal prolapse.

Hysterectomy has historically been a mainstay in the surgical treatment of uterovaginal prolapse, even in cases in which the removal of the uterus is not indicated. However, uterine-sparing procedures have a long history and are now becoming more popular. Whereas research on these operations is underway, hysteropexy for the treatment of prolapse is not as well studied as hysterectomy-based repairs. Compared with hysterectomy and prolapse repair, hysteropexy is associated with a shorter operative time, less blood loss, and a faster return to work. Other advantages include maintenance of fertility, natural timing of menopause, and patient preference. Disadvantages include the lack of long-term prolapse repair outcomes and the need to continue surveillance for gynecological cancers. Although the rate of unanticipated abnormal pathology in this population is low, women who have uterine abnormalities or postmenopausal bleeding are not good candidates for uterine-sparing procedures. The most studied approaches to hysteropexy are the vaginal sacrospinous ligament hysteropexy and the abdominal sacrohysteropexy, which have similar objective and subjective prolapse outcomes compared with hysterectomy and apical suspension. Pregnancy and delivery have been documented after vaginal and abdominal hysteropexy approaches, although very little is known about outcomes following parturition. Uterine-sparing procedures require more research but remain an acceptable option for most patients with uterovaginal prolapse after a balanced and unbiased discussion reviewing the advantages and disadvantages of this approach.

Minimally Invasive Hysterectomy: An Analysis of Different Techniques.

To compare conventional minimally invasive (MIS) approaches and newer technology approaches in women undergoing hysterectomy for benign disease. PubMed was searched for all pertinent randomized-controlled trials (RCTs). Selected outcomes were compared using standard meta-analysis methods. Three RCTs compared conventional MIS to robotic-assisted hysterectomy and 5 RCTs compared conventional laparoscopy to single-incision hysterectomy. There were no significant differences in outcomes. A subanalysis comparing conventional to robotic-assisted laparoscopy found an association between conventional laparoscopy and shorter operative time. Newer technology approaches do not confer an advantage over conventional MIS approaches in women undergoing hysterectomy for benign disease.

Hysterectomy Versus Hysteropexy at the Time of Native Tissue Pelvic Organ Prolapse Repair: A Cost-Effectiveness Analysis.

OBJECTIVE: The aim of the study was to determine whether a hysterectomy at the time of native tissue pelvic organ prolapse repair is cost-effective for the prevention of endometrial cancer. METHODS: We created a decision analysis model using TreeAge Pro. We modeled prolapse recurrence after total vaginal hysterectomy with uterosacral ligament suspension (TVH-USLS) versus sacrospinous ligament fixation hysteropexy (SSLF-HPXY). We modeled incidence and diagnostic evaluation of postmenopausal bleeding, including risk of endometrial pathology and diagnosis or death from endometrial cancer. Modeled costs included those associated with the index procedure, subsequent prolapse repair, endometrial biopsy, pelvic ultrasound, hysteroscopy, dilation and curettage, and treatment of endometrial cancer. RESULTS: TVH-USLS costs US $587.61 more than SSLF-HPXY per case of prolapse. TVH-USLS prevents 1.1% of women from experiencing postmenopausal bleeding and its diagnostic workup. It prevents 0.95% of women from undergoing subsequent major surgery for the treatment of either prolapse recurrence or suspected endometrial cancer. Using our model, it costs US $2,698,677 to prevent one cancer death by performing TVH-USLS. As this is lower than the value of a statistical life, it is cost-effective to perform TVH-USLS for cancer prevention. Multiple 1-way sensitivity analyses showed that changes to input variables would not significantly change outcomes. CONCLUSIONS: TVH-USLS increased costs but reduced postmenopausal bleeding and subsequent major surgery compared with SSLF-HPXY. Accounting for these differences, TVH-USLS was a cost-effective approach for the prevention of endometrial cancer. Uterine preservation/removal at the time of prolapse repair should be based on the woman's history and treatment priorities, but cancer prevention should be one aspect of this decision.

Delineation of 15q13.3 microdeletions.

The increasing use of array-comparative genomic hybridization (array-CGH) to identify copy number variations (CNVs) in patients with developmental delay (DD), mental retardation and/or dysmorphic features has allowed the recent recognition of numerous genomic imbalances, including the 15q13.3 microdeletion. Patients with this microdeletion generally present with relatively consistent breakpoints at BP4 and BP5, which include the CHRNA7 gene. About 100 index cases have been reported since the first publication in 2008. This large number of patients ascertained through highly variable samples has been necessary to describe the full phenotypic spectrum of this microdeletion, ranging from mental retardation with dysmorphic features, epilepsy, neuropsychiatric disturbances with or without cognitive impairment to complete absence of anomalies. Here, we describe a collaborative study reporting a new cohort of 12 index patients and 13 relatives carrying a heterozygous BP4-BP5 microdeletion out of a series of 4625 patients screened by array-CGH for DD. We confirm the clinical expressivity of the disease as well as the incomplete penetrance in seven families. We showed through a review of the literature that males are more likely to be symptomatic. Sequence analysis of CHRNA7 yielded no data to support the unmasking of recessive variants as a cause of phenotypic variability. We also report the first patient carrying a 15q13.3 homozygous microdeletion inherited from both parents. He had severe epileptic encephalopathy with retinopathy, autistic features and choreoathetosis. Besides the classical approximately 1.5 Mb BP4-BP5 microdeletion, we also describe three index patients and two relatives with a smaller 500 kb microdeletion, including the CHRNA7 gene.

A retrospective study by oligonucleotide array-CGH analysis in 50 fetuses with multiple malformations.

OBJECTIVE: To retrospectively define the frequency and the nature of submicroscopic chromosomal imbalances among fetuses with multiple congenital anomalies (MCA). METHODS: We used oligonucleotide arrays to perform comparative genomic hybridization after termination of pregnancy in 50 polymalformated fetuses with a normal karyotype. These fetuses presented with at least three significant malformations (42 cases) or a severe brain anomaly (eight cases). RESULTS: We identified a deleterious copy number variation (CNV) in five fetuses (10%). De novo genomic imbalances identified in this study consisted of a 6qter deletion in a fetus with brain and renal malformations, a mosaicism for a 8p tetrasomy in a fetus with agenesis of corpus callosum, growth retardation, mild facial dysmorphic features, and vertebral anomalies, a 17p13.3 deletion in a fetus with a complex brain malformation, and a partial 11p trisomy in a fetus with severe growth retardation and oligoamnios. In one case, we identified a partial 17q trisomy resulting from malsegregation of a cryptic-balanced translocation. CONCLUSIONS: This study shows that array comparative genomic hybridization (aCGH) is particularly effective for identifying the molecular basis of the disease phenotype in fetuses with multiple anomalies. Our study should help to define clinical relevant regions that would need to be included in targeted arrays designed for prenatal testing.

Aberrant GRIA3 transcripts with multi-exon duplications in a family with X-linked mental retardation.

Investigation of chromosomal rearrangements in patients with mental retardation (MR) is particularly informative in the search for novel genes involved in MR. We report on a family with a genomic duplication at Xq25 identified by oligo array-CGH. Further characterization showed a partial tandem duplication of GRIA3 extending from exon 1 to exon 12. This duplication is present in two brothers with MR and on one allele in their sister with normal phenotype and completely skewed X-chromosome inactivation. The duplication is inherited from the mother, whose cognitive level is low and X-chromosome inactivation is random. This is the second family with partial duplication of GRIA3 associated with MR. GRIA3 expression studies in our case demonstrated a new mechanism for GRIA3 dysfunction with the presence of aberrant GRIA3 transcripts carrying multi-exon duplications leading to a frameshift. Our study gives additional support to the implication of GRIA3 in X-linked MR.

Variation of the obturator foramen and pubic arch of the female bony pelvis.

OBJECTIVE: The purpose of this study was to determine dimensions of the obturator foramen and pubic arch of the female pelvis and to assess for variability. STUDY DESIGN: Ninety-six female pelvises were selected from the Cleveland Natural History Museum. The obturator foramen area, pubic arch angle, pubic ramus, pubic symphysis, and anterior urogenital triangle area were measured. Linear regression was used to evaluate independent associations. RESULTS: There was considerable variability of the bony architecture. The mean obturator foramen area was 12.2 +/- 2.1 cm(2) (range, 7.38-18.22 cm(2)). After controlling for height, the pubic ramus width, pubic symphysis length, and interobturator foramina distance were significantly greater in European American women compared with African American women. Obturator foramen area increased with increasing height (P = .0008) but was not associated with race. CONCLUSION: There is considerable variability in the bony architecture of the obturator foramen and pubic arch of the female pelvis. Race and height may account for some of these variabilities.

American Urogynecologic Society Best-Practice Statement on Evaluation of Obstructed Defecation.

The symptoms of constipation and obstructed defecation are common in women with pelvic floor disorders. Female pelvic medicine and reconstructive surgery specialists evaluate and treat women with these symptoms, with the initial consultation often occurring when a woman has the symptom or sign of posterior compartment pelvic organ prolapse (including rectocele or enterocele) or if a rectocele or enterocele is identified in pelvic imaging. This best-practice statement will review techniques used to evaluate constipation and obstructed defecation, with a special focus on the relationship between obstructed defecation, constipation, and pelvic organ prolapse.

Homozygous Truncating Intragenic Duplication in TUSC3 Responsible for Rare Autosomal Recessive Nonsyndromic Intellectual Disability with No Clinical or Biochemical Metabolic Markers.

Intellectual disability (ID), which affects around 2-3% of the general population, is classically divided into syndromic and nonsyndromic forms, with several modes of inheritance. Nonsyndromic autosomal recessive ID (NS-ARID) appears extremely heterogeneous with numerous genes identified to date, including inborn errors of metabolism. The TUSC3 gene encodes a subunit of the endoplasmic reticulum (ER)-bound oligosaccharyltransferase complex, which mediates a key step of N-glycosylation. To date, only five families with NS-ARID and TUSC3 mutations or rearrangements have been reported in the literature. All patients had speech delay, moderate-to-severe ID, and moderate facial dysmorphism. Microcephaly was noted in one third of patients, as was short stature. No patients had congenital malformation except one patient with unilateral cryptorchidism. Glycosylation analyses of patients' fibroblasts showed normal N-glycan synthesis and transfer. We present a review of the 19 patients previously described in the literature and report on a sixth consanguineous family including two affected sibs, with intellectual disability, unspecific dysmorphic features, and no additional malformations identified by high-resolution array-CGH. A homozygous truncating intragenic duplication of the TUSC3 gene leading to an aberrant transcript was detected in two siblings. This observation, which is the first reported case of TUSC3 homozygous duplication, confirms the implication of TUSC3 in NS-ARID and the power of the high-resolution array-CGH in identifying intragenic rearrangements of genes implicated in nonsyndromic ID and rare diseases.

Separation of two different populations of granulocytes of Nereis diversicolor (Annelida) by selective agglutination with lectins.

Methods for obtaining coelomocyte populations from Nereis diversicolor by selective agglutination have been developed. Two main types of granulocytes have been successfully separated and recovered using respectively galactose and fucose specific lectins. 85 to 90% of the separated cells were viable.

Distribution and nature of membrane receptors for different plant lectins in the coelomocyte subpopulations of the Annelida Nereis diversicolor.

Studies on membrane receptors have been performed on the Nereis coelomocytes using various lectins. In the agglutination assay, only LCA and WGA appeared nonreactive. Fluorescent lectins showed the poor reactivity of the eleocytes and the diversity of the receptors according to the granulocyte types. Types I-granulocytes reacted only with Con A. Type II-granulocyte membrane contained mannose and galactose receptors (reactivity with Con A, PNA and SBA). The type III-granulocyte membrane revealed the presence of mannose and fucose receptors (UEA, AAA). Electron microscope investigations with HRP-DAB or mannosyl labelled Con A, RCAI and LTA have confirmed the distribution of the membrane receptors.