PADUA score as a predictor for pulmonary embolism: a potential strategy for reducing unnecessary imaging.

An objective tool that is easy to integrate with an electronic medical record may help reduce unnecessary imaging for diagnosing a pulmonary embolism (PE). In this study, we assess the PADUA score in stratifying patients based on their risk of a PE. We reviewed charts of patients that underwent a computed tomography pulmonary angiogram (CT-PA) between January 2014 and September 2015 at our institution. Patient demographics including gender, age, race, and variables of the PADUA score were collected. The primary outcome was a positive CT-PA for a PE. Univariate and multivariate analysis was performed to derive predictors for a positive CT-PA. A receiver operator curve was calculated for the PADUA score and an optimal cutoff was calculated. Diagnostic test statistics were performed. Our study included 1067 patients. Of these, 185 (17.3%) had a PE. These patients tended to be older (64.3 SD 15.9 vs. 59.7 years SD 17.4, p < 0.01), have a higher proportion of Black patients (38.9% vs. 31.9%, p = 0.03), have a higher median [IQR] PADUA score (4.0 [3-6] vs. 3.0 [1-4], p < 0.01), and a higher rate of a DVT/PE history (30.3% vs. 5.2%, p < 0.01). Independent predictors included a DVT/PE history (OR: 7.65, 95% CI 4.89-12.0, p < 0.01), limited mobility (OR: 1.47, 95% CI 1.01-2.14, p = 0.046), and age 70 or greater (OR: 1.47, 95% CI 1.03-2.11, p = 0.03). The PADUA score had an AUC of 0.64 (95% CI 0.60-0.69, p = 0.046). The optimal cutoff was 4 and the sensitivity and specificity were 57.3% and 66.8%, respectively. The positive predictive and negative predictive values were 22.6% and 88.2%, respectively. The PADUA is a possible tool to stratify patients prior to performing a CT-PA. By using the score to guide management, we may be able to reduce unnecessary imaging through the implementation of the score in an EMR system. Further prospective research is warranted.

Accumulating deficits model of frailty and postoperative mortality and morbidity: its application to a national database.

BACKGROUND: Frailty has been associated with a number of adverse outcomes. One model of frailty is the "accumulating deficits" concept. We hypothesized that this model can be applied to a national database to predict postoperative mortality and morbidity. METHODS: We accessed the National Surgical Quality Improvement Program (NSQIP) Participant Use File for the years 2005-2009 for inpatient surgical patients who had undergone cardiac, general, gynecologic, neurosurgical, orthopedic, otolaryngologic, plastic, general thoracic, urologic, and vascular surgical operations. Items of the Canadian Study of Health and Aging-frailty index (FI) were compared with preoperative clinical variables recorded by NSQIP. Eleven items were matched, and a simplified FI, defined as the number of deficits present divided by the number of deficits matched, using the number of items present was determined for each patient. The 30-d morbidity and mortality were correlated to this simplified FI and stratified by operation complexity based on the operation's relative value units. RESULTS: Of the 971,434 patients identified, there was a stepwise increase in risk of both mortality (odds ratios ranged from 1.33 to 46.33) and morbidity (odds ratios ranged from 1.24 to 3.36) for each unit increase in FI for each specialty and each level of operation complexity (trend of odds P value <0.0001 for all comparisons). CONCLUSIONS: A simple 11-point FI correlated with both mortality and morbidity for all surgical specialties. This may be applicable to other national databases and clinical practice.

Nonreplication of the type 5 17beta-hydroxysteroid dehydrogenase gene association with polycystic ovary syndrome.

CONTEXT: Increased androgen production is a primary feature of polycystic ovary syndrome (PCOS) and appears to be an inherited trait. The gene for the steroidogenic enzyme type 5 17beta hydroxysteroid dehydrogenase (HSD17B5) was implicated as a candidate for the hyperandrogenemia of PCOS by a previous study that demonstrated an association of a single nucleotide polymorphism (SNP) in the promoter of this gene with PCOS. OBJECTIVE: The objective of the study was to replicate the previous report of association between the HSD17B5 gene and PCOS risk by genotyping the promoter SNP (as well as other SNPs in the region to provide improved coverage of the gene) in a large, well-characterized cohort suitable for replication study. DESIGN: Women with and without PCOS were genotyped for five SNPs in HSD17B5. SNPs and haplotypes were determined and tested for association with PCOS risk and phenotypic markers of PCOS. SETTING: Subjects were recruited from the reproductive endocrinology clinic at the University of Alabama at Birmingham; controls were recruited from the surrounding community. Genotyping took place at Cedars-Sinai Medical Center in Los Angeles. PARTICIPANTS: Participants included 287 white women with PCOS and 187 white controls. MAIN MEASUREMENTS: HSD17B5 genotype, PCOS risk, and testosterone levels were measured. RESULTS: No SNP or haplotype was significantly associated with PCOS risk, testosterone, or any of the traits tested. CONCLUSIONS: These data suggest that polymorphisms in the HSD17B5 gene are not associated with PCOS risk or elevated testosterone as previously reported.

Association of androgen receptor CAG repeat polymorphism and polycystic ovary syndrome.

CONTEXT: Genetically determined heightened androgen sensitivity may influence the phenotype of polycystic ovary syndrome (PCOS). To date, studies of the androgen receptor exon 1 polymorphic CAG repeat have produced conflicting results in PCOS. OBJECTIVE: We tested the hypothesis that a lower number of CAG repeats is associated with increased odds of PCOS. We also compared X-chromosome inactivation between cases and controls. DESIGN: Women with and without PCOS were genotyped for the CAG repeat and assessed for X-chromosome methylation. Association analyses were performed. SETTING: Subjects were recruited from the reproductive endocrinology clinic at the University of Alabama at Birmingham; controls were recruited from the surrounding community. Genotyping took place at Cedars-Sinai Medical Center in Los Angeles. PARTICIPANTS: Participants included 330 women with PCOS and 289 controls (77% white, 23% black). MAIN MEASUREMENTS: Androgen receptor genotype, X-chromosome methylation, and phenotyping for PCOS were measured. RESULTS: A smaller biallelic mean of CAG repeats was associated with increased odds of PCOS. X-chromosome inactivation was not different comparing cases with controls; however, in the subset with nonrandom inactivation, the chromosome bearing the shorter CAG allele was preferentially active in PCOS women. CONCLUSIONS: Association of shorter CAG repeats with PCOS is consistent with in vitro functional studies demonstrating higher activity of androgen receptors expressed from alleles with fewer CAG repeats, suggesting inherited alteration in androgen sensitivity may contribute to PCOS. In some women, such heightened sensitivity may also result from preferential expression of androgen receptors with shorter alleles. Thus, genetic and epigenetic changes may be involved in the pathogenesis of PCOS.

Laparoscopic Conversion of a Vertical Banded Gastroplasty to a Sleeve Gastrectomy in a Morbidly Obese Patient with a Complicated Medical History.

PURPOSE: We present our technique for performing a laparoscopic conversion of vertical banded gastroplasty (VBG) to sleeve gastrectomy (SG) in a morbidly obese patient. MATERIALS AND METHODS: A 58-year-old female with history of hypertension, diabetes, and morbid obesity (BMI 41). She had initially undergone an open VBG (BMI 58) and cholecystectomy (2002) and subsequently underwent two laparotomies for small bowel obstructions and two open ventral hernia repairs. She initially presented for repair of her large ventral hernia; however, to minimize the risk of recurrence and complications during the abdominal wall reconstruction, she was referred first for surgical weight loss and scheduled for laparoscopic conversion of VBG to gastric bypass. RESULTS: Initial access was obtained using an Optiview trocar and significant amount of adhesions were noted to the omentum, abdominal wall, stomach, and liver, including dense interloop adhesions precluding us from proceeding with a gastric bypass, our initial choice for conversion. Adhesions were taken down with a LigaSure device and sharp dissection. The previous vertical staple line was identified endoscopically. The banded area was narrowed, but intact, so the Marlex ring was divided to allow space for the new SG staple line. Stapler firings were oriented to divide the stomach parallel to the lesser curve and through the middle of the prior EEA opening, then up towards the Angle of His. Using Endo Stitch, the entire staple line was oversewn in a Lembert fashion. There was no evidence of narrowing on repeat endoscopy and leak test was negative. CONCLUSIONS: This video demonstrates the feasibility and safety of one-step laparoscopic conversion of vertical banded gastroplasty to sleeve gastrectomy.

Genes for enzymes regulating dehydroepiandrosterone sulfonation are associated with levels of dehydroepiandrosterone sulfate in polycystic ovary syndrome.

CONTEXT: The adrenal androgen (AA) metabolite dehydroepiandrosterone sulfate (DHEAS) is often elevated in women with polycystic ovary syndrome (PCOS); AA excess in PCOS appears to be, in part, a heritable trait. Dehydroepiandrosterone (DHEA) sulfonation is controlled by the enzymes DHEA sulfotransferase (SULT2A1) and steroid sulfatase (STS). Polymorphisms in these genes have not been evaluated as modulators of DHEAS level in PCOS. OBJECTIVE: The aim was to test the hypothesis that variants in the SULT2A1 and STS genes are associated with DHEAS levels in women with PCOS. DESIGN: Women with and without PCOS were genotyped for seven single nucleotide polymorphisms (SNPs) in SULT2A1 and seven SNPs in STS. SNPs and haplotypes were determined and tested for association with DHEAS. SETTING: Subjects were recruited from the reproductive endocrinology clinic at the University of Alabama at Birmingham; controls were recruited from the surrounding community. Genotyping took place at Cedars-Sinai Medical Center in Los Angeles. PARTICIPANTS: A total of 287 white women with PCOS and 187 controls participated in the study. MAIN MEASUREMENTS: SULT2A1 and STS genotype and DHEAS levels were measured. RESULTS: In women with PCOS, SNP rs182420 in SULT2A1 was associated with DHEAS (P = 0.0035). Two haplotypes carrying the minor allele of rs182420 were also associated with DHEAS (P = 0.04 each). Variants within STS were not associated with DHEAS level. No associations were observed in control women. CONCLUSION: This study presents genetic evidence suggesting a potential role of SULT2A1, but not STS, in the inherited AA excess of PCOS.

Variants in the 5alpha-reductase type 1 and type 2 genes are associated with polycystic ovary syndrome and the severity of hirsutism in affected women.

CONTEXT: Despite the importance of dihydrotestosterone in androgen action, polymorphisms in the genes for the two isoforms of 5alpha-reductase (SRD5A1 and SRD5A2) have not been evaluated as risk factors for polycystic ovary syndrome (PCOS). OBJECTIVE: The objective of the study was to test the hypothesis that haplotypes in the SRD5A1 and SRD5A2 genes are risk factors for PCOS and the severity of hirsutism in affected women. DESIGN: PCOS and control subjects were genotyped for seven single-nucleotide polymorphisms in SRD5A1 and eight single-nucleotide polymorphisms in SRD5A2. Haplotypes were determined and tested for association with PCOS diagnosis and component phenotypes. SETTING: Subjects were recruited from the reproductive endocrinology clinic at the University of Alabama at Birmingham; control subjects were recruited from the general surrounding community. Genotyping took place at Cedars-Sinai Medical Center in Los Angeles. PARTICIPANTS: A total of 287 White women with PCOS and 187 controls participated. MAIN MEASUREMENTS: SRD5A1 and SRD5A2 genotype, quantitative hirsutism score, and hormonal and metabolic phenotypes were assessed. RESULTS: Haplotypes within both genes were associated with PCOS risk. The Leu allele of the Val89Leu variant in SRD5A2 was associated with protection against PCOS; this allele is known to modestly reduce 5alpha-reductase activity. Haplotypes in SRD5A1 but not SRD5A2 were also associated with the degree of hirsutism in affected women. CONCLUSIONS: This study presents genetic evidence suggesting an important role of both isoforms of 5alpha-reductase in the pathogenesis of PCOS. That only SRD5A1 haplotypes were associated with hirsutism suggests that only this isoform is important in the hair follicle.

Use of the modified frailty index to predict 30-day morbidity and mortality from spine surgery.

OBJECTIVE Limited tools exist to stratify perioperative risk in patients undergoing spinal procedures. The modified frailty index (mFI) based on the Canadian Study of Health and Aging Frailty Index (CSHA-FI), constructed from standard demographic variables, has been applied to various other surgical populations for risk stratification. The authors hypothesized that it would be predictive of postoperative morbidity and mortality in patients undergoing spine surgery. METHODS The 2006-2010 National Surgical Quality Improvement Program (NSQIP) data set was accessed for patients undergoing spine surgeries based on Current Procedural Terminology (CPT) codes. Sixteen preoperative clinical NSQIP variables were matched to 11 CSHA-FI variables (changes in daily activities, gastrointestinal problems, respiratory problems, clouding or delirium, hypertension, coronary artery and peripheral vascular disease, congestive heart failure, and so on). The outcomes assessed were 30-day occurrences of adverse events. These were then summarized in groups: any infection, wound-related complication, Clavien IV complications (life-threatening, requiring ICU admission), and mortality. RESULTS A total of 18,294 patients were identified. In 8.1% of patients with an mFI of 0 there was at least one morbid complication, compared with 24.3% of patients with an mFI of ≥ 0.27 (p < 0.001). An mFI of 0 was associated with a mortality rate of 0.1%, compared with 2.3% for an mFI of ≥ 0.27 (p < 0.001). Patients with an mFI of 0 had a 1.7% rate of surgical site infections and a 0.8% rate of Clavien IV complications, whereas patients with an mFI of ≥ 0.27 had rates of 4.1% and 7.1% for surgical site infections and Clavien IV complications, respectively (p < 0.001 for both). Multivariate analysis showed that the preoperative mFI and American Society of Anesthesiologists classification of ≥ III had a significantly increased risk of leading to Clavien IV complications and death. CONCLUSIONS A higher mFI was associated with a higher risk of postoperative morbidity and mortality, providing an additional tool to improve perioperative risk stratification.

The 3' untranslated region of the lipoprotein lipase gene: haplotype structure and association with post-heparin plasma lipase activity.

CONTEXT: Haplotypes comprising six single nucleotide polymorphisms (SNPs) (intron 7 to intron 9) of the lipoprotein lipase (LPL) gene appear to influence risk for atherosclerosis and insulin resistance in Mexican-Americans. OBJECTIVE: Based on rodent studies, we hypothesized that these haplotypes are in linkage disequilibrium with functional variants in the 3' untranslated region of LPL, which is encoded by exon 10, and that these variants influence phenotype by altering LPL expression. DESIGN: We sequenced exon 10 in subjects with divergent insulin sensitivity and divergent haplotypes. We also sequenced the other common LPL haplotypes. Variants identified by sequencing were genotyped in a large, family-based population along with the six SNPs spanning intron 7 to intron 9. We tested the potential functional significance of variation in exon 10 by evaluating association of haplotypes with post-heparin plasma LPL activity. SETTING: The study took place within the general community, with the Mexican-American Coronary Artery Disease Project cohort. PARTICIPANTS: Participants included 847 subjects from 163 families. MAIN OUTCOME MEASURES: We determined LPL haplogenotype and post-heparin plasma LPL activity. RESULTS: Exon 10 sequencing identified 15 variants. Thirteen of these variants were genotyped in large-scale along with the six SNPs spanning intron 7 to intron 9. LPL haplotypes and their relative frequencies in Mexican-Americans were determined. The fourth most common haplotype based on 19 SNPs (haplotype 19-4) was associated with increased LPL activity as well as multiple phenotypes related to the metabolic syndrome. CONCLUSIONS: These results support the possibility that variation in the 3' untranslated region of LPL affects LPL expression and activity, consequently influencing risk of atherosclerosis and insulin resistance, and provides important tools for further dissection of LPL regulation.

Genetic variants in peroxisome proliferator-activated receptor gamma influence insulin resistance and testosterone levels in normal women, but not those with polycystic ovary syndrome.

OBJECTIVE: To investigate the relationship of the peroxisome proliferator-activated receptor gamma (PPARG) Pro12Ala and silent exon 6 (His447His) polymorphisms with the clinical features of polycystic ovary syndrome (PCOS). DESIGN: Patients with PCOS and control subjects were genotyped for Pro12Ala and His447His. Associations between genotype, diagnosis, and hormonal/metabolic parameters were assessed. SETTING: Subjects were recruited from the reproductive endocrinology clinic at the University of Alabama at Birmingham, Birmingham, Alabama. Control subjects were recruited from the surrounding community. Genotyping was performed at the Cedars-Sinai Medical Center in Los Angeles, California. PATIENT(S): Participants included 285 white women with PCOS and 187 controls. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The Pro12Ala and His447His genotypes, and hormonal and metabolic phenotypes. RESULT(S): The Pro12Ala and His447His genotypes did not influence risk of PCOS or its component phenotypes in patients with PCOS. In controls, Pro12Ala did not influence measures of insulin resistance or androgen production. However, carriers of the His447His T-allele had significantly decreased free and total T levels, and a significantly decreased homeostasis model assessment index of insulin resistance. Furthermore, haplotypes in controls bearing the His447His T-allele were also associated with decreased T. CONCLUSION(S): Peroxisome proliferator-activated receptor gamma does not appear to be an important modifier gene in PCOS. In controls, however, the His447His T-allele may be in linkage disequilibrium with a functional variant that influences insulin resistance and T production.

Preliminary evidence of glycogen synthase kinase 3 beta as a genetic determinant of polycystic ovary syndrome.

In this study of 352 women with polycystic ovary syndrome (PCOS) and 289 control women, haplotypes spanning the gene for glycogen synthase kinase 3beta (GSK3B) were constructed on the basis of nine single-nucleotide polymorphisms in white and black subjects separately. In each racial group, we observed that a specific, although different, GSK3B haplotype was associated with increased frequency of PCOS, suggesting that GSK3beta contributes to the pathophysiology and inherited basis of PCOS.