Weak Risk Factor Research Articles

Orchiopexy: one procedure, two diagnoses - different male infertility outcomes.

Infertility, affecting one in six couples, is often related to the male partner's congenital and/or environmental conditions or complications postsurgery. This retrospective study examines the link between orchiopexy for undescended testicles (UDT) and testicular torsion (TT) in childhood and adult fertility as assessed through sperm analysis. The study involved the analysis of semen samples from 7743 patients collected at Soroka University Medical Center (Beer Sheva, Israel) between January 2009 and December 2017. Patients were classified into two groups based on sperm concentration: those with concentrations below 5 × 10 6 sperm per ml (AS group) and those above (MN group). Medical records and surgical histories were reviewed, categorizing orchiopexies by surgical approach. Among 140 individuals who had undergone pediatric surgery, 83 (59.3%) were placed in the MN group and 57 (40.7%) in the AS group. A higher likelihood of being in the MN group was observed in Jewish compared to Arab patients (75.9% vs 24.1%, P = 0.006). In cases of childhood UDT, 45 (78.9%) patients exhibited sperm concentrations below 5 × 10 6 sperm per ml ( P < 0.001), and 66 (76.7%) had undergone unilateral and 18 (20.9%) bilateral orchiopexy. Bilateral orchiopexy was significantly associated with lower sperm concentration, total motility, and progressive motility than unilateral cases ( P = 0.014, P = 0.001, and P = 0.031, respectively). Multivariate analysis identified UDT as a weak risk factor for low sperm concentration (odds ratio [OR]: 2.712, P = 0.078), with bilateral UDT further increasing this risk (OR: 6.314, P = 0.012). Jewish ethnicity and TT diagnosis were associated with a reduced risk of sperm concentrations below 5 × 10 6 sperm per ml. The findings indicate that initial diagnosis, surgical approach, and ethnicity markedly influence male fertility outcomes following pediatric orchiopexy.

Trends in gastro-oesophageal reflux in a Norwegian general population: the Tromsø Study 1979–2016

Background The prevalence of overweight and smoking has changed over time. However, whether the changes in the risk factors are reflected in the prevalence of gastro-oesophageal reflux disease (GORD) is unknown. The aims of this study were to assess the changes in prevalence of GORD and the associated risk factors over time in a general population. Methods This was a population-based study using repeated surveys of the Tromsø Study: Tromsø2 (1979–1980, n = 14,279), Tromsø6 (2007–2008, n = 11,460) and Tromsø7 (2015–2016, n = 20,664). Complaints of heartburn and acid regurgitation and common risk factors were reported, and height and weight were measured. The prevalence of GORD was calculated and the association with risk factors was assessed at each time point by odds ratios (OR) and 95% confidence intervals (CI) using multivariable logistic regression. Results The prevalence of GORD was 13% in 1979–1980, 6% in 2007–2008 and 11% in 2015–2016. In all three surveys, the risk of GORD was consistently increased with overweight and smoking. However, overweight was a weaker risk factor in the first (OR 1.58, 95% CI 1.42–1.76) compared to the last (OR 2.16, 95% CI 1.94–2.41) survey. Smoking was a stronger risk factor in the first (OR 1.45, 95% CI 1.31–1.60) than at the last (OR 1.14, 95% CI 1.01–2.29) survey. Conclusion During four decades of follow-up of the same population, no clear change in prevalence of GORD was found. GORD was clearly and consistently associated with overweight and smoking. However, overweight has become a more important risk factor than smoking over time.

Genetic Validation of Psoriasis Phenotyping in UK Biobank Supports the Utility of Self-Reported Data and Composite Definitions for Large Genetic and Epidemiological Studies

Genetic Validation of Psoriasis Phenotyping in UK Biobank Supports the Utility of Self-Reported Data and Composite Definitions for Large Genetic and Epidemiological Studies

1877. COVID-19-Associated Hospitalizations among Long-Term Care Facility Residents Ages ≥65 Years — COVID-NET, 14 U.S. States, March 2020–January 2022

Abstract Background Adults aged ≥65 years and those with underlying medical conditions, including residents of long-term care facilities (LTCF), are at increased risk for COVID-19-associated hospitalizations and other severe outcomes. Methods Hospitalizations among LTCF residents aged ≥ 65 years from March 2020–January 2022 were described using data on a representative sample of hospitalizations from the CDC’s COVID-19-Associated Hospitalization Surveillance Network (COVID-NET), a population-based surveillance network of &amp;gt; 250 acute care hospitals in 99 counties across 14 states. A Poisson regression model adjusting for age, race/ethnicity, underlying medical conditions, vaccination status, month of admission, and do-not-resuscitate/intubate-or-provide comfort-measures-only (DNR/DNI/CMO) code status examined the relationship of LTCF residency to death during COVID-19-associated hospitalization. Results Of 11,901 hospitalizations among adults aged ≥ 65 years reported during the study period, 2,965 (24.9%) were LTCF residents; most resided in nursing homes (53.8%) or assisted living facilities (26.8%). LTCF residents hospitalized with COVID-19 were older and more likely to have cardiovascular disease, congestive heart failure, a neurologic condition, dementia, or ≥ 3 underlying medical conditions than non-residents (Figure). The proportion of LTCF residents vs non-residents who required intensive care unit admission or invasive mechanical ventilation were not statistically different (23.2% vs 23.5% and 10.7 vs 13.5%, respectively). The proportion of in-hospital death was higher among LTCF residents than non-residents (22.8% vs 14.4%, p &amp;lt; 0.01). More LTCF residents have a DNR/DNI/CMO code status (48%) compared to non-residents (19%). The fully adjusted regression model found the risk ratio for death was 1.03 (95% CI, 1.01–1.05) among LTCF residents compared to non-residents. Conclusion Compared to non-residents, LTCF residents were older, had more underlying conditions, and had a higher risk of in-hospital death. After adjusting for multiple potential confounders, results suggest that LTCF residency is a weak but significant independent risk factor for death during COVID-19-associated hospitalization. Disclosures All Authors: No reported disclosures.

Prevalence of acute neurological complications and pathological neuroimaging findings in critically ill COVID-19 patients with and without VV-ECMO treatment

Acute brain injuries such as intracerebral hemorrhage (ICH) and ischemic stroke have been reported in critically ill COVID-19 patients as well as in patients treated with veno-venous (VV)-ECMO independently of their COVID-19 status. The purpose of this study was to compare critically ill COVID-19 patients with and without VV-ECMO treatment with regard to acute neurological symptoms, pathological neuroimaging findings (PNIF) and long-term deficits. The single center study was conducted in critically ill COVID-19 patients between February 1, 2020 and June 30, 2021. Demographic, clinical and laboratory parameters were extracted from the hospital’s databases. Retrospective imaging modalities included head computed tomography (CT) and magnetic resonance imaging (MRI). Follow-up MRI and neurological examinations were performed on survivors > 6 months after the primary occurrence. Of the 440 patients, 67 patients received VV-ECMO treatment (15%). Sixty-four patients (24 with VV-ECMO) developed acute neurological symptoms (pathological levels of arousal/brain stem function/motor responses) during their ICU stay and underwent neuroimaging with brain CT as the primary modality. Critically ill COVID-19 patients who received VV-ECMO treatment had a significantly lower survival during their hospital stay compared to those without (p < 0.001). Among patients treated with VV-ECMO, 10% showed acute PNIF in one of the imaging modalities during their ICU stay (vs. 4% of patients in the overall COVID-19 ICU cohort). Furthermore, 9% showed primary or secondary ICH of any severity (vs. 3% overall), 6% exhibited severe ICH (vs. 1% overall) and 1.5% were found to have non-hemorrhagic cerebral infarctions (vs. < 1% overall). There was a weak, positive correlation between patients treated with VV-ECMO and the development of acute neurological symptoms. However, the association between the VV-ECMO treatment and acute PNIF was negligible. Two survivors (one with VV-ECMO-treatment/one without) showed innumerable microhemorrhages, predominantly involving the juxtacortical white matter. None of the survivors exhibited diffuse leukoencephalopathy. Every seventh COVID-19 patient developed acute neurological symptoms during their ICU stay, but only every twenty-fifth patient had PNIF which were mostly ICH. VV-ECMO was found to be a weak risk factor for neurological complications (resulting in a higher imaging rate), but not for PNIF. Although logistically complex, repeated neuroimaging should, thus, be considered in all critically ill COVID-19 patients since ICH may have an impact on the treatment decisions and outcomes.

Molecular ecology and risk factors for third-generation cephalosporin-resistant Escherichia coli carriage by dogs living in urban and nearby rural settings.

ObjectivesTo compare faecal third-generation cephalosporin-resistant (3GC-R) Escherichia coli isolates from dogs living in a city and in a rural area ∼30 km away; to compare isolates from dogs, cattle and humans in these regions; and to determine risk factors associated with 3GC-R E. coli carriage in these two cohorts of dogs.MethodsSix hundred dogs were included, with faecal samples processed to recover 3GC-R E. coli using 2 mg/L cefotaxime. WGS was by Illumina and risk factor analyses were by multivariable linear regression using the results of an owner-completed survey.Results3GC-R E. coli were excreted by 20/303 rural and 31/297 urban dogs. The dominant canine 3GC-R ST was ST963 (blaCMY-2), which also accounted for 25% of CMY-2-producing E. coli in humans. Phylogenetic overlap between cattle and rural dog CTX-M-14-producing E. coli ST117 was observed as well as acquisition of pMOO-32-positive E. coli ST10 by a rural dog, a plasmid common on cattle farms in the area. Feeding raw meat was associated with carrying 3GC-R E. coli in rural dogs, but not in urban dogs, where swimming in rivers was a weak risk factor.ConclusionsGiven clear zoonotic potential for resistant canine E. coli, our work suggests interventions that may reduce this threat. In rural dogs, carriage of 3GC-R E. coli, particularly CTX-M producers, was phylogenetically associated with interaction with local cattle and epidemiologically associated with feeding raw meat. In urban dogs, sources of 3GC-R E. coli appear to be more varied and include environments such as rivers.

Beach-Chair Versus Lateral Decubitus Positioning for Arthroscopic Posterior Shoulder Labral Repair: A Retrospective Comparison of Clinical and Patient-Reported Outcomes

Background: Both beach-chair and lateral decubitus patient positioning are often utilized for shoulder arthroscopy, with each offering its unique advantages and disadvantages. The surgical position is often selected according to each surgeon's preference, with no clear superiority of one position over the other. Purpose/Hypothesis: The purpose was to compare clinical and patient-reported outcomes between patients who underwent arthroscopic posterior labral repair in the beach-chair versus the lateral decubitus position. We hypothesized that patient positioning would not affect clinical and patient-reported outcomes. Study Design: Cohort study; Level of evidence, 3. Methods: A list of all patients diagnosed with the Current Procedural Terminology codes 29806 and 29807 between 2015 and 2019 was obtained from the medical records. Patients were only included if arthroscopic posterior labral repair with or without concomitant superior labral anterior to posterior repair was confirmed. Data collected for eligible patients included the number of anchors used, perioperative and postoperative complications, redislocations, subjective instability, reoperation, and revision. Patients were also contacted to complete several patient-reported outcome surveys. Preoperative data, perioperative data, and postoperative outcomes were compared between patients who underwent surgery in the beach-chair versus lateral decubitus position. Results: Overall, 126 patients were included—69 patients underwent surgery in the lateral decubitus position and 57 in the beach-chair position—with a mean follow-up of 2.6 ± 1.7 years. There were no significant pre- or perioperative differences between groups. Rates of postoperative dislocations, subjective instability, reoperations, revisions, all complications, and return to sports rates also did not differ between groups (all, P > .05). Finally, there was no difference between groups regarding postoperative pain, function, and subjective instability scores (all, P > .05). Results of the multivariate regression analysis showed that increased age was a weak independent risk factor for subjective recurrent posterior shoulder instability (odds ratio, 1.04; P = .036). Conclusion: Surgical positioning for arthroscopic posterior shoulder labral repair did not affect postoperative clinical and patient-reported outcomes. Both beach-chair and lateral decubitus position provided good outcomes for posterior shoulder labral repair, with an overall recurrence rate of 8.7%. Increased age was a weak independent risk factor for subjective recurrent instability.

Dissociation between fatigued power output and traditional peak torque for isokinetic hamstring:quadriceps ratios in professional soccer players

BackgroundMuscle strength imbalance assessment (e.g., hamstring-to-quadriceps ratio, H:Q) using traditional peak torque isokinetic measurements has been shown to be a weak risk factor predictor of future lower-limb injuries (e.g., hamstring strain and anterior cruciate ligament tear). In soccer, power-related tasks are commonplace and injuries are most likely to occur during fatigued high-velocity actions. Thus, it is reasonable to that calculating H:Q using power output and may serve as an alternative to traditional peak torque-based H:Q.AimsWe aimed to investigate the relationship of isokinetic H:Q calculated from traditional peak torque and power output during non-fatigue and fatigue conditions.MethodsSeventy-nine professional soccer players (25.6 ± 4.9 years old; 78.7 ± 8.1 kg; 179.4 ± 6.7 cm) performed concentric knee extension-flexion contractions at 60°.s−1 (five repetitions) and 300°.s−1 (30 repetitions, fatigue trial). Traditional peak torque H:Q was calculated using the highest torque obtained during five repetitions at 60°.s−1. Power output H:Qnon-fatigued was calculated using the average from the 2nd, 3rd and 4th repetitions, and power output H:Qfatigued was obtained as the average of the power output of the last three repetitions of the fatigue trial.ResultsWeak (rs = 0.27) and moderate (rs = 0.49) correlations were found between traditional peak torque and power output H:Qfatigued, and traditional peak torque and power output H:Qnon-fatigued, respectively.ConclusionThe present data suggested that power H:Q differs from traditional H:Q, particularly during fatigue in professional soccer players, which warrants further investigation on the potential use of power output H:Q ratios for injury prediction.

Recommendations from the EGAPP Working Group: Routine testing for Factor V Leiden (R506Q) and prothrombin (20210G>A) mutations in adults with a history of idiopathic venous thromboembolism and their adult family members

Summary of RecommendationsThe Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group found adequate evidence to recommend against routine testing for Factor V Leiden (FVL) and/or prothrombin 20210G>A (PT) in the following circumstances: (1) adults with idiopathic venous thromboembolism (VTE). In such cases, longer term secondary prophylaxis to avoid recurrence offers similar benefits to patients with and without one or more of these mutations. (2) Asymptomatic adult family members of patients with VTE and an FVL or PT mutation, for the purpose of considering primary prophylactic anticoagulation. Potential benefits are unlikely to exceed potential harms. The overall certainty of these findings was deemed “moderate.” The evidence was insufficient to determine whether FVL/PT testing might have clinical utility in some circumstances, such as for identifying FVL homozygosity among asymptomatic family members of adults with idiopathic VTE or counseling patients about the risks and benefits of antithrombotic therapy. Based on the available evidence, the certainty of net health benefit was deemed “low.” The recommendations do not extend to patients with other risk factors for thrombosis, such as contraceptive use, as the evidence review that serves as the basis for the recommendations focused primarily on idiopathic VTE. RationaleIn developing these recommendations the EGAPP Working Group considered evidence in the following three areas. Analytic ValidityThere is adequate evidence that testing accurately and reliably detects the R506Q (FVL) and 20210G>A (PT) variants in the Factor V and PT genes, respectively (a more complete definition of analytic validity, clinical validity, and clinical utility is contained under the “Clinical Considerations” section). Clinical ValidityThe presence of a heterozygous FVL variant seems to be a weak risk factor for recurrence of VTE (odds ratio [OR]: 1.56). Rare homozygous FVL mutations present somewhat greater risks of VTE recurrence (OR: 2.65). The evidence for this increased risk is convincing, but the magnitude of excess risk is not as great as previously thought. The evidence is insufficient to draw conclusions about excess VTE recurrence risk resulting from compound heterozygosity (FVL and PT), but it is likely to be at least as high as with FVL alone. The OR for compound heterozygosity is 6.69. The evidence is insufficient to draw conclusions about VTE recurrence risks associated with PT mutations alone. For family members of index VTE cases, there is convincing evidence that both heterozygosity and homozygosity for FVL are associated with higher risks for VTE occurrence (ORs 3.49 and 17.84, respectively) than for family members without FVL variants. Clinical UtilityThere is convincing evidence that longer term secondary prophylaxis after an initial idiopathic VTE event yields comparable benefits to those with and without a FVL or PT mutation. For asymptomatic family members of index cases, no prophylaxis trials have been reported. Hence, there is no direct evidence of particular benefit to family members. Potential net harm is possible if primary prophylaxis is administered to asymptomatic family members with one or more mutations, because the absolute risk of an initial VTE event is low, and the risk of anticoagulant-induced hemorrhage is relatively high.

Association of Polypharmacy with Colorectal Cancer Survival Among Older Patients.

BackgroundIn geriatric oncology, polypharmacy is often assessed during a comprehensive geriatric assessment. Previous studies about its association with survival among patients with colorectal cancer (CRC) were inconclusive and had high risk for indication bias.Patients and MethodsA cohort study was conducted with 3,239 patients with CRC, aged ≥65 years, who were recruited in Germany between 2003 and 2016, while being hospitalized for CRC surgery. We defined polypharmacy as the concurrent use of five or more drugs, and excessive polypharmacy (EPP) as concurrent use of eight or more drugs. Cox proportional hazards regression models were performed to assess the associations of polypharmacy with 5‐year overall (OS), CRC‐specific (CSS), and non‐cancer‐specific survival (NCS) with rigorous adjustment for morbidity to minimize indication bias (e.g., for cancer stage, functional status, and 13 common diseases/conditions).ResultsThe prevalence of polypharmacy was 54.7% and that of EPP was 24.2%. During up to 5 years of follow‐up, 1,070 participants died, among whom 615 died of CRC and 296 died of other causes than cancer. EPP was statistically significantly associated with poorer up‐to‐5‐year OS (hazard ratio [HR], 1.23; 95% confidence interval [CI], 1.02–1.47) and CSS (HR, 1.31; 95% CI, 1.03–1.68). HR point estimate for NCS was higher than 1 (1.22) but not statistically significant.ConclusionPolypharmacy was very common and EPP was a weak risk factor for mortality in this large cohort of older patients with CRC. Clinical trials are needed to address the causality of this relationship because older patients with CRC might benefit from deprescribing drugs without an indication.Implications for PracticeThe results of this study support the hypothesis that excessive polypharmacy, defined as use of eight or more concurrently used active substances, has a negative impact on the prognosis of older patients with colorectal cancer (CRC). This study suggests to oncologists that performing a medication review for older patients with CRC with eight drugs or more is indicated (especially when a broader comprehensive geriatric assessment is being performed). Such a medication review should not only focus on reducing the number of medications (by deprescribing drugs without an indication) but also check the appropriateness of indicated drugs for older patients with cancer.

Gestational hypertension and childhood atopy: a Millennium Cohort Study analysis

Gestational hypertension may confer risk of atopic disease in offspring through a direct biological mechanism, but another possibility is that risk is mediated through complications of pregnancy. To explore these associations, we conducted an analysis of a nationally representative birth cohort based in the UK involving children born 2000–2002. We included 12,450 mother-child pairs. We used logistic regression to estimate the association between hypertensive disease and asthma, hay fever, or eczema by age 5, and parentally reported early wheeze and severe wheeze. Mediation by gestation at delivery and caesarean delivery was explored using causal mediation analysis. Odds ratios (95% CI) for gestational hypertension and childhood asthma, hay fever, and eczema were 1.32 (1.09, 1.59), 1.22 (0.97, 1.55), and 1.12 (0.96, 1.32) respectively, adjusted for confounding. The population attributable fractions were 2.4% (1.0–3.8%), 0.9% (−0.3% to 2.1%), and 1.8% (0.0–3.7%), respectively. Accounting for mediation by gestational age and caesarean delivery, odds ratios (95% CI) for the potential direct effects of gestational hypertension were 1.21 (0.97, 1.50), 1.17 (0.91, 1.49), and 1.11 (0.94, 1.31) for the same.Conclusion: Gestational hypertension was weakly positively associated with asthma and this was partly mediated by earlier delivery. Only a small proportion of early childhood asthma was attributable to gestational hypertensive disease in this representative UK-based birth cohort.What is known:• Gestational hypertension has been shown to be an inconsistent risk factor for the atopic diseases.• The in utero immune environment may modify the risk of atopy in offspring; alternatively, complications of pregnancy including caesarean delivery and prematurity may explain an association between hypertensive disease and atopy.What is new:• Self-reported gestational hypertension was a weak risk factor for asthma and wheeze in the Millennium Cohort Study.• Part of the association between gestational hypertensive disease and asthma was explained by earlier delivery.

Mannose-binding lectin and risk of infections in type 2 diabetes: A Danish cohort study.

In individuals at increased risk of infections, e.g., patients with type 2 diabetes, low MBL may have detrimental effects. We used the Mendelian randomization principle to examine whether genetically low MBL is a risk factor for developing infections in patients with type 2 diabetes. Serum MBL (n = 7305) and MBL genotype (n = 3043) were determined in a nationwide cohort of patients with new type 2 diabetes and up to 8 years follow-up for hospital-treated infections and community-based antimicrobial prescriptions. The associations were examined in spline and Cox regression analyses. 1140 patients (16%) were hospitalized with an infection and 5077 patients (70%) redeemed an antimicrobial prescription. For low (≤100 μg/L) versus intermediate (101-1000 μg/L) serum MBL concentration, the adjusted hazard ratios (aHRs) were 1.13(95% confidence interval, 0.96-1.33) for any hospital-treated infections and 1.19(1.01-1.41) for bacterial infections. Low MBL expression genotype was not associated with risk of any hospital-treated infections except for diarrheal diseases (aHR 2.23[1.04-4.80]). Low MBL expression genotype, but not low serum MBL, was associated with increased risk for antimicrobial prescriptions (aHR 1.18[1.04-2.34] and antibacterial prescriptions 1.20[1.05-1.36]). Low MBL is a weak causal risk factor for developing infections in patients with type 2 diabetes.

Development and Baseline Characterization of a Thrombosis Risk Alert Tool: A Quality Assessment Project

Introduction: The Khorana Score (KS) is a validated tool to assess the risk of thrombosis in cancer patients, prior to initiation of chemotherapy. The AVERT and CASSINI studies evaluated prophylactic anticoagulation with apixaban or rivaroxaban for patients with KS of 2 or higher. Both studies demonstrated that while patients were taking prophylactic anticoagulant, the Hazard Ratio of cancer associated thrombosis was approximately 0.4. The NCCN and other societies are now recommending oral anticoagulant prophylaxis should be considered for up to 6 months, for patients with an intermediate or high-risk score of ≥2. Methods: We have developed a medical record tool, that identifies all MSKCC patients prior to initiation of a new chemotherapy regimen, captures the KS parameters, and generates the KS. Once fully implemented, it is anticipated that this tool and appropriate use of prophylactic anticoagulation, will reduce the burden of cancer associated thrombosis. To accurately document a potential reduction in rates of cancer associated thrombosis, we need to establish current baseline rates of cancer associated thrombosis via a contemporary verification of the KS, reflecting potential changes in oncology in the 12 years since the score was first published. We applied our KS capture tool to a 2-year period (10/17/2017 to 11/29/2019). 13,992 patients were identified with a new chemotherapy order, of whom 13,176 were found to have cancer and had complete parameters for the KS. We tracked all patients for 6 months, to identify possible episodes of Venous Thromboembolism (VTE). VTE episodes were identified by capturing the impressions of all contrast imaging studies, Doppler ultrasounds, and V/Q scans, combined with keyword and phrase computer identification, and manual review. To identify possible VTE events that occurred at an outside emergency department or hospital, we also queried new prescriptions for therapeutic doses of anticoagulants and ICD10 codes. In this analysis we focus on deep vein thrombosis (DVT) and pulmonary embolism (PE). Results: The 6-month rate of VTE (DVT or PE) was 6.4%. The VTE rate was 4.1% in the KS 0 cohort, and &amp;gt;18% for patients with a score of 4 or greater. We assessed the contribution of each parameter of the KS, in univariate analysis. Of the cancers assigned 2 points in the KS, pancreatic cancer had the highest VTE rate of 13.7%, but gastric/esophageal cancer did not have an increased rate. Of the cancers assigned 1 point, germ cell/testis, gynecologic, and lung cancer, also had increased risk of VTE, but bladder and non-Hodgkin lymphoma did not. Renal/urothelial cancers and cholangiocarcinoma/biliary tract cancers were also associated with high rates of VTE, although were not assigned points using the KS. Elevated BMI (≥35 kg/m2) was a weak risk factor. However, baseline anemia (&amp;lt;10 gm/dL), leukocytosis (&amp;gt;11,000/mcL) and thrombocytosis (≥350,000/mcL) were all strong predictors of VTE rate. Conclusions: The purpose of this QA project was to provide contemporary data on baseline cancer associated thrombosis rates, anticipating implementation of a program of targeted primary thrombosis prophylaxis. It remains clear that the KS provides a valuable risk assessment tool, stratifying 6-month VTE risk from 4.1% to &amp;gt;18%. Cancer type is typically the parameter that gets the first consideration. And most of the cancers with 1 or 2 points did predict increased risk. We don't have an explanation as to why, gastric/esophageal cancers and non-Hodgkin lymphoma were not associated with increased risk, but this finding may reflect the stage of their treatment at which patients begin care at MSKCC. Renal/urothelial, and cholangiocarcinoma/biliary tract cancers are associated with a high risk of VTE, and one may choose to include them for consideration of prophylactic anticoagulation. The relative contribution of pre-chemotherapy blood counts has been questioned in the past, but in this cohort, they clearly contributed to appropriate risk assessment. These data will serve as baseline for future assessment of thrombosis risk reduction upon implementation of a program of targeted prophylactic anticoagulation. Table Disclosures Khorana: Leap: Research Funding; BMS: Honoraria, Research Funding; Merck: Research Funding; Array: Other: Research funding (to institution); Janssen: Honoraria; Bayer: Honoraria; Pfizer: Honoraria; Sanofi: Honoraria; Medscape: Honoraria; Leo Pharma: Honoraria; Seattle Genetics: Honoraria; Pharmacyte: Honoraria; Pharmacyclics: Honoraria. Mantha:MJH Associates: Honoraria; Physicians Education Resource: Honoraria. Soff:Amgen: Research Funding; Amgen: Honoraria; Janssen Scientific Affairs: Honoraria; Dova Pharmaceuticals: Honoraria; Bristol-Myers Squibb, Pfizer: Honoraria; Janssen Scientific Affairs: Research Funding; Dova Pharmaceuticals: Research Funding.

Evaluation of non-coding region sequence variants and mitochondrial haplogroups as potential biomarkers of sporadic breast cancer in individuals of Sri Lankan Sinhalese ethnicity.

Mitochondrial DNA (mtDNA) mutations have been reported to be associated with various diseases, including cancer. The present study investigated the mtDNA non-coding region mutations and mitochondrial haplogroups as potential biomarkers of sporadic breast cancer in Sri Lankan Sinhalese women. Mitochondrial macro-haplogroups were determined using PCR-restriction fragment length polymorphism, whereas non-coding region sequences were determined using Sanger sequencing. The sequence of the non-coding region was also used to confirm haplogroup status. Neither the mutations in the non-coding region nor the mitochondrial haplogroups that were reported as risk factors in other populations, were determined to be potential risk factors for sporadic breast cancer in the present study. Furthermore, several novel mutations were identified in the present matched pairs case-controlled study. The M65a haplogroup with an additional mutation at position 16311 (P=0.0771) and mutations at the ori-b site (P=0.05) were considered a weak risk factor and protective factor, respectively, for sporadic breast cancer in Sinhalese women. Previous studies have indicated the use of mtDNA mutations as a biomarker; however, the present study showed that such biomarkers need to be validated for individual ethnic groups before they can be recommended for use in the prediction of disease.

Placenta previa and risk of congenital malformations among singleton births

Background: Placenta previa constitutes a major complication in pregnancy, with implantation differences in relation to whether it covers or lies close to the internal os of the cervix. Objective: The aim of our study was to examine the association between placenta previa and congenital malformations among singleton births. Materials and methods: In our study, which was conducted on 90223 patients admitted from three tertiary university-affiliated and teaching Hospitals [Bab El-Shaareia University Hospital_Al Mataria Teaching Hospital_ El Galaa Teaching Hospital] in the period from 2012 to 2015 their age ranged from 16 – 47 years. Results: In comparison between both groups regarding placenta previa as a risk factor of congenital anomaly we found that 1.7% of cases with congenital with maternal placenta previa versus 1.2% with no congenital anomalies and there was statistically significant difference between both groups with p value 0.042. With using multivariate logistic regression we found that (age, parity, C.S delivery, fetal sex, DM, HTN, smoking, previous abortion, IUGR with attenuation of placenta previa as independent risk factor so placenta previa considered weak risk factor for congenital anomalies. Our risk estimate was attenuated compared with previous estimates, possibly because of controlling several potential confounders in our analysis that were not examined in previously. Conclusion: Our study provides further evidence suggesting a weak, but positive association between placenta previa and major congenital malformations, including all structural anomalies, chromosomal defects, and congenital hypothyroidisms, in the offspring.

Clinical Faceoff: Should Orthopaedic Surgeons Have Strict BMI Cutoffs for Performing Primary TKA and THA?

Clinical Faceoff: Should Orthopaedic Surgeons Have Strict BMI Cutoffs for Performing Primary TKA and THA?

414 The Association Between Cigarette Smoking and Gastroesophageal Reflux Disease in Japan: Analysis of Symptoms and Endoscopic Findings

INTRODUCTION: Cigarette smoking is regarded as a weak or moderate risk factor of gastroesophageal reflux disease (GERD), and smoking cessation may reduce GERD symptoms. However, the evidence for these associations is limited. This study aimed to investigate the effects of cigarette smoking or smoking cessation on the development of GERD by using endoscopic findings and the Gastrointestinal Symptom Rating Scale (GSRS). METHODS: The subjects were 848 patients who received upper endoscopy and answered the GSRS questionnaire as health checkup at our hospital in Japan. The patients were divided into three groups; non-smoking, smoking-cessation, and current-smoking group (322, 371 and 155 patients, respectively). Endoscopic findings of GERD were graded by the Los Angeles classification, and grade B or more were defined as severe GERD. The GSRS questionnaire is an interview-based seven-graded rating scale including the questions on heart burn and acid regurgitation. The prevalence of patients with positive GSRS scores (i.e. 2 or more) was compared between three groups. Data were analyzed statistically using the Kruskal-Wallis, Mann-Whitney U, or chi-square test. RESULTS: The overall prevalence of endoscopic GERD and positive GSRS scores on heart burn and acid regurgitation was 19.2, 14.5, and 19.7%, respectively. The prevalence of patients with severe endoscopic GERD in smoking group was significantly higher than that in non-smoking group (OR: 4.64; 95% CI: 1.47-14.67; P = 0.007). In contrast, the prevalence of patients with positive GSRS scores on heart burn in smoking group was significantly lower than that in non-smoking group (OR: 0.46; 95% CI: 0.26-0.80; P = 0.006). As for smoking cessation, there was no significant difference in the prevalence of patients with severe endoscopic GERD between smoking-cessation and current-smoking group (OR: 0.37; 95% CI: 0.11-1.18; P = 0.149). Also, there was no significant difference in positive GSRS scores between smoking-cessation and current-smoking group (heart burn; P = 0.077, and acid regurgitation; P = 0.871). CONCLUSION: Cigarette smoking increases risk of developing endoscopic GERD severity, while not developing GERD symptoms. Upper endoscopy may be useful for Japanese using cigarette even if they have no GERD symptoms. Although smoking cessation is not associated with improvement of endoscopic GERD severity in this study, prospective studies should be performed to evaluate the effects of smoking cessation on GERD.

Annotation: travel and thrombosis.

Travel appears to be a weak risk factor for venous thromboembolism (VTE) and is more relevant for passengers with additional VTE risk factors. The association is not limited to air travel and is related to duration of travel. Life-threatening pulmonary embolism (PE) is rare. There is limited evidence to support interventions, including 'sensible measures', graduated compression stockings (GCS) and low-molecular-weight heparin (LMWH). It is difficult to confidently define a population who would benefit from thromboprophylaxis and no validated risk assessment exists for this purpose. LMWH has traditionally been used for flight thromboprophylaxis but a direct oral anticoagulant (DOAC) would be a more appealing oral option.

Investigation on potential associations of oxidatively generated DNA/RNA damage with lung, colorectal, breast, prostate and total cancer incidence

Oxidative stress has been linked to cancer development in previous studies. However, the association between pre-diagnostic oxidatively generated DNA/RNA damage levels and incident cancer has rarely been investigated. Urinary oxidized guanine/guanosine (OxGua) concentrations, including 8-hydroxy-2′-deoxyguanosine, were assessed in 8,793 older adults in a population-based German cohort. 1,540 incident cancer cases, including 207 lung, 196 colorectal, 218 breast and 245 prostate cancer cases were diagnosed during over 14 years of follow-up. Associations of OxGua levels with cancer outcomes were not observed in the total population in multi-variable adjusted Cox regression models. However, in subgroup analyses, colorectal cancer incidence increased by 8%, 9% and 8% with one standard deviation increase in OxGua levels among current non-smokers, female and non-obese participants, respectively. Additionally, among non-smokers, overall and prostate cancer incidences statistically significantly increased by 5% and 13% per 1 standard deviation increase in OxGua levels, respectively. In contrast, OxGua levels were inversely associated with the risk of prostate cancer among current smokers. However, none of the subgroup analyses had p-values below a threshold for statistical significance after correction for multiple testing. Thus, results need to be validated in further studies. There might be a pattern that oxidatively generated DNA/RNA damage is a weak cancer risk factor in the absence of other strong risk factors, such as smoking, obesity and male sex.

Predictors of gleno-humeral bone loss in traumatic anterior shoulder instability

Purpose: Is to predict the risk factors causing gleno-humeral bone loss and affecting its size in patients with traumatic anterior shoulder instability. Patients and methods: At a median follow-up of 26 months, 60 patients having unilateral traumatic anterior shoulder instability were included in the study. The proposed risk factors for gleno-humeral bone loss were recorded. All patients underwent clinical evaluation and scoring. True AP radiography and CT scan of the shoulder were done to all patients to detect and quantify gleno-humeral bone loss. The collected data were analyzed to detect the factors correlating with the presence of gleno-humeral bone.Results: The number of dislocations was a significant risk factor for the presence of glenoid bone loss and large glenoid defect (P value: 0.023 and 0.001 respectively). Moreover, it was a significant risk factor for longer and deeper Hill-Sachs lesions (P value: 0.002 and 0.004 respectively). The age of 1st dislocation 20 years showed a negative correlation against larger Hill-Sachs lesions. Contact sports were a significant risk factor for the presence of glenoid bone loss and deeper Hill-Sachs lesions (P value: 0.002 and 0.003 respectively). Smoking was another but weak risk factor for large glenoid defects and longer Hill-Sachs lesions (P value: 0.050 and 0.034 respectively). The glenoid and humeral head bone loss showed highly significant correlation between each other.Conclusion: The number of dislocations, young age at 1st dislocation, contact sports and smoking are considered risk factors and predictors for gleno-humeral bone loss in traumatic anterior shoulder instability.Level of evidence: Case series study; Level of evidence, 4.