Presence Of Clinical Risk Factors Research Articles

Atrial Fibrillation Burden: Impact on Stroke Risk and Beyond.

Atrial fibrillation (AF) is an important independent risk factor for stroke. Current guidelines handle AF as a binary entity with risk driven by the presence of clinical risk factors, which guides the decision to treat with an oral anticoagulant. Recent studies in the literature suggest a dose-response relationship between AF burden and stroke risk, in both clinical AF and subclinical atrial fibrillation (SCAF), which differs from current guidance to disregard burden and utilize clinical risk scores alone. Within clinical classification and at the same risk levels in various scores, the risk of stroke increases with AF burden. This opens the possibility of incorporating burden into risk profiles, which has already shown promise. Long-term rhythm monitoring is needed to elucidate SCAF in patients with stroke. Recent data from randomized trials are controversial regarding whether there is an independent risk from AF episodes with a duration of less than 24 h, including the duration of SCAF greater than six minutes but less than 24 h.

Abstract WP161: Characterizing the Underlying Microangiopathy of Deep Cerebellar Intracerebral Hemorrhage

Introduction: Superficial (gray matter, vermis) cerebellar intracerebral hemorrhage (cICH) is associated with strictly lobar supratentorial cerebral microbleeds—a strong marker for cerebral amyloid angiopathy. However, for deep (white matter, deep nuclei, cerebellar peduncle) cICH, it is unclear whether hypertensive cerebral small vessel disease (HTN-cSVD) is the underlying microangiopathy. Hypothesis: We hypothesized that left ventricular hypertrophy (LVH), a marker for hypertensive end-organ damage, and non-hemorrhagic imaging markers of HTN-cSVD such as peri-basal ganglia (BG) white matter hyperintensity (WMH) pattern, deep lacunes, and severe BG enlarged perivascular spaces (EPVS) would be associated with deep vs. superficial cICH. Methods: Brain MRI scans from a prospective database of consecutive non-traumatic ICH patients admitted to a single referral center (2003 to 2019) were analyzed for the presence of cerebral microbleeds (CMBs) and non-hemorrhagic neuroimaging markers. The presence of clinical risk factors, LVH, and neuroimaging markers were compared between patients with deep and superficial cICH in univariate and multivariable models. Results: Of 1,791 patients with spontaneous ICH, 129 (7%) were found to have cICH (mean age 73±12 years, 46% female). Of these, 83 (64%) patients had deep cICH and 46 (36%) patients had superficial cICH. Hypertension (94% vs. 67%, p < 0.01) and LVH (60% vs. 28%, p < 0.01) were more common among patients with deep vs. superficial cICH. Among those who received a brain MRI (74%), the frequency of peri-BG WMH pattern (24% vs. 5%, p = 0.02), deep lacunes (59% vs. 14%, p < 0.01), severe BG EPVS (27% vs. 3%, p < 0.01), deep CMBs (51% vs. 16%, p < 0.01), and mixed location CMBs (37% vs. 11%, p < 0.01) was greater among patients with deep cICH compared to superficial cICH. When these variables were entered into a multivariable regression model, LVH (OR 3.10, 95% CI [1.07-8.97], p = 0.04) and deep lacunes (OR 4.38, 95% CI [1.25-15.31], p = 0.02) remained significantly associated with deep cICH. Conclusions: Because supratentorial HTN-cSVD imaging markers are common in deep cICH, and deep lacunes and LVH are independently associated with deep cICH, it is likely that HTN-cSVD is the underlying microangiopathy of deep cICH.

Predictors of planned home birth before and during the COVID-19 pandemic.

To determine how demographic and clinical predictors of home birth have changed since the onset of the COVID-19 pandemic in the US. Using National Vital Statistics birth certificate data, a retrospective population-based cohort study was performed with planned home births and hospital births among women age≥18 years during calendar years 2019 (pre-pandemic) and 2021 (pandemic-era). Birth location (planned home birth vs. hospital birth) was analyzed using univariate and multivariable logistic regression, systematically examining the interaction of each demographic and clinical covariate with study year. After exclusions, a total of 6,087,768 birth records were retained for analysis, with the proportion of home births increasing from 0.82 % in 2019 to 1.24 % in 2021 (p<0.001). In the final multivariable logistic regression model of planned home birth, five demographic variables retained a statistically significant interaction with year: race and ethnicity, age, educational attainment, parity, and WIC participation. In each case, demographic differences between those having planned home births and hospital births became smaller (odds ratios closer to 1) in 2021 compared to 2019. Planned home births increased by more than 50 % during the pandemic, with greater socioeconomic diversity in the pandemic-era home birth cohort. The presence of clinical risk factors remained a strong predictor of hospital birth, with no evidence that pandemic-era home births had a higher clinical risk profile as compared to the pre-pandemic period.

Left atrial strain and long-term risk of atrial fibrillation in hypertrophic cardiomyopathy

Abstract Background The prevalence of atrial fibrillation (AF) in hypertrophic cardiomyopathy (HCM) patients is higher than in the general population, and it is associated with an increased risk of adverse outcomes, such as stroke, heart failure, and mortality. The left atrium (LA) plays an important role in maintaining normal cardiac function, and alterations in its structure and function can contribute to the development of AF. LA strain, a surrogate of LA remodeling, has been suggested a predictor of future AF. Purpose The aim of this study was to explore risk factors of new onset AF highlighting LA strain in patients with HCM. Methods Among a prospective cohort of 865 HCM patients collected at two large tertiary centers, 696 with adequate echocardiographic images to measure LA strain without a history of AF were included in the analysis. LA strain was measured on apical four-chamber view at initial evaluation using vendor-independent speckle-tracking software. The primary endpoint was new onset AF during 10 years after initial evaluation. Results The median age was 55.0 years and 74.3% were male. A median value of LA reservoir strain (LARS) was 26.2 % [interquartile range 20.4, 33.3]. Among the 696 patients, 66 had new onset AF 10 years, with a 10-year incidence of 15.8%. The unadjusted risk factors for new onset AF were previous stroke, non-apical HCM, family history of HCM, non-sustained ventricular tachycardia, obstructive HCM, extensive late gadolinium enhancement, larger LA diameter, larger LA volume, and lower LARS. LARS remained an independent predictor of new onset AF in multivariable analysis. The best cut-off value of LARS was 17.9% (hazard ratio 4.00, 95% confidence interval 2.44–6.55, p&amp;lt;0.001). Compared with LARS ≥17.9%, LARS &amp;lt;17.9% was significantly associated with a higher incidence of new onset AF, irrespective of presence of clinical risk factors (Figure 1) and LA enlargement (Figure 2). Conclusions In patients with HCM, low LA strain is an independent predictor of new onset AF.

PNPLA3 Genotype and Diabetes Identify Patients With Nonalcoholic Fatty Liver Disease at High Risk of Incident Cirrhosis

Non-alcoholic fatty liver disease (NAFLD) can progress to cirrhosis and hepatic decompensation, but whether genetic variants influence the rate of progression to cirrhosis or are useful in risk stratification among patients with NAFLD is uncertain. We included participants from 2 independent cohorts, they Michigan Genomics Initiative (MGI) and UK Biobank (UKBB), who had NAFLD defined by elevated alanine aminotransferase (ALT) levels in the absence of alternative chronic liver disease. The primary predictors were genetic variants and metabolic comorbidities associated with cirrhosis. We conducted time-to-event analyses using Fine-Gray competing risk models. We included 7893 and 46,880 participants from MGI and UKBB, respectively. In univariable analysis, PNPLA3-rs738409-GG genotype, diabetes, obesity, and ALT of ≥2× upper limit of normal were associated with higher incidence rate of cirrhosis in both MGI and UKBB. PNPLA3-rs738409-GG had additive effects with clinical risk factors including diabetes, obesity, and ALT elevations. Among patients with indeterminate fibrosis-4 (FIB4) scores (1.3-2.67), those with diabetes and PNPLA3-rs738409-GG genotype had an incidence rate of cirrhosis comparable to that of patients with high-risk FIB4 scores (>2.67) and 2.9-4.8 times that of patients with diabetes but CC/CG genotypes. In contrast, FIB4 <1.3 was associated with an incidence rate of cirrhosis significantly lower than that of FIB4 of >2.67, even in the presence of clinical risk factors and high-risk PNPLA3 genotype. PNPLA3-rs738409 genotype and diabetes identified patients with NAFLD currently considered indeterminate risk (FIB4 1.3-2.67) who had a similar risk of cirrhosis as those considered high-risk (FIB4 >2.67). PNPLA3 genotyping may improve prognostication and allow for prioritization of intensive intervention.

Isolated para-aortic nodal recurrence after treatment of early stage cervical carcinoma

ObjectiveSurgical evaluation of lymph node metastasis is paramount in the treatment of cervical cancer. We sought to explore the outcomes of patients with and without para-aortic lymphadenectomy undergoing curative-intent radical hysterectomy for stage IA-IIA cervical cancer. MethodsInstitutional data were retrospectively reviewed to identify women undergoing curative-intent radical hysterectomy with concurrent lymphadenectomy for stage IA-IIA cervical carcinoma from 2004 to 2021. Any carcinoma histology was allowed. Clinical risk stratification was performed according to GOG 92 and GOG 109 protocols. Disease outcomes, patterns of recurrence, and survival were analyzed with Chi square, t-test, Kaplan-Meier, and Cox proportional hazards multivariable statistics. Results300 patients were identified, 265 met inclusion criteria. Median follow up was 56 months. Pelvic lymphadenectomy (PLND) was performed in 71%, with the remainder undergoing combined para-aortic dissection (PPaLND). Baseline patient demographics and presence of clinical risk factors were well balanced between groups. PPaLND was more common in patients undergoing open surgery (OR 10.58, p <.0001), and tumors were larger in this group (2.96 vs 2.12 cm, p = .0002) and more likely non-squamous histology (OR 2.02, p = .017). Recurrence of disease was present in 13% of cases, with no difference between PLND and PPaLND regardless of histology. There were zero cases of isolated PaLN recurrence in either group. Neither progression free nor overall survival was different between groups. Prophylactic extended field radiation (EFRT) was not prescribed. ConclusionOmission of PaLN dissection, in the absence of suspicious nodes, did not decrease survival. There were no isolated PaLN recurrences after PLND alone.

Prevalence and predictors of acquired long QT syndrome in the ER department

Abstract Introduction Long QT syndrome (LQTS) is a rare heterogeneous syndrome that may be congenital or acquired, the latter being more common. Its real-world prevalence remains to be determined. We aimed to determine the prevalence of this syndrome in patients admitted to the emergency room (ER) and characterize the subset of patients with severely prolonged QT. Methods A retrospective analysis of ECG of all consecutively admitted patients in the ER of a tertiary hospital between the 28th of January and the 17th of March 2020 was made. All patients with Bazzett corrected QT interval greater than 470ms in men and 480ms in women were included. Repeated ECGs or with bad electrocardiographic quality, congenital LQTS, atrial fibrillation and pacemaker rhythm were excluded. Clinical data with a special focus on QT prolonging drugs and clinical factors were recorded. Statistical comparison was made between the groups with and without QT interval greater than 500ms. Results A total of 6280 ECGs of 5056 patients were analysed. After evaluation, 390 ECGs from 387 different patients were considered. Prevalence of LQTS at admission was 7.95%. Patients were more commonly men (53.1%) with an average age of 73.6±14.7 years old and mean QTc interval of 502.14±32.2ms. Only 20% of the patients were symptomatic, with the most common form of presentation being syncope (50%). No ventricular arrhythmias were recorded. Regarding patients with a QT interval greater than 500ms, these were more frequently female (59.9% vs 37.2%, p&amp;lt;0.001), were more frequently on QT prolonging drugs (77.8% vs 67.3%; p=0.002). Presence of clinical risk factors was not a risk factor per se (p=0.811) but a greater number of risk factors was linked to more severely prolonged QT (p=0.040). The main contributing factor was intake of antibiotics (odds ratio (OR) 3.497; CI 95% 1.074–11.321; p=0.038) followed by female gender (OR 2.518; CI 95% 1.668–3.800; p&amp;lt;0.001) and use of antipsychotics (OR 1.960; CI 95% 1.159–3.316; p=0.012). Conclusions Acquired LQTS is particularly prevalent in the ER setting. The complex interaction of clinical factors and drug iatrogenesis and the unpredictability of its manifestations render its management and recognition difficult but essential. Female patients on antibiotics and antipsychotics are at particularly high risk. Efforts must be made in order to avoid, detect and treat acquired LQTS as early as possible. Funding Acknowledgement Type of funding sources: None.

Thyroid nodules and thyroid cancer in women with positive thyroid screening in pregnancy: a double-centric, retrospective, cohort study.

ObjectiveThyroid nodules are a common finding in the general population. The primary aim of the study was to determine the prevalence of thyroid nodules and cancer found by ultrasound (US) in women who underwent screening for thyroid dysfunction during pregnancy.DesignA double-centric, retrospective, cohort study.Patients and methodsWe searched through medical records, including thyroid ultrasonography, of pregnant women who were positively screened for thyroid disorders (using thyroid-stimulating hormone and thyroid antibodies) from an unselected population (‘universal screening group’, n = 690) and of women who underwent the testing based on the presence of clinical risk factors defined by American Thyroid Association (’case-finding group’, n = 249).ResultsPrevalence of benign and malignant thyroid nodules was lower in the ‘universal screening group’ than in the ‘case-finding group’ (9.9% vs 17.7%, P= 0.002, and 0.9% vs 7.2%, P< 0.001, respectively). Consistently, the thyroid cancer rate was lower among the nodules in the ‘universal screening group’ than in the ‘case-finding group’ (8.1% vs 29.0%, P= 0.003). Ultrasound EU-TIRADS (European Thyroid Imaging and Reporting Data System) category ≥4 had a 95.8% sensitivity for thyroid cancer. In palpable nodules, the prevalence of cancer was significantly higher than in the non-palpable ones (44.0% vs 2.2%, P < 0.001). In a multivariate regression analysis, thyroid nodules were associated with a history of infertility and parity.ConclusionsCompared to the data from cancer registries, universal screening allowed detecting thyroid cancer in pregnancy three to five times more frequently, but the cancer rate among nodules (8.1%) did not differ from the common population. US had very good sensitivity for thyroid cancer in pregnancy.

Relationship between the D-dimer and von Willebrand factor levels and the development of gastrointestinal bleeding in patients with stable coronary artery disease: data from the registry of long-term antithrombotic therapy REGATTA-1

Aim. To study the role of von Willebrand factor (VWF) and D-dimer (DD) as predictors of upper gastrointestinal bleeding (GIB) in patients with stable coronary artery disease (CAD).Material and methods. The study included patients with stable CAD who are members of the prospective registry of long-term antithrombotic therapy (REGATTA-1) (ClinicalTrials.gov Identifier: NCT04347200). The primary endpoints were actionable GIBs (Bleeding Academic Research Consortium type 2-5). Cut-off points for DD and VWF were determined by ROC analysis. The predictive significance of an increase in VWF and DD was assessed by the logistic regression.Results. The study included 408 patients (men, 77,5%; mean age, 61,3±10,8 years). The median follow-up period was 2,5 [1,1-14,7] years. DD was determined in all patients, including 36 patients with GIB, while VWF — in 169 patients (28 patients with GIB). An increase in DD &gt;928 ng/ml was an independent predictor of GIB, including taking into account clinical risk factors (odds ratio (OR), 3,26 [95% confidence interval (CI), 1,43-7,42] (p=0,0047), or the previously developed REGATTA scale score (OR, 3,73, 95% CI: 1,65-8,43 (p=0,0015)). VWF &gt;105% was also an independent predictor of GIB (OR, 14,02; 95% CI: 1,41-139,42 (p=0,023)); in the REGATTA scale model — OR 11,3, 95% CI: 1,43-88,83 (p=0,021). The increase in both markers was most unfavorable, since the proportion of those with GIB was 41,4%, while among patients with normal DD and increased VWF — 14,9%, and with low values of both markers — 0%. OR of GIB in patients with an increase in both markers was 4,1 (95% CI: 1,6-10,3 (p=0,003)).Conclusion. In patients with stable CAD, an increase in VWF and DD was associated with an increase in GIB risk regardless of the presence of clinical risk factors.

958-P: Clinical Risk Factors and Adverse Pregnancy Outcomes in Overweight and Obese Women

Diabetes screening in early pregnancy is recommended by professional organizations, and some of these recommendations are based on the presence of clinical risk factors. We sought to assess the relationship between the number of diabetes risk factors and the prevalence of both GDM and other adverse pregnancy outcomes among a retrospective cohort of overweight and obese women. We collected information on diabetes-associated risk factors including maternal age, race, hypertension, prior GDM, and a first-degree relative with diabetes. Out of 1212 pregnant overweight and obese women, 313 (26%) had zero, 546 (45%) had one, and 353 (29%) had 2 or more risk factors. Women with 2 or more risk factors were more like to be older (p Disclosure M. N. Feghali: None. C. M. Scifres: None. Funding Eunice Kennedy Shriver National Institute of Child Health and Human Development (K23HD092893)

Utility of measuring serum creatinine to detect renal compromise in ED patients receiving IV contrast-enhanced CT scan.

The objectives of this study are to determine the efficacy of a roster of clinical factors in identifying risk for renal insufficiency in emergency department (ED) patients requiring intravenous contrast-enhanced CT scan (IVCE-CT) and to help mitigate potential for developing contrast-induced nephropathy (CIN). A review was conducted of consecutive ED patients who received IVCE-CT during a 4-month period in our urban ED. The values of ED serum creatinine (SCr) performed were tabulated. The medical records of all patients with an elevated SCr (> 1.4mg/dL) were reviewed to determine and correlate the presence of clinical risk factors for underlying renal insufficiency. During the 4-month study period, there were 2260 consecutive cases who received IVCE-CT; of these, 2250 (99.6%) had concomitant measurement of SCr. Elevated SCr occurred in 141 patients (6.2%); of these, 75 had a SCr > 2mg/dL. In all, 139/141 (98.6%) with an elevated SCr had an underlying chronic or acute medical condition identified by medical record review which potentially compromised renal function, including chronic renal disease, diabetes mellitus, HIV infection, cancer, hypertension, congestive heart failure, sepsis/septic shock, chronic alcoholism, and sickle cell disease. Two patients with no identified risk factor each had (mildly) elevated SCr; both had a normal SCr measured post-CT scan. The total cost of performing serum basic metabolic panel to measure SCr in all patients during the 4-month study period was $94,500. Elevated SCr is rarely present in ED patients without recognized risk factors who receive IVCE-CT scan. The vast majority with underlying renal insufficiency are readily identified by a review of the patient's medical history and/or clinical findings. Routine SCr measurement on all ED patients regardless of risk stratification prior to IVCE imaging is neither time nor cost-effective.

Prevalence of fracture risk among middle-aged and elderly population of Gujarat, India: an observational study

Background: This study was conducted to estimate the prevalence of fracture risk among middle-aged and elderly population of Gujarat and to find out the prevalence of the clinical risk factors (CRF) and its significance with risk of fracture. To compare the risk of fracture among men and women.Methods: An observational study included 500 participants both men and women, in age group of 40-80 years. Participants were assessed with the fracture risk assessment tool (FRAX) without BMD to evaluate the 10-year probability of risk of Major osteoporotic fracture (MOF) and Hip fracture (HF). India-specific age-dependent thresholds were used to categorize the participants into safety zone and treatment zone followed by statistical analysis. Level of significance was kept at 5%.Results: Total 500 participants, 56.8% males and 43.2% females with mean age 56.3±9.7 years. As per the estimated prevalence, 22% participants were in treatment zone and 78% were in safety zone for HF risk and for major osteoporotic fracture risk, 24% participants were in treatment zone and 76% were in safety zone. In 18.6% participants the hip fracture risk was ≥3% and in 2% participants the major osteoporotic fracture risk was ≥20%. Women had more fracture risk compare to men, for HF [t (464.6)=-3.04, p=0.002] and for MOF [t (441.3)=-5.13, p&lt;0.001]. Significant difference in fracture risk was found with presence of CRF except with smoking and alcohol use.Conclusions: FRAX can be used to identify the 10-year probability of fracture risk. The prevalence showed fewer participants in treatment zone and more in safety zone. Women had higher fracture probabilities than men.

Defining Extreme Phenotypes of OSA Across International Sleep Centers

Extreme phenotypes of OSA have not been systematically defined. This study developed objective definitions of extreme phenotypes of OSA by using a multivariate approach. The utility of these definitions for identifying characteristics that confer predisposition toward or protection against OSA is shown in a new prospective sample. In a large international sample, race-specific liability scores were calculated from a weighted logistic regression that included age, sex, and BMI. Extreme cases were defined as individuals with an apnea-hypopnea index (AHI)≥ 30 events/hour but low likelihood of OSA based on age, sex, and BMI (liability scores > 90th percentile). Similarly, extreme controls were individuals with an AHI< 5 events/hour but high likelihood of OSA (liability scores< 10th percentile). Definitions were applied to a prospective sample from the Sleep Apnea Global Interdisciplinary Consortium, and differences in photography-based craniofacial and intraoral phenotypes were evaluated. This study included retrospective data from 81,338 individuals. A total of 4,168 extreme cases and 1,432 extreme controls were identified by using liability scores. Extreme cases were younger (43.1 ± 14.7 years), overweight (28.6 ± 6.8kg/m2), and predominantly female (71.1%). Extreme controls were older (53.8 ± 14.1 years), obese (34.0 ± 8.1kg/m2), and predominantly male (65.8%). These objective definitions identified 29 extreme cases and 87 extreme controls among 1,424 Sleep Apnea Global Interdisciplinary Consortium participants with photography-based phenotyping. Comparisons suggest that a greater cervicomental angle increases risk for OSA in the absence of clinical risk factors, and smaller facial widths are protective in the presence of clinical risk factors. This objective definition can be applied in sleep centers throughout the world to consistently define OSA extreme phenotypes for future studies on genetic, anatomic, and physiologic pathways to OSA.

Implications of the Fracture Risk Assessment Algorithm for the assessment and improvement of bone health in patients with prostate cancer: A comprehensive review.

Maintaining the optimum bone health is one of the important concerns in patients with prostate cancer, but it usually remains neglected. Failure to screen these patients is detrimental to both the length and the quality of life. The estimation of bone mineral density (BMD) and more recently the World Health Organization's fracture risk assessment (FRAX) algorithm in appropriate patients is recommended by several specialty organizations/associations at the time of instituting androgen deprivation therapy (ADT) for metastatic and high-risk individuals. It provides a 10-year risk evaluation of hip and major osteoporotic fractures (MOF). Using this web-based new investigating tool, candidates at high risk of fractures can be predicted more accurately according to clinical risk factors (CRF) alone or in combination with the femoral neck BMD. The FRAX application for senile osteoporosis has been studied and reviewed extensively, but no systematic review has ever been conducted for assessing the implication of FRAX in prostate cancer. This review article will give insight about the validity, role, and utility of this investigating tool in clinical practice for fracture risk assessment in these individuals. This systematic review was carried out as per the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines and Cochrane review principles. We searched the PubMed, Cochrane database of systematic reviews, and the EMBASE electronic database until December 2018 using the medical subject heading terms prostate cancer and FRAX. A total of nine studies meet the inclusion criteria and were included in the review. These studies enrolled a total of 3704 patients (sample size range, 78-1220) of localized, metastatic, castration resistant prostate cancer with or without ADT and/or on photon or radiotherapy. The factors that influenced FRAX included age, ethnicity, baseline BMD, duration of ADT, presence of CRF, and measurement methods (CRF, with/without BMD, computed tomography based). An advanced age and duration of ADT were the most robust risk factors. A 10-year MOF and hip fracture risk estimation was higher when the femoral neck BMD was not incorporated in the FRAX measurement. Despite several well-known strengths of using FRAX in the fracture risk assessment of suitable candidates with prostate cancer, several risk factors such as the mode/duration of ADT, mode of radiotherapy, Vitamin D levels, bone remodeling markers, and recent/recurrent fractures need to be incorporated in the FRAX calculator for improving the predictive ability. In contrast to senile osteoporosis with a longer life expectancy, the fracture risk in patients with prostate cancer need to be measured more frequently and for a shorter time. Therefore, models like Garvan calculator with both 5- and 10-year risk estimates have to be developed for these patients. Additionally, its utilization is of limited value in the presence of recurrent fractures or falls. The FRAX algorithm is beneficial in identifying patients who require early intervention or bone-directed therapy as an early step to decrease skeletal-related events and other morbidity. Several risk factors need to be added for improving the FRAX predictive value. This model is still underutilized in the clinical practice and increasing the awareness among treating physicians will help in optimizing the bone health and the quality of life of this important population subgroup.

Tests for latent tuberculosis in candidates for solid organ transplantation: A systematic review and meta-analysis.

Reactivation of latent tuberculosis following solid organ transplantation has serious consequences for the recipient. The most useful diagnostic test for latent TB is not clear. We conducted a systematic review and meta-analysis to assess the relative test performance of interferon gamma release assays (IGRAs) and the tuberculin skin test (TST) in people undergoing solid organ transplantation. The clinical or radiological risk factors were used as the proxy reference standard. Test performance was expressed as an odd ratio (OR). We identified 24 studies (N=7811), 12 studies compared IGRAs with TST directly, nine studies evaluated only TST and three studies only IGRAs. Direct comparison between tests and clinical risk factors indicated both tests were strongly associated with the presence of clinical risk factors for TB (TST: OR 3.17; 95%CI 1.55-6.48, IGRA: OR 2.78; 95%CI 1.55-5.01), and radiological evidence of past TB (TST: OR 3.26; 95%CI 1.85-5.73, IGRA: OR 3.85; 95%CI 2.16-6.86). Relative comparison indicated IGRAs positivity was more strongly associated with presence of radiological evidence of TB than TST (relative OR: 3.24; 95%CI 1.10-9.56). While there is no strong evidence in supporting use of IGRAs over TST for diagnosing latent TB, IGRAs positivity is more associated with the presence of radiological evidence of previous TB.

Clinical risk factors of acute severe or fatal violence among forensic mental health patients

Existing violence risk assessment studies of mental health patients focus mostly on the association of historical presence of clinical risk factors and long-term violence, with little emphasis on the short-term temporal proximity between clinically relevant risk factors and the occurrence of violent behaviors. This research examined the proximal clinical risk factors (within days to a week prior) of acute severe or fatal violence among a group of forensic patients with serious mental illness (N = 287) found Not Criminally Responsible for offenses that involved violence against person(s), based on file review. Command hallucinations (OR = 2.35, 95% CI = 1.05 – 5.24), Threat/control-override symptoms (OR = 3.10, 95% CI = 1.51 – 6.35) and Capgras syndrome (OR = 3.58, 95% CI = 1.06 – 12.15) were identified as independent significant risk factors associated with acute severe or fatal violence. First degree relatives and intimate partners were significantly associated with being a victim of acute severe or fatal violence. Gender, recent alcohol use and recent drug use were not significantly associated with acute severe or fatal violence. Clinical utilities of the results and future directions for research are discussed.

Could obesity be considered as risk factor for non-vertebral low-impact fractures?

BackgroundIt has long been established that obesity plays a positive role against osteoporosis (OP) and low-impact fractures (Fx). However, more recent data has shown higher fracture risk in obese individuals. The aim of this study was to investigate the association between BMI, particularly obesity, OP and low-impact Fx in Brazilian women, as well as to evaluate the SAPORI (Sao Paulo Osteoporosis Risk Index) tool performance to identify low BMD according BMI category.MethodsA total of 6182 women aged over 40 years were included in this cross-sectional analysis using data from two large Brazilian studies. All participants performed hip and spine bone mineral density (BMD) measurements and answered a detailed questionnaire about the presence of clinical risk factors (CRFs) related to low BMD and risk fractures. The World Health Organization (WHO) criteria were used to define obesity.ResultsAge-adjusted osteoporosis prevalence was 20.8, 33.6, 47 and 67.1% in obese, overweight, normal and underweight category, respectively. Obesity was present in 29,6% (1.830 women) in the study population and the likelihood of osteoporosis and low-impact Fx compared to a normal BMI in this subgroup was of 0.24 (95% CI 0.20–0.28; p < 0.001) and of 1.68 (95% CI 1.35–2.11; p < 0.001), respectively. However, the hip Fx likelihood was lower in obese compared with non-obese women (OR = 0.44; 95% CI 0.20–0.97). Using an originally validated cut-off, the SAPORI tool sensitivity was significantly hampered in overweight and obese women although the accuracy had remained suitable because of increasing in specificity.ConclusionsThe osteoporosis prevalence reduced as BMI increased and obesity was associated with low-impact Fx, regardless of the BMD measurements. Moreover, the SAPORI performance was impaired in obese women.

Diagnostic accuracy of magnetic resonance imaging in detecting the severity of abnormal invasive placenta: a systematic review and meta-analysis.

Accurate prenatal diagnosis of abnormally invasive placenta (AIP) is fundamental because it significantly reduces maternal morbidities. Medline, Embase, CINAHL and the Cochrane databases were searched. The primary aim of the present review was to elucidate the diagnostic accuracy of prenatal magnetic resonance imaging (MRI) in recognizing the severity of AIP, defined as the depth and topography of invasion. The secondary aim was to ascertain the strength of association between each MRI sign and the depth of placental invasion and to test their individual predictive accuracy in detecting such invasion. Inclusion criteria were studies on women who had prenatal MRI for ultrasound suspicion or the presence of clinical risk factors for AIP. Estimates of sensitivity, specificity, positive and negative likelihood ratios and diagnostic odds ratio were calculated using the hierarchical summary receiver characteristics curve model, and individual data random-effect logistic regression was used to calculate OR. Twenty studies (1080 pregnancies undergoing MRI mainly for the ultrasound suspicion of AIP) were included. MRI showed a sensitivity of 94.4% [95% confidence interval (CI) 15.8-99.9], 100% (95% CI 75.3-100) and 86.5% (95% CI 74.2-94.4) for detection of placenta accreta, increta and percreta, respectively; the corresponding values for specificity were 98.8% (95% CI 70.7-100), 97.3% (95% CI 93.3-99.3), 96.8% (95% CI 93.5-98.7). MRI identified 100% of cases with S1 and 100% of those with S2 invasion confirmed at surgery. Among the different MRI signs, intra-placental dark bands showed the best sensitivity for the detection of placenta accreta, increta and percreta; as well as abnormal intra-placental vascularity, uterine bulging was associated with a higher risk of increta and percreta, exophitic mass and bladder tenting with placenta percreta. Prenatal MRI has an excellent diagnostic accuracy in identifying the depth and the topography of placental invasion. However, these findings come mainly from studies in which MRI was performed as a secondary imaging tool in women already screened for AIP on ultrasound and might not reflect its actual diagnostic performance in detecting the severity of these disorders.

Pilot screening study of targeted genetic polymorphisms for association with seasonal influenza hospital admission.

Host response to influenza is highly variable, suggesting a potential role of host genetic variation. To investigate the host genetics of severe influenza in a targeted fashion, 32 single nucleotide polymorphisms (SNPs) within viral immune response genes were evaluated for association with seasonal influenza hospitalization in an adult study population with European ancestry. SNP allele and genotype frequencies were compared between hospitalized influenza patients (cases) and population controls in a case-control study that included a discovery group (26 cases and 993 controls) and two independent, validation groups (1 with 84 cases and 4076 controls; the other with 128 cases and 9187 controls). Cases and controls had similar allele frequencies for variant rs12252 in interferon-inducible transmembrane protein 3 (IFITM3) (P > 0.05), and the study did not replicate the previously reported association of rs12252 with hospitalized influenza. In the discovery group, the preliminary finding of an association with a nonsense polymorphism (rs8072510) within the schlafen family member 13 (SFLN13) gene (P = 0.0099) was not confirmed in either validation group. Neither rs12252 nor rs8072510 showed an association according to the presence of clinical risk factors for influenza complications (P > 0.05), suggesting that these factors did not modify associations between the SNPs and hospitalized influenza. No other SNPs showed a statistically significant association with hospitalized influenza. Further research is needed to identify genetic factors involved in host response to seasonal influenza infection and to assess whether rs12252, a low-frequency variant in Europeans, contributes to influenza severity in populations with European ancestry.

Cell autonomous expression of CXCL-10 in JAK2V617F-mutated MPN.

Myeloproliferative neoplasms (MPN) are clonal disorders of hematopoietic stem- and progenitor cells. Mutation of Janus-Kinase 2 (JAK2) is the most frequent genetic event detected in Philadelphia-negative MPN. In advanced phases, the clinical hallmark of the disease is a striking inflammatory syndrome. So far, the cellular and molecular basis of inflammation is not fully understood. We, therefore, sought to investigate the relationship of activating JAK2 mutation and aberrant cytokine expression in MPN. Cytokine array was performed to identify Jak2V617F-related cytokine expression and secretion. CXCL10 mRNA expression was analyzed by qPCR in peripheral blood cells. To exclude paracrine/autocrine stimulation as a potential mechanism, we generated Ba/F3-EpoR-JAK2WT or EpoR-JAK2V617F cells lacking CXCL10 receptor. Pharmacologic inhibition of JAK2 kinase was achieved by JAK-Inhibitor treatment. Signaling pathways and downstream effectors were characterized by Western blotting, immunofluorescence microscopy, luciferase reporter assays, qPCR, and chromatin-immunoprecipitation studies. We identified CXCL10 as the most highly induced cytokine in JAK2-mutated cell lines. In MPN patients, CXCL10 is highly expressed in JAK2V617F but not JAK2WT MPN or healthy donor controls. Moreover, CXCL10 expression correlates with JAK2V617F allelic burden. High CXCL10 correlates with the presence of clinical risk factors but not with clinical symptoms and quality of life. Pharmacologic inhibition of mutated JAK2 kinase inhibits CXCL10 expression. NFκB signaling is activated downstream of JAK2V617F receptor and directly induces CXCL10 expression. Our data provide first evidence for a link between oncogenic JAK2V617F signaling and cell intrinsic induction of CXCL10 induced by activated NFkB signaling.