History Of Failure Research Articles

Efficacy of Brodalumab in Patients with Psoriasis and Risk Factors for Treatment Failure: A Review of Post Hoc Analyses.

Factors such as obesity, alcohol consumption, and tobacco use are associated with both increased psoriasis severity and inadequate response to systemic and biologic therapies. Obesity is linked to chronic inflammation, which can contribute to psoriasis pathogenesis. Fixed-dose therapies may have reduced efficacy in patients with a higher body mass index, while weight-based dosing can increase the burden of drug-specific side effects. Alcohol and nicotine from tobacco have also been shown to stimulate keratinocyte and immune cell proliferation and production of proinflammatory cytokines. While these risk factors are prevalent among patients with moderate-to-severe psoriasis, their influence on treatment outcomes may be overlooked when evaluating therapeutic options. Brodalumab is a fully human interleukin-17 receptorA antagonist approved for the treatment of moderate-to-severe psoriasis. In this review, we describe the lifestyle-related risk factors associated with decreased response to treatment. We further summarize the post hoc analyses of brodalumab in participant subgroups with moderate-to-severe psoriasis and a history of prior biologic failure, obesity, and alcohol or tobacco use from two phase 3 clinical trials (AMAGINE-2 and AMAGINE-3; ClinicalTrials.gov identifiers: NCT01708603 and NCT01708629, respectively). Our review of clinical trial and real-world data suggests that brodalumab is an efficacious and safe treatment option for patients with lifestyle factors that increase the likelihood of treatment failure, allowing them to achieve skin clearance and improve quality of life.

Lower Late Development Rate of Acute Respiratory Distress Syndrome in Patients with Lower Mechanical Power or Driving Pressure.

For patients on ventilation without acute respiratory distress syndrome (ARDS), there are, as yet, limited data on ventilation strategies. We hypothesized that driving pressure (DP) and mechanical power (MP) may play key roles for the late development of ARDS in patients without initial ARDS. A post hoc analysis of a database from our previous cohort was performed. The mean DP/MP was computed from the data before ARDS development or until ventilator support was discontinued within 28 days. The association between DP/MP and late development of ARDS within 28 days was determined. One hundred and twelve patients were enrolled, among whom seven developed ARDS. Univariate Cox regression showed that congestive heart failure (CHF) history and higher levels of mean MP and DP were associated with ARDS development. Multivariate models revealed that the mean MP and mean DP were still factors independently associated with ARDS development at hazard ratios of 1.177 and 1.226 after adjusting for the CHF effect. Areas under the receiver operating characteristic curves for mean DP/MP in predicting ARDS development were 0.813 and 0.759, respectively. In conclusion, high mean DP and MP values may be key factors associated with late ARDS development. The mean DP had a better predicted value for the development of ARDS than the mean MP.

The change over time in the prescription pattern of the first targeted drug after failure of conventional therapy in patients with rheumatoid arthritis: a 20-year real-world experience.

To evaluate the change over time in the pattern of the first biologic/targeted synthetic drug (b/tsDMARD) prescription and baseline characteristics in patients with rheumatoid arthritis (RA) from 1999 to the present. A retrospective data analysis from RA patients enrolled in an Italian single-center registry was conducted. The analysis was limited to all the patients who received the first b/tsDMARD between October 1999 and December 2022. Patients were stratified according to the date of b/tsDMARD initiation into 4 groups (1999-2004, 2005-2010, 2011-2016, and 2017-2022) and a comparative analysis of prescription patterns and patients' baseline characteristics was performed. The study population included 1206 patients. The characteristics of patients at baseline in the 4 groups were similar overall, with the exception of disease duration (12.26, 10.5, 9.7, 8.1 years, respectively; p<0.0001), mean number of conventional DMARDs used before the first b/tsDMARD (3, 2.5, 2.1, 1.4, respectively; p<0.0001), and mean clinical disease activity index (CDAI) score (30.1, 24.3, 21.8, 20.4, respectively; p<0.0001). A progressive reduction (from 95 to 43% of patients) in the prescription of first-line TNF-α inhibitors toward other mechanisms of action has been observed. The rate of patients treated with b/tsDMARDs as monotherapy progressively increased (from 18 to 26%) especially among those not receiving a TNFα inhibitor. The expansion of the therapeutic armamentarium has changed the management strategy of RA over time towards an earlier introduction of targeted drugs (increasingly often as monotherapy) in patients with progressive lower disease activity and a history of failure with fewer previous conventional drugs.

Development and validation of a prognostic scoring system for 1-year mortality in older patients with hip fractures.

Hip fractures in older people result in increased mortality. We developed and validated an accurate and simple prognostic scoring system for hip fractures that can be used preoperatively. Retrospective study. Multicenter. Patients aged ≥65years with hip fractures who underwent surgery between 2011 and 2021 were enrolled. The significant factors were determined with logistic regression analysis, and a scoring system was developed. The patients were classified into three groups, and a log-rank test was performed to evaluate 1-year survival rates. The model was internally and externally validated using the 5-fold cross-validation and data from another hospital, respectively. We included 1026 patients. The analysis revealed eight significant prognostic factors: sex, body mass index, history of chronic heart failure and malignancy, activities of daily living (ADLs) before injury, hemoglobin and the prognostic nutritional index (PNI) at injury, and the American Society of Anesthesiologists Physical Status. The area under the receiver operating characteristic curve (AUC) after internal validation was 0.853. The external validation data consisted of 110 patients. The AUC of the model for the validation data was 0.905, showing outstanding discrimination. Sensitivity and specificity were 88.7% vs. 100% and 93.3% vs. 95.2% for the development and validation data, respectively. We developed and validated an accurate and simple prognostic scoring system for hip fractures using only preoperative factors. Our findings highlight PNI as an important predictor of prognosis in hip fracture patients.

Abstract P149: Sex-Specific Blood Pressure Thresholds in Middle-Aged Adults: Results from the Atherosclerosis Risk in Communities (ARIC) Study

Background: Recent studies reported higher coronary heart disease (CHD) risk at lower blood pressure (BP) in females than males, implying a need for sex-specific hypertension (HTN) thresholds. Whether these observations apply to diagnosis thresholds and/or treatment targets remains unclear. Objectives: To determine whether CHD risk differs by BP levels between males and females according to HTN treatment status. Methods: The ARIC Study measured seated BP during Visit 1 (1987-1989), averaging the second and third of three measurements. HTN treatment was determined based on pill-bottle review. We excluded participants with a history of CHD, heart failure, or stroke. Incident CHD events were adjudicated. We examined 10-year CHD risk scores using the PREVENT risk estimator, CHD incidence rates (IR), and the hazard ratios (HR) of CHD events via the Pooled Estimating Equation, Poisson regression, and Cox proportional hazard models, controlling for CHD risk factors ( Table Footnote ). Results: Of 13,426 participants (56% female, mean age [54±5.7 years]), 25% were treated for HTN. Males in both groups had higher average 10-year CHD risk scores across SBP categories than females ( P comparing trends &lt;0.001) ( Table ). While IRs were lower among females in the untreated group, they did not differ significantly from males in treated participants ( P comparing trends &gt; 0.05). Notably, while similar in untreated populations, treated females may experience higher risk (HR) of incidence CHD events than treated males across all SBP categories. Conclusion: While there were differences in absolute and relative risk of CHD between males and females, we did not find consistent evidence that untreated males and females experience different risk of CHD risk by SBP threshold. These findings do not support a sex-specific threshold for hypertension diagnosis or treatment.

Abstract MP07: Efficacy and safety of aprocitentan in patients with resistant hypertension and elevated NT-proBNP

Background and Objectives: The endothelin ETA/ETB receptor antagonist aprocitentan (APRO) decreased blood pressure (BP) in patients with confirmed resistant hypertension (RHT) in the PRECISION study. 19.6% of the overall population (143 subjects) had a reported history of Heart Failure (HF). It is well known that in subjects with RHT, HF is often underdiagnosed. In PRECISION, NT-proBNP (a marker of HF) was measured. Here we report the efficacy and safety of APRO in patients with increased NT-proBNP. Methods: 730 patients with RHT were switched to a standardized fixed-dose combination of amlodipine/valsartan/hydrochlorothiazide from their existing anti-hypertensive and diuretic medication and then randomized to APRO (12.5 mg or 25 mg) or placebo in PRECISION. This analysis considers subjects with baseline blood levels of NT-proBNP &gt;125 pg/mL. Change in BP, incident cases of edema/fluid retention and change in body weight were assessed. Descriptive statistics are presented. Results: 236 enrolled subjects (32.3%) had NT-proBNP levels from 125–1125 pg/mL. At Week 4, APRO 12.5 mg decreased trough sitting systolic BP (SiSBP) by mean (SD) 14.2 (16.7) mm/Hg, APRO 25 mg by 15.8 (13.5) mm/Hg and placebo by 9.9 (18.0) mm/Hg, confirming that the effect was greater for APRO than placebo with no apparent difference between 12.5 and 25 mg, as observed in the overall population enrolled in PRECISION. The effect was maintained with APRO 25 mg at Week 36 with a decrease of 18.4 (15.2) mm/Hg versus baseline. Adverse events of edema/fluid retention were reported with an incidence of 13.4%, 25.7% and 1.2% in the 12.5 mg, 25 mg and placebo group, respectively, at Week 4. During the SB part up to 36 weeks edema/fluid retention was reported by 26.1% of subjects with 25 mg. Body weight change at Week 4 was +0.5, +0.7 and -0.2 Kg with 12.5 mg, 25mg and placebo, respectively. This weight increase was reversible: a subsequent decrease resulted in a difference versus baseline of 0.4 kg at Week 36. NT-proBNP ratio vs baseline (geometric mean) was 0.94, 0.86 and 0.78 with 12.5 mg, 25 mg and placebo, respectively, at Week 4. There was no increase over time, the ratio vs baseline was still below 1 (0.91) at Week 36. Conclusion: Aprocitentan is effective in patients with RHT and elevated NT-proBNP. Edema and fluid retention are more common in this sub-group compared with the overall population included in PRECISION, but it is not linked to significant weight gain or increase of NT-proBNP.

A Multicentre Prospective Cohort Study to Identify High-Risk Transient Ischemic Attack/Minor Stroke Patients Benefitting from Echocardiography

BackgroundWe aimed to derive a clinical decision rule to identify patients with transient ischemic attack (TIA) or minor stroke most likely to benefit from echocardiography. MethodsThis multicentre prospective cohort study enrolled adults diagnosed with TIA/minor stroke in the emergency department who underwent echocardiograms within 90 days, from 13 Canadian academic emergency departments from October 2006 to May 2017. Our outcome was clinically significant echocardiogram findings. ResultsIn 7149 eligible patients, a clinically significant finding was found in 556 (7.8%). There were a further 2421 (33.9%) with potentially significant findings. History of heart failure (adjusted odds ratio [OR], 3.9) or coronary artery disease (OR, 2.7) were the factors most strongly associated with clinically significant echocardiogram findings, whereas young age, male sex, valvular heart disease, and infarct (any age) on neuroimaging were modestly associated (OR, 1.3-1.9). The model combining these predictors into a score (range: 0-15), had a C-statistic of 0.67 (95% confidence interval [CI], 0.65-0.70). A cut point of 6 points or more classified 6.6% of cases as high likelihood, defined as > 15% for clinically significant echocardiogram findings. ConclusionsEchocardiography is a very useful test in the investigations of patients with TIA/minor stroke. We identified high-risk clinical features—combined to create a clinical decision rule—to identify which patients with TIA/minor stroke are likely to have clinically significant echocardiogram findings requiring an immediate change in management. These patients should have echocardiography prioritized, whereas others may continue to have echocardiography conducted in a less urgent fashion.

Diagnostic accuracy of a machine learning algorithm using point-of-care high-sensitivity cardiac troponin I for rapid rule-out of myocardial infarction: a retrospective study

Point-of-care (POC) high-sensitivity cardiac troponin (hs-cTn) assays have been shown to provide similar analytical precision despite substantially shorter turnaround times compared with laboratory-based hs-cTn assays. We applied the previously developed machine learning based personalised Artificial Intelligence in Suspected Myocardial Infarction Study (ARTEMIS) algorithm, which can predict the individual probability of myocardial infarction, with a single POC hs-cTn measurement, and compared its diagnostic performance with standard-of-care pathways for rapid rule-out of myocardial infarction. We retrospectively analysed pooled data from consecutive patients of two prospective observational cohorts in geographically distinct regions (the Safe Emergency Department Discharge Rate cohort from the USA and the Suspected Acute Myocardial Infarction in Emergency cohort from Australia) who presented to the emergency department with suspected myocardial infarction. Patients with ST-segment elevation myocardial infarction were excluded. Safety and efficacy of direct rule-out of myocardial infarction by the ARTEMIS algorithm (at a pre-specified probability threshold of <0·5%) were compared with the European Society of Cardiology (ESC)-recommended and the American College of Cardiology (ACC)-recommended 0 h pathways using a single POC high-sensitivity cardiac troponin I (hs-cTnI) measurement (Siemens Atellica VTLi as investigational assay). The primary diagnostic outcome was an adjudicated index diagnosis of type 1 or type 2 myocardial infarction according to the Fourth Universal Definition of Myocardial Infarction. The safety outcome was a composite of incident myocardial infarction and cardiovascular death (follow-up events) at 30 days. Additional analyses were performed for type I myocardial infarction only (secondary diagnostic outcome), and for each cohort separately. Subgroup analyses were performed for age (<65 years vs ≥65 years), sex, symptom onset (≤3 h vs >3 h), estimated glomerular filtration rate (<60 mL/min per 1·73 m2vs ≥60 mL/min per 1·73 m2), and absence or presence of arterial hypertension, diabetes, a history of coronary artery disease, myocardial infarction, or heart failure, smoking, and ischaemic electrocardiogram signs. Among 2560 patients (1075 [42%] women, median age 58 years [IQR 48·0-69·0]), prevalence of myocardial infarction was 6·5% (166/2560). The ARTEMIS-POC algorithm classified 899 patients (35·1%) as suitable for rapid rule-out with a negative predictive value of 99·96% (95% CI 99·64-99·96) and a sensitivity of 99·68% (97·21-99·70). For type I myocardial infarction only, negative predictive value and sensitivity were both 100%. Proportions of missed index myocardial infarction (0·05% [0·04-0·42]) and follow-up events at 30 days (0·07% [95% CI 0·06-0·59]) were low. While maintaining high safety, the ARTEMIS-POC algorithm identified more than twice as many patients as eligible for direct rule-out compared with guideline-recommended ESC 0 h (15·2%) and ACC 0 h (13·8%) pathways. Superior efficacy persisted across all clinically relevant subgroups. The patient-tailored, medical decision support ARTEMIS-POC algorithm applied with a single POC hs-cTnI measurement allows for very rapid, safe, and more efficient direct rule-out of myocardial infarction than guideline-recommended pathways. It has the potential to expedite the safe discharge of low-risk patients from the emergency department including early presenters with symptom onset less than 3 h at the time of admission and might open new opportunities for the triage of patients with suspected myocardial infarction even in ambulatory, preclinical, or geographically isolated care settings. The German Center for Cardiovascular Research (DZHK).

Variations in antihypertensive medication treatment and blood pressure control among Veterans with HIV and existing hypertension

BackgroundHypertension is a leading risk factor for cardiovascular disease among patients living with HIV (PLWH). Understanding the predictors and patterns of antihypertensive medication prescription and blood pressure (BP) control among PLWH with hypertension (HTN) is important to improve the primary prevention efforts for this high-risk population. We sought to assess important patient-level correlates (eg, race) and inter-facility variations in antihypertension medication prescriptions and BP control among Veterans living with HIV (VLWH) and HTN. MethodsWe studied VLWH with a diagnosis of HTN who received care in the Veterans Health Administration (VHA) from January 2018 to December 2019. We evaluated HTN treatment and blood pressure control across demographic variables, including race, and by medical comorbidities. Data were also compared among VHA facilities. Predictors of HTN treatment and control were assessed in 2-level hierarchical multivariate logistic regression models to estimate odds ratios (ORs). The VHA facility random-effects parameters from the hierarchical models were used to calculate the median odds ratios to characterize the variation across the different VHA facilities. ResultsA total of 17,468 VLWH with HTN (mean age 61 years, 97% male, 54% Black, 40% White) who received care within the VHA facilities in 2018-2019 were included. 73% were prescribed antihypertension medications with higher prescription rates among Black vs White patients (75% vs 71%) and higher prescription rates among patients with a history of cardiovascular disease, diabetes, and kidney disease (>80%), and those receiving antiretroviral therapy and with controlled HIV viral load (∼75%). Only 27% of VLWH with HTN had optimal BP control of systolic BP <130 mmHg and diastolic BP <80 mmHg, with a lower rate of control among Black vs White patients (24% v. 31%). In multivariate regression, Black patients had a higher likelihood of HTN medication prescription (OR 1.32, 95% CI: 1.22-1.42) but were less likely to have optimal BP control (OR 0.82; 0.76-0.88). Important positive correlates of antihypertensive prescription and optimal BP control included: number of outpatient visits in prior year, and histories of diabetes, coronary artery disease, and heart failure. There was about 10% variability in both antihypertensive prescription and BP control patterns between VHA facilities for patients with similar characteristics. There was increased inter-facility variation in antihypertensive prescription among those with a history of heart failure and those not receiving antiretroviral therapy. ConclusionIn a retrospective analysis of large VHA data, we found that VLWH with HTN have suboptimal antihypertensive medication prescription and BP control. Black VLWH had higher HTN medication prescription rates but lower optimal BP control.

Relationship between systolic blood pressure and renal function on clinical outcomes in patients with atrial fibrillation: a report from the prospective AF-GEN-UK Registry.

Blood pressure (BP) extremes and renal (dys)function contribute to poor outcomes in patients with atrial fibrillation (AF). Using data from the prospective AF-GEN-UK study, we investigated the effect of systolic BP and interaction with renal function for prognostication. Baseline systolic BP (SBP) values were recorded for 1580 patients (mean [SD] age 71 [11] years, 60% male) and categorized as follows: 120-129 mmHg (n = 289, reference group) <110 mmHg (n = 165), 110-119 mmHg, (n = 254), 130-139 mmHg (n = 321), 140-159 mmHg (n = 385) and ≥160 mmHg (n = 166). Cox regression analysis, adjusted for age, oral anticoagulation (OAC) and CHA2DS2-VASc score established the impact of SBP, renal function and their interaction on 1-year outcomes. SBP groups were compared using ANOVA and chi-square tests. OAC use was 84% and similar across SBP groups. Renal dysfunction [estimated baseline glomerular filtration rate (eGFR) < 60 ml/min] was present in 24%, with significantly lower eGFR values in the SBP 110-119 mmHg group. History of heart failure was significantly higher in those with SBP <110 mmHg. SBP <110 mmHg was predictive of all cause-death on univariate [hazard ratio (HR) 2.36, 95% confidence interval (CI) 1.20-4.64] and adjusted (aHR 9.71, 95% CI 1.73-54.5) regression. There was no statistically significant interaction between SBP and eGFR, no associations of SBP with haemorrhagic or thromboembolic events. In people with AF, SBP <110 mmHg was independently predictive of all-cause death, with no significant interaction between SBP and renal (dys)function. This may reflect general poor health and/or excessive antihypertensive therapy, which should be avoided.

Ilizarov Distraction for Congenital Pseudoarthrosis of the Tibia in Adults.

The clinical evidence on the management for congenital pseudoarthrosis of the tibia (CPT) in adults is limited. The aim of this study is to assess the functional and radiological outcomes of Ilizarov distraction for treating CPT in adults. A retrospective analysis was conducted. Between 2013 and 2022, an Ilizarov distraction technique was performed on 14 adults (14 limbs) with CPT in our limb deformity center. There were seven females and seven males with a mean age of 33.7 (range, 18 ~ 53) years. The diagnosis of NF-1 was confirmed in seven (50.0%) patients. Eight patients had a history of previous surgical failure. The pseudoarthrosis occurred in the middle and lower tibia in all limbs (six left and eight right). The CPT was classified by Crawford classification and Paley classification. The surgical procedures, external fixation time (EFT), and all outcomes and complications were recorded. The Kolmogorov-Smirnov test was performed to test the normality of the data. The American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score at the preoperative and final follow-up was compared by using the Wilcoxon's signed-rank test. The limb-length discrepancy (LLD) and a self-made exercise capacity score at the preoperative and final follow-up were compared by using the student's t-test. The clinical and radiological outcomes were assessed by the Inan scale. The mean EFT of Ilizarov fixator was 19.5 months (range, 7.3 ~ 39.1). At a median follow-up of 26.8 months (IQR, 20.2 ~ 34.3), bone union of the pseudarthrosis and consolidation of the distraction zone were achieved in all patients. The mean LLD was decreased from 11.3 cm (range, 3.4 ~ 17.3) preoperatively to 1.1 cm (range, 0.3 ~ 3.7) (p < 0.05). The mean or median AOFAS ankle-hindfoot score was improved from 53.5 (IQR, 26.5 ~ 60.5) preoperatively to 63.9 (range, 53 to 73) at final follow-up (p < 0.05). The mean score for exercise capacity were improved from 4.9 (range, 1 to 8) preoperatively to 9.6 (range, 7 ~ 12) at final follow-up (p < 0.05). According to the criteria described by Inan et al., the clinical results were classified as good in 10 and fair in 4, while the radiological results were classified as excellent in three, good in 8, and fair in 2. The success rate was 92.9%, as refracture was defined as treatment failure and occurred in one patient. Ilizarov distraction provided a suitable treatment option for the CPT in adults, as it could achieve a high rate of bone union, a good correction of secondary deformity, a low risk of refracture, and consequently restore a relatively functional limb.

The effect of educational interventions by nurses through Orem's self-care theory on the ability of self-care in myocardial Infarction patients in public sector hospital: A quasi-experimental study.

To assess the impact of educational intervention by nurses guided by Orem's theory to reinforce the self-care abilities of patients experiencing myocardial infarction. The prospective, quasi-experimental case-control study was conducted from September 2020 to April 2021 at Dr. Ruth K.M. Pfau Civil Hospital, Karachi, and comprised myocardial infarction and heart failure patients with comorbidities diabetes mellitus and hypertension. The patients were randomised into experiment group A and control group B. Group A received educational intervention one day before and one day after discharge in line with the American Heart Association guidelines. Two 30-45-minute sessions of seven modules were conducted. Group B received routine information from ward staff. Assessment was done at baseline and first month and second month post-intervention using the Heart Failure Self-Care Index version 6.2. Data was analysed using SPSS 21. Of the 80 patients, 40(50%) were in group A; 27(76.5%) males and 13(32.5%) females. The remaining 40(50%) patients were in group B; 20(50%) males and 20(50%) females. The overall age of the sample ranged 36-65 years and 48(60%) had a previous history of heart failure. The mean score of maintenance, management, confidence and overall self-care were significantly higher in group A compared to group B (p<0.05). Nursing self-care educational intervention based on Orem's theory was found to be highly effective among patients of myocardial infarction and heart failure with respect to their self-efficacy ability.

Measurement of safety state of cross-jointed segmental lining based on system performance index

The correlation between convergence deformation and the safety state of a cross-jointed segmental lining is investigated and clarified. The limitations of convergence deformation as a measuring scale is explored also. Firstly, an analytical algorithm (known as the relative stiffness method, RSM) is developed and verified for tracing the mechanical response of a cross-jointed segmental lining in failure history. Then, an explicit mapping relationship between convergence deformation and the causal factors is established using the RSM. Finally, the root causes of the limitations in using convergence deformation as a scale to evaluate tunnel safety state are discussed, and an alternative quantity, the system performance index (SPI), is proposed. It shows that: (1) The convergence deformation consists of three components induced by segment bending, elastic joint rotation, and joint stiffness attenuating, respectively. The deformation induced by attenuating joint stiffness is dependent on the failure index of segment joints and provides crucial information about the load-bearing state of the segment joints; (2) The components of elastic joint rotation and joint stiffness attenuating are significantly affected by the contact stiffness of the segment joint interface, including the physical and mechanical properties of the packing material. The magnitudes of convergence deformation and its components are not suitable for use as a quantitative scale to evaluate the safety state of the lining due to their inherent drawbacks; (3) The proposed dimensionless variable SPI can eliminate the influence of packing material on the safety state of the segment lining and reflect the comprehensive influence of the failure indexes of the segment joints.

Relationship of the trajectory of the triglyceride-glucose index with heart failure: the Kailuan study

BackgroundA high triglyceride-glucose index (TyG) is associated with a higher risk of incident heart failure. However, the effects of longitudinal patterns of TyG index on the risk of heart failure remain to be characterized. Therefore, in the present study, we aimed to characterize the relationship between the trajectory of TyG index and the risk of heart failure.MethodsWe performed a prospective study of 56,149 participants in the Kailuan study who attended three consecutive surveys in 2006–2007, 2008–2009, and 2010–2011 and had no history of heart failure or cancer before the third wave survey (2010–2011). The TyG index was calculated as ln [fasting triglycerides (mg/dL) × fasting plasma glucose (mg/dL)/2], and we used latent mixture modeling to characterize the trajectory of the TyG index over the period 2006–2010. Additionally, Cox proportional risk models were used to calculate the hazard ratio (HR) and 95% confidence interval (CI) for incident heart failure for the various TyG index trajectory groups.ResultsFrom 2006 to 2010, four different TyG trajectories were identified: low-stable (n = 13,554; range, 7.98–8.07), moderate low-stable (n = 29,435; range, 8.60–8.65), moderate high-stable (n = 11,262; range, 9.31–9.30), and elevated-stable (n = 1,898; range, 10.04–10.25). A total of 1,312 new heart failure events occurred during a median follow-up period of 10.04 years. After adjustment for potential confounders, the hazard ratios (HRs) and 95% confidence intervals (CIs) for incident heart failure for the elevated-stable, moderate high-stable, and moderate low-stable groups were 1.55 (1.15, 2.08), 1.32 (1.08, 1.60), and 1.17 (0.99, 1.37), respectively, compared to the low-stable group.ConclusionsHigher TyG index trajectories were associated with a higher risk of heart failure. This suggests that monitoring TyG index trajectory may help identify individuals at high risk for heart failure and highlights the importance of early control of blood glucose and lipids for the prevention of heart failure.

Development of fluid pathways and associated diagenetic variations in a natural CO2 leaking fault zone.

Abstract Permeability within fault zones can vary through time due to repeated deformation events and rock–fluid interactions. Understanding the history of fault zone alteration is critical when building hydrogeologic models and evaluating the risk of mechanical rock failure during subsurface storage. Newly acquired drill core recovered within the fault damage zone and fault core of the Little Grand Wash fault (LGWF) is combined with observations from outcrop, optical petrography, computerized tomography image analysis, and ultrasonic velocity measurements to characterize the rock types and preserved structural deformation features within this fault zone. These data are used to understand the history of mechanical rock failure and mineralization associated with this fluid-charged fault system. We identify multiple structural features and use their cross-cutting relationships to understand the history of deformation and their association with changes in fault zone permeability and rock mechanical properties. At the LGWF zone, structural deformation features vary temporally and are used to recognize a decoupling between fault slip and fluid flow. The formation of most open-mode veins occurred after shear failure within the LGWF zone. Early-developed shear bands are cut by carbonate veins, that are in turn cut by shear fractures, followed by a second phase of vein formation and ultimately by folding in the fault core. This sequence of formation reflects changes in mechanical rock properties due to subsurface rock–fluid interactions and indicates that the alteration of rock matrix by secondary carbonate cement results in increased unconfined compressive strength, decreased permeability, and increased ultrasonic velocity. In this fault zone, and possibly other fault zones, the changes in rock properties associated with deformation can be detected through their geophysical response.

Molecular detection of Chlamydia abortus in endometrial biopsies of mares from western Canada.

Chlamydia abortus is a reported cause of infertility and endometritis in sheep, cattle, and pigs; however, the association between uterine disease and C. abortus is poorly understood in horses. Recently, a high prevalence of C. abortus in equine aborted chorioallantoises was reported in horses in western Canada. Based on this high prevalence, investigation into the effects of C. abortus on infertility and endometritis in western Canadian mares is prudent. We examined 98 formalin-fixed, paraffin-embedded endometrial biopsies from western Canada submitted between 2014 and 2022 using a Chlamydia-specific 16S rRNA PCR test; 40 samples tested positive for Chlamydia on PCR, and 28 were sequenced as C. abortus. The C. abortus-positive cases were primarily associated with a history of failure to conceive, early embryonic loss, or abortion. Our findings suggest that C. abortus may be a cause of conception failure and abortion in horses in western Canada.

A Rare Case of Late Onset-Pompe’s Disease: Presented as Heart Failure

Pompe disease is a hereditary lysosomal storage disorder characterized by a deficiency in the acid alpha-glucosidase (GAA) enzyme, leading to glycogen accumulation in muscle and neurons. Clinical manifestations vary from severe infantile-onset with hypertrophic cardiomyopathy and early mortality due to respiratory insufficiency to late-onset with proximal muscle weakness, gross motor delay, and progressive respiratory insufficiency. A case of an 11-year-old boy who reported to the pediatric emergency department with a nine-year history of progressive muscle weakness and a one-month history of anemia symptoms (easy fatigue, shortness of breath, pale appearance) and heart failure (orthopnea, dyspnea). His family history included consanguineous marriages and similar conditions in his brother and maternal uncle. On examination, he appeared pale, malnourished, and exhibited signs of respiratory distress and tachypnea. His cardiovascular examination revealed apex beat displacement, elevated JVP, bilateral pedal edema, mild ascites, positive hepatojugular reflux, and systolic murmurs. Respiratory examination indicated bilateral crepitation and wheezes. Musculoskeletal examination showed decreased muscle mass and power, especially in proximal muscles. Abdominal examination revealed hepatosplenomegaly and mild ascites. Radiological findings included an enlarged cardiac shadow with pleural effusion and bilateral radio-opaque shadows on chest x-ray, while echocardiography showed impaired left ventricular systolic function with mild to moderate mitral and tricuspid regurgitation. Laboratory tests indicated elevated aspartate aminotransferase, LDH, and creatine kinase levels, along with normocytic, normochromic anemia. Muscle biopsy from the hamstring revealed PAS stain positive granules. These clinical, radiological, and laboratory findings strongly suggest late-onset Pompe disease, marking this as potentially the second reported case in Pakistan.

Undetected intraabdominal sepsis due to prolonged corticosteroid therapy in systemic lupus erythematosus: a case report and literature review

Gastrointestinal manifestations are not included in the criteria for diagnosing systemic lupus erythematosus (SLE) by the European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) 2019, however, gastrointestinal disorders are one of the potentially fatal complications of SLE. Mesenteric vasculitis and thrombosis are the two main mechanisms that cause gastrointestinal disorders in SLE patients. Long-term immunosuppressants used by SLE patients might alter the immune system’s response to infection, leading to immunoparalysis. The delay in recognizing might cause sepsis, thus increasing the mortality risk. A 47-year-old woman with a history of SLE complained of hematochezia. The patient had been consistently consuming 12 mg of methylprednisolone every day for the past five years without doctor’s supervision. Past medical history of congestive heart failure (CHF) caused by coronary arterial disease (CAD). After 24 days hospitalized for observation of hematochezia, an emergency laparotomy was performed due to deterioration caused by peritonitis. Intraoperative, 60 cm of jejunal necrosis was identified and intestinal resection was done. The patient’s condition improved in two days after emergency laparotomy and intensive treatment. The undetected intraabdominal sepsis caused by jejunal infarction and gut necrosis due to long-term use of corticosteroid that masked the manifestations of severe infection in the gastrointestinal tract infarction and necrosis. Abbreviations: NLR - neutrophil to lymphocyte ratio; SGOT - serum glutamic oxaloacetic transminase; SGPT - serum glutamic pyruvic transminase; eGFR - estimated glomerular filtration rate; PT - prothrombin time; APTT - activated partial thromboplastin time; INR - international normalized ratio Keywords: Systemic lupus erythematosus, Intraabdominal sepsis, Immunoparalysis, Corticosteroid Citation: Leman YE, Irawany V, Manggala SK. Undetected intraabdominal sepsis due to prolonged corticosteroid therapy in systemic lupus erythematosus: a case report and literature review. Anaesth. pain intensive care 2024;28(4):765−771; DOI: 10.35975/apic.v28i4.2525 Received: March 13, 2024; Reviewed: May 17, 2024; Accepted: May 21, 2024

Utility of thromboelastography to assess the effect of anticoagulation reversal in intracranial hemorrhage.

Intracranial hemorrhage (ICH) is a serious complication associated with oral anticoagulant use and is associated with significant morbidity and mortality. Although anticoagulation reversal agents are utilized as standard of care, practitioners are limited in their ability to assess degree of anticoagulation reversal for direct oral anticoagulants (DOACs). There is a clinical need identify biomarkers to assess anticoagulation status in patients with DOAC-associated ICH to ensure hemostatic efficacy of anticoagulation reversal agents in the acute setting. The purpose of this study was to assess the utility of thromboelastography (TEG) to assess the impact of anticoagulation reversal in patients presenting to the emergency department (ED) with DOAC-associated ICH. We conducted a prospective, observational cohort study in adult patients presenting to the ED with acute DOAC-associated ICH. Patients were excluded if last DOAC dose was >48 hours prior to hospital arrival, if they experienced polytrauma, were pregnant, incarcerated, had a history of hepatic failure or coagulopathy, or received anticoagulation reversal with products other than prothrombin complex concentrates (PCCs). We collected baseline TEG samples from participants prior to anticoagulation reversal, as well as 30-minutes, 12-hours, and 24-hours post-reversal. TEG samples were also collected from participants who transferred to our facility after reversal at ED presentation, as well as 12- and 24-hours post-reversal. Pre-reversal TEG was collected on 10 participants prior to DOAC reversal. A significant decrease in TEG R-time was observed at 30 minutes post-reversal. R-time increased at 12- and 24-hours to baseline levels. Significant changes were not observed in K-time, clot strength, maximum amplitude, or coagulation index. TEG R-time may be able to detect a change in anticoagulation activity of DOACs in ICH after anticoagulation reversal. R-time decreases acutely after anticoagulation reversal and rebounds at 12- and 24-hours post-reversal.

Trends in prognosis and use of SGLT2i and GLP-1 RA in patients with diabetes and coronary artery disease

ObjectiveTo explore trends in prognosis and use of glucose-lowering drugs (GLD) in patients with diabetes and coronary artery disease (CAD).Research design and methodsAll patients with diabetes and CAD undergoing a coronary angiography between 2010 and 2021 according to the Swedish Angiography and Angioplasty Registry were included. Information on GLD (dispended 6 months before or after coronary angiography) was collected from the Swedish Prescribed Drug Registry. Data on major cardiovascular events (MACE; mortality, myocardial infarction, stroke, heart failure) through December 2021 were obtained from national registries. Cox proportional survival analysis was used to assess outcomes where cardioprotective GLD (any of Sodium Glucose Lowering Transport 2 receptor inhibitors [SGLT2i] and Glucagon Like Peptide Receptor Agonists [GLP-1 RA]) served as a reference.ResultsAmong all patients (n = 38,671), 31% had stable CAD, and 69% suffered an acute myocardial infarction. Mean age was 69 years, 67% were male, and 81% were on GLD. The use of cardioprotective GLD increased rapidly in recent years (2016–2021; 7–47%) and was more common in younger patients (66 vs. 68 years) and men (72.9% vs. 67.1%) than other GLD. Furthermore, compared with other GLD, the use of cardioprotective GLD was more common in patients with a less frequent history of heart failure (5.0% vs. 6.8%), myocardial infarction (7.7% vs. 10.5%) and chronic kidney disease (3.7% vs. 5.2%). The adjusted hazard ratio (HR) (95% CI) for MACE was greater in patients on other GLD than in those on cardioprotective GLD (1.10; 1.03–1.17, p = 0.004). Trend analyses for the years 2010–2019 revealed improved one-year MACE in patients with diabetes and CAD (year 2019 vs. 2010; 0.90; 0.81-1.00, p = 0.045), while 1-year mortality was unchanged.ConclusionsThe prescription pattern of diabetes medication is changing quickly in patients with diabetes and CAD; however, there are worrying signals of inefficient use prioritizing cardioprotective GLD to younger and healthier individuals at lower cardiovascular risk. Despite this, there are improving trends in 1-year morbidity.