Disease-specific Risk Factors Research Articles

Venetoclax-Related Neutropenia in Leukemic Patients: A Comprehensive Review of the Underlying Causes, Risk Factors, and Management.

Venetoclax is a Bcl-2 homology domain 3 (BH3) mimetic currently approved for the treatment of chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML) that has proven to be highly effective in reinstating apoptosis in leukemic cells through the highly selective inhibition of the anti-apoptotic protein B-cell lymphoma-2 (Bcl-2). Clinically, venetoclax has provided lasting remissions through the inhibition of CLL and AML blasts. However, this activity has often come at the cost of grade III/IV neutropenia due to hematopoietic cells' dependence on Bcl-2 for survival. As life-threatening infections are an important complication in these patients, an effective management of neutropenia is indispensable to maximize patient outcomes. While there is general consensus over dose reduction and scheduling modifications to minimize the risk of neutropenia, the impact of these modifications on survival is uncertain. Moreover, guidelines do not yet adequately account for patient-specific and disease-specific risk factors that may predict toxicity, or the role combination treatment plays in exacerbating neutropenia. The objective of this review is to discuss the venetoclax-induced mechanism of hematological toxicity, the potential predictive risk factors that affect patient vulnerability to neutropenia, and the current consensus on practices for management of neutropenia.

A Prospective, Multinational Study of Clinical and Biological Factors Associated with Short Overall Survival in Multiple Myeloma

Introduction: Multiple myeloma (MM) is an incurable cancer, but a subset of patients can achieve long-term remission and overall survival (OS). We aimed to study the clinical and biological factors associated with short OS defined as less than 3 years. Methods: A prospective, observational, multinational study was conducted by Australian and New Zealand (ANZ) and Asia-Pacific (APAC) Myeloma and Related Disease Registry (MRDR) from January 2013 to January 2023, across 5 countries (Australia, New Zealand, Korea, Singapore, Malaysia). Eligible patients were ≥18 years old, diagnosed with MM per International Myeloma Working Group (IMWG) criteria, received a bortezomib-containing triplet, and had at least 3 years of follow-up or had deceased within 3 years. Descriptive analysis was completed using chi-squared test for categorical variables and Wilcoxon rank-sum test for continuous variables. The Kaplan-Meier method was used for analysing OS and follow-up data. The ‘stepwise’ function in Stata was used for the forward stepwise logistic regression, with the p-value set to 0.1. All analyses were completed using Stata 16. Results: Of the 1539 patients enrolled, majority were from ANZ (1071 and 359, respectively), with male preponderance (61.0%). Half were above 65 years old. High risk cytogenetic abnormalities, a criterion of the Revised International Staging System (R-ISS), was unknown for half of the patients (49.4%). 45.3% patients presented as ISS stage 1, 21.9% stage II, and 32.8% stage III, respectively at study entry . The most frequent front-line agent used in combination with bortezomib-based triplet was cyclophosphamide [VCd, 1380 (89.7%)], followed by thalidomide [VTd, 92(6.0%)], lenalidomide [VRd, 63 (4.1%)] and daratumumab [DVd, 4 (0.3%)]. The median follow-up was 29.9 months (95%CI: 28.3-31.8) and the median OS was 87.7 months (95%CI: 80.9-93.2). Thirty percent patients had OS<3 years. Clinical and biological factors associated with long OS (≥3 years) were compared with those <3 years (Table 1). Baseline factors associated with higher odds of short OS included age≥65, Eastern Cooperative Oncology Group performance status (ECOG PS)≥2, ISS III, lower creatinine clearance and platelet count, high LDH and poor cytogenetic abnormalities (Table 1). In a multivariate analysis, age≥65 (OR:2.50; p<0.001), ECOG≥2 (OR:2.08; p<0.001), ISS III (OR:2.48; p<0.001), t(4;14)[OR:2.04; p=0.004], t(14;16)[OR:6.33; p=0.004] and 17p deletion (OR:2.77; p =0.001) were associated with a significantly shorter OS. Conclusion: From clinician perspective, identifying patients with an increased likelihood of shorter OS through the determination of patient- and disease-specific risk factors might be clinically relevant to facilitate better treatment decisions.

Atrial Fibrillation Prevalence and Its Management in Transfusion-Dependent Thalassemias: The Fathal Study

Atrial fibrillation (AF) represents an emerging issue in the thalassemia population related to increased life expectancy. However, data on AF in these patients are limited, and the current management is based on the guidelines for the general population. Nevertheless, AF in these patients has distinctive features that could require specific management. We conducted a multicentric retrospective study supported by the Italian Society of Thalassemia and Hemoglobinopathies (SITE) to elucidate the prevalence of AF in transfusion-dependent thalassemia (TDT) adults in Italy and to study its management, particularly the use of transcatheter ablation and anticoagulation management. Patients followed between June 1, 2003 and May 31, 2023 with a diagnosis of alpha- or beta-transfusion-dependent thalassemia with at least one episode of AF were included in the study. Clinical data of patients have been retrospectively collected with dedicated digital case report form (CRF). So far, 3 centers (Cagliari, Ferrara, Milano) have participated in the study. Eight-hundred-sixty-one adult TDT patients are regularly followed in the participating centers. Data from 130 adult TDT with AF were included. At enrollment, 119 patients were alive (71 males, 60%), the mean age at enrollment was 51.9 years, and 71% were splenectomized. Almost all (98%) had beta-thalassemia, of which 20% had thalassemia intermedia and became transfusion dependent during their life. The mean age at the first AF episode was 39.7 yr. Overall, AF prevalence in TDT was 13.8%, with a significant rise above the age of 50 (age 51-65: prevalence 26.4%, age>65 33.3%), differently from the general population in which the prevalence is 2-4%, and patients are older. As in the general population, prevalence was higher in males (18.2% vs 10.2%). Among the known risk factors for AF, the most frequent were diabetes (16%, n=111) and previous heart failure (22%, n=111). Regarding disease-specific factors contributing to the pathophysiology of AF, cardiac iron overload, defined as at least one between T2*<20 ms and serum ferritin>2500 ng/ml, was present in half of the patients (48.7%, n=76) at any time before AF and in approximately one-third (29%, n=93) at the time of the first event. Thirty-eight patients did not show cardiac iron overload before or at the time of the first AF episode. Most subjects had left atrial dilatation (58.1%), which can result from chronically increased cardiac output due to anemia. In most patients (87%), a rhythm control strategy was chosen at any time. Amiodarone was the most widely used drug. Transcatheter ablation was performed in 29 patients (22%), with a total of 39 procedures, and 20 (77%) patients reported improvement in symptoms after the last ablation. CHA 2DS 2-VASc score at the first AF episode detected a low risk of thromboembolism in 66 (50.8%) patients and a high risk in 19 (14.6%). However, 72 patients, including 40 low-risk subjects, initiated anticoagulation after the first episode. Four patients had a hemorrhagic event (3.1%), but only one had major bleeding during anticoagulant therapy without significant sequelae. Interestingly, management was heterogenous between different centers for both transcatheter ablation use and anticoagulation strategy. The prevalence of stroke in TDT AF patients was 5%, rising to 7.6% when also considering transient ischemic attacks. Compared to the literature, this prevalence is at least 10-fold higher than the general TDT population. Of note, splenectomy, a well-known risk factor for thrombosis, was present in all patients with stroke at the time of the event. In conclusion, AF represents significant morbidity in adult TDT, and its management is heterogeneous. It generally occurs at a younger age than the general population, and iron overload and atrial dilatation play a central role in its genesis. For symptomatic patients, we propose a rhythm control strategy to improve their quality of life, among which ablation could be the best option. Moreover, because stroke represents a major and frequent complication in TDT patients with AF, early detection of AF and prompt initiation of anticoagulant therapy, irrespective of CHA 2DS 2-VASc, which does not capture potential disease-specific risk factors, including splenectomy, should be considered. Further studies to support our approach are needed.

RAI-measured frailty predicts non-home discharge following metastatic brain tumor resection: national inpatient sample analysis of 20,185 patients.

Preoperative risk stratification for patients undergoing metastatic brain tumor resection (MBTR) is based on established tumor-, patient-, and disease-specific risk factors for outcome prognostication. Frailty, or decreased baseline physiologic reserve, is a demonstrated independent risk factor for adverse outcomes following MBTR. The present study sought to assess the impact of frailty, measured by the Risk Analysis Index (RAI), on MBTR outcomes. All MBTR were queried from the National Inpatient Sample (NIS) from 2019 to 2020 using diagnosis and procedural codes. The relationship between preoperative RAI frailty score and our primary outcome - non-home discharge (NHD) - and secondary outcomes - complication rates, extended length of stay (eLOS), and mortality - were analyzed via univariate and multivariable analyses. Discriminatory accuracy was tested by computation of concordance statistics in area under the receiver operating characteristic (AUROC) curve analysis. There were 20,185 MBTR patients from the NIS database from 2019 to 2020. Each patient's frailty status was stratified by RAI score: 0-20 (robust): 34%, 21-30 (normal): 35.1%, 31-40 (very frail): 13.9%, 41+ (severely frail): 16.8%. Compared to robust patients, severely frail patients demonstrated increased complication rates (12.2% vs. 6.8%, p < 0.001), eLOS (37.6% vs. 13.2%, p < 0.001), NHD (52.0% vs. 20.6%, p < 0.001), and mortality (9.9% vs. 4.1%, p < 0.001). AUROC curve analysis demonstrated good discriminatory accuracy of RAI-measured frailty in predicting NHD after MBTR (C-statistic = 0.67). Increasing RAI-measured frailty status is significantly associated with increased complication rates, eLOS, NHD, and mortality following MBTR. Preoperative frailty assessment using the RAI may aid in preoperative surgical planning and risk stratification for patient selection.

External validation of postoperative nausea and vomiting risk scores in patients with liver cancer: A single-centre prospective cohort study

Objectives This study aimed to test the external validity of postoperative nausea and vomiting (PONV) risk assessment tools in patients undergoing hepatectomy, and to guide healthcare professionals’ assessment of postoperative patients. Background The identification of PONV risk is particularly important in the context of prevention. However, the predictive performance of the current PONV risk scores has not been confirmed in patients with liver cancer, and its applicability is still unknown. These uncertainties pose difficulties in performing routine risk assessment of PONV for patients with liver cancer in a clinical practice setting. Methods Patients diagnosed with liver cancer and undergoing hepatectomy were prospectively consecutively recruited. All enrolled patients received PONV assessments and PONV risk assessments via the Apfel risk score and the Koivuranta risk score. Receiver operating characteristic curves (ROC curves) and calibration curves were used to assess the external validity. This study was reported according to the TRIPOD Checklist. Results Among 214 PONV–assessed patients, 114 patients (53.3%) developed PONV. For the Apfel simplified risk score, the ROC area was 0.612 (95% confidence interval [CI]: 0.543–0.678) in the validation dataset, which demonstrated imperfect discrimination; the calibration curve showed poor calibration with a slope of 0.49. For the Koivuranta score, the ROC area was 0.628 (CI: 0.559–0.693) in the validation dataset, which showed limited discrimination; the calibration curve indicated an unsatisfactory calibration with a slope of 0.71. Conclusions The Apfel risk score and the Koivuranta risk score were not well validated in our study and disease-specific risk factors should be taken into account when updating or developing PONV risk stratification instruments.

Traditional and Disease Specific Risk Factors for Cardiovascular Events in ANCA-Associated Vasculitis: A Multinational Retrospective Study.

Traditional and Disease Specific Risk Factors for Cardiovascular Events in ANCA-Associated Vasculitis: A Multinational Retrospective Study.

Prevalence, risk factors and outcomes of cardiac disease in cystic fibrosis: a multinational retrospective cohort study.

Although people living with cystic fibrosis (PwCF) often have some risk factors for cardiovascular disease, including diabetes and chronic inflammation, little is known about the long-term cardiac risk in this condition. We aimed to determine the characteristics, rates and outcomes for cardiac disease in CF. We looked at rates and outcomes for cardiac disease in 5649 adult PwCF in the UK CF Registry and 6265 adult PwCF in TriNetX (a global federated database of electronic healthcare record data). We used propensity matching to compare risk of major adverse cardiac events (MACE) (myocardial infarction, left-sided heart failure and atrial fibrillation) in PwCF against matched non-CF comparators in the general population and other inflammatory diseases. PwCF had a high prevalence of diabetes but low rates of hypertension and obesity. Some cardiac risk factors (age, diabetes and hypertension) were associated with MACE, but relationships between disease-specific risk factors (lung function and intravenous antibiotic days) were also observed. In propensity score-matched analyses, PwCF had higher risk of MACE than matched general population comparators (hazard ratio (HR) 1.65, 95% CI 1.40-1.95; p<0.001) and an equivalent or higher relative risk compared with other inflammatory conditions considered "high risk" for cardiovascular disease, including systemic lupus erythematosus (HR 0.95, 95% CI 0.82-1.09; p=0.44), rheumatoid arthritis (HR 1.21, 95% CI 1.00-1.48; p<0.001) and HIV (HR 0.93, 95% CI 0.82-1.06; p=0.29). PwCF are at increased risk of adverse cardiac disease events. Future work should focus on defining determinants of cardiovascular risk such that appropriate risk stratification can be employed.

Estimating survival in patients with melanoma brain metastases: prognostic value of lactate dehydrogenase.

Patients with melanoma brain metastases (MBM) have poor prognosis, albeit advances in locoregional and systemic treatments. The melanoma-specific Graded Prognostic Assessment (GPA) effectively stratifies survival for patients with MBM. Nevertheless, lactate dehydrogenase (LDH), a well known prognostic factor for patients with melanoma, is not represented in the GPA scores and might add prognostic information for patients with MBM. In this study, 150 consecutive patients with MBM were retrospectively analyzed with the aim of evaluating independent prognostic factors for MBM patients, including LDH. Furthermore, we implemented a disease-specific prognostic score and estimated survival according to treatment modalities. On the basis of multivariable Cox regression analyses, six prognostic factors (age, BRAF status, number of MBM, number of extracranial metastatic sites, performance status, and LDH level) resulted statistically significant in terms of survival and were combined in a prognostic score to stratify patients in distinct prognostic groups ( P < 0.0001). Among treatment modalities, a multimodal approach with stereotactic radiosurgery or neurosurgery associated with systemic therapy showed the best outcome (median overall survival: 12.32 months, 95% confidence interval, 7.92-25.30). This is the first study to demonstrate that LDH has independent prognostic value for patients with MBM and might be used to improve prognostic stratification, albeit external validation is mandatory. Survival of patients with MBM is affected by both disease-specific risk factors and treatment modalities, with locoregional treatments associated with better outcomes.

Gender-Based Frailty in Multiple Orthopedic Fractures.

The 5-factor modified frailty index (mFI-5) has been used as a prognostic tool to identify patients at higher risk for complications and mortality but has not been used to assess the relationship between frailty and extent of injury following ground-level falls. The aim of this study was to determine if mFI-5 is associated with increased risk for combined femur-humerus fractures compared to isolated femur fractures in geriatric patients. A retrospective analysis of 2017-2018 American College of Surgeons Trauma Quality Improvement Program (ACS-TQIP) data identified 190 836 patients with femur fractures and 5054 patients with combined femur-humerus fractures. In multivariate analysis, gender was the only statistically significant predictor for risk of combined vs isolated fractures (OR 1.69, 95% CI [1.65, 1.74], P < .001). While outcome data for the mFI-5 repeatedly shows increased risk for adverse events, this tool may over-estimate the disease specific risk factors rather than the overall frailty state of the patient and diminish its predictive power.

Factors associated with cardiovascular events in systemic lupus erythematosus in a monocentric cohort with up to 40 years of follow-up

ObjectivesSystemic lupus erythematosus (SLE) is associated with an increased cardiovascular risk. Several traditional and disease-specific risk factors have been shown to correlate with the occurrence of cardiovascular events (CVE) in patients with SLE. However, results of previous studies are diverse. The objectives of this study were to report number, type and those factors associated with CVE in patients with SLE in a large, single-center, ethnically diverse cohort with a long follow-up duration. MethodsMedical records of patients treated at the Lupus Clinic at University College London Hospital (UCLH) between 1979 and 2020 were retrospectively reviewed. Data about CVE, traditional cardiovascular risk factors, demographic and disease features, and treatment history were collected. Only patients with complete available information were included in the study. Regression analyses were performed to identify factors associated with CVE. ResultsFour hundred and nineteen patients were included in the study. Maximum follow-up length was 40 years. Seventy-one (17%) patients had at least one CVE. Multivariable analysis showed that only antiphospholipid antibody positivity (p-value<0.001) was associated with CVE. When analysing different types of CVE, antiphospholipid antibodies were specifically associated with both venous thromboembolic events (p-value<0.001) and cerebrovascular events (p-value=0.007). Dedicated subanalyses revealed that cumulative glucocorticoid dose (p-value=0.010) and a diagnosis of SLE before 2000 (p-value<0.001) were significantly associated with CVE. ConclusionsCardiovascular disease is highly prevalent among patients with SLE and is associated with antiphospholipid antibodies, glucocorticoid therapy, and diagnosis before 2000.

Risk factors for cardiovascular diseases in patients with systemic lupus erythematosus: an umbrella review.

Cardiovascular disease in patients with systemic lupus erythematosus(SLE) remains one of the most common causes of death and is caused by several factors, including both traditional and disease-specific risk factors. We aimed to systematically appraise the evidence of cardiovascular disease risk factors focusing on the SLE population. The protocol for thisumbrella review is registered in PROSPERO (registration no. CRD42020206858). A systematic literature search was conducted in PubMed, Embase, and the Cochrane Library from database inception to June 22, 2022, for systematic reviews and meta-analyzes that examined cardiovascular disease risk factors in patients with SLE. Two reviewers independently extracted data and assessed the quality of the included studies using the "Assessing the Methodological Quality of Systematic Reviews 2(AMSTER 2)" tool. Of the 102 identified articles, nine systematic reviews were included in this umbrella review. All included systematic reviews were assessed as critically low quality according to the AMSTER 2 tool. The traditional risk factors identified in this study were older age, male sex, hypertension, dyslipidemia, smoking, and a family history of cardiovascular disease. SLE-specific risk factors were long-term disease duration, lupus nephritis, neurological disorders, high disease activity, organ damage, use of glucocorticoids, azathioprine, and antiphospholipid antibodies, including anticardiolipin antibodies and lupus anticoagulant. This umbrella review identified some cardiovascular disease risk factors in patients with SLE; however, the study quality of all included systematic reviews was critically low. Key Points • We examined the evidence of cardiovascular disease risk factors focusing on patients with systemic lupus erythematosus. • We found that long-term disease duration, lupus nephritis, neurological disorders, high disease activity, organ damage, use of glucocorticoids, azathioprine, and antiphospholipid antibodies, including anticardiolipin antibodies and lupus anticoagulant, were cardiovascular disease risk factors among patients with systemic lupus erythematosus. • The review indicates the need for well-validated and high-quality future reviews that assess major adverse cardiovascular events as an outcome in patients with systemic lupus erythematosus.

What Is the Risk? Epidemiology and Evidence for Surveillance Regimens.

Patients with inflammatory bowel disease (IBD) have increased risk of colorectal cancer (CRC). The risk for CRC is positively correlated to the duration of disease, extent of colonic involvement, and severity of inflammation. After 8 to 10 years of IBD diagnosis, the risk for CRC rises substantially and screening colonoscopy is recommended. Surveillance colonoscopy interval ranges from 1 to 5 years depending on patient and disease-specific risk factors. IBD patients with high risk factors such as having concomitant primary sclerosing cholangitis, moderate-to-severe inflammation, first-degree relative with CRC at early age, or history of invisible dysplasia or high-risk visible dysplasia should undergo surveillance colonoscopy in 1 year. Meanwhile, those with minimal colonic involvement or ≥2 consecutive unremarkable examinations while in continuous remission may consider extending the surveillance interval to 5 years. Advance in colonoscopy technique such as chromoendoscopy using dyes and/or image digital processing (virtual chromoendoscopy) may enhance dysplasia detection and is the preferred method for IBD surveillance. In the era of high-definition colonoscope, the practice of obtaining extensive biopsies throughout the colon remains controversial but is generally recommended to improve the detection rate of invisible dysplasia. Endoscopic surveillance in IBD has been shown to result in earlier detection of CRC and improved prognosis.

Abstract P4-03-42: Evaluating the Impact of Race and Body Mass Index on the Diagnosis and Prognosis of Early Onset Breast Cancer

Abstract Background: Early-onset breast cancer is typically defined as a diagnosis of disease before age 40-45. Prior studies have shown interesting associations between race and obesity on the incidence and prognosis of breast cancer. Data from the SEER program at the National Cancer Institute has shown increased mortality amongst African American women (0.2%) compared to Non-Hispanic White (NHW) women (0.1%) who were diagnosed with breast cancer at age 45 years or younger. This is despite a similar risk of diagnosis between racial groups of this age range (1.27%, 1.27%). Other large studies have shown that African American patients tended to present with more advanced disease had worse clinical outcomes. Our study sought to determine the impact of race and obesity on the diagnosis and prognosis of early onset breast cancer amongst the patient population at Georgetown University Hospital (GUH). Methods: We compiled a database of all new patients, 652 in total, seen at Lombardi Cancer Center at Medstar GUH from 10/2020- 6/2022. We reviewed patient charts in the EMR and documented age at diagnosis, race, ethnicity, stage at diagnosis, and BMI. The BMI was categorized by underweight (BMI &amp;lt; 18.5), healthy weight (BMI 18.5-24.9), overweight (BMI 25-25.9), obese (BMI 30-34.9), and morbidly obese (BMI ≥ 35). Stage at diagnosis was determined by comparing the pathology report with the NCCN guidelines version 4.2022. We identified 136 patients who were diagnosed at GUH at age 45 years old or younger and compared our findings to SEER data from 2017-2019. Results: Out of 136 patients who met our age criteria, 131 had racial data available: 29 AA (0.22), 68 NHW (0.52), 4 Hispanic (0.03), 30 Other (0.23). Out of the 34 patients with advanced disease (stage 3 and 4) 16 were NHW (0.47), 4 were AA (0.12), 2 were Hispanic (0.06) and 12 were Other (0.35). 131 patients had BMI data available: 5 underweight (0.04), 56 healthy weight (0.43), 41 overweight (0.31), 21 obese (0.16), and 8 morbidly obese (0.06). 18 patients with advanced disease were overweight or obese, out of which 11 were NHW (0.61), 3 were AA (0.16), 3 were Other (0.16), and 1 was Hispanic (0.06). Conclusion: In contrast with the SEER data, our study found that the patient population at GUH had a much higher proportion of Non-Hispanic White (NHW) patients who were diagnosed with advanced disease compared to African American (AA) patients. It also found a higher proportion of NHW patients amongst those who were diagnosed with advanced stage disease and were overweight or obese compared to AA patients. This data suggests that in our patient population, Non-Hispanic White women who were overweight or obese at the time of diagnosis of early onset breast cancer (≤ 45 years old) were more likely to be diagnosed with advanced stage disease than women in other demographic groups. It is possible that this discrepancy is related to racial variations in receptor status. Further investigation is required to correlate these associations in clinical practice with other known demographic variables and disease-specific risk factors in order to better understand how they impact the diagnosis and prognosis of early-onset breast cancer. Citation Format: Austin Kordic, Amanda Reyes, Nadia Ashai. Evaluating the Impact of Race and Body Mass Index on the Diagnosis and Prognosis of Early Onset Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-03-42.

Assessing the Efficacy of a Virtual Assistant in the Remote Cardiac Rehabilitation of Heart Failure and Ischemic Heart Disease Patients: Case-Control Study of Romanian Adult Patients.

Cardiovascular diseases (CVDs) are the leading cause of mortality in Europe, with potentially more than 60 million deaths per year, with an age-standardized rate of morbidity-mortality higher in men than women, exceeding deaths from cancer. Heart attacks and strokes account for more than four out of every five CVD fatalities globally. After a patient overcomes an acute cardiovascular event, they are referred for rehabilitation to help them to restore most of their normal cardiac functions. One effective way to provide this activity regimen is via virtual models or telerehabilitation, where the patient can avail themselves of the rehabilitation services from the comfort of their homes at designated timings. Under the funding of the European Union's Horizon 2020 Research and Innovation program, grant no 769807, a virtual rehabilitation assistant has been designed for elderly patients (vCare), with the overall objective of supporting recovery and an active life at home, enhancing patients' quality of life, lowering disease-specific risk factors, and ensuring better adherence to a home rehabilitation program. In the vCare project, the Carol Davila University of Bucharest (UMFCD) was in charge of the heart failure (HF) and ischemic heart disease (IHD) groups of patients. By creating a digital environment at patients' homes, the vCare system's effectiveness, use, and feasibility was evaluated. A total of 30 heart failure patients and 20 ischemic heart disease patients were included in the study. Despite the COVID-19 restrictions and a few technical difficulties, HF and IHD patients who performed cardiac rehabilitation using the vCare system had similar results compared to the ambulatory group, and better results compared to the control group.

A rare occurrence of an incidental primary intra-abdominal Cystic Lymphangioma in a Middle Eastern adult female: A case report.

The authors hereby demonstrate the case of a 46-year-old lady who presented to the outpatient general surgery clinic at our university hospital complaining of chronic right hypochondriac abdominal pain. Investigative radiological imaging marked a cystic formation with well-defined borders and homogenous content extending from the lower pole of the right kidney to the lower hepatic border. Surgical intervention was performed by completely resecting the lesion in question. Directly afterward, histopathological analysis was achieved and established the diagnosis of a CL.Conclusion:CL is a rare neoplasm with ill-defined symptoms and ambiguous clinical presentations. They remain poorly studied due to their rarity and lack of sufficient data in the published literature. This magnifies the importance of clinical awareness and time-efficient surgical intervention. Documenting these cases aids in identifying their subsequent etiological origins, disease-specific risk factors, clinical course, and yields proposals of novel therapeutic approaches.

Traditional and disease specific risk factors for cardiovascular events in ANCA-associated vasculitis: a multinational retrospective study.

To investigate the occurrence of cardiovascular events (CVE) in a large cohort of patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) across the European Union, China, Turkey, Russia, UK, and USA. Patients with a definite diagnosis of AAV who were followed ≥3 months and had sufficient documentation were included. Data on myocardial infarction (MI) and stroke were collected retrospectively from tertiary vasculitis centers. Univariate and multivariate Cox regression models were used to estimate hazard ratios (HRs) and 95% CIs. Over a median follow-up of 62 (interquartile range: 23, 100) months, CVE (mostly MI) occurred in 245 (10.7%) of 2286 AAV patients with a higher frequency in China and the UK. On multivariate regression analysis, older age (55-64.9 years; HR 2.93, 95% CI: 1.99, 4.31), smoking (HR 1.98, 95% CI: 1.48, 2.64), Chinese origin (HR 4.24, 95% CI: 3.07, 5.85), pulmonary (HR 1.50, 95% CI: 1.09, 2.06) and kidney (HR 3.02, 95% CI: 2.08, 4.37) involvement were independent variables associated with a higher occurrence of CVE. We showed that geographic region and both traditional and disease specific (kidney involvement in particular) factors were independently associated with CVE. Proper assessment and management of modifiable cardiovascular risk factors are essential for prevention of cardiovascular morbidity in AAV patients.

Comorbidities of COPD: Mechanisms and Treatment. Update 2023

Chronic obstructive pulmonary disease (COPD) is chronic disease that affects mostly the lungs but there is growing evidence that it is also a systemic condition associated with a number of accompanying diseases known as comorbidities. Chronic inflammation and oxidative stress are the highlight pathogenic processes that interrelate COPD and comorbidities with additional disease specific risk factors and mechanisms. Through complex interactions COPD increases the risk for certain comorbidities and they in turn have negative impact on health status and contribute to mortality in COPD patients. Treatment of comorbidities in terms of coexistence with COPD may require more specific personalized therapeutic approach. Here we review the pathogenic mechanisms which define COPD as a systemic disease; the most common comorbidities of COPD: cardiovascular disease, diabetes and metabolic syndrome, cachexia, osteoporosis, depression/anxiety and obstructive sleep apnea; the pathways which connect these diseases with COPD and the latest treatment approaches.

A blood DNA methylation biomarker for predicting short-term risk of cardiovascular events

BackgroundRecent evidence highlights the epidemiological value of blood DNA methylation (DNAm) as surrogate biomarker for exposure to risk factors for non-communicable diseases (NCD). DNAm surrogate of exposures predicts diseases and longevity better than self-reported or measured exposures in many cases. Consequently, disease prediction models based on blood DNAm surrogates may outperform current state-of-the-art prediction models. This study aims to develop novel DNAm surrogates for cardiovascular diseases (CVD) risk factors and develop a composite biomarker predictive of CVD risk. We compared the prediction performance of our newly developed risk score with the state-of-the-art DNAm risk scores for cardiovascular diseases, the ‘next-generation’ epigenetic clock DNAmGrimAge, and the prediction model based on traditional risk factors SCORE2.ResultsUsing data from the EPIC Italy cohort, we derived novel DNAm surrogates for BMI, blood pressure, fasting glucose and insulin, cholesterol, triglycerides, and coagulation biomarkers. We validated them in four independent data sets from Europe and the USA. Further, we derived a DNAmCVDscore predictive of the time-to-CVD event as a combination of several DNAm surrogates. ROC curve analyses show that DNAmCVDscore outperforms previously developed DNAm scores for CVD risk and SCORE2 for short-term CVD risk. Interestingly, the performance of DNAmGrimAge and DNAmCVDscore was comparable (slightly lower for DNAmGrimAge, although the differences were not statistically significant).ConclusionsWe described novel DNAm surrogates for CVD risk factors useful for future molecular epidemiology research, and we described a blood DNAm-based composite biomarker, DNAmCVDscore, predictive of short-term cardiovascular events. Our results highlight the usefulness of DNAm surrogate biomarkers of risk factors in epigenetic epidemiology to identify high-risk populations. In addition, we provide further evidence on the effectiveness of prediction models based on DNAm surrogates and discuss methodological aspects for further improvements. Finally, our results encourage testing this approach for other NCD diseases by training and developing DNAm surrogates for disease-specific risk factors and exposures.

COVID-19 in patients with B cell immune deficiency

This article aims to describe the clinical manifestations and management of COVID-19 in patients with primary and secondary B cell deficient states. We describe the epidemiologic and clinical features as well as unique management paradigm including isolation precautions with COVID-19. We then focus upon primary and secondary preventive approaches including vaccination and pre- as well as post-exposure prophylaxis. Further, we elaborate upon the important disease specific risk factors in these patients and the need to conduct prospective clinical trials to develop individualized management strategies in this population.

Osteoporosis in COPD patients: Risk factors and pulmonary rehabilitation.

ObjectivesTo present a review on the pathogenesis, risk factor and treatment of chronic obstructive pulmonary disease complicated with osteoporosis and provide new ideas for the diagnosis and treatment.Data sourceA systematic search is carried out using keywords as chronic obstructive pulmonary disease, osteoporosis, risk factors, and pulmonary rehabilitation.ResultsPatients with chronic obstructive pulmonary disease have a high prevalence of osteoporosis and a high risk of fracture. The mechanisms of osteoporosis in COPD patients are associated with general risk factors, such as smoking, reduced physical activity, low weight, and disease‐specific risk factors, such as systemic inflammatory, Vitamin D deficiency, use of glucocorticoid, anemia, hypoxemia, and hypercapnia. The treatment of osteoporosis in COPD emphasizes comprehensive intervention, which mainly include basic treatment and anti‐osteoporosis drugs. Noticeably, pulmonary rehabilitation program is an important part of treatment.ConclusionsThis work summarizes the pathogenesis, risk factor, prevention, and treatment of chronic obstructive pulmonary disease complicated with osteoporosis, and the latest progress of studies on chronic obstructive pulmonary disease and osteoporosis is discussed.