Disease Syndrome Research Articles

Effective PPI Therapy: Ensuring Appropriate Dosage of PPI in Patients with Different Comorbidities in Medicine, Surgery and Gastroenterology Ward

Background: Proton pump inhibitors (PPIs) are widely prescribed medications used to treat conditions related to excessive stomach acid, such as gastroesophageal reflux disease (GERD), peptic ulcers, and Zollinger-Ellison syndrome. Despite their efficacy in managing acid-related disorders, the appropriate use of PPIs, particularly concerning the correct dosage remains a critical issue in clinical practice. Objective: This study aimed to assess the effectiveness of PPI therapy by ensuring appropriate dosage of PPI in patients with different comorbidities in medicine, surgery, and gastroenterology wards in Dhaka Medical College Hospital. Methods: This cross-sectional observational study was conducted at the Department of Pharmacology and Therapeutics, Dhaka Medical College, Dhaka, from July 2019 to June 2020. A total of 600 patients were selected as study subjects by purposive sampling technique. Data were collected and evaluated considering USFDA-approved indications, and the systematic review by Scarpignato et al. recommendations. Data were analyzed using descriptive statistics. Analysis of data was carried out by using Statistical Package for Social Science (SPSS) 22.0 for Windows. Results: Among 255 patients, who were prescribed PPIs for an appropriate indication, 129 (50.6%) patients were given PPIs in an appropriate dose, whereas the dose was inappropriate in 126 (49.4%) patients. The appropriate dose was followed mostly in the gastroenterology department (83.1%), followed by the medicine department (47.3%). Whereas in the surgery department, only 35% of patients were given PPIs with an appropriate dose and the difference in the usage of appropriate doses of PPIs among the three departments is significant with p-value <0.001. The most common comorbid condition was diabetes (110; 18.3%), followed by hypertension (91; 15.2%) and stroke (24; 4.0%). Conclusion: This study estimates that only 50.6% of the 255 patients received the appropriate PPI dosage. The gastroenterology department had the highest adherence to appropriate dosing (83.1%). Diabetes was the most common comorbidity among patients (18.3%), followed by hypertension (15.2%) and stroke. These results highlight the need for improved adherence to PPI dosing guidelines across departments to enhance therapy effectiveness. J Rang Med Col. September 2024; Vol. 9, No. 2: 44-49

Wrist Circumference as a Novel Predictor of Coronary Artery Disease and Metabolic Syndrome

Introduction: Wrist circumference is a good predictor of obesity and insulin resistance. Wrist circumference may be considered as an indirect determinant of hyperinsulinemia and insulin resistance. The present study aimed to assess wrist circumference as an alternative tool for differentiating patients with coronary artery disease and metabolic syndrome from those without coronary artery disease and metabolic syndrome. Materials and Methods: The study was conducted on patients ≥ 30 years old undergoing coronary angiography following acute coronary syndrome or for evaluation of coronary artery disease. Results: Diabetic, hypertensive, and obese patients had more wrist circumference. High TG, low HDL levels were associated with higher wrist circumference (p=0.005). Wrist circumference was positively correlated with waist-hip ratio (p<0.001). Patients with Metabolic Syndrome have a mean Wrist circumference of 16.54 whereas patients without Metabolic Syndrome have a mean wrist circumference of 15.89(p<0.001). Coronary artery disease patients had higher mean wrist circumference than non-coronary artery disease patients (16.59 vs 15.9) (p<0.001). Triple-vessel disease patients have higher wrist circumference than double-vessel-disease patients; Doublevessel- disease patients have higher wrist circumference than single-vessel disease (p<0.001). Multivariate logistic model shows the main predictors for coronary artery disease are male sex, smoking, high BMI, low HDL, and wrist circumference. Conclusion: Measurement of Wrist circumference can serve as an easy anthropometric marker to identify individuals at risk of cardio-metabolic disorder, and predict the severity of Coronary Artery Disease can be used in large epidemiological studies.

Education, intelligence, and 20 gastrointestinal disorders: A Mendelian randomization study.

Previous observational studies have suggested that higher levels of education attainment and intelligence (IQ) are associated with better health outcomes in humans. However, the causal link between education attainment and IQ and their association with health outcomes remains unclear. This study aims to investigate the distinct impacts of intelligence and educational attainment on gastrointestinal symptoms. From the genome-wide association between educational attainment and the IQ study database, results were obtained from the FinnGen summary database. We used univariate and multivariate Mendelian randomization (MR) techniques to explore the relationship between exposures and outcomes. To assess the validity of inverse-variance-weighted-based results, we used several supplementary analytical techniques and performed sensitivity analysis. Our multivariate MR study confirmed the findings from univariable analyses and showed a genetically predicted causal association between educational attainment and 8 gastrointestinal disorders, including gastroesophageal reflux disease, chronic gastritis, gastroduodenal ulcer, cirrhosis, cholelithiasis, acute pancreatitis, chronic pancreatitis, and irritable bowel syndrome. Our univariate MR study found an association between IQ and 6 gastrointestinal conditions: gastroesophageal reflux disease, cirrhosis, cholelithiasis, acute pancreatitis, pancreatic malignancy, and irritable bowel syndrome. However, the connection was much weaker in multivariate MR analysis. Our study revealed causal relationships between gastrointestinal disorders and educational attainment. Educational attainment may mediate between intelligence and the impacts on the gastrointestinal system. However, further research is required to understand the underlying pathogenic processes completely.

Degenerative joint disease and Bi Syndrome: diagnostic bases and main integrative therapies in equine sports medicine

Chronic pain in horses is generally associated with diseases such as osteoarthritis and laminitis, characterized as chronic degenerative joint diseases. These consequently lead to reduced performance, early retirement and loss of animal welfare. According to Traditional Chinese Veterinary Medicine (MVTC), joint pain is characterized within the so-called Bi Syndrome, which relates to degenerative joint diseases. It is necessary, therefore, to recognize and evaluate pain aiming at the animals' quality of life and advances in the creation of diagnostic and anti-inflammatory and analgesic therapeutic possibilities in an integrative way. At MVTC, there are integrative techniques with significant potential to promote quality of life for these patients. Such therapies have anti-inflammatory and immunomodulatory properties, are safe, without side effects, effective and easy to perform with adequate training. The objective of this review is to bring together the main bases for the integration of diagnostic and therapeutic interventions in degenerative joint disease in equine sports medicine.

Leaky gut in systemic inflammation: exploring the link between gastrointestinal disorders and age-related diseases.

Global average life expectancy has steadily increased over the last several decades and is projected to reach ~ 77years by 2050. As it stands, the number of people > 60years currently outnumbers children younger than 5years, and by 2050, it is anticipated that the global population of people aged > 60years will double, surpassing 2.1 billion. This demographic shift in our population is expected to have substantial consequences on health services globally due to the disease burden associated with aging. Osteoarthritis, chronic obstructive pulmonary disease, diabetes, cardiovascular disease, and cognitive decline associated with dementia are among the most common age-related diseases and contribute significantly to morbidity and mortality in the aged population. Many of these age-related diseases have been linked to chronic low-grade systemic inflammation which often accompanies aging. Gastrointestinal barrier dysfunction, also known as "leaky gut," has been shown to contribute to systemic inflammation in several diseases including inflammatory bowel disease and irritable bowel syndrome, but its role in the development and/or progression of chronic low-grade systemic inflammation during aging is unclear. This review outlines current literature on the leaky gut in aging, how leaky gut might contribute to systemic inflammation, and the links between gastrointestinal inflammatory diseases and common age-related diseases to provide insight into a potential relationship between the intestinal barrier and inflammation.

Yogurt Supplementation Can Ameliorate Fatty Liver Diseases and Metabolic Syndrome in High Fat‐Induced Conditions in Mice

Yogurt Supplementation Can Ameliorate Fatty Liver Diseases and Metabolic Syndrome in High Fat‐Induced Conditions in Mice

The prevalence of metabolic syndrome in patients with non-alcoholic fatty liver disease in Erbil city

Background and objectives: Non-alcoholic fatty liver disease is the accumulation of fatty units in the liver in the absence of other triggers. Its development may have been primarily caused by metabolic syndrome, so the purpose of this study is to identify the prevalence of metabolic syndrome in non-alcoholic fatty liver disease and then to discover which parameter has the strongest link with non-alcoholic fatty liver disease. Methods: This cross-sectional study of 90 participants more than 18 years old with non-alcoholic fatty liver disease diagnosed by sonography in Erbil from August 2022 to May 2023. In each individual, metabolic syndrome criteria were taken and measured according to the National Cholesterol Education Program's Adult Treatment Panel III criteria, which were diagnosed by having three or more of these criteria, and ultrasound was used for the grading of fatty liver. Results: Metabolic syndrome were revealed in 69 (76.67%) of the participants. A higher proportion of patients were female 51 (56.67%) and male 39 (43.33%). It revealed a statistically significant correlation between gender and metabolic syndrome, with females and males having a corresponding 44 (49%) and 25 (28%) correlation, respectively. The most frequent factor was an expanded waist circumference in 66 (73.33%) of participants, followed by triglyceride in 62 (68.89%). Conclusion: In this study, among patients with non-alcoholic fatty liver disease significant number of the subjects had metabolic syndrome, with an increased waist circumference being the most prevalent feature, followed by high triglyceride levels, hyperglycemia, hypertension, and low high-density lipoprotein.

Comparing Outcomes of Moyamoya Disease and Moyamoya Syndrome in a Real-World Scenario: A Cohort Study.

Moyamoya disease (MMD) and moyamoya syndrome (MMS) are rare cerebrovascular conditions with unclear distinctions in clinical presentation and prognosis. This study assessed potential differences between MMD and MMS patients using real-world data on clinical manifestations, surgical outcomes, and stroke risk factors. This multicenter, retrospective cohort study examined patients with MMD or MMS treated at three tertiary academic hospitals in China, with a mean follow-up of 11.2 ± 3.1 years. Clinical differences were compared between MMD and MMS, and postoperative cerebrovascular events were compared between patients who underwent surgery and those with conservative management. Primary outcomes were postoperative ischemic and hemorrhagic strokes. Risk factors were evaluated via multivariate Cox regression analysis. Of the 2565 patients, 2349 had MMD and 216 had MMS. After 1:1 propensity-score matching, no significant differences were observed between these two cohorts. Surgical patients had fewer cerebrovascular events than those who received conservative treatment (HR, 0.487; 95% CI, 0.334-0.711; p < 0.001). Preadmission modified Rankin scale scores > 2 (HR, 3.139; 95% CI, 1.254-7.857; p = 0.015) and periprocedural complications (HR, 8.666; 95% CI, 3.476-21.604; p < 0.001) were independent stroke risk factors in patients with MMD. Periprocedural complications (HR, 31.807; 95% CI, 10.916-92.684; p < 0.001) increased stroke risk in patients with MMS. This real-world study revealed substantial clinical overlap between MMD and MMS. Both groups derived significant benefits from surgical revascularization, suggesting distinction may not be necessary to guide surgical management decisions. Optimizing preoperative status and preventing periprocedural complications may improve outcomes in these rare cerebrovascular conditions. This study has been registered in the Chinese Clinical trial registry (registration number: ChiCTR2200064160).

Periodontal Disease and Metabolic Syndrome in Women at Prior High Risk for Gestational Diabetes.

This study aimed to assess the association between periodontal disease and metabolic syndrome (MetS) among women at prior high risk for gestational diabetes with the hypothesis that women with MetS show more signs of periodontal disease than women without MetS. A total of 112 women from an original study cohort of 348 women at high risk of gestational diabetes were examined 4-6 years postpartum. Diagnosis of MetS was based on the National Cholesterol Education Program Adult Treatment Panel III diagnostic criteria. Insulin resistance was approximated by the homeostatic model assessment for insulin resistance. Full-mouth examinations and panoramic radiographs provided the total dental index, number of teeth, and decayed, missing, and filled teeth index. Clinical examination assessed bleeding on probing, probing depth, visible plaque index, signs of infection, and clinical attachment levels. The periodontal inflammatory burden index (PIBI) was also calculated. Information on oral health habits, symptoms, and individual opinions on oral health was collected through questionnaires. Five years after delivery, 21% of the women had MetS, and they had more gingivitis compared to those without MetS (bleeding on probing: 52% and 44%, p = 0.011). Women with MetS tended to have more periodontitis than those without (39% and 25%, p = 0.13). A high PIBI correlated with insulin resistance (partial correlation of PIBI and homeostatic model assessment for insulin resistance: 0.25 p < 0.05). Periodontal disease was associated with insulin resistance and MetS in women at prior high risk of developing gestational diabetes.

Cross-sectional survey of 43,517 dogs in the Dog Aging Project identifies owner-reported lifetime prevalence and characteristics of gastrointestinal disease.

To evaluate the prevalence of and characteristics associated with owner-reported gastrointestinal (GI) disease in companion dogs within the US. Cross-sectional owner-reported survey study of 43,517 dogs enrolled in the DAP between December 26, 2019, and December 31, 2022. Dogs were grouped on the basis of having an owner-reported GI disorder (ORGID) versus not having that ORGID at any point in their history (control group). Multivariable logistic regression analysis was used to estimate the association between dog characteristics and ORGIDs with prevalence ORs (PORs). Of the 43,517 dogs in the DAP Pack, 30,677 (70%) had no history of ORGIDs and 12,840 (30%) had at least 1 ORGID. The most common ORGIDs included infectious diseases (7,580 of 43,517 [17%]), chronic diarrhea (1,316 [3%]), foreign bodies (1,086 [2%]), anal sac impactions (1,031 [2%]), pancreatitis (857 [2%]), inflammatory GI disease (615 [1%]), chronic vomiting (519 [1%]), and acute hemorrhagic diarrhea syndrome (388 [1%]). Compared to controls, dogs with noninfectious ORGIDs had greater odds of having a history of being castrated (POR, 2.55; 95% CI, 2.29 to 2.85), underweight (POR, 1.58; 95% CI, 1.47 to 1.70), or fed primarily canned food (POR, 2.51; 95% CI, 2.21 to 2.85) or receiving probiotics (POR, 1.69; 95% CI, 1.58 to 1.81) or nonprescription GI medications (POR, 4.06; 95% CI, 3.80 to 4.33). Dog owners in the US recruited from the general public reported a high prevalence of GI disorders in their dogs. Infectious and noninfectious ORGIDs were reported with approximately equal frequency. Dogs with ORGIDs were more likely to have a history of receiving probiotics or nonprescription GI medications, which may indicate that owners are changing lifestyle practices to accommodate these GI disorders, although future longitudinal research is needed.

Prediction of metabolic syndrome and its associated risk factors in patients with chronic kidney disease using machine learning techniques.

Chronic kidney disease (CKD) and metabolic syndrome (MS) are recognized as public health problems which are related to overweight and cardiometabolic factors. The aim of this study was to develop a model to predict MS in people with CKD. This was a prospective cross-sectional study of patients from a reference center in São Luís, MA, Brazil. The sample included adult volunteers classified according to the presence of mild or severe CKD. For MS tracking, the k-nearest neighbors (KNN) classifier algorithm was used with the following inputs: gender, smoking, neck circumference, and waist-to-hip ratio. Results were considered significant at p < 0.05. A total of 196 adult patients were evaluated with a mean age of 44.73 years, 71.9% female, 69.4% overweight, and 12.24% with CKD. Of the latter, 45.8% had MS, the majority had up to 3 altered metabolic components, and the group with CKD showed statistical significance in: waist circumference, systolic blood pressure, diastolic blood pressure, and fasting blood glucose. The KNN algorithm proved to be a good predictor for MS screening with 79% accuracy and sensitivity and 80% specificity (area under the ROC curve - AUC = 0.79). The KNN algorithm can be used as a low-cost screening method to evaluate the presence of MS in people with CKD.

Utility of Tau PET in the diagnostic work up of neurodegenerative dementia among Indian patients

Background and objectivesTau PET is being increasingly appraised as a novel diagnostic modality for dementia work up. Given limited data among South Asians, we assessed the frequency, patterns, phenotypic associations and incremental value of positive Tau PET scans in clinically diagnosed neurodegenerative dementia. MethodsThis cross-sectional study recruited consecutive patients of Alzheimer's disease (AD) and non-AD syndromes (September 2021 to October 2022, India). Participants underwent clinical interview, cognitive assessment, MRI brain and tau PET scan ([F-18]ML-104). Visual read in a priori regions of interest was used to identify patterns of tau deposition in the brain. ResultsWe recruited 54 participants (mean age: 63.2 ± 9.2 years, 70.4 % men, 77.8 % dementia, 70.4 % early onset cases, 37.8 % APOE4+). The analysis identified abnormal tau uptake in 40/54 (74.1 %) participants; with uptake in AD signature areas in 27/40 (67.5 %) cases [cortical subtype (74.1 %), limbic (14.8 %), combined cortical/limbic (11.1 %)], and patterns not conforming to AD in 13/40 (32.5 %) cases. Tau PET substantiated the diagnosis of AD among 17/19 (89.5 %) cases with clinically diagnosed AD dementia, 8/23 (34.8 %) cases with suspected non-AD cause, and 2/12 (16.7 %) cases with mild cognitive impairment. A trend for increasing proportion of early onset cases, and worsening cognition, behavior and functional ability was seen, from ‘limbic’ to ‘combined cortical/limbic’ to ‘cortical’ subgroups. ConclusionTau PET is a useful modality to differentiate AD dementia from other neurodegenerative causes in the Indian setting where amyloid biomarkers are not widely available. Biological subtypes of AD map well onto clinical phenotypes and need study in larger cohorts.

Features of hyperinflammation link the biology of EBV infection and cytokine storm syndromes

BackgroundOvert immune activation by viral infections can lead to cytokine storm syndromes, such as hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS). ObjectiveWe aim to compare the immune response to different viral pathogens to understand the connection between infections and cytokine storm syndromes. MethodsWe recruited children who presented to the emergency room with fever for ≥ 3 days. We performed immune profiling using Olink proximity extension assay and flow cytometry. We compared the findings with cases of HLH, MAS, Kawasaki disease (KD), and multisystem inflammatory syndrome in children (MIS-C). ResultsWe enrolled 352 febrile patients and studied 110 cases with confirmed common viral infections. We found that Epstein-Barr virus (EBV) uniquely triggered high levels of multiple cytokines (IL-18, IL-27, tumor necrosis factor, FLT3 ligand, and lymphotoxin alpha) and IFN-γ-induced chemokines (CXCL9/10/11 and CCL19). These patterns are similar to the hyperinflammatory response associated with HLH / MAS, but less consistent with the findings in KD and MIS-C. Flow cytometry analysis revealed that CD38+HLA-DR+ T lymphocytes, which are pathogenic cells responsible for IFN-γ production in HLH / MAS, are vastly expanded in patients with acute EBV infection. Cell sorting identified CD38+HLA-DR+ T cells as atypical lymphocytes that are classically associated with acute EBV infection. ConclusionThis work broadens our understanding of common viral infections in children and provides an immunologic basis for the link between EBV infection and HLH / MAS.

Cognitive impairment in Parkinson's disease and other parkinsonian syndromes.

In this narrative review, we address mild cognitive impairment, a frequent complication of Parkinson's disease (PD) and atypical parkinsonian disorders (APDs). Recent diagnostic criteria have blurred the lines between PD and dementia with Lewy bodies (DLB), particularly in the cognitive domain. Additionally, atypical parkinsonian syndromes like progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) often present with significant cognitive decline. Even multiple system atrophy (MSA) can be associated with cognitive impairment in some cases. Several biomarkers, including imaging techniques, such brain magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography (FDG-PET), as well as pathological proteins either of the cerebrospinal fluid (CSF), such as Tau, amyloid beta, and synuclein, or of the serum, such as neurofilament light chain (Nfl) are more and more often utilized in the early differential diagnosis of APDs. The complex interplay between these conditions and the evolving understanding of their underlying pathologies highlight the need for further research to refine diagnostic criteria, possibly incorporate the new findings from the biomarker's field into the diagnostic criteria and develop targeted therapeutic strategies.

Overlap syndrome of Erdheim-Chester disease and Langerhans cell histiocytosis: A case report

Langerhans cell histiocytosis (LCH) and Erdheim–Chester disease (ECD) are exceptionally rare disorders characterized by varied clinical presentations, posing several challenges for clinicians. The concomitant occurrence of LCH and ECD is exceedingly rare and has no known etiology. In this report, we present a rare case of mixed histiocytosis (both ECD and LCH) with multisystem involvement. The patient, a 49-year-old female, initially presented with a rash 2 years ago and progressively developed exophthalmos, fatigue, and shortness of breath. She lacked the mutation in codon 600 of exon 15 of B-Raf proto-oncogene (BRAF-V600E) and subsequently underwent treatment with corticosteroids, interferon-alpha, and chemotherapy, all of which proved ineffective. This work highlights the urgent need to improve treatment outcomes for such patients. Therefore, we discuss the latest advancements in understanding treatment strategies for mixed histiocytic syndromes.

Decreased levels of vitamin D in Post-Corona Virus-19 Disease syndrome (PCS) patients compared to a control group

Background & AimsVitamin D deficiency is defined by most experts as a level of less than 20 ng/ml. Studies have shown a relationship between musculoskeletal pain, muscle weakness, headache, and fatigue with low vitamin D level. The term Post-Corona Virus-19 Disease syndrome (PCS) describes new, returning or ongoing symptoms more than 12 weeks after Corona Virus Disease -19 (COVID-19) infection which cannot be explained by any other disorders or illnesses. The most prominent symptoms in PCS are fatigue, headache, and attention disorders. These similarities in PCS and vitamin D deficiency leads to the hypothesis of an association. The aim of this study was to find possible differences in vitamin D levels between PCS patients and a control group without PCS. MethodsWe measured vitamin D levels from April 2021 to December 2022 in 75 (2021) and 73 (2022) subjects (PCS) and compared these values with data from 2019 to 2022 in a non-PCS control group (non-PCS). ResultsWe found significantly lower (p<0,05) vitamin D levels in the PCS cohort (2021: 17,04±8,0 ng/ml; 2022: 17,6±6,6 ng/ml) compared to all years of the non-PCS group (2019: 23,7±14,7 ng/ml; 2020:22,3±13,7 ng/ml; 2021: 22,4±12,3 ng/ml; 2022: 22,6±11,0 ng/ml). There were no significant differences in vitamin D levels within the different years of the non-PCS group and when comparing the two PCS groups. ConclusionThe results of the study recorded for the first-time decreased vitamin D values in a PCS cohort compared to a control group. This raises the question of whether vitamin D deficiency influences PCS symptoms or whether they are merely the consequences of the limitations of PCS.

Prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) and its association with arterial stiffness in adolescents: Results from the EVA4YOU study.

To determine the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) among Western Austrian adolescents and its association with arterial stiffness as a marker of early vascular ageing. In the cross-sectional Early Vascular Ageing in the YOUth study, liver fat content was assessed by controlled attenuation parameter (CAP) using signals acquired by FibroScan (Echosense, Paris, France) in 14- to 19-year-old Austrian adolescents. Arterial stiffness was determined by carotid-femoral pulse wave velocity (cfPWV) and cardiovascular risk factors by a face-to-face interview, physical examination, and fasting blood analyses. Linear regression models and one-way analysis of variance were performed to analyze the association between liver fat content, MASLD and cfPWV. A total of 1292 study participants (65.2% female) aged 17.2 ± 1.3 years were included. MASLD was detected in 62 (4.8%) adolescents. CAP value showed a significant association with cfPWV in the unadjusted model (p < 0.001) but lost its significant influence in the multivariable model after adjusting for sex, age and cardiovascular risk criteria (increased BMI or waist circumference, impaired glucose metabolism, elevated blood pressure, elevated plasma triglycerides, and decreased HDL cholesterol; p = 0.540). In the analysis of variance, a significant increase in cfPWV was observed in adolescents with any of the five cardiovascular risk criteria for MASLD (p < 0.001), but not with the additional presence of steatotic liver disease (p = 0.291). In our adolescent cohort, liver fat content and MASLD were not found to be independent predictors for early vascular ageing. Nevertheless, the determination of liver fat content can be a useful tool to identify adolescents at high risk for cardiovascular disease and metabolic syndrome.

Urinary Dickkopf-3 as a Potential Marker for Estimated Glomerular Filtration Rate Decline in Patients With Heart Failure.

Patients with chronic heart failure (HF) show an increased risk for the occurrence of chronic kidney disease and cardiorenal syndrome. Urinary Dickkopf-3 (uDKK3), a stress-induced, tubular profibrotic glycoprotein, may be elevated in HF as early as in New York Heart Association class I HF and may indicate subsequent decline in estimated glomerular filtration rate (eGFR). uDKK3 levels in patients with HF and controls were measured by enzyme-linked immunosorbent assay. eGFR was determined up to 5 years in HF. Change in eGFR was assessed with respect to baseline uDKK3 using (mixed-effect) linear and logistic regression models. A total of 488 patients with chronic HF and 45 control patients were included. Patients with HF showed higher median uDKK3 levels than controls (259.6 pg/mg creatinine [interquartile range (IQR), 119.2-509.4 pg/mg creatinine] versus 107.5 pg/mg creatinine [IQR, 60.5-181.2 pg/mg creatinine], P<0.001). Regression models demonstrated a significant association between log uDKK3 and the decline in eGFR during a median of 13 months (IQR, 12-59 months) (estimated higher eGFR loss, 0.8039 mL/min per 1.73 m2/year [95% CI, 0.002-1.606 mL/min per 1.73 m2/year], P=0.049; odds ratio, 1.345 [95% CI, 1.049-1.741], P=0.021). uDKK3 levels ≥354 pg/mg creatinine were associated with a significantly higher risk for eGFR decline at 1-year follow-up (estimated higher eGFR loss, 4.538 mL/min per 1.73 m2 [95% CI, 1.482-9.593 mL/min per 1.73 m2]), P=0.004). Even patients with HF without chronic kidney disease (n=334) had higher uDKK3 levels compared with controls (233.4 [IQR, 109.0-436.9 pg/mg creatinine] versus 107.5 [IQR, 60.5-181.2 pg/mg creatinine], P<0.001). The present findings indicate that uDKK3 is a promising prognostic biomarker for subsequent eGFR decline in patients with HF, irrespective of the presence of chronic kidney disease and even in the early stages of HF. This potential allows for early intervention to mitigate the deterioration of kidney function. Further investigation is warranted to validate its clinical utility.

Update on cancer screening in children with syndromes of bone lesions, hereditary leiomyoma and renal cell carcinoma syndrome, and other rare syndromes.

The management of children with syndromes associated with an increased risk of benign and malignant neoplasms is a complex challenge for healthcare professionals. The 2023 AACR Childhood Cancer Predisposition Workshop provided updated consensus guidelines on cancer surveillance in these syndromes, aiming to improve early detection, intervention, and reduce morbidity associated with such neoplasms. In this paper, we review several of the rare conditions discussed in this workshop. Ollier disease and Maffucci syndrome are enchondromatoses (disorders featuring benign bone lesions) with up to 50% risk of malignancy, including chondrosarcoma. These patients require surveillance with baseline whole-body MRI and routine monitoring of potential malignant transformation of bony lesions. Hereditary Multiple Osteochondromas carry a lower risk of chondrosarcoma (<6%) but still require lifelong surveillance and baseline imaging. Related syndromes of benign bone lesions are also described. Hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC), associated with fumarate hydratase pathogenic variants, is discussed in detail. Surveillance for RCC in pediatric age is recommended, as well as prompt intervention when a lesion is detected. Schinzel-Giedion Syndrome and Rubinstein-Taybi Syndrome are described for their associated malignancies and other complications, as well as expert consensus on the need for childhood cancer surveillance. Clinical recommendations, including imaging modalities and frequency of screenings, were proposed and are tailored to each syndrome's age-specific tumor risk profile. In all syndromes, patients and their families should be educated about the potential malignancy risk and advised to seek medical care for rapid growth of a mass, persistent pain, or other unexplained symptoms.

Eisenmenger Syndrome: Pathophysiology, Clinical Manifestations, and Contemporary Management Approaches in Advanced Cardiopulmonary Disease

Eisenmenger syndrome, a complex and severe form of congenital heart disease, results from prolonged left-to-right shunting due to underlying cardiac defects such as ventricular septal defects, atrial septal defects, or patent ductus arteriosus, ultimately leading to irreversible pulmonary arterial hypertension and a reversal of the initial shunt. This syndrome represents the most severe spectrum of pulmonary vascular disease associated with congenital heart defects and is characterized by hypoxemia, erythrocytosis, and systemic cyanosis. Despite advances in early diagnosis and intervention in congenital heart disease, Eisenmenger syndrome remains a significant concern due to the irreversible nature of pulmonary vascular changes and associated multisystem complications. This article provides a comprehensive review of the pathophysiology, clinical manifestations, and the role of pharmacologic and non-pharmacologic therapies, including advanced palliative care, to improve patient quality of life. Emerging therapies such as endothelin receptor antagonists, phosphodiesterase-5 inhibitors, and prostacyclin analogs show promise in symptom management, though surgical interventions, such as heart-lung transplantation, remain reserved for selected cases. Given the high mortality associated with Eisenmenger syndrome, a multidisciplinary approach is critical in managing complications, improving patient outcomes, and supporting functional status.