Established Diagnostic Criteria Research Articles

Survey on diagnosis of post-brain injury “higher brain dysfunction” in patients with cognitive impairment. Family/caregiver response

In Japan, the diagnostic criteria for the higher brain dysfunction (HBD) emerged in 2005 in response to social needs for support for the patients and their families. The issue of cognitive dysfunction after brain trauma is not unique to Japan. The purpose of this study was to reveal the current status of family members of HBD patients from their perspective, focusing on the changes before and after the establishment of diagnostic criteria in Japan. We conducted a questionnaire survey for family members supporting the HBD patients. The questionnaire included the causative condition, explanation on HBD by health professionals, and problems/difficulties they encountered. This research involved family members of 278 HBD cases (males = 211, age 49 years). The major underlying cause was head injury (n = 139). Compared to patients diagnosed pre-2005, a significantly larger proportion of family members after 2005 received information on the condition during the acute phase (within one month) (p < 0.001), including that from physicians (p < 0.001). Nearly half of the families cited a lack of awareness of HBD among the professionals as a problem. In Japan, awareness of HBD in the society is gradually increasing especially after the current diagnostic criteria were implemented, and there has been a steady increase over time in early diagnosis. Yet, there still remain those not appropriately diagnosed. To salvage those patients and the families left behind, we are suggesting several recommendations to further augment clinical practice and the healthcare systems in Japan.

Understanding Creutzfeldt-Jakob disease in Iran: a systematic review of case reports.

To systematically review the reported cases of Creutzfeldt-Jakob disease (CJD) in Iran. A comprehensive literature review of CJD cases in Iran was undertaken using the PubMed®, Scopus® and Google Scholar databases. In addition, the Iranian database MagIran was searched for Persian language reports. Case selection used the following criteria: (i) patients of Iranian origin; (ii) publication in peer-reviewed journals or reputable medical databases; (iii) a definitive diagnosis of CJD based on established diagnostic criteria. Thirteen cases from twelve reports were included in this systematic review. The majority of the cases were female (11 of 13; 84.6%). The mean ± SD age of patients at hospital admission was 59.38 ± 7.44 years. The findings of the case review suggested that the prevalence of CJD in Iran is not fully established. CJD may be misdiagnosed alongside other clinical signs. The most prevalent early indications of the disease were psychiatric and neurological in nature. A considerable delay in diagnosis was observed in some cases and there was a shortage of brain autopsy records. Efforts to improve diagnostic capabilities, promote awareness and establish monitoring systems are necessary for managing the challenges of providing an early diagnosis of CJD in Iran.

Epidemiology of Fontan-associated liver disease in Japan: Results from a nationwide survey in 2021.

Although the Fontan procedure has improved the survival of patients with single-ventricle heart disease, the long-term consequences of the procedure have been a concern. This study aimed to explore the patients' postoperative clinical characteristics, including a diagnosis of Fontan-associated liver disease (FALD). A nationwide Japanese epidemiological survey of post-Fontan patients was undertaken in 2021. The survey targets were selected from all departments of pediatrics, pediatric surgery, cardiology, cardiovascular surgery, and gastroenterology using stratified random sampling by the number of beds. Each department was asked to complete a mail-back questionnaire on the numbers of patients and their clinical characteristics. The diagnosis of FALD was made by each attending physician. The estimated number of post-Fontan patients was 7810 (95% confidence interval, 5430-10200) in 2020, with a period prevalence of 61.9 per million. During the follow-up of 13.8years after the Fontan procedure, 40% of patients were diagnosed with FALD. An elevated γ-glutamyl transpeptidase level was the most common finding leading to the FALD diagnosis (41%), and 45% of the patients also showed liver fibrosis. Compared with non-FALD patients, FALD patients were older, had longer duration since the Fontan procedure, and had more severe cardiac or liver conditions. However, more than half of the non-FALD patients had elevated liver enzyme levels, suggesting underestimation of the number of FALD patients. In 2020, approximately 40% of post-Fontan patients underwent follow-up with a diagnosis of FALD, although the lack of established diagnostic criteria for FALD could affect the reported prevalence of FALD.

Adult Vitamin B12 Deficiency-Associated Pseudo-Thrombotic Microangiopathy: A Systematic Review of Case Reports.

Cobalamin-deficient thrombotic microangiopathy or vitamin B12 deficiency presenting as pseudo-thrombotic microangiopathy is a rare disorder that can be misdiagnosed as thrombotic thrombocytopenic purpura. Patients with this condition are at risk of receiving unnecessary plasmapheresis with a potential delay in appropriate therapy with vitamin B12 supplementation. There are no established diagnostic criteria for this condition in clinical practice. We performed a systematic review of case reports published between January 2018 and January 2023 to analyze the clinical characteristics, risk factors, and patterns of laboratory markers to improve the diagnostic criteria for this condition.

Protective effect of bilingualism on aging, MCI, and dementia: A community-based study.

Lifelong bilingualism is associated with a delayed age at onset of dementia, but evidence from community-based studies is limited. We investigated the relationship between bilingualism and the prevalence of cognitive impairment in a linguistically diverse community. A door-to-door community study was conducted from January to December 2021 in urban Bengaluru, India. 1234 individuals aged ≥60 years participated in the study. Participants were diagnosed with no cognitive impairment (NCI), mild cognitive impairment (MCI), or dementia using established diagnostic criteria. Dementia prevalence was higher in monolinguals (4.9%) than bilinguals (0.4%) (P=.001). The prevalence of MCI was also higher in monolinguals (8.5%) than bilinguals (5.3%) (P=.001). The study also revealed better cognitive function in bilinguals than monolinguals with NCI, after controlling for confounding variables. The current study provides significant support for the protective effect of bilingualism on cognitive impairment in an urban community with extensive bilingual interactional contexts in everyday life. Bilingualism has been demonstrated to protect against dementia and mild cognitive impairment in a linguistically diverse community with extensive code-switching contexts. Bilingual older individuals had superior baseline cognitive performance compared to monolingual older individuals. Bilingualism was found to have an independent effect on general cognition after adjusting for major social determinants of health in the group without cognitive impairment.

Survival outcomes correlate with the level of cell-free circulating DNA in ST-elevation myocardial infarction.

Myocardial infarction (MI) can lead to higher cellular damage, making cell-free DNA (cfDNA) a potential biomarker for assessing disease severity. The aim of this study is to evaluate survival predictions using cfDNA measurements and assess its correlation with MI. A direct fluorescence assay was employed to measure cfDNA content in the blood samples of participants. The inclusion criteria included patients who gave informed consent, suffering from ST-elevation myocardial infraction (STEMI) based on established diagnostic criteria (joint ESC/ACC guidelines), between the age of 18 and 80 years old, and had elevated troponin biomarker levels. The study included 150 patients diagnosed with STEMI and 50 healthy volunteers as controls. Serial monitoring of patients was conducted to track their postdisease status. The rate of change of cfDNA was calculated and daily measurements for 7 days were recorded. Mean levels of cfDNA were found to be 5.93 times higher in patients with STEMI compared to healthy controls, providing clear evidence of a clinical correlation between cfDNA and STEMI. Patients were further categorized based on their survival status within a 90-day period. The study observed a strong predictive relationship between the rate of change of cfDNA during daily measurements and survival outcomes. To assess its predictive capability, a receiver operating characteristics (ROC) curve analysis was performed. The ROC analysis identified an optimal cutoff value of 2.50 for cfDNA, with a sensitivity of 81.5% and specificity of 74.0% in predicting disease outcomes. This study demonstrates a robust association between cfDNA and STEMI, indicating that cfDNA levels can be a valuable early prognostic factor for patients. Serial measurements of cfDNA during early disease onset hold promise as an effective approach for predicting survival outcomes in MI patients.

A missense variant in MYOF is associated with ARVC and sudden cardiac death

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is rare autosomal dominant genetic disorder that leads to severe arrhythmia and sudden cardiac death. Although previous studies in clinical, pathological and genetics of ARVC established consensus diagnostic criteria and expanded the spectrum of pathogenic genes, there is still a proportion of patients with unclear causative factors.Here, whole-exome sequencing was employed to investigate the genetic etiology of a 15-year-old sudden cardiac death female caused by ARVC. A novel variant of MYOF (NM_013451.3: c.4723G > C: p.D1575H) was identified, which is a member of the Ferlin family of proteins is associated with cardiomyopathy. And the bioinformatics analysis predicted the pathogenicity of this variant. We report the first variant of MYOF in ARVC, which imply a vital role of MYOF in cardiomyopathy.

The use of topical Rapamycin in successfully treating non-Langerhans cell histiocytosis in a pediatric patient

Non-Langerhans cell histiocytosis (non-LCH) refers to a collection of medical conditions distinguished by the excessive growth of histiocytes in bodily tissues. It is important to note that these conditions do not meet the established diagnostic criteria for Langerhans cell histiocytosis (LCH). Juvenile xanthogranuloma (JXG) and benign cephalic histiocytosis (BCH) represent the prevailing forms of cutaneous non-LCH. We present a case of JXG which responded to topical treatment with a 0.1% topical ointment of Rapamycin. Rapamycin, an immunosuppressive and antineoplastic agent, can thus be a viable alternative non-invasive topical modality for managing JXG. However, it is imperative to conduct prolonged observations to evaluate the efficacy and potential adverse reactions.

Contribution of neurophysiology to the diagnosis and monitoring of ALS.

This chapter describes the role of neurophysiological techniques in diagnosing and monitoring amyotrophic lateral sclerosis (ALS). Despite many advances, electromyography (EMG) remains a keystone investigation from which to build support for a diagnosis of ALS, demonstrating the pathophysiological processes of motor unit hyperexcitability, denervation and reinnervation. We consider development of the different diagnostic criteria and the role of EMG therein. While not formally recognised by established diagnostic criteria, we discuss the pioneering studies that have demonstrated the diagnostic potential of transcranial magnetic stimulation (TMS) of the motor cortex and highlight the growing evidence for TMS in the diagnostic process. Finally, accurately monitoring disease progression is crucial for the successful implementation of clinical trials. Neurophysiological measures of disease state have been incorporated into clinical trials for over 20 years and we review prominent techniques for assessing disease progression.

Iron deficiency in heart failure with preserved ejection fraction: rationale and design of the FAIR-HFpEF trial

Background: Iron deficiency is highly prevalent in patients with heart failure and has well established diagnostic criteria. Its occurrence is associated with reduced quality of life, exercise capacity and increased hospitalization rates and mortality. The clinical efficacy of treating iron deficiency has not been tested in patients with heart failure with preserved ejection fraction (HFpEF). Methods: The FAIRHFpEF trial aims to enroll patients with HFpEF, reduced exercise capacity and iron deficiency (defined as serum ferritin &lt;100 ng/mL or serum ferritin 100299 ng/mL with transferrin saturation &lt;20%). Patients will be treated in a multicenter, doubleblind, randomized clinical trial with intravenous ferric carboxymaltose (FCM) at doses aimed to replenish iron stores vs. placebo. The primary endpoint is the difference in exercise capacity from baseline to week 24 as assessed by the 6minute walk test. Secondary endpoints include healthrelated quality of life assessments such as the Kansas City Cardiomyopathy Questionnaire, the European Quality of Life5 Dimensions questionnaire and global function tests. Conclusions: The FAIRHFpEF trial is designed to investigate the effect of intravenous iron repletion in iron deficient patients with HFpEF using FCM.

Iron deficiency in heart failure with preserved ejection fraction: rationale and design of the FAIR-HFpEF trial

Background: Iron deficiency is highly prevalent in patients with heart failure and has well established diagnostic criteria. Its occurrence is associated with reduced quality of life, exercise capacity and increased hospitalization rates and mortality. The clinical efficacy of treating iron deficiency has not been tested in patients with heart failure with preserved ejection fraction (HFpEF). Methods: The FAIRHFpEF trial aims to enroll patients with HFpEF, reduced exercise capacity and iron deficiency (defined as serum ferritin &lt;100 ng/mL or serum ferritin 100299 ng/mL with transferrin saturation &lt;20%). Patients will be treated in a multicenter, doubleblind, randomized clinical trial with intravenous ferric carboxymaltose (FCM) at doses aimed to replenish iron stores vs. placebo. The primary endpoint is the difference in exercise capacity from baseline to week 24 as assessed by the 6minute walk test. Secondary endpoints include healthrelated quality of life assessments such as the Kansas City Cardiomyopathy Questionnaire, the European Quality of Life5 Dimensions questionnaire and global function tests. Conclusions: The FAIRHFpEF trial is designed to investigate the effect of intravenous iron repletion in iron deficient patients with HFpEF using FCM.

Iron deficiency in heart failure with preserved ejection fraction: rationale and design of the FAIR-HFpEF trial

Background: Iron deficiency is highly prevalent in patients with heart failure and has well established diagnostic criteria. Its occurrence is associated with reduced quality of life, exercise capacity and increased hospitalization rates and mortality. The clinical efficacy of treating iron deficiency has not been tested in patients with heart failure with preserved ejection fraction (HFpEF). Methods: The FAIRHFpEF trial aims to enroll patients with HFpEF, reduced exercise capacity and iron deficiency (defined as serum ferritin &lt;100 ng/mL or serum ferritin 100299 ng/mL with transferrin saturation &lt;20%). Patients will be treated in a multicenter, doubleblind, randomized clinical trial with intravenous ferric carboxymaltose (FCM) at doses aimed to replenish iron stores vs. placebo. The primary endpoint is the difference in exercise capacity from baseline to week 24 as assessed by the 6minute walk test. Secondary endpoints include healthrelated quality of life assessments such as the Kansas City Cardiomyopathy Questionnaire, the European Quality of Life5 Dimensions questionnaire and global function tests. Conclusions: The FAIRHFpEF trial is designed to investigate the effect of intravenous iron repletion in iron deficient patients with HFpEF using FCM.

The Detection of Neoplastic Cells Using Objective Cytomorphologic Parameters in Malignant Lymphoma

Pathologic evaluation is the most crucial method for diagnosing malignant lymphomas. However, there are no established diagnostic criteria for evaluating pathologic morphology. We manually circled cell nuclei in the lesions of 10 patients with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, and reactive lymphadenitis. Seventeen parameters related to nuclear shape, color, and other characteristics were measured. We attempted to compare the statistical differences between these subtypes and extract distinctive disease-specific populations on the basis of these parameters. Statistically significant differences were observed between the different types of lymphoma for many of the 17 parameters. Through t-distributed stochastic neighbor embedding analysis, we extracted a cluster of cells that showed distinctive features of DLBCL and were not found in follicular lymphoma or reactive lymphadenitis. We created a decision tree to identify the characteristics of the cells within that cluster. Based on a 5-fold cross-validation study, the average sensitivity, specificity, and accuracy obtained were 84.1%, 98.4%, and 97.3%, respectively. A similar result was achieved using a validation experiment. Important parameters that indicate the features of DLBCL include Area, ConcaveCount, MaxGray, and ModeGray. By quantifying pathologic morphology, it was possible to objectively represent the cell morphology specific to each lymphoma subtype using quantitative indicators. The quantified morphologic information has the potential to serve as a reproducible and flexible diagnostic tool.

A comparison of the original ADAS‐cognitive subscale and a novel extended version in mild cognitive impairment and Alzheimer’s disease.

AbstractBackgroundThe Original Alzheimer’s disease Assessment Scale‐cognitive subscale (oADAS) is the gold standard for assessing cognition in Alzheimer’s disease (AD) medication clinical trials. One criticism is that this measure is not sensitive to pre‐dementia syndromes such as mild cognitive impairment (MCI), possibly due to ceiling effects for many of the subtests in the original ADAS‐cog (oADAS). In this study, we examined group differences between individuals with MCI, AD, and normal controls (NC) on the oADAS and a novel extended version of the ADAS (eADAS). We hypothesized the eADAS would be more sensitive than the oADAS at detecting differences between the groups after controlling for age, education, and sex.MethodThe oADAS was administered using standardized methods. The eADAS included short‐delay recall and recognition trials for the first wordlist, a short‐delay true‐false word recognition trial for the second word‐list, a letter‐digit timed psychomotor test, supermarket fluency, spontaneous clock drawing, three additional items to the object naming subtest, three additional figures to copy, and a similarities test. MCI and possible AD were diagnosed using established diagnostic criteria. The NC group was significantly younger and more educated than the MCI and AD groups. A 3×2 ANCOVA model with group as the between subject factor and ADAS type as the within subject factor was used. Total error scores from the oADAS and eADAS were converted to z‐scores.ResultThere was no main effect of ADAS type or ADAS type X education or ADAS type X group interactions. There were ADAS type x age and ADAS type x gender interactions (p’s = 0.01). Pairwise comparisons demonstrated that the NC group had lower total error scores compared to the MCI and AD groups and the MCI group had lower total error scores compared to the AD group for both the oADAS and eADAS (p’s&lt;0.001).ConclusionThe results of the current study indicate that oADAS and eADAS are sensitive to group differences between MCI and AD, which was contrary to our hypothesis. We suggest more rigorous diagnostic criteria for MCI in the present study may explain some of the conflicting findings in the literature.

BREAKING NEW GROUND: STANDARDIZING RAT MODELS FOR CRUSH SYNDROME INVESTIGATIONS.

Crush syndrome (CS), alternatively termed traumatic rhabdomyolysis, is a paramount posttraumatic complication. Given the infeasibility of conducting direct simulation research in humans, the role of animal models is pivotal. Regrettably, the dearth of standardized animal models persists. The objective of this study was to construct a repeatable standardized rat CS models and, based on this, simulate specific clinical scenarios. Methods: Using a self-developed multichannel intelligent small-animal crush injury platform, we applied a force of 5 kg to the hind limbs of 8-week-old rats (280-300 g), subjecting them to a continuous 12 h compression to establish the CS model. Continuous monitoring was conducted for both the lower limbs and the overall body status. After decompression, biochemical samples were collected at 3, 6, 12, and 24 h. In addition, we created a CS model after resection of the left kidney (UNx-CS), which was conceptualized to simulate a more challenging clinical scenario to investigate the physiological and pathological responses rats with renal insufficiency combined with crush injury. The results were compared with those of the normal CS model group. Results : Our experiments confirm the stability of the crush injury platform. We defined the standardized conditions for modeling and successfully established rats CS model in bulk. After 12 h of compression, only 40% of the rats in the CS group survived for 24 h. Systemically, there was clear evidence of insufficient perfusion, reflecting the progression of CS from localized to generalized. The injured limbs displayed swelling, localized perfusion deficits, and severe pathological alterations. Significant changes were observed in blood biochemical markers: aspartate transaminase, lactate dehydrogenase, K+, creatine kinase, creatinine, and blood urea nitrogen levels rose rapidly after decompression and were significantly higher than the sham group. The kidney demonstrated characteristic pathological changes consistent with established CS diagnostic criteria. Although the UNx-CS rat model did not exhibit significant biochemical differences and pathological scores when compared with the standard CS model, it did yield intriguing results with regard to kidney morphology. The UNx-CS group manifested a higher incidence of cortical and medullary protein casts compared with the NC-CS group. Conclusion: We developed and iteratively refined a novel digital platform, addressing the multiple uncontrollable variables that plagued prior models. This study validated the stability of the platform, defined the standardized conditions for modeling and successfully established the CS model with good repeatability in bulk. In addition, our innovative approach to model a clinically challenging scenario, the UNx-CS rat model. This offers an opportunity to delve deeper into understanding the combined effects of preexisting renal compromise and traumatic injury. In summary, the development of a standardized, reproducible CS model in rats represents a significant milestone in the study of Crush syndrome. This study is of paramount significance as it advances the standardization of the CS model, laying a solid foundation for subsequent studies in related domains, especially in CS-AKI.

Brucella-infected abdominal aortic aneurysm: management strategies for an uncommon aneurysm.

The occurrence of Brucella-induced abdominal aortic aneurysms is an exceedingly rare phenomenon, yet it stands as one of the most severe complications within this context. The combined utilization of serological testing and imaging diagnostics has been validated as an effective approach for the identification of Brucella-induced abdominal aortic aneurysms. Presently, the predominant therapeutic strategies encompass antibiotic treatment and surgical intervention. Nonetheless, ongoing controversies persist concerning the establishment of diagnostic criteria, the optimal timing and selection of antibiotic regimens, and the nuanced decision between open surgical procedures and endovascular interventions. Through a meticulous analysis of cases originating from our institution as well as a comprehensive review of previously documented instances, we aim to engage in a detailed discourse on the salient diagnostic and therapeutic facets surrounding Brucella-induced abdominal aortic aneurysms. We conducted a retrospective summary of three cases involving Brucella-induced abdominal aortic aneurysms treated within our institution. Furthermore, we performed a comprehensive PubMed search, without imposing restrictions on language or publication year, to identify pertinent literature pertaining to Brucella-induced abdominal aortic aneurysms. The selection criteria primarily focused on case reports delineating occurrences of abdominal aortic aneurysms attributed to Brucella infection. We present three distinct cases of Brucella-induced abdominal aortic aneurysms managed at our institution, providing comprehensive insights into the employed diagnostic and therapeutic approaches. Additionally, over the past five decades, a total of 24 cases in 23 publications of Brucella-induced abdominal aortic aneurysms have been reported on PubMed. The earliest report dates back to 1976. Our analysis suggests that Brucella-induced abdominal aortic aneurysm is characterized by a remarkably low incidence but is associated with a substantial risk of life-threatening complications. The integration of serological and imaging assessments assumes pivotal importance in facilitating prompt diagnosis of this condition. The prompt initiation of targeted antibiotic therapy is recommended, and the selection of appropriate surgical strategies should be guided by considerations including aneurysm dimensions and morphological attributes. The timely identification and intervention carry utmost significance in retarding disease advancement and ameliorating unfavorable clinical outcomes.

Phenotypes of Disseminated Intravascular Coagulation.

Two phenotypes of disseminated intravascular coagulation (DIC) are systematically reviewed. DIC is classified into thrombotic and fibrinolytic phenotypes characterized by thrombosis and hemorrhage, respectively. Major pathology of DIC with thrombotic phenotype is the activation of coagulation, insufficient anticoagulation with endothelial injury, and plasminogen activator inhibitor-1-mediated inhibition of fibrinolysis, leading to microvascular fibrin thrombosis and organ dysfunction. DIC with fibrinolytic phenotype is defined as massive thrombin generation commonly observed in any type of DIC, combined with systemic pathologic hyperfibrinogenolysis caused by underlying disorder that results in severe bleeding due to excessive plasmin formation. Three major pathomechanisms of systemic hyperfibrinogenolysis have been considered: (1) acceleration of tissue-type plasminogen activator (t-PA) release from hypoxic endothelial cells and t-PA-rich storage pools, (2) enhancement of the conversion of plasminogen to plasmin due to specific proteins and receptors that are expressed on cancer cells and endothelial cells, and (3) alternative pathways of fibrinolysis. DIC with fibrinolytic phenotype can be diagnosed by DIC diagnosis followed by the recognition of systemic pathologic hyperfibrin(ogen)olysis. Low fibrinogen levels, high fibrinogen and fibrin degradation products (FDPs), and the FDP/D-dimer ratio are important for the diagnosis of systemic pathologic hyperfibrin(ogen)olysis. Currently, evidence-based treatment strategies for DIC with fibrinolytic phenotypes are lacking. Tranexamic acid appears to be one of the few methods to be effective in the treatment of systemic pathologic hyperfibrin(ogen)olysis. International cooperation for the elucidation of pathomechanisms, establishment of diagnostic criteria, and treatment strategies for DIC with fibrinolytic phenotype are urgent issues in the field of thrombosis and hemostasis.

Regional differences in the incidence of lymphocytic and collagenous colitis over time

Background In microscopic colitis (MC), the incidence has increased over the last decades. The aim of the present study was to determine the incidence of lymphocytic (LC) and collagenous colitis (CC) in the county Skåne (Scania), southern Sweden, during the period 2010–20 with focus both on the temporal and spatial variations. Methods The MC diagnosis was retrieved from the biopsy registries at the Departments of Pathology. Established diagnostic criteria (increased lymphocyte count, inflammation in lamina propria and in CC a collagen band) were used for diagnosis. Age, gender, date for diagnosis and municipality of residence were retrieved for all patients. Results In total 1985 patients could be identified with a mean age of 62.9 years (SD 15.7) whereof 1415 were women. The incidence for CC was stable with a total age-standardized rate (ASR) per 100 000 person-years of 6.34, (range 4.6–8.1). In LC the ASR was 7.90 (range 1.7–15.2) but increased markedly 2015–20 reaching 15.2 in 2019. Also, the northwest part of the region showed significantly higher ASR:s of LC during the last part of the decade in comparation to the whole region. Conclusions The incidence of CC was stable during the period while LC differed substantially in a way that indicates that it most probably must be two different disease entities. In LC, in view of the marked and rapid increase, although no definitive explanation could be found, causative environmental factors could be contemplated, why further studies are indicated.

A cardiologist-like computer-aided interpretation framework to improve arrhythmia diagnosis from imbalanced training datasets

Arrhythmias can pose a significant threat to cardiac health, potentially leading to serious consequences such as stroke, heart failure, cardiac arrest, shock, and sudden death. In computer-aided electrocardiogram interpretation systems, the inclusion of certain classes of arrhythmias, which we term "aggressive" or "bullying," can lead to the underdiagnosis of other "vulnerable" classes. To address this issue, a method for arrhythmia diagnosis is proposed in this study. This method combines morphological-characteristic-based waveform clustering with Bayesian theory, drawing inspiration from the diagnostic reasoning of experienced cardiologists. The proposed method achieved optimal performance in macro-recall and macro-precision through hyperparameter optimization, including spliced heartbeats and clusters. In addition, with increasing bullying by aggressive arrhythmias, our model obtained the highest average recall and the lowest average drop in recall on the nine vulnerable arrhythmias. Furthermore, the maximum cluster characteristics were found to be consistent with established arrhythmia diagnostic criteria, lending interpretability to the proposed method.

Drug induced nephrotoxicity- A mechanistic approach.

The main goal of the treatment of patients is its effectiveness and safety. However, all currently prescribed drugs being used also have certain adverse effects, which might be seen as an unavoidable but necessary cost of pharmacotherapy. The kidney is the primary organ for xenobiotics elimination, making it particularly susceptible to the harmful effects of drugs and their metabolites during their excretion from the body. Moreover, certain medications have a preferential nephrotoxicity potential, which means that using them increases the risk of kidney injury. Drug nephrotoxicity is, therefore, both a significant problem and a complication of pharmacotherapy. It should be noted that, there is presently no accepted definition of drug-induced nephrotoxicity and no established diagnostic criteria. The current review briefly describes the pathogenic mechanism of drug-induced nephrotoxicity, the various basic drugs with nephrotoxicity potential and the renal biomarkers for the treatment of the drug-related kidney damage.