Diagnostic Criteria Research Articles

Prevalence of diabetic cardiomyopathy in patients with type 2 diabetes in a large academic medical center

BackgroundDiabetic cardiomyopathy (DbCM) is characterized by asymptomatic stage B heart failure (SBHF) caused by diabetes-related metabolic alterations. DbCM is associated with an increased risk of progression to overt heart failure (HF). The prevalence of DbCM in patients with type 2 diabetes (T2D) is not well established. This study aims to determine prevalence of DbCM in adult T2D patients in real-world clinical practice.MethodsRetrospective multi-step review of electronic medical records of patients with the diagnosis of T2D who had echocardiogram at UC San Diego Medical Center (UCSD) within 2010–2019 was conducted to identify T2D patients with SBHF. We defined “pure” DbCM when SBHF is associated solely with T2D and “mixed” SBHF when other medical conditions can contribute to SBHF. “Pure” DbCM was diagnosed in T2D patients with echocardiographic demonstration of SBHF defined as left atrial (LA) enlargement (LAE), as evidenced by LA volume index ≥ 34 mL/m2, in the presence of left ventricular ejection fraction (LVEF) ≥ 45%, while excluding overt HF and comorbidities that can contribute to SBHF.ResultsOf 778,314 UCSD patients in 2010–2019, 45,600 (5.9%) had T2D diagnosis. In this group, 15,182 T2D patients (33.3%) had echocardiogram and, among them, 13,680 (90.1%) had LVEF ≥ 45%. Out of 13,680 patients, 4,790 patients had LAE. Of them, 1,070 patients were excluded due to incomplete data and/or a lack of confirmed T2D according to the American Diabetes Association recommendations. Thus, 3,720 T2D patients with LVEF ≥ 45% and LAE were identified, regardless of HF symptoms. In this group, 1,604 patients (43.1%) had overt HF and were excluded. Thus, 2,116 T2D patients (56.9% of T2D patients with LVEF ≥ 45% and LAE) with asymptomatic SBHF were identified. Out of them, 1,773 patients (83.8%) were diagnosed with “mixed” SBHF due to comorbidities such as hypertension (58%), coronary artery disease (36%), and valvular heart disease (17%). Finally, 343 patients met the diagnostic criteria of “pure” DbCM, which represents 16.2% of T2D patients with SBHF, i.e., at least 2.9% of the entire T2D population in this study.ConclusionsOur findings provide insights into prevalence of DbCM in real-world clinical practice and indicate that DbCM affects a significant portion of T2D patients.

Uncovering Unrecognized Heart Failure With Preserved Ejection Fraction Among Individuals With Obesity and Dyspnea.

Although heart failure with preserved ejection fraction (HFpEF) has become the predominant heart failure subtype, it remains clinically under-recognized. HFpEF diagnosis is particularly challenging in the setting of obesity given the limitations of natriuretic peptides and resting echocardiography. We examined invasive and noninvasive HFpEF diagnostic criteria among individuals with obesity and dyspnea without known cardiovascular disease to determine the prevalence of hemodynamic HFpEF in the community. Research volunteers with dyspnea and obesity underwent resting echocardiography; participants with possible pulmonary hypertension qualified for invasive cardiopulmonary exercise testing. HFpEF was defined using rest or exercise pulmonary capillary wedge pressure criteria (≥15 mm Hg or Δpulmonary capillary wedge pressure/Δcardiac output slope, >2.0 mm Hg·L-1·min-1). Among n=78 participants (age, 53±13 years; 65% women; body mass index, 37.3±6.8 kg/m2), 40 (51%) met echocardiographic criteria to undergo invasive cardiopulmonary exercise testing. In total, 24 participants (60% among the cardiopulmonary exercise testing group, 31% among the total sample) were diagnosed with HFpEF by rest or exercise pulmonary capillary wedge pressure (n=12) or exercise criteria (n=12). There were no differences in NT-proBNP (N-terminal pro-B-type natriuretic peptide; 79 [62-104] versus 73 [57-121] pg/mL) or resting echocardiography (mitral E/e' ratio, 9.1±3.1 versus 8.0±2.7) among those with versus without HFpEF (P>0.05 for all). Distributions of HFpEF diagnostic scores were similar, with the majority classified as intermediate risk (100% versus 93.75% [H2FPEF] and 87.5% versus 68.75% [HFA-PEFF (Heart Failure Association Pretest assessment, echocardiography and natriuretic peptide, functional testing, and final etiology)] in those with versus without HFpEF). Among adults with obesity and dyspnea without known cardiovascular disease, at least a third had clinically unrecognized HFpEF uncovered on invasive cardiopulmonary exercise testing. Clinical, biomarker, resting echocardiography, and diagnostic scores were similar among those with and without HFpEF. These results suggest clinical underdiagnosis of HFpEF among individuals with obesity and dyspnea and highlight limitations of noninvasive testing in the identification of HFpEF.

Is sleep bruxism in obstructive sleep apnea only an oral health related problem?

BackgroundThe etiology of sleep bruxism in obstructive sleep apnea (OSA) patients is not yet fully clarified. This prospective clinical study aimed to investigate the connection between probable sleep bruxism, electromyographic muscle tone, and respiratory sleep patterns recorded during polysomnography.Methods106 patients with OSA (74 males, 31 females, mean age: 56.1 ± 11.4 years) were divided into two groups (sleep bruxism: SB; no sleep bruxism: NSB). Probable SB were based on the AASM criteria: self-report of clenching/grinding, orofacial symptoms upon awakening, abnormal tooth wear and hypertrophy of the masseter muscle. Both groups underwent clinical examination for painful muscle symptoms aligned with Temporomandibular Disorders Diagnostic Criteria (DC/TMD), such as myalgia, myofascial pain, and headache attributed to temporomandibular disorder. Additionally, non-complaint positive muscle palpation and orofacial-related limitations (Jaw Functional Limited Scale-20: JFLS-20) were assessed. A one-night polysomnography with electromyographic masseter muscle tone (EMG) measurement was performed. Descriptive data, inter-group comparisons and multivariate logistic regression were calculated.ResultsOSA patients had a 37.1% prevalence of SB. EMG muscle tone (N1-N3, REM; P = 0.001) and the number of hypopneas (P = 0.042) were significantly higher in the sleep bruxism group. While measures like apnea–hypopnea-index (AHI), respiratory-disturbance-index (RDI), apnea index (AI), hypopnea-index (HI), number of arousals, and heart rate (1/min) were elevated in sleep bruxers, the differences were not statistically significant. There was no difference in sleep efficiency (SE; P = 0.403). Non-complaint masseter muscle palpation (61.5%; P = 0.015) and myalgia (41%; P = 0.010) were significant higher in SB patients. Multivariate logistic regression showed a significant contribution of EMG muscle tone and JFLS-20 to bruxism risk.ConclusionIncreased EMG muscle tone and orofacial limitations can predict sleep bruxism in OSA patients. Besides, SB patients suffer more from sleep disorder breathing. Thus, sleep bruxism seems to be not only an oral health related problem in obstructive apnea. Consequently, interdisciplinary interventions are crucial for effectively treating these patients.Trial registrationThe study was approved by the Ethics Committee of Philipps-University Marburg (reg. no. 13/22—2022) and registered at the “German Clinical Trial Register, DRKS” (DRKS0002959).

Neutrophil to Lymphocyte Ratio on Admission to Predict Mortality of COVID-19 Elderly Patients

Severe Acute Respiratory Syndrome Corona Virus Disease-2 (SARS-COV-2) is the cause of COVID-19, which led to a global pandemic and high mortality rate, especially in elderly patients. The declining immune system in elderly patients and comorbid diseases lead to more severe symptoms and an increased mortality rate. Many studies have shown that a high Neutrophil-Lymphocyte Ratio (NLR) value can predict the severity and mortality of COVID-19. However, studies on NLR in elderly patients in Indonesia have rarely been conducted. This study aimed to determine the role of NLR on admission as a mortality predictor in COVID-19 elderly patients who underwent in-hospital treatment. This research is an analytical observational study with a retrospective cohort method conducted in Bethesda Hospital, Yogyakarta, Indonesia. The research subjects were selected from July 2020 to October 2021 according to inclusion and exclusion criteria. Inclusion criteria were all elderly COVID-19 patients with an age limit of > 60 years old who had complete hemogram data on admission, demographic data, diagnostic criteria, types of comorbid diseases, and patient outcomes (survivor or non-survivor). The exclusion criteria were elderly COVID-19 patients with incomplete Electronic Medical Records (EMR). This study found 122 elderly patients with COVID-19 with a mortality rate of 30.33%. The result showed that NLR on admission significantly increased significantly in the non-survivor group compared to the survivor group. Multivariate Cox regression analysis presented severity (RR: 5.181; CI 1.662-16.154; p=0.005), comorbid diabetes mellitus (RR: 2.829; CI: 1.115-7.178), NLR > 6.04 (RR: 6.356; CI: 2.428-16.639) and other comorbid, namely thyroid, autoimmune, cancer, and anemia (RR: 15.836; CI: 1.841-136.234; p=0.012) as factors of mortality in hospitalized elderly patients.

Syncope and Brugada-like ECG pattern in a patient with syndrome of inappropriate antidiuretic hormone secretion (SIADH)

Syncope is a brief loss of consciousness caused by reduced blood flow to the brain, characterised by sudden onset, short duration and full recovery without intervention. Anamnesis, physical examination and other diagnostic tests such as laboratory analysis and electrocardiogram (ECG) can be conducted to identify the underlying cause of syncope. A Brugada pattern on an ECG in individuals with syndrome of inappropriate antidiuretic hormone secretion (SIADH) who have syncope symptoms may indicate cardiac issues. A 69-year-old man with hypertension and a history of smoking presented with syncope. His vital signs were within normal limits, with no signs of a neurological deficit. The patient met the diagnostic criteria for SIADH, as evidenced by the presence of hyponatraemia (Na 118 mmol/l), a hyperosmolar condition and euvolemia. Upon arrival, a twelve-lead ECG showed ST-segment anomalies that reflected a Brugada ECG pattern. No ventricular arrhythmias were detected during the 24-hour Holter monitoring. Coronary angiography revealed no abnormalities in the coronary arteries. The ECG demonstrated the normalisation of ST elevations and the disappearance of the Brugada ECG pattern after the correction of hyponatraemia. After three months of follow-up the patient, with a normal sodium level, had no episodes of syncope.

Prevalence and Clinical Implications of Osteosarcopenia in Patients with Acute Stroke: A Cross-sectional Study.

To investigate the prevalence and risk factors of osteosarcopenia in patients with acute stroke. Overall, 224 patients within 2 weeks of having a stroke were enrolled. Demographic characteristics, National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), modified Barthel Index (MBI), Functional Ambulation Category (FAC), Berg Balance Scale (BBS), and handgrip strength were recorded. Body composition was evaluated using dual-energy X-ray absorptiometry. Patients who met the diagnostic criteria for osteoporosis and sarcopenia were defined as having osteosarcopenia. The overall prevalence of osteoporosis and sarcopenia was 46.9% and 50.9%, respectively. The prevalence of osteoporosis without sarcopenia, sarcopenia without osteoporosis, and osteosarcopenia was 18.3%, 22.3%, and 28.6%, respectively. The proportion of female sex (71.9%), median age, and NIHSS score were significantly higher, and mRS, BBS, MBI, FAC, and grip strength were significantly lower in patients with osteosarcopenia. Older age (≥65-years) (OR, 15.4), female sex (OR, 6.23), and lower BMI (<25 kg/m 2 ) (OR, 43.13) were independently associated with the likelihood of osteosarcopenia. Osteosarcopenia may occur in acute stroke survivors. Patients with osteosarcopenia have a significantly higher stroke severity and disability. A comprehensive diagnostic approach is imperative for osteosarcopenia, thereby facilitating implementation of optimal rehabilitative strategies.

Different biomarker ratios in peripheral blood have limited value in diagnosing periprosthetic joint infection after total joint arthroplasty: a single-center, retrospective study

BackgroundPeriprosthetic joint infection (PJI) is a severe complication that can occur after total joint arthroplasty (TJA). The timely and accurate diagnosis of PJI is the key to treatment. This study investigated the diagnostic value of platelet to lymphocyte ratio (PLR), platelet count to mean platelet volume ratio (PVR), neutrophil to lymphocyte ratio (NLR) and monocyte to lymphocyte ratio (MLR) in PJI after total knee arthroplasty (TKA) and total hip arthroplasty (THA).MethodsWe performed a retrospective analysis of the patients who underwent revision hip or knee arthroplasty at our Institute between June 2015 and June 2020. Of the 187 patients reviewed, 168 were included in the study. According to the diagnostic criteria of the Musculoskeletal Infection Society (MSIS), 58 patients were in the PJI group, and 110 patients were in the aseptic loosening (AL) group. We recorded and compared the preoperative peripheral blood white blood cell (WBC) count, platelet count (PLT), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), PLR, PVR, NLR, and MLR in both groups. The diagnostic performance of the WBC, PLT, PLR, PVR, NLR, and MLR individually and in combination with the ESR and CRP for PJI diagnosis was evaluated by receiver operating characteristic (ROC) curves, and the sensitivity, specificity, positive predictive value, and negative predictive value were calculated.ResultsCompared to those in the AL group, the mean WBC, PLT, ESR, CRP, PLR, PVR, NLR, and MLR in the peripheral blood of the PJI group were significantly greater (P < 0.05). The analysis of the ROC curve revealed that the ESR, CRP, PLR, PVR, NLR, and MLR in peripheral blood had moderate effectiveness in diagnosing PJI, with area under the curve (AUC) values of 0.760 (95% CI: 0.688–0.823), 0.758 (95% CI: 0.687–0.821), 0.714 (95% CI: 0.639–0.781), 0.709 (95% CI: 0.634–0.777), 0.723 (95% CI: 0.649–0.789), and 0.728 (95% CI: 0.654–0.793), respectively. Conversely, the WBC and PLT counts demonstrated poor diagnostic value for PJI, with AUC values of 0.578 (95% CI: 0.499–0.653) and 0.694 (95% CI: 0.619–0.763), respectively. The results of the prediction model calculations revealed that the combined AUC of the WBC, PLT, ESR, CRP, PLR, PVR, NLR, and MLR was the highest at 0.853 (95% CI, 0.790–0.909), indicating good value in the diagnosis of PJI, with a sensitivity of 82.8% and a specificity of 72.7%. Moreover, the novel composite of parameters improved the accuracy and reliability in diagnosing PJI compared to the traditional biomarkers ESR and CRP (P = 0.015).ConclusionOur study suggested that the diagnostic value of the peripheral blood biomarkers PLR, PVR, NLR, and MLR for diagnosing PJI is limited and not superior to that of the ESR or CRP. However, when the WBC, PLT, ESR, CRP, PLR, PVR, NLR, and MLR are combined, the diagnostic performance of PJI in TJA patients can be improved.

Development and validation of a novel criterion of histologic healing in ulcerative colitis defined by inflammatory cell enumeration in lamina propria mucosae: A multicenter retrospective cohort in China.

Histological healing is closely associated with improved long-term clinical outcomes and lowered relapses in patients with ulcerative colitis (UC). Here, we developed a novel diagnostic criterion for assessing histological healing in UC patients. We conducted a retrospective cohort study in UC patients, whose treatment was iteratively optimized to achieve mucosal healing at Shanghai Tenth People's Hospital of Tongji University from January 2017 to May 2022. We identified an inflammatory cell enumeration index (ICEI) for assessing histological healing based on the proportions of eosinophils, CD177+ neutrophils, and CD40L+ T cells in the colonic lamina propria under high power field (HPF), and the outcomes (risks of symptomatic relapses) of achieving histological remission vs. persistent histological inflammation using Kaplan-Meier curves. Intrareader reliability and inter-reader reliability were evaluated by each reader. The relationships to the changes in the Nancy index and the Geboes score were also assessed for responsiveness. The ICEI was further validated in a new cohort of UC patients from other nine university hospitals. We developed an ICEI for clinical diagnosis of histological healing, i.e., Y=1.701X1 + 0.758X2 + 1.347X3 - 7.745 (X1, X2, and X3 represent the proportions of CD177+ neutrophils, eosinophils, and CD40L+ T cells, respectively, in the colonic lamina propria under HPF). The receiver operating characteristics curve (ROC) analysis revealed that Y <-0.391 was the cutoff value for the diagnosis of histological healing and that an area under the curve (AUC) was 0.942 (95% confidence interval [CI]: 0.905-0.979) with a sensitivity of 92.5% and a specificity of 83.6% (P<0.001). The intraclass correlation coefficient (ICC) for the intrareader reliability was 0.855 (95% CI: 0.781-0.909), and ICEI had good inter-reader reliability of 0.832 (95% CI: 0.748-0.894). During an 18-month follow-up, patients with histological healing had a substantially better outcome compared with those with unachieved histological healing (P<0.001) using ICEI. During a 12-month follow-up from other nine hospitals, patients with histological healing also had a lower risk of relapse than patients with unachieved histological healing. ICEI can be used to predict histological healing and identify patients with a risk of relapse 12 months and 18 months after clinical therapy. Therefore, ICEI provides a promising, simplified approach to monitor histological healing and to predict the prognosis of UC. Chinese Clinical Trial Registry, No. ChiCTR2300077792.

Unsupervised machine learning for clustering forward head posture, protraction and retraction movement patterns based on craniocervical angle data in individuals with nonspecific neck pain

ObjectivesThe traditional understanding of craniocervical alignment emphasizes specific anatomical landmarks. However, recent research has challenged the reliance on forward head posture as the primary diagnostic criterion for neck pain. An advanced relationship exists between neck pain and craniocervical alignment, which requires a deeper exploration of diverse postures and movement patterns using advanced techniques, such as clustering analysis. We aimed to explore the complex relationship between craniocervical alignment, and neck pain and to categorize alignment patterns in individuals with nonspecific neck pain using the K-means algorithm.MethodsThis study included 229 office workers with nonspecific neck pain who applied unsupervised machine learning techniques. The craniocervical angles (CCA) during rest, protraction, and retraction were measured using two-dimensional video analysis, and neck pain severity was assessed using the Northwick Park Neck Pain Questionnaire (NPQ). CCA during sitting upright in a comfortable position was assessed to evaluate the resting CCA. The average of midpoints between repeated protraction and retraction measures was considered as the midpoint CCA. The K-means algorithm helped categorize participants into alignment clusters based on age, sex and CCA data.ResultsWe found no significant correlation between NPQ scores and CCA data, challenging the traditional understanding of neck pain and alignment. We observed a significant difference in age (F = 140.14, p < 0.001), NPQ total score (F = 115.83, p < 0.001), resting CCA (F = 79.22, p < 0.001), CCA during protraction (F = 33.98, p < 0.001), CCA during retraction (F = 40.40, p < 0.001), and midpoint CCA (F = 66.92, p < 0.001) among the three clusters and healthy controls. Cluster 1 was characterized by the lowest resting and midpoint CCA, and CCA during pro- and -retraction, indicating a significant forward head posture and a pattern of retraction restriction. Cluster 2, the oldest group, showed CCA measurements similar to healthy controls, yet reported the highest NPQ scores. Cluster 3 exhibited the highest CCA during protraction and retraction, suggesting a limitation in protraction movement.DiscussionAnalyzing 229 office workers, three distinct alignment patterns were identified, each with unique postural characteristics; therefore, treatments addressing posture should be individualized and not generalized across the population.

Prevalence and correlates of mental disorders among Chinese overseas students during the COVID-19: A multi-regional cross-sectional analysis.

The global impact of the COVID-19 pandemic extends beyond physical health, significantly affecting mental health. Chinese overseas students are particularly susceptible to the adverse psychological effects of the pandemic. Understanding the prevalence and correlates of mental disorders in this population is essential for developing targeted interventions and support systems. Employing a snowball sampling technique, this study recruited Chinese overseas students from diverse regions. The 50-item Self-evaluation Table was utilized to assess the presence of mental disorders. Descriptive statistics, including percentages, 95% confidence intervals, means, and standard deviations, characterized the survey population. The chi-square test identified disparities among categorical variables, while logistic regression explored risk factors for mental disorders among Chinese overseas students. Out of the total sample size of 10,864 Chinese overseas students, a staggering 7,090 (65.4%) met the diagnostic criteria for mental disorders. Furthermore, the degree of mental disorder varied significantly across different regions (p < 0.001), education levels (p < 0.05), the duration of anti-epidemic measures (p < 0.05), and age (p < 0.05), while no significant differences were observed in terms of gender (p > 0.05). Several risk factors contributing to the mental disorder burden among Chinese overseas students during the pandemic were identified, including the seriousness of the epidemic in their residential area, the apprehension of getting infected, anxieties regarding academic performance, the infection control policies implemented by the host government, preventive measures taken locally to counter the epidemic, and challenges encountered in returning to their home country. Given the significant challenges in mental health faced by Chinese overseas students during the COVID-19 crisis, addressing their specific needs and implementing tailored measures is imperative. Future public health emergencies should consider the potential mental disorders and disease risks faced by Chinese overseas students. By providing comprehensive support and targeted interventions, policymakers, educational institutions, and healthcare providers can help mitigate the adverse psychological effects and promote the well-being of this vulnerable population.

COVID-19 in patients with Good syndrome: report of 4 cases and literature review

Objective: To summarize the clinical characteristics of coronavirus disease 2019 (COVID-19) in patients with Good's syndrome. Methods: We included all cases of COVID-19 in patients with Good's syndrome in the Second Xiangya Hospital of Central South University from January 1, 2023 to August 31, 2023. In addition to our cases, we searched the published literature in Wanfang database and PubMed database using the keywords "Good's syndrome" and "COVID-19". The clinical characteristics, treatment and outcome of the patients were summarized and analyzed. Results: A total of four patients with Good's syndrome complicated by COVID-19 were identified in our hospital, all of them were male, and the days of hospitalization were 17, 23, 7, and 13 days, respectively. Databases were searched for a total of six patients with Good's syndrome complicated by COVID-19, including three females and three males, all foreign patients, with hospitalization days of 12, 22, 13, 25, 21, and 34 days respectively. All ten patients met the diagnostic criteria for severe or critical COVID-19, and three(all middle-aged males) of them died, two from sepsis and one from respiratory failure. They were. Conclusion: COVID-19 in patients with Good's syndrome are prone to develop severe or critical disease and are more likely to be infected with multiple pathogens. Timely immunoglobulin supplementation is the key to treatment.

Biochemical Analysis of Congenital Hypogonadotropic Hypogonadism in the Context of Male Infertility: A Comprehensive Review

Background: Male infertility encompasses various etiologies, with Congenital Hypogonadotropic Hypogonadism (CHH) standing out as a significant factor. CHH arises from multiple systems, including genetic abnormalities and hormonal imbalances that impair reproductive capabilities. Objective: This review aims to dissect the biochemical underpinnings of CHH and evaluate its impact on male infertility, highlighting the complexities in its diagnosis and therapeutic management. Methods: The analysis involved a review of current literature on the genetic causes and hormonal disruptions associated with CHH. Diagnostic criteria were assessed based on biochemical markers and clinical symptoms. Treatment efficacy was evaluated through outcomes of hormone replacement therapy, surgical interventions, and assisted reproductive technologies. Results: The majority of CHH patients treated with hormone replacement therapy demonstrated improved sexual maturation and fertility, with approximately 70% achieving spermatogenesis. Surgical interventions corrected anatomical defects in 90% of cases, while assisted reproductive technologies resulted in successful pregnancies in 60% of treated individuals. Conclusion: CHH significantly affects male reproductive health, influencing testicular development and endocrine function. Advances in diagnostic and treatment strategies have enhanced management outcomes, but ongoing research is essential for developing more targeted therapies.

Liver non-contrast perfusion in diffuse liver diseases diagnostic algorithm: the new diagnostic criteria

Purpose: to define the new criteria for contrast-free ASL perfusion using for the management of diffuse liver diseases (DLD).Material and methods. Clinical and laboratory data, results of MRI with non-contrast MR perfusion (ASL-perfusion) of the liver were estimated in a group of patients with DLD (three-year research).Results. Potentials of assessment of liver ASL perfusion for patients with DLD (including complicated cases) are described in the article. It was established that ASL liver perfusion is useful for DLD clinical forms differential diagnosis, predicting the risk of liver cirrhosis, as well as complications (hepatic encephalopathy, sialoadenitis) and DLD exacerbation. The strategy of contrast-free MR perfusion using in patients with DLD management algorithm was developed.Conclusion. Liver ASL perfusion is a promising for the study and application method for the management of DLD.

Critical re-evaluation of the identification of iron deficiency states and effective iron repletion strategies in patients with chronic heart failure.

According to current guidelines, iron deficiency is defined by a serum ferritin level <100 ng/ml or a transferrin saturation (TSAT) <20% if the serum ferritin level is 100-299 μg/L. These criteria were developed to encourage the use of intravenous iron as an adjunct to erythropoiesis-stimulating agents in the treatment of renal anaemia. However, in patients with heart failure, these criteria are not supported by any pathophysiological or clinical evidence that they identify an absolute or functional iron deficiency state. A low baseline TSAT-but not serum ferritin level-appears to be a reliable indicator of the effect of intravenous iron to reduce major heart failure events. In randomized controlled trials, intravenous iron decreased the risk of cardiovascular death or total heart failure hospitalization in patients with a TSAT <20% (risk ratio 0.67 [0.49-0.92]) but not in patients with a TSAT ≥20% (risk ratio 0.99 [0.74-1.30]), with the magnitude of the risk reduction being proportional to the severity of hypoferraemia. Patients who were enrolled in clinical trials solely because they had a serum ferritin level <100 μg/L showed no significant benefit on heart failure outcomes, and it is noteworthy that serum ferritin levels of 20-300 μg/L lie entirely within the range of normal values for healthy adults. Current guidelines reflect the eligibility criteria of clinical trials, which inadvertently adopted unvalidated criteria to define iron deficiency. Reliance on these guidelines would lead to the treatment of many patients who are not iron deficient (serum ferritin level <100 μg/L but normal TSAT) and ignores the possibility of iron deficiency in patients with a low TSAT but with serum ferritin level of >300 μg/L. Importantly, analyses of benefit based on trial eligibility-driven guidelines substantially underestimate the magnitude of heart-failure-event risk reduction with intravenous iron in patients who are truly iron deficient. Based on all available data, we recommend a new mechanism-based and trial-tested approach that reflects the totality of evidence more faithfully than the historical process adopted by clinical investigators and by the guidelines. Until additional evidence is forthcoming, an iron deficiency state in patients with heart failure should be defined by a TSAT <20% (as long as the serum ferritin level is <400 μg/L), and furthermore, the use of a serum ferritin level <100 μg/L alone as a diagnostic criterion should be discarded.

Proposal and Validation of a Clinically Relevant Modification of the Japanese Association for Acute Medicine Disseminated Intravascular Coagulation Diagnostic Criteria for Sepsis.

Japanese Association for Acute Medicine (JAAM) disseminated intravascular coagulation (DIC) criteria were launched nearly 20 years ago. Following the revised conceptual definition of sepsis and subsequent omission of systemic inflammatory response syndrome (SIRS) score from the latest sepsis diagnostic criteria, we omitted the SIRS score and proposed a modified version of JAAM DIC criteria, the JAAM-2 DIC criteria. To validate and compare performance between new JAAM-2 DIC criteria and conventional JAAM DIC criteria for sepsis. We used three datasets containing adult sepsis patients from a multicenter nationwide Japanese cohort study (J-septic DIC, FORECAST, and SPICE-ICU registries). JAAM-2 DIC criteria omitted the SIRS score and set the cutoff value at ≥3 points. Receiver operating characteristic (ROC) analyses were performed between the two DIC criteria to evaluate prognostic value. Associations between in-hospital mortality and anticoagulant therapy according to DIC status were analyzed using propensity score weighting to compare significance of the criteria in determining introduction of anticoagulants against sepsis. Final study cohorts of the datasets included 2,154, 1,065, and 608 sepsis patients, respectively. ROC analysis revealed that curves for both JAAM and JAAM-2 DIC criteria as predictors of in-hospital mortality were almost consistent. Survival curves for the anticoagulant and control groups in the propensity score-weighted prediction model diagnosed using the two criteria were also almost entirely consistent. JAAM-2 DIC criteria were equivalent to JAAM DIC criteria regarding prognostic and diagnostic values for initiating anticoagulation. The newly proposed JAAM-2 DIC criteria could be potentially alternative criteria for sepsis management.

Criteria for melanocytic lesions in LC-OCT.

Line-field confocal optical coherence tomography (LC-OCT) is an emerging diagnostic tool with imaging depth reaching ~400 μm and a novel three-dimensional (3D) cube providing cellular resolution. As far as we are aware, there are only a limited number of papers that have reported diagnostic criteria for melanocytic lesions using this technique, and none of them have been multicentric. Our aim was to establish the diagnostic criteria for melanocytic lesions using LC-OCT and identify the most significant architectural and cytologic features associated with malignancy. A retrospective evaluation of 80 consecutive melanocytic lesions from a prospective multicentric data set spanning three European centres was conducted. We excluded facial, acral and mucosal lesions from the study. Dermoscopic and LC-OCT images were evaluated by a consensus of four observers. Multivariate logistic regression with backward elimination was employed. The main melanoma diagnostic criteria include detecting >10 pagetoid cells in 3D acquisition, irregular 3D epidermal architecture, disrupted dermoepidermal junction (DEJ) and clefting. Significant risk factors were irregular 3D epidermal architecture, >10 pagetoid cells, dendritic cells at DEJ without underlying inflammation. Novel malignancy criteria in vertical view were DEJ disruption and clefting around atypical melanocyte nests. Exclusive melanoma features were epidermal nests, epidermal consumption, dense dermal nests with atypia. Protective features in the absence of any malignancy indicators were DEJ ring pattern, cobblestone, elongated rete ridges (vertical), well-defined DEJ and wave pattern (vertical). A series of diagnostic criteria for the identification of melanocytic lesions with LC-OCT have been established. Validation of these criteria in clinical practice through future studies is essential to further establish their utility.

Behavioral evidence of impaired self-referential processing in patients with affective disorders and first-episode schizophrenia

Despite the critical role of self-disturbance in psychiatric diagnosis and treatment, its diverse behavioral manifestations remain poorly understood. This investigation aimed to elucidate unique patterns of self-referential processing in affective disorders and first-episode schizophrenia. A total of 156 participants (41 first-episode schizophrenia [SZ], 33 bipolar disorder [BD], 44 major depressive disorder [MDD], and 38 healthy controls [HC]) engaged in a self-referential effect (SRE) task, assessing trait adjectives for self-descriptiveness, applicability to mother, or others, followed by an unexpected recognition test. All groups displayed preferential self- and mother-referential processing with no significant differences in recognition scores. However, MDD patients showed significantly enhanced self-referential recognition scores and increased bias compared to HC, first-episode SZ, and BD. The present study provides empirical evidence for increased self-focus in MDD and demonstrates that first-episode SZ and BD patients maintain intact self-referential processing abilities. These findings refine our understanding of self-referential processing impairments across psychiatric conditions, suggesting that it could serve as a supplementary measure for assessing treatment response in first-episode SZ and potentially function as a discriminative diagnostic criterion between MDD and BD.

Metabolic syndrome in children and adolescents

Background: Metabolic syndrome is a serious condition associated with multiple diseases. The prevalence of metabolic syndrome is increasing caused by an increase in obesity rates among children and adolescents.Current Concepts: Owing to the various definitions used, there is lack of consensus regarding the diagnostic criteria for metabolic syndrome in children and adolescents. Although the exact pathogenesis remains unclear, insulin resistance and subsequent inflammation are key mechanistic contributors. Metabolic syndrome is characterized by overweight and obesity accompanied by abnormalities in glucose metabolism, dyslipidemia, and hypertension and is associated with other conditions such as fatty liver, polycystic ovary syndrome, and a pro-inflammatory state. Prevention and management of metabolic syndrome can be achieved through lifestyle modifications, behavioral interventions, pharmacotherapy, and surgical interventions.Discussion and Conclusion: Childhood and adolescent obesity serves as a risk factor for metabolic syndrome during later life. Early identification and intervention are important to prevent the progression of metabolic syndrome. Clinicians must identify at-risk children and adolescents and provide guidance for the prevention and management of metabolic syndrome.

A Digital Cognitive-Physical Intervention for Attention-Deficit/Hyperactivity Disorder: Randomized Controlled Trial.

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders among children. Pharmacotherapy has been the primary treatment for ADHD, supplemented by behavioral interventions. Digital and exercise interventions are promising nonpharmacologic approaches for enhancing the physical and psychological health of children with ADHD. However, the combined impact of digital and exercise therapies remains unclear. The aim of this study was to determine whether BrainFit, a novel digital intervention combining gamified cognitive and exercise training, is efficacious in reducing ADHD symptoms and executive function (EF) among school-aged children with ADHD. This 4-week prospective randomized controlled trial included 90 children (6-12 years old) who visited the ADHD outpatient clinic and met the diagnostic criteria for ADHD. The participants were randomized (1:1) to the BrainFit intervention (n=44) or a waitlist control (n=46) between March and August 2022. The intervention consisted of 12 30-minute sessions delivered on an iPad over 4 weeks with 3 sessions per week (Monday, Wednesday, and Friday after school) under the supervision of trained staff. The primary outcomes were parent-rated symptoms of attention and hyperactivity assessed according to the Swanson, Nolan, and Pelham questionnaire (SNAP-IV) rating scale and EF skills assessed by the Behavior Rating Inventory of Executive Function (BRIEF) scale, evaluated pre and post intervention. Intention-to-treat analysis was performed on 80 children after attrition. A nonparametric resampling-based permutation test was used for hypothesis testing of intervention effects. Among the 145 children who met the inclusion criteria, 90 consented and were randomized; ultimately, 80 (88.9%) children completed the study and were included in the analysis. The participants' average age was 8.4 (SD 1.3) years, including 63 (78.8%) male participants. The most common ADHD subtype was hyperactive/impulsive (54/80, 68%) and 23 (29%) children had severe symptoms. At the endpoint of the study, the BrainFit intervention group had a significantly larger improvement in total ADHD symptoms (SNAP-IV total score) as compared to those in the control group (β=-12.203, 95% CI -17.882 to -6.523; P<.001), owing to lower scores on the subscales Inattention (β=-3.966, 95% CI -6.285 to -1.647; P<.001), Hyperactivity/Impulsivity (β=-5.735, 95% CI -8.334 to -3.137; P<.001), and Oppositional Defiant Disorder (β=-2.995, 95% CI -4.857 to -1.132; P=.002). The intervention was associated with significant reduction in the Metacognition Index (β=-6.312, 95% CI -10.973 to -1.650; P=.006) and Global Executive Composite (β=-5.952, 95% CI -10.214 to -1.690; P=.003) on the BRIEF. No severe intervention-related adverse events were reported. This novel digital cognitive-physical intervention was efficacious in school-age children with ADHD. A larger multicenter effectiveness trial with longer follow-up is warranted to confirm these findings and to assess the durability of treatment effects. Chinese Clinical Trial Register ChiCTR2300070521; https://www.chictr.org.cn/showproj.html?proj=177806.

A Novel Objective Pathologic Criterion for Isolated Hypoganglionosis.

Isolated hypoganglionosis (IHG) is histologically characterized by small numbers of myenteric ganglion cells and small myenteric ganglia; however, no numerical diagnostic criteria for IHG have been established. Therefore, this study aimed to develop quantitative pathologic criteria for IHG. We evaluated 160 resected intestinal tissue specimens from 29 pediatric autopsies and 10 IHG cases. These specimens were obtained from the jejunum, ileum, ascending colon, transverse colon, and rectum. Morphologic features of the myenteric ganglion cells and myenteric ganglia were quantified and analyzed in digitized HuC/HuD-immunostained and CD56-immunostained sections, respectively. Quantitative criteria were developed with a scoring system that used parameters with the area under the receiver operating characteristic curve (AUC) values >0.7 and sensitivity and specificity exceeding 70%. The selected parameters were the number of myenteric ganglion cells per cm and the number of myenteric ganglia with an area >2500µm2per cm. The score for each parameter ranged from -1 to 2, and the total score of the scoring system ranged from -2 to 4. With a cutoff value of ≥2 (AUC, 0.98; 95% CI: 0.96-1.00), the scoring system had a sensitivity of 96% (95% CI: 0.82-1.00) and a specificity of 99% (95% CI: 0.95-1.00). We devised a novel pathologic criterion based on the quantification of the number of myenteric ganglion cells and ganglia. Furthermore, this criterion showed high diagnostic accuracy and could lead to a definitive diagnosis of IHG in clinical practice.