Clinical Correlates Research Articles

Clinical Correlates and Prognostic Impact of Cognitive Dysfunction in Patients With Heart Failure and Preserved Ejection Fraction: Insights From PARAGON-HF.

Cognitive impairment is common in patients with heart failure and preserved ejection fraction but its clinical correlates and prognostic associations are poorly understood. We analyzed cognitive function, using the Mini-Mental State Examination (MMSE), in patients with heart failure and preserved ejection fraction enrolled in a prespecified substudy of the PARAGON-HF trial (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin Receptor Blocker Global Outcomes in Heart Failure With Preserved Ejection Fraction). Logistic regression analyses were performed to determine the variables associated with lower MMSE scores at baseline and postbaseline decline in MMSE scores at 48 weeks. Cox proportional hazards regression and semiparametric proportional rates models were used to examine the risk of clinical outcomes related to baseline MMSE scores, and decline in MMSE scores during follow-up, adjusted for prognostic variables including NT-proBNP (N-terminal pro-B-type natriuretic peptide). At baseline, cognitive function was normal (MMSE score 28-30) in 1809 of 2895 patients (62.5%), borderline (score 24-27) in 794 (27.4%), and impaired (score <24) in 292 (10.1%). Variables associated with both a lower MMSE score at baseline and a decline in score from baseline included older age, a history of stroke or transient ischemia attack, and lower serum albumin. Compared with those with baseline MMSE scores of 28 to 30, patients in the lower MMSE score categories had a stepwise increase in the risk of the composite of time to first HF hospitalization or cardiovascular death, with an adjusted hazard ratio of 1.27 (95% CI, 1.06-1.53) for those with scores of 24 to 27 and 1.58 (95% CI, 1.21-2.06) for those with scores <24, respectively. These associations were also found for the individual components of the composite and all-cause death. Likewise, cognitive impairment was associated with a 50% higher risk of total (first and repeat) heart failure hospitalizations and cardiovascular deaths. Examining the change in MMSE score from baseline, a decrease in MMSE score during follow-up was associated with a higher risk of death. In patients with heart failure and preserved ejection fraction, even modest baseline impairment of cognitive function was associated with worse outcomes, including death. A decline in MMSE score during follow-up was a strong predictor of mortality, independent of other prognostic variables.

Myeloid gasdermin D drives early-stage T cell immunity and peripheral inflammation in a mouse model of Alzheimer's disease.

It is now realized that peripheral inflammation and abnormal immune responses, especially T cells, contribute to the development of Alzheimer's disease (AD). Gasdermin D (GSDMD) -mediated pyroptosis has been associated with several neuroinflammatory diseases, but whether GSDMD is involved in the peripheral inflammation and T cell immunity during AD remains unclear. We dynamically investigated GSDMD activation in the peripheral and central nervous system of 5×FAD mouse model and dissected the role of myeloid GSDMD using genetic knockout mice, especially its influence on peripheral T cell responses and AD inflammation. RNA sequencing and in vitro coculture were used to elucidate the underlying immune mechanisms involved. Targeted inhibitor experiments and clinical correlation analysis were used to further verify the function of GSDMD in AD. In the present study, caspase activated GSDMD in the spleen of 5×FAD mice earlier than in the brain during disease progression. Loss of myeloid cell GSDMD was shown to impair early-stage effector T cell activation in the periphery and prevent T cell infiltration into the brain, with an overall reduction in neuroinflammation. Furthermore, myeloid cell GSDMD induced T cell PD-1 expression through the IL-1β/NF-κB pathway, restricting regulatory T cells. The administration of a GSDMD inhibitor combined with an anti-PD-1 antibody was found to mitigate the development of AD-associated inflammation. In some AD patients, plasma sPD-1 is positively correlated with IL-Iβ and clinical features. Our study systematically identified a role for GSDMD in the AD-related peripheral inflammation and early-stage T cell immunity. These findings also suggest the therapeutic potential of targeting GSDMD for the early intervention in AD.

One-year trajectories of physical and mental health-related quality of life, fatigue and dyspnoea in COVID-19 survivors.

A substantial number of people experience a persisting impact on health-related quality of life (HRQoL) after COVID-19. The current study aims to identify different trajectories of physical and mental HRQoL, fatigue severity, and dyspnoea severity following hospitalisation with COVID-19, and associated factors of these trajectories. 500 patients with COVID-19 were followed for one year in a longitudinal cohort study. Self-reported outcomes were measured at 3, 6, 9, and 12 months after hospitalisation. Distinct trajectories were characterised using Growth Mixture Modelling. Sociodemographic and clinical correlates of trajectories were investigated using multivariable (multinomial) logistic regression analyses. Three trajectories ('stable high' (16%), 'improving' (40%), and 'stable low' (44%)) were found for physical HRQoL, and four ('stable high' (43%), 'improving' (14%), 'middle declining' (17%), and 'low' (26%)) for mental HRQoL. Older age, overweight and obesity, lower education, and comorbidities were associated with 'low' physical HRQoL. Younger age was associated with 'low' mental HRQoL. Four fatigue trajectories ('no fatigue' (15%), 'improving' (40%), 'low-severe' (27%), and 'high-severe' (18%)) were found. Participants either experienced almost never ('no dyspnoea', 75%) or almost always ('severe', 25%) dyspnoea. High co-occurrences between low HRQoL and severe fatigue and dyspnoea symptom trajectories were found. A substantial number of COVID-19 survivors continue to struggle with reduced HRQoL over time. However, large variations in these physical and mental HRQoL trajectories exist, and trajectories are associated with persisting COVID-19-related symptoms or pre-hospitalised health status. Regular measurement of HRQoL and post-COVID symptoms may help identify those that may benefit from timely interventions.

Electrocardiographic Findings in Patients with Severe COVID-19: Characterisation and Clinical Correlations

In a prospective study of 200 COVID-19 patients, categorised into mild symptoms (category A; n=39), mild symptoms with cardiopulmonary comorbidities (category B; n=68) and severe symptoms with haemodynamic compromise (category C), category C showed higher incidences of left axis deviations, left atrial enlargement, prolonged QRS, elevated left ventricular amplitude, poor R wave progression and T inversion in V1–V6. A novel marker, rS complex – R/S ratio &gt;1 in lead III, was noted. Univariate analysis revealed left atrial enlargement, left axis deviation, left ventricular amplitude and poor R wave progression as mortality predictors. Multivariate analysis identified age and left atrial enlargement as independent predictors. These findings suggest possible elevated left ventricular end-diastolic pressure, which will help in categorising disease severity and predicting outcomes.

Prevalence and Clinical Correlates of Endometriosis in Patients With IC/BPS.

Interstitial cystitis/bladder pain syndrome (IC/BPS) presents as a complex heterogeneous disorder that poses a significant clinical challenge both for diagnosis and treatment. The identification of patient subgroups with significant overlap in their nonurological associated symptoms, including endometriosis, may enable a more targeted therapeutic approach. This study investigated the prevalence, clinical correlates, and clinical sequelae associated with concurrent endometriosis in patients with IC/BPS. Demographic, clinical, surgical, and questionnaire data from female patients (n = 533) with a diagnosis of IC/BPS were evaluated in this retrospective cohort study. Surgical history was obtained from patient electronic medical records, using Current Procedural Terminology (CPT) and International Classification of Diseases (ICD) codes. Data from participants with and without concurrent endometriosis were compared using univariate analysis, followed by binary logistic regression to identify associated variables. Of 533 participants, 108 (20.3%) reported a history of endometriosis. Those with concurrent endometriosis were younger, had a larger bladder capacity, and had a higher number of nonurological associated symptoms. Patients with concurrent endometriosis were less likely to have a history of cystectomy (the surgical removal of the bladder) and report allergies but more prone to report comorbidities such as chronic pelvic pain, chronic fatigue, fibromyalgia, migraines, and pelvic floor dysfunction. Binary logistic regression identified a positive association between endometriosis and chronic pelvic pain, and a negative association between allergies and low bladder capacity for those with concurrent endometriosis. Endometriosis is common in younger female patients with IC/BPS and is associated with a non-bladder-centric (ie, systemic pain disorder) phenotype.

Prevalence and correlates of emotion dysregulation among children and adolescents in Lebanon: results from a National Survey

BackgroundData on Emotion Dysregulation among youth in Lebanon is scarce. Given that Emotion Dysregulation is associated with psychopathology and has a negative impact on youth outcomes, there is a need to better understand the prevalence, clinical and demographic correlates of Emotion Dysregulation.MethodsThis study is a secondary analysis of the Psychopathology in Children and Adolescents in Lebanon Study which recruited 1517 youth and one parent from a nationally representative sample. Participants completed The Screen for Child Anxiety Related Emotional Disorders, Mood and Feelings Questionnaire, Strengths and Difficulties Questionnaire, Peer Relations Questionnaire, Conflict Behavior Questionnaire (CBQ).Parents completed a sociodemographic questionnaire and the General Health Questionnaire (GHQ). The Strengths and Difficulties Questionnaire-Dysregulation Profile was used to measure Emotion Dysregulation.ResultsThe prevalence of Emotion Dysregulation was 11.26% among children aged 5 to < 8 years, 9.40% among children aged 8 to < 12 years and 6.60% among those older than 12 years. Emotion Dysregulation was associated with psychopathology across age groups and a number of correlates were identified. In the final regression models, among children aged 5 to < 8 years; Emotion Dysregulation was associated with lower odds of father employment (OR = 0.235;CI[0.078,0.704]). For those aged 8 to < 12 years old, Emotion Dysregulation was associated with acceptable school performance (OR = 2.246,CI[1.209,4.173]) as opposed to a good school performance, having a chronic physical illness (OR = 2.962; CI [1.495,5.867)], and higher parental GHQ scores (OR = 1.034;CI [1.010,10.58)] indicating worse parental mental health. Adolescents aged 12 years and older who screened positive for Emotion Dysregulation were more likely to be younger (OR = 0.688, CI[0.527,0.899]), be a bully (OR = 2.467;CI[1.036,5.875] and to have higher parental CBQ scores (OR = 1.092;CI [1.011,1.180]), indicating worse parent-child conflict. Youth who screened positive for emotion dysregulation were more likely to seek psychiatric care than their counterparts who screen negative for emotion dysregulation.ConclusionAge, school performance, parental mental health, parental conflict, chronic physical illness and bullying emerge as important correlates of Emotion Dysregulation. Findings add to the limited data on Emotion Dysregulation in Lebanon and the region and are a first step towards developing intervention and prevention strategies.

Morphometric measurements of intraoral anatomy in children with Beckwith-Wiedemann syndrome: a novel approach

BackgroundAn easy-to-use tool to objectively measure intraoral anatomy with meaningful clinical correlations may improve care for patients with Beckwith-Wiedemann syndrome (BWS), who commonly have symptomatic macroglossia.MethodsChildren aged 2–17 years with BWS were enrolled between 12/2021 and 01/2024. Digital intraoral photographs with a laser ruler were taken, and morphometric measurements were made using ImageJ software. Relationships between morphometrics and outcomes including BWS clinical score, percentage mosaicism, and incidence of tongue reduction surgery were examined using t-tests and multivariate linear models.ResultsPharyngeal morphometric measurements were obtained in 49 patients with BWS. Mouth area, width, and height differed significantly across BWS molecular subtypes. Right-to-left tongue width and mouth width were larger in those with loss of methylation at imprinting control region 2 (IC2 LOM) than other BWS variants. Patients with paternal uniparental isodisomy of chromosome 11p15 (pUPD11) had narrower mouths than others. Those with tongue reduction surgery had more tongue ridging than those without surgery. There were correlations between mouth area and BWS clinical score, tongue width and BWS clinical score, and tongue length and percentage mosaicism.ConclusionIntraoral morphometric measurements are associated with phenotypic burden in BWS. Tongue morphology varies across the BWS spectrum, with IC2 LOM having wider tongues and mouths, and pUPD11 having narrower mouths. Tongue ridging is more common in those selected for surgery. Intraoral morphometric measurements may be safely obtained at low costs across centers caring for children with BWS or others at risk of upper airway obstruction.

Gender-specific correlates for suicide mortality in people with schizophrenia: a 9-year population-based study

BackgroundSchizophrenia is associated with a high mortality rate due to the high risk of suicide. However, there is still a lack of evidence on the gender-specific risk factors for suicide among people with schizophrenia. In this study, we aimed to measure the sociodemographic and clinical correlates of suicide deaths in different genders among people with schizophrenia.MethodsData on patients with schizophrenia from 2013 to 2021 in Guangzhou, China were obtained from the National Information System for Psychosis (NISP), involving a total of 33,080 patients. Cox regression and Fine-Gray models were used to explore the sociodemographic and clinical risk factors for suicide mortality in different genders.ResultsThe overall age-standardized mortality rates due to suicide were 133.89 (95% CI: 124.31-143.47) per 100,000 person-years for females and 163.25 (95% CI: 152.92-173.59) per 100,000 person-years for males. To be specific, lack of medical insurance, history of non-treatment, and history of suicidal behavior was associated with a higher risk for suicide mortality for females, while an age of 35–54, being hospitalized once, and the age of onset being > 28 years were linked to lower risk for suicide mortality for males. For both genders, a lower risk for suicide mortality was observed in patients at an older age (≥ 55 years) and with a history of hospitalization more than once, and a higher suicide mortality risk was found in married patients and those residing in rural areas.ConclusionThe present study found that gender differences should be taken into account in the development of suicide prevention programs for people with schizophrenia, and future research is still required to verify our preliminary results.

Androgen blockage impairs proliferation and function of Sertoli cells via Wee1 and Lfng

BackgroundAndrogens are essential hormones for testicular development and the maintenance of male fertility. Environmental factors, stress, aging, and psychological conditions can disrupt androgen production, impacting the androgen signaling pathway and consequently spermatogenesis. Within the testes, testosterone is produced by Leydig cells and acts on Sertoli cells by activating the androgen receptor (AR), which then translocates to the nucleus to function as a transcription factor. Despite clinical correlations between low testosterone levels and diminished sperm quality, the precise mechanism remains unclear.MethodsThis study explores the hypothesis that reduced androgen levels impair Sertoli cell function by disrupting AR transcriptional regulation. Using an androgen blockade model with enzalutamide, we investigated the impact of low androgen levels on AR target genes in Sertoli cells through ChIP-seq and RNA-seq assays.ResultsOur results reveal that androgen blockage increases AR enrichment on the promoter region of Wee1, promoting Wee1 expression, while decreasing binding to the promoter region of Lfng, inhibiting its expression. Increased WEE1 protein inhibits Sertoli cell proliferation, whereas reduced LFNG affects Notch modification, leading to decreased production of glial cell line-derived neurotrophic factor (GDNF), a key growth factor for spermatogonial stem cell self-renewal.ConclusionsThese findings provide new insights into the molecular mechanisms by which low androgen levels interfere with Sertoli cell functions, offering novel perspectives for the clinical treatment of male reproductive disorders.

LncRNA LYPLAL1, miR-204-5p, and SIRT1: novel signatures for risk assessment of diabetic macrovascular complications

Long-term, uncontrolled diabetes mellitus can lead to micro- and macrovascular problems. The protective function of lncRNA LYPLAL1 is to reduce endothelium cell inflammation by upregulating sirtuin 1 (SIRT1) and reducing microRNA (miR)-204-5p. This work attempted to examine the lncRNA LYPLAL1/miR-204-5p/SIRT1 molecules as diagnostic biomarkers for diabetic MVC and to assess their clinical correlations. The study enrolled 32 controls, 32 patients with diabetes alone, and 32 patients with diabetic MVC. RT-qPCR, or quantitative real-time PCR, was utilized to determine the expression levels of lncRNA and miR. SIRT1 was measured by ELISA. When comparing cases with MVC to those without MVC, the lncRNA LYPLAL1 and SIRT1 values were significantly lower. Conversely, patients with MVC had significantly higher miR-204-5p levels than those without MVC. The LncRNA LYPLAL1 performed best in terms of detecting MVC. It attained 90.6% specificity and 96.9% sensitivity. A combination of three markers (lncRNA LYPLAL1, miR-204-5p, and SIRT1) yielded the best accuracy at 98.4%. LYPLAL1 expression appeared to be an independent MVC predictor. Adjusted OR for LYPLAL1 expression was 405 (95% CI: 1.4–1200) (p = 0.039). When we compared cases with MVC to those without MVC, the lncRNA LYPLAL1 and SIRT1 values were significantly lower. Patients with MVC had significantly higher miR-204-5p levels than those without MVC. LYPLAL1 LncRNA demonstrated the best performance characteristics. LncRNA LYPLAL1 expression is an independent predictor of MVC.

ONYCHOMATRICOMA, A RARE NAIL TUMOR

Abstract Introduction/Objective Nail apparatus tumors are rare and can pose diagnostic challenges. Onychomatricoma (also called onychomatrixoma) is a rare tumor first described in 1992. It is a benign biphasic fibroepithelial tumor of the nail. It has been reported in Caucasians, often in females with a peak incidence in the fifth decade of life. Rare cases are also reported in children. The common location is in the fingernail (75%), presenting with yellowing of the nail plate (xanthonychia) and thick longitudinal band. Cutaneous horn, melanonychia, nail bleeding, and nail deformity with or without bony extension can also be seen. Histologic findings show increased nail thickness surrounded by a layer of Malpighian epithelium. The fibroepithelial tumor shows hyperplasia of two components including onychogenic epithelium and mesenchymal stroma. Methods/Case Report A 65-year-old Vietnamese female presented with longstanding dark yellowish ridging discoloration, thickening and nail plate deformity of the left fourth fingernail with appearance of onychomycosis. However, KOH mount and fungal cultures of the nail plate were negative for fungal microorganisms. There was no history of pain, trauma, or prior treatment. Microscopic analysis of transverse and longitudinal sections of the nail shows a biphasic neoplasm that penetrates the nail plate with multiple digitations. There was deep finger-like epithelial cell strands that form anastomosis as well as invaginations into the dermis. Characteristic filiform projections are lined by onychogenic epithelium composed mostly of basal and supra-basal cells that lack granular and corneum layers. The stroma was hypercellular and fibrillary with spindle-shaped fibroblastic cells, and a deep layer with dense collagen. Immunohistochemical stains of the lesion show diffuse expression for CD10 and CD34 in the stroma and negativity for Periodic Acid Schiff staining. Results (if a Case Study enter NA) N/A Conclusion While most of the literature on onychomatricoma has been reported in Caucasian population, little is known about this tumor in non-Caucasians. This case report of onychomatricoma in a Vietnamese woman contributes to the emerging literature of this rare nail apparatus tumor in non-Caucasian population. Clinical and histopathologic correlation is important to achieve prompt and correct diagnosis since delay would result in nail dystrophy and deformity.

UNDERSTANDING THE MANAGEMENT OF MALIGNANT GLIOMAS DURING COVID-19 PANDEMIC IN A HIGH VOLUME TERTIARY GOVERNMENT HOSPITAL IN THE PHILIPPINES

Abstract AIMS Malignant glioma is a common primary brain tumor with a great burden of disease. When COVID-19 set in, it became a challenge to manage an already difficult treatment process in low-resource-setting centers. Despite this, conventional recommendations and standard treatment protocols are followed. However, outcomes were perceived to deviate from the convention, hence the reason for this study which is to understand the nature of outcomes in the management of malignant gliomas during the COVID-19 pandemic in Southern Philippines Medical Center (SPMC), the largest government tertiary hospital in the Philippines. METHOD A retrospective chart review of nine clinically and histologically diagnosed cases of malignant gliomas admitted in SPMC between April 2020 to September 2021 was performed. The clinical presentations, image correlation, and outcomes were listed. Then, classified as desirable, undesirable but acceptable, or unacceptable based on factors identified. Qualitative analysis by deduction including outcomes determining possible modifications in treatment of future cases was done. RESULTS Of the nine cases, one was listed as desirable, one with unacceptable outcome due to management complications, and the rest were labeled as undesirable but acceptable either because of advanced disease or poor KPS score. Three major factors were determined: the roles of pre-hospital and initial treatment delays, the decision for surgical treatment, and the COVID-19 pandemic. CONCLUSION The shift in the outcomes of malignant gliomas during COVID-19 shows the management challenge in low resource centers. There is an increase in highly malignant cases with guarded prognosis due to lack of education, support, and resources in terms of early diagnosis, treatment, and post-surgical care. This was aggravated by the restrictions imposed by the pandemic and financial crisis, especially for patients below the poverty line. Delays in management show a significant influence on prognosis regardless of treatment. As such, possible modifications in the current treatment algorithm are hereby recommended.

Prevalence and clinical correlates of impaired fasting blood glucose in children and adolescents with depressive disorder and relationship with triglyceride and high-density lipoprotein ratio

Depressive disorder is a significant public health problem worldwide, which adversely affects children and adolescents’ health. Impaired fasting blood glucose (IFG) is more common in depressive disorder, which becomes a clinical problem that needs to be focused on. The study purposed to determine the prevalence and related factors of IFG in Chinese children and adolescents with depressive disorder and the relationship between triglyceride and high-density lipoprotein cholesterol (TG/HDL-C) ratio and IFG. This research encompassed 756 individuals aged 8 to 18 with major depressive disorders, all diagnosed under DSM-5 criteria at the Third People’s Hospital of Fuyang from January 2020 to December 2021. We detected fasting blood glucose (FBG) and lipid levels and assessed the suicidal behaviors and depressive symptoms severity of each participant. The sociodemographic and included study variables were collected and analyzed. Our study employed multiple logistic regression to discern independent factors affecting IFG in conjunction with depressive disorders among children and adolescents. The prevalence of IFG was 6.5% (49/756). IFG was positively correlated with FBG, BMI, TG, TG/HDL-C, and was negatively correlated with gender and the type of antidepressant drug taken. Binary logistic analysis showed that male (OR = 2.57, 95% CI: 1.43–4.63, P = 0.002) and higher levels of TG (OR = 1.63, 95% CI: 1.11–2.38, P = 0.013) were independently associated with IFG in children and adolescents with depressive disorder. The incidence of IFG in children and adolescents with depressive disorder was high and was positively related to the TG/HDL-C ratio. The evaluation and management of IFG in pediatric depression should extend beyond pharmacological interventions. Comprehensive strategies in both assessment and management of IFG are essential to address this condition effectively in young patients facing depressive disorders.

Characterizing cognitive phenotypes and clinical correlates in type 2 diabetes using fuzzy clustering and decision tree analysis

Cognitive impairment is frequently seen in patients with type 2 diabetes (T2DM), ranging from mild impairment to dementia. However, our knowledge of the specific profiles and risk factors for these different levels of impairment is limited. In this study involving 152 patients with T2DM, cognitive function was assessed using the Montreal Cognitive Assessment test. The Fuzzy C-means clustering algorithm was utilized to group individuals with similar cognitive characteristics. The study evaluated how well clinical parameters could classify characteristics of clusters using the Classification and Regression Trees algorithm. ROC analysis was then used to assess the classification success. Three distinct cognitive clusters were identified. Cluster 1 had the poorest cognitive performance and was characterized by more women, lower education levels, and lower levels of iron, hemoglobin, and creatine. Cluster 3, the amnestic cluster, was distinguished by low TSH levels. The decision tree model highlighted several parameters, including education level, hemoglobin, duration of diabetes mellitus (DM), iron, TSH, gender, family history of diabetes, and microalbumin/creatinine ratio, as significantly affecting the distinction of cognitive clusters. Diabetes-associated cognitive impairment stems from multifaceted pathophysiological mechanisms influenced by complex risk factors, resulting in diverse types of cognitive deficits.

Pre-operative stereotactic radiosurgery and peri-operative dexamethasone for resectable brain metastases: a two-arm pilot study evaluating clinical outcomes and immunological correlates

Enhancing the efficacy of immunotherapy in brain metastases (BrM) requires an improved understanding of the immune composition of BrM and how this is affected by radiation and dexamethasone. Our two-arm pilot study (NCT04895592) allocated 26 patients with BrM to either low (Arm A) or high (Arm B) dose peri-operative dexamethasone followed by pre-operative stereotactic radiosurgery (pSRS) and resection (n= 13 per arm). The primary endpoint, a safety analysis at 4 months, was met. The secondary clinical endpoints of overall survival, distant brain failure, leptomeningeal disease and local recurrence at 12-months were 66%, 37.3%, 6%, and 0% respectively and were not significantly different between arms (p= 0.7739, p= 0.3884, p= 0.3469). Immunological data from two large retrospective BrM datasets and confirmed by correlates from both arms of this pSRS prospective trial revealed that BrM CD8 T cells were composed of predominantly PD1+ TCF1+ stem-like and PD1+ TCF1-TIM3+ effector-like cells. Clustering of TCF1+ CD8 T cells with antigen presenting cells in immune niches was prognostic for local control, even without pSRS. Following pSRS, CD8 T cell and immune niche density were transiently reduced compared to untreated BrM, followed by a rebound 6+ days post pSRS with an increased frequency of TCF1- effector-like cells. In sum, pSRS is safe and therapeutically beneficial, and these data provide a framework for how pSRS may be leveraged to maximize intracranial CD8 T cell responses.

Pulmonary amyloidosis: clinical, radiological, and pathological correlations

Pulmonary amyloidosis: clinical, radiological, and pathological correlations

Staining patterns of aldosterone synthase in patients undergoing surgery for primary aldosteronism: Proposal for system of categorization and investigation of clinical and biochemical correlation

BackgroundHow aldosterone synthase (CYP11B2) staining patterns impact patient outcomes in those with unilateral primary aldosteronism is not well described. We hypothesized that a system of categorization would benefit future research and that clinical and biochemical outcomes after unilateral adrenalectomy are impacted by different CYP11B2 staining patterns. MethodsA retrospective review of patients undergoing adrenalectomy for primary aldosteronism from January 2015 to September 2023 was conducted. Demographics, clinical, and pathologic data were analyzed. A system of categorization of staining patterns was developed. Clinical and biochemical outcomes were compared with staining patterns to assess differences and determine correlation. Descriptive and statistical analyses were performed using SPSS. ResultsForty-three patients were included. The following CYP11B2 staining patterns were identified: (1) single adenoma; (2) aldosterone producing nodule(s) or micronodule(s); (3) combination of type 1 and type 2; (4) hyperplasia; and (5) aldosterone-producing adrenocortical cancer. In total, 23 of 43 revealed CYP11B2 staining in a single adenoma only. Staining in 3/23 involved a portion of the adenoma. 4/9 patients age <40 had areas of CYP11B2 staining in nonadenomatous tissue. Complete biochemical cure was noted in 37 of 43 (86%) and complete clinical cure in 23.2%. There were no differences between staining pattern and sex, race, or age. CYP11B2 staining pattern did not correlate with early clinical or biochemical outcomes. ConclusionAdrenalectomy specimens from patients treated for primary aldosteronism reveal multiple CYP11B2 staining patterns, including in nonadenomatous tissue in many patients. The impact of these patterns on clinical outcomes requires additional investigation. Uniform categorization of staining patterns will allow for consistent reporting across studies.

Clinical correlates and pathology of non-diabetic renal disease in diabetes mellitus

Objectives: Early identification and differentiation of patients with non-diabetic renal disease (NDRD) from diabetic nephropathy (DN) or those with NDRD superimposed on DN improves the prognosis and reduces associated morbidity. The objectives of the study were to compare the clinical profile, nature of renal involvement, and etiopathogenesis (renal biopsy) of patients with isolated NDRD and NDRD superimposed on DN. Materials and Methods: It is a descriptive study in patients with T2D and renal involvement suggestive of non-diabetic etiology further evaluated with renal biopsy and grouped as NDRD alone or NDRD with DN. Results: Of the total 50, 66% were male, the mean age was 55.57 ± 12.28 years, and all were proteinuric. Overall, isolated NDRD and NDRD superimposed on DN were observed in 64% and 36% of patients, respectively. Diabetic retinopathy was absent in 82% of cases. The most common finding in isolated NDRD was membranous nephropathy, followed by immunoglobulin A (IgA) nephropathy and rapid progression of glomerular nephritis (RPGN). At the same time, in the NDRD and DN group, maximum patients displayed IgA nephropathy followed by acute tubular necrosis and RPGN. The incidence of atypical features of renal disease was almost twice as high in the isolated NDRD group than in the group with both NDRD + DN. Conclusion: NDRDs are highly prevalent, and DN may superimpose these. Recognizing NDRD solely on the basis of clinical indicators is challenging. Therefore, histopathological analysis seems essential to accurately diagnose NDRD in diabetic patients to reduce the probability of missed NDRD diagnosis and initiate prompt treatment.

Molecular and clinical heterogeneity within MYC-family amplified medulloblastoma is associated with survival outcomes: A multicenter cohort study.

MYC/MYCN are the most frequent oncogene amplifications in medulloblastoma (MB) and its primary biomarkers of high-risk (HR) disease. However, while many patients' MYC(N)-amplified tumors are treatment-refractory, some achieve long-term survival. We therefore investigated clinicobiological heterogeneity within MYC(N)-amplified MB and determined its relevance for improved disease management. We characterized the clinical and molecular correlates of MYC- (MYC-MB; n = 64) and MYCN-amplified MBs (MYCN-MB; n = 95), drawn from >1600 diagnostic cases. Most MYC-MBs were molecular group 3 (46/58; 79% assessable) and aged ≥3 years at diagnosis (44/64 [69%]). We identified a "canonical" very high-risk (VHR) MYC-amplified group (n = 51/62; 82%) with dismal survival irrespective of treatment (11% 5-year progression-free survival [PFS]), defined by co-occurrence with ≥1 additional established risk factor(s) (subtotal surgical-resection [STR], metastatic disease, LCA pathology), and commonly group 3/4 subgroup 2 with a high proportion of amplified cells. The majority of remaining noncanonical MYC-MBs survived (i.e. non-group 3/group 3 without other risk features; 11/62 (18%); 61% 5-year PFS). MYCN survival was primarily related to molecular group; MYCN-amplified SHH MB, and group 3/4 MB with additional risk factors, respectively defined VHR and HR groups (VHR, 39% [35/89]; 20% 5-year PFS/HR, 33% [29/89]; 46% 5-year PFS). Twenty-two out of 35 assessable MYCN-amplified SHH tumors harbored TP53 mutations; 9/12 (75%) with data were germline. MYCN-amplified group 3/4 MB with no other risk factors (28%; 25/89) had 70% 5-year PFS. MYC(N)-amplified MB displays significant clinicobiological heterogeneity. Diagnostics incorporating molecular groups, subgroups, and clinical factors enable their risk assessment. VHR "canonical" MYC tumors are essentially incurable and SHH-MYCN-amplified MBs fare extremely poorly (20% survival at 5 years); both require urgent development of alternative treatment strategies. Conventional risk-adapted therapies are appropriate for more responsive groups, such as noncanonical MYC and non-SHH-MYCN MB.

Fragmented QRS in patients with preeclampsia.

This study aims to investigate the prevalence, clinical correlates, and prognostic implications of fragmented QRS complexes (fQRS) in pregnant women with preeclampsia (PE), shedding light on the potential role of electrocardiographic markers in identifying cardiac involvement in hypertensive disorders of pregnancy. Patients with PE and age-matched low-risk control patients were recruited at a tertiary hospital between January 2015 and January 2023. A comprehensive assessment, including heart rate, PR duration, QRS duration, corrected QT duration, and fragmented QRS, was conducted by 12-lead electrocardiography. Baseline clinical characteristics, laboratory parameters, and electrocardiographic findings were compared between the study groups. 128 preeclampsia patients and 122 age- and comorbidity-matched controls were included in the study. The prevalence of fQRS was significantly higher in preeclamptic women compared to normotensive controls (14.1% vs. 3.3%, p = 0.04). ALT levels of pregnant women with preeclampsia and without preeclampsia groups were 43,77 (35.25-48.22) and 23,18 (13.75-33.00) (p: 0.038), respectively. In univariate regression analyses, Na and fragmented QRS were found to be associated with preeclampsia. (p: 0.016 and 0.009, respectively). After multivariable adjustment for variables, Na and fragmented QRS remained strongly associated with preeclampsia (OR: 4.787 (1.556-14.720), p: 0.06; 0.941 (0.893-0.992), p: 0.023, respectively). This study provides compelling evidence of an association between preeclampsia and fragmented QRS complexes, implicating electrolyte imbalances and hemodynamic stress as potential contributors to myocardial electrical instability in hypertensive disorders of pregnancy. Further research is warranted to validate these findings and improve risk stratification and clinical outcomes in affected women. Number: 2023/4705 Retrospectively Registered.