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Resuscitation Jun 2024The incidence of sudden cardiac arrest (SCA) during acute coronary syndrome is somewhat unclear, since often subjects dying before the first healthcare contact are not...
BACKGROUND
The incidence of sudden cardiac arrest (SCA) during acute coronary syndrome is somewhat unclear, since often subjects dying before the first healthcare contact are not included in the estimates. We aimed to investigate the complete incidence of SCA during ACS.
METHODS
The study population consists of two cohorts. The first cohort includes 472 ACS patients from Northern Ostrobothnia, Finland from year 2016 and the second cohort 162 autopsy-verified SCD subjects (extrapolated) from the same region and year, whose death was attributable to coronary artery disease (CAD) and ACS. An extrapolation of SCA incidence during ACS was done by utilizing autopsy data and data from prior autopsy study on this sample.
RESULTS
The overall incidence of SCA in the setting of ACS was 17.5%. The incidence of SCA was 20.6% in all ACS subjects without prior CAD diagnosis, and 25.4% in STEMI subjects without prior CAD diagnosis. In subjects with previously diagnosed CAD, the incidence of SCA was 10.9% in all ACS subjects and 16.1% in STEMI subjects. There was a statistically significant difference in the incidence of SCA between subjects with and without prior CAD diagnoses (p=0.0052).
CONCLUSION
The inclusion of ACS-SCA subjects dying before the first emergency medical service (EMS) contact results in a higher and likely more accurate estimation of SCA during ACS. The incidence of SCA was higher among subjects without prior CAD diagnosis. The high mortality rate highlights the importance of early ACS detection to reduce the burden of CAD-related premature deaths.
PubMed: 38942268
DOI: 10.1016/j.resuscitation.2024.110297 -
Journal of Forensic and Legal Medicine Jun 2024Pheochromocytoma is a neuroendocrine tumor that secretes catecholamines; excessive catecholamine secretion can lead to pheochromocytoma crisis (PCC), a rare and...
Pheochromocytoma is a neuroendocrine tumor that secretes catecholamines; excessive catecholamine secretion can lead to pheochromocytoma crisis (PCC), a rare and life-threatening condition. Sibutramine, a serotonin and norepinephrine reuptake inhibitor, was previously used for obesity treatment but is now banned due to its cardiovascular side effects. Although fatalities related to PCC and adverse events associated with sibutramine have been frequently reported individually, there is no documented literature addressing PCC-induced by sibutramine. Here we report a rare case of fatal sibutramine-induced PCC in a previously asymptomatic young female with undiagnosed pheochromocytoma. The 25-year-old patient took a weight-loss pill containing sibutramine for the first time and subsequently experienced nausea, vomiting, chest tightness, and other symptoms. She went to hospital about 6 hours after taking the pill but died approximately 4 hours later despite the resuscitation efforts. An autopsy revealed a pheochromocytoma in the right adrenal gland. The cause of death was attributed to sibutramine-induced PCC. To our knowledge, this is the first report to document the occurrence of sibutramine-induced PCC.
PubMed: 38941912
DOI: 10.1016/j.jflm.2024.102711 -
Medicine Jun 2024Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare but serious complication in patients with malignancy; its main manifestation includes acute pulmonary... (Review)
Review
RATIONALE
Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare but serious complication in patients with malignancy; its main manifestation includes acute pulmonary hypertension with severe respiratory distress. More than 200 cases have been reported since it was first identified in 1990. PTTM accounts for approximately 0.9% to 3.3% of deaths due to malignancy, but only a minority of patients are diagnosed ante-mortem, with most patients having a definitive diagnosis after autopsy.
PATIENT CONCERNS
Two middle-aged women both died within a short period of time due to progressive dyspnea and severe pulmonary hypertension.
DIAGNOSES
One patient was definitively confirmed as a gastrointestinal malignant tumor by liver puncture biopsy pathology. Ultimately, the clinical diagnosis was pulmonary tumor thrombotic microangiopathy.
INTERVENTIONS
The patient was treated symptomatically with oxygen, diuresis, and anticoagulation, while a liver puncture was perfected to clarify the cause.
OUTCOMES
Two cases of middle-aged female patients with rapidly progressive pulmonary hypertension and respiratory failure resulted in death with malignant neoplasm.
LESSONS
PTTM has a rapid onset and a high morbidity and mortality rate. Our clinicians need to be more aware of the need for timely diagnosis through a targeted clinical approach, leading to more targeted treatment and a better prognosis.
Topics: Humans; Female; Thrombotic Microangiopathies; Middle Aged; Fatal Outcome; Hypertension, Pulmonary; Gastrointestinal Neoplasms; Lung Neoplasms
PubMed: 38941435
DOI: 10.1097/MD.0000000000038618 -
Biological Trace Element Research Jun 2024Metals are used in orthopedic implants. The wear of arthroplasty implant can lead to the release of arthroprosthetic metals, both locally and systemically, after...
Metals are used in orthopedic implants. The wear of arthroplasty implant can lead to the release of arthroprosthetic metals, both locally and systemically, after migration into the organs. While the toxicity of metal-on-metal arthroplasty implants is well-known and monitored, the toxicity associated with metal-on-polyethylene (MoP) ones is not as comprehensively understood. This study aimed to investigate the release of metals from MoP arthroplasty implants and their impact on the tissue metal profile in autopsied individuals, comparing them to deceased controls without prostheses. High-resolution ICP-MS was employed to analyze 39 metals in the blood, urine, hair, organs, and periprosthetic tissue of 25 deceased individuals with arthroplasty implants and 20 control subjects (Prometox study, protocol ID: APHP180539, NCT03812627). Eight metals (beryllium, chromium, cobalt, lanthanum, molybdenum, nickel, tellurium, titanium) exhibited significant impacts in arthroplasty implant wearers across various organs. Increased concentrations of La and Be were observed, the origin of which could not be precisely defined within the scope of this study. Notably, the lungs emerged as the primary target organ for metallic ions contained in implants. This study suggests that MoP arthroplasty implants, even when functional and not visibly worn, release arthroprosthetic metals into the body, potentially causing disturbances. Furthermore, considering the presence of an arthroplasty implant in autopsy reports may be relevant, as the released metals could influence the tissue metal profile.
PubMed: 38941062
DOI: 10.1007/s12011-024-04278-2 -
JACC. Advances Jul 2023Obesity cardiomyopathy (OCM) can be associated with sudden cardiac death (SCD) but its pathologic features are not well described.
BACKGROUND
Obesity cardiomyopathy (OCM) can be associated with sudden cardiac death (SCD) but its pathologic features are not well described.
OBJECTIVES
The objective of this study was to characterize the clinical and pathological features of OCM associated with SCD.
METHODS
This was a retrospective case control autopsy study. OCM was identified by an increased heart weight (>550 g in males; >450 g in females) in individuals with obesity (body mass index [BMI] ≥30 kg/m) in the absence of other causes. Cases of OCM with SCD were compared to sex and age matched SCD controls with obesity or with normal weight (BMI 18.5-24.9 kg/m) and morphologically normal hearts. Autopsy measures included: heart weight, atrial dimensions, ventricular wall thickness, and epicardial adipose tissue. Fibrosis was assessed microscopically.
RESULTS
Of 6,457 SCD cases, 53 cases of OCM were identified and matched to 106 controls with obesity and 106 normal weight controls. The OCM mean age at death of individuals with OCM was 42 ± 12 with a male predominance (n = 34, 64%). Males died younger than females (40 ± 13 vs 45 ± 10, = 0.036). BMI was increased in OCM cases compared to controls with obesity (42 ± 8 vs 35 ± 5). The average heart weight was 598 ± 93 g in OCM. There were increases in right and left ventricular wall thickness (all < 0.05) in OCM cases compared to controls. Right ventricular epicardial fat was increased in OCM compared to normal weight controls only. Left ventricular fibrosis was identified in 7 (13%) cases.
CONCLUSIONS
OCM may be a specific pathological entity associated with SCD. It is most commonly seen in young males with increased BMI.
PubMed: 38938994
DOI: 10.1016/j.jacadv.2023.100414 -
JACC. Advances Nov 2023The prevalence and degree of lower extremity artery disease in hemodialysis (HD) patients is higher than in the general population. However, the pathological features...
BACKGROUND
The prevalence and degree of lower extremity artery disease in hemodialysis (HD) patients is higher than in the general population. However, the pathological features have not yet been evaluated.
OBJECTIVES
The aim of the study was: 1) to compare lesion characteristics of lower extremity artery disease in HD vs non-HD patients; and 2) to determine factors associated with severe medial calcification.
METHODS
Seventy-seven lower limb arteries were assessed from 36 patients (median age 77 years; 23 men; 21 HD and 15 non-HD) who underwent autopsy or lower limb amputation. Arteries were serially cut at 3- to 4-mm intervals creating 2,319 histological sections. Morphometric analysis and calcification measurements were performed using ZEN software. Calcification with a circumferential angle (arc) ≥180° was defined as severe calcification. Multivariable logistic regression was used to identify risk factors for severe medial calcification.
RESULTS
The degree of the medial calcification arc was significantly higher in the HD group compared to the non-HD group ( < 0.0001). In the multivariable analysis, HD was associated with severe medial calcification in below-the-knee lesions (OR: 17.1; = 0.02). The degree of intimal calcification in above-the-knee lesions was also significantly higher in HD patients with a higher prevalence of advanced atherosclerotic plaque ( = 0.02). The prevalence of severe bone formation was more common in the HD patients ( = 0.01).
CONCLUSIONS
Hemodialysis patients demonstrated a higher degree of medial and intimal calcification compared with non-HD patients. The difference was more prominent in the medial calcification of below-the-knee lesions.
PubMed: 38938733
DOI: 10.1016/j.jacadv.2023.100656 -
Frontiers in Aging Neuroscience 2024At least one-third of the identified risk alleles from Genome-Wide Association Studies (GWAS) of Alzheimer's disease (AD) are involved in lipid metabolism, lipid...
INTRODUCTION
At least one-third of the identified risk alleles from Genome-Wide Association Studies (GWAS) of Alzheimer's disease (AD) are involved in lipid metabolism, lipid transport, or direct lipid binding. In fact, a common genetic variant (ε4) in a cholesterol and phospholipid transporter, Apolipoprotein E (), is the primary genetic risk factor for late-onset AD. In addition to genetic variants, lipidomic studies have reported severe metabolic dysregulation in human autopsy brain tissue, cerebrospinal fluid, blood, and multiple mouse models of AD.
METHODS
We aimed to identify an overarching metabolic pathway in lipid metabolism by integrating analyses of lipidomics and transcriptomics from the Religious Order Study and Rush Memory Aging Project (ROSMAP) using differential analysis and network correlation analysis.
RESULTS
Coordinated differences in lipids were found to be dysregulated in association with both mild cognitive impairment (MCI) and carriers. Interestingly, these correlations were weakened when adjusting for education. Indeed, the cognitively non-impaired carriers have higher education levels in the ROSMAP cohort, suggesting that this lipid signature may be associated with a resilience phenotype. Network correlation analysis identified multiple differential lipids within a single module that are substrates and products in the Lands Cycle for acyl chain remodeling. In addition, our analyses identified multiple genes in the Lands Cycle acyl chain remodeling pathway, which were associated with cognitive decline independent of amyloid-β (Aβ) load and tau tangle pathologies.
DISCUSSION
Our studies highlight the critical differences in acyl chain remodeling in brain tissue from carriers and individual non-carriers with MCI. A coordinated lipid profile shift in dorsolateral prefrontal cortex from both carriers and MCI suggests differences in lipid metabolism occur early in disease stage and highlights lipid homeostasis as a tractable target for early disease modifying intervention.
PubMed: 38938596
DOI: 10.3389/fnagi.2024.1419253 -
Brain : a Journal of Neurology Jun 2024Population-based cohort studies are essential for understanding the pathological basis of dementia in older populations. Previous studies have shown that...
Population-based cohort studies are essential for understanding the pathological basis of dementia in older populations. Previous studies have shown that limbic-predominant age-related TDP-43 encephalopathy neuropathological change (LATE-NC) increases with age, but there have been only a few studies, which have investigated this entity in a population-based setting. Here we studied the frequency of LATE-NC and its associations with other brain pathologies and cognition in a population aged ≥ 85 years. The population-based Vantaa 85+ study cohort includes all 601 individuals aged ≥ 85 years who were living in Vantaa, Finland in 1991. A neuropathological examination was performed on 304 subjects (50.5%) and LATE-NC staging was possible in 295 of those. Dementia status and Mini-Mental State Examination (MMSE) scores were defined in the baseline study and 3 follow-ups (1994-99). The LATE-NC stages were determined based on TDP-43 immunohistochemistry, according to recently updated recommendations. Arteriolosclerosis was digitally assessed by calculating the average sclerotic index of five random small arterioles in amygdala and hippocampal regions, and frontal white matter. The association of LATE-NC with arteriolosclerosis and previously determined neuropathological variables including Alzheimer's disease neuropathological change (ADNC), Lewy-related pathology (LRP), hippocampal sclerosis (HS), and cerebral amyloid angiopathy (CAA), and cognitive variables were analysed by Fisher's exact test, linear and logistic regression (univariate and multivariate) models. LATE-NC was found in 189 of 295 subjects (64.1%). Stage 2 was the most common (28.5%) and stage 3 the second most common (12.9%), whereas stages 1a, 1b and 1c were less common (9.5%, 5.1% and 8.1%, respectively). Stages 1a (P < 0.01), 2 (P < 0.001) and 3 (P < 0.001) were significantly associated with dementia and lower MMSE scores. LATE-NC was associated with ADNC (P < 0.001), HS (P < 0.001), diffuse neocortical LRP (P < 0.002), and arteriolosclerosis in amygdala (P < 0.02). In most cases LATE-NC occurred in combination alongside other neuropathological changes. There were only six subjects with dementia who had LATE-NC without high levels of ADNC or LRP (2% of the cohort, 3% of the cases with dementia), and five of these had HS. In all multivariate models, LATE-NC was among the strongest independent predictors of dementia. When LATE-NC and ADNC were assessed in a multivariate model without other dementia-associated pathologies, the attributable risk was higher for LATE-NC than ADNC (24.2% vs. 18.6%). This population-based study provides evidence that LATE-NC is very common and one of the most significant determinants of dementia in the general late-life aged population.
PubMed: 38938199
DOI: 10.1093/brain/awae212 -
Alzheimer's & Dementia : the Journal of... Jun 2024Primary age-related tauopathy (PART), often regarded as a minimally symptomatic pathology of old age, lacks comprehensive cohorts across various age groups.
INTRODUCTION
Primary age-related tauopathy (PART), often regarded as a minimally symptomatic pathology of old age, lacks comprehensive cohorts across various age groups.
METHODS
We examined PART prevalence and clinicopathologic features in 1589 forensic autopsy cases (≥40 years old, mean age ± SD 70.2 ± 14.2 years).
RESULTS
PART cases meeting criteria for argyrophilic grain diseases (AGD) were AGD+PART (n = 181). The remaining PART cases (n = 719, 45.2%) were classified as comorbid conditions (PART-C, n = 90) or no comorbid conditions (pure PART, n = 629). Compared to controls (n = 208), Alzheimer's disease (n = 133), and AGD+PART, PART prevalence peaked in the individuals in their 60s (65.5%) and declined in the 80s (21.5%). No significant clinical background differences were found (excluding controls). However, PART-C in patients inclusive of age 80 had a higher suicide rate than pure PART (p < 0.05), and AGD+PART showed more dementia (p < 0.01) and suicide (p < 0.05) than pure PART.
DISCUSSION
Our results advocate a reevaluation of the PART concept and its diagnostic criteria.
HIGHLIGHTS
We investigated 1589 forensic autopsy cases to investigate the features of primary age-related tauopathy (PART). PART peaked in people in their 60s in our study. Many PART cases over 80s had comorbid pathologies in addition to neurofibrillary tangles pathology. Argyrophilic grain disease and Lewy pathology significantly affected dementia and suicide rates in PART. Our results suggest that the diagnostic criteria of PART need to be reconsidered.
PubMed: 38938196
DOI: 10.1002/alz.14037 -
BMC Infectious Diseases Jun 2024Tuberculosis (TB), one of the leading causes of death worldwide, has a higher incidence among indigenous people. Albeit uncommon, autoimmune hemolytic anemia (AIHA) has...
BACKGROUND
Tuberculosis (TB), one of the leading causes of death worldwide, has a higher incidence among indigenous people. Albeit uncommon, autoimmune hemolytic anemia (AIHA) has been deemed a risk condition to develop mycobacterial infection, as a result of the immunosuppressive treatments. TB, in turn, can be a predisposing factor for secondary infections.
CASE PRESENTATION
Here we present a case of a 28-year-old indigenous woman from Colombia, previously diagnosed with AIHA and pulmonary TB. Despite various treatments, therapies and medical interventions, the patient died after severe medullary aplasia of multiple causes, including secondary myelotoxicity by immunosuppressive therapy and secondary disseminated infections, underlining infection by Staphylococcus aureus, Klebsiella pneumoniae and Candida glabrata, which were identified as drug-resistant microorganisms. Together, this led to significant clinical complications. Invasive aspergillosis was diagnosed at autopsy.
CONCLUSIONS
This report presents a rarely finding of AIHA followed by TB, and highlights the great challenges of dealing with co-infections, particularly by drug resistant pathogens. It also aims to spur governments and public health authorities to focus attention in the prevention, screening and management of TB, especially among vulnerable communities, such as indigenous people.
Topics: Humans; Female; Adult; Coinfection; Fatal Outcome; Anemia, Hemolytic, Autoimmune; Colombia; Klebsiella pneumoniae; Staphylococcus aureus; Candida glabrata; Tuberculosis, Pulmonary; Staphylococcal Infections; Indigenous Peoples; Candidiasis
PubMed: 38937714
DOI: 10.1186/s12879-024-09557-w