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Acta Cirurgica Brasileira 2024Acute-on-chronic liver failure (ACLF) is a leading cause of death in cirrhotic patients. This study aims to describe the outcomes of in-patients with ACLF at a liver...
PURPOSE
Acute-on-chronic liver failure (ACLF) is a leading cause of death in cirrhotic patients. This study aims to describe the outcomes of in-patients with ACLF at a liver transplantation (LT) center in Brazil.
METHODS
Retrospective study analyzing patient data from 2017 to 2022. Re-transplant cases and patients without previous chronic liver disease were excluded. The ACLF diagnosis was based on the European Association for the Study of the Liver-Chronic Liver Failure criteria and assessments repeated on days 3 and 7 after the initial diagnosis.
RESULTS
Among 381 patients, 10.49% (n = 40) were diagnosed with ACLF. Bacterial infection was the most common precipitating factor (45%). Kidney failure occurred in 65% of the cases. The 28-day mortality rate was 35% and varied according to ACLF severity at diagnosis, from single organ failure (ACLF-1) at 22% to three organ failures (ACLF-3) at 60%. Eighteen patients (45%) were transplanted with a 100% 28-day survival rate. For ACLF-3 cases at diagnosis (n = 15), the 28-day and 1-year survival rates with a transplant (n = 4) were 100% and 80%, respectively, and without transplant (n = 11), 10 and 0%, respectively.
CONCLUSIONS
ACLF was associated with high mortality rates. LT was an effective therapeutic option, particularly for ACLF-3 cases.
Topics: Humans; Retrospective Studies; Acute-On-Chronic Liver Failure; Brazil; Male; Female; Middle Aged; Liver Transplantation; Adult; Aged; Survival Rate; Liver Cirrhosis; Severity of Illness Index; Treatment Outcome
PubMed: 38896629
DOI: 10.1590/acb392624 -
Metabolic Brain Disease Jun 2024Oxidative stress from generation of increased reactive oxygen species or has been reported to play an important role in dementia. Oxidative stress due to free radicals...
Oxidative stress from generation of increased reactive oxygen species or has been reported to play an important role in dementia. Oxidative stress due to free radicals of oxygen or reactive oxygen species could be precipitating factors in the etiology of dementia. Apomorphine has been reported to have neuroprotective effects. To monitor memory enhancing and neuroprotective effects of apomorphine, we determined the antioxidant enzymes activities, lipid peroxidation, acetylcholine esterase (AChE) activity in brain and plasma, following repetitive administration of apomorphine in rat model of dementia. Biogenic amine levels were also monitored in hippocampus. Repeated administration of scopolamine was taken as an animal model of dementia. Decreased glutathione peroxidase, superoxide dismutase and catalase activities were observed in these animal models of dementia. While increased lipid peroxidation was also observed in the brain and plasma samples. The results showed significant effects of apomorphine. The activities of antioxidant enzymes displayed increased activities in both brain and plasma. Glutathione peroxidase and catalase activities were found to be significantly higher in brain and plasma of apomorphine treated rats. Superoxide dismutase (SOD) was significantly decreased in plasma of scopolamine injected rats; and a decreased tendency (non-significant) of SOD in brain was also observed. AChE activity in brain and plasma was significantly decreased in scopolamine treated rats. Learning and memory of rats in the present study was assessed by Morris Water Maze (MWM). Short-term memory and long-term memory was impaired significantly in scopolamine treated rats, which was prevented by apomorphine. Moreover, a marked decrease in biogenic amines was also found in the brain of scopolamine treated rats and was reverted in apomorphine treated rats. Results showed that scopolamine-treatment induced memory impairment and induced oxidative stress in rats as compared to saline-treated controls. These impairments were significantly restored by apomorphine administration. In conclusion, our data suggests that apomorphine at the dose of 1 mg/kg could be a potential therapeutic agent to treat dementia and related disorders.
PubMed: 38896206
DOI: 10.1007/s11011-024-01372-1 -
BioRxiv : the Preprint Server For... Jun 2024DNA double-strand breaks (DSBs) present a critical threat to genomic integrity, often precipitating genomic instability and oncogenesis. Repair of DSBs predominantly...
DNA double-strand breaks (DSBs) present a critical threat to genomic integrity, often precipitating genomic instability and oncogenesis. Repair of DSBs predominantly occurs through homologous recombination (HR) and non-homologous end joining (NHEJ). In HR-deficient cells, DNA polymerase theta (Polθ) becomes critical for DSB repair via microhomology-mediated end joining (MMEJ), also termed theta-mediated end joining (TMEJ). Thus, Polθ is synthetically lethal with BRCA1/2 and other HR factors, underscoring its potential as a therapeutic target in HR-deficient cancers. However, the molecular mechanisms governing Polθ-mediated MMEJ remain poorly understood. Here we present a series of cryo-electron microscopy structures of the Polθ helicase domain (Polθ-hel) in complex with DNA containing 3'-overhang. The structures reveal the sequential conformations adopted by Polθ-hel during the critical phases of DNA binding, microhomology searching, and microhomology annealing. The stepwise conformational changes within the Polθ-hel subdomains and its functional dimeric state are pivotal for aligning the 3'-overhangs, facilitating the microhomology search and subsequent annealing necessary for DSB repair via MMEJ. Our findings illustrate the essential molecular switches within Polθ-hel that orchestrate the MMEJ process in DSB repair, laying the groundwork for the development of targeted therapies against the Polθ-hel.
PubMed: 38895274
DOI: 10.1101/2024.06.07.597860 -
The Israel Medical Association Journal... Jun 2024Diabetic ketoacidosis (DKA) is an acute metabolic, life-threatening complication of diabetes mellitus with a mortality rate that now stand at less than 1%. Although...
BACKGROUND
Diabetic ketoacidosis (DKA) is an acute metabolic, life-threatening complication of diabetes mellitus with a mortality rate that now stand at less than 1%. Although mortality is coupled with the etiology of DKA, literature on the influence of DKA etiology on patient outcome is scarce.
OBJECTIVES
To study different triggers for DKA and their effect on outcomes.
METHODS
We conducted a retrospective study that include 385 DKA patients from 2004 to 2017. The study compared demographics, clinical presentation, and mortality rates by different precipitating factors.
RESULTS
Patients with DKA due to infections had a higher risk to develop in-hospital mortality after controlling for age and sex (odds ratio 4.40, 95% confidence interval 1.35-14.30), had a higher Charlson Comorbidity Index score, a higher risk of being mechanical ventilated (14% vs. 3%, P < 0.01), and a longer duration of hospitalization (5 days vs. 3 days, P < 0.001).
CONCLUSIONS
It is crucial to find the triggers that precipitate DKA and start the treatment as early as possible in addition to the metabolic aspect of the treatment especially when the trigger is an infectious disease.
Topics: Humans; Diabetic Ketoacidosis; Male; Female; Retrospective Studies; Prognosis; Middle Aged; Hospital Mortality; Adult; Risk Factors; Length of Stay; Precipitating Factors; Respiration, Artificial; Infections; Israel; Aged
PubMed: 38884305
DOI: No ID Found -
Cureus May 2024A myasthenic crisis denotes a severe exacerbation of myasthenia gravis, leading a patient to enter a life-threatening state due to progressing muscle weakness that...
A myasthenic crisis denotes a severe exacerbation of myasthenia gravis, leading a patient to enter a life-threatening state due to progressing muscle weakness that ultimately results in respiratory failure. A crisis can require intubation, mechanical ventilation, and additional critical care to prevent further decompensation and potentially death. Numerous well-documented precipitating factors exist, such as infections, surgery, stress, and various medications. We present the case of a 43-year-old woman recently diagnosed with myasthenia gravis who has experienced two myasthenic crises since diagnosis without evident triggers such as surgery, changes in medication, or infection. Following an unremarkable initial diagnostic test and continued treatment for the crisis, we sought additional information from the patient's family member at the bedside. We were informed that two weeks prior to both times of crisis with intubation, the patient had dyed her hair blue. The common chemical component in the two different hair dyes used was methylisothiazolinone, which is suspected to have contributed to the exacerbation of the patient's myasthenia gravis. As more evidence for new precipitating factors of myasthenic crises develops, it is crucial for physicians to quickly identify signs and symptoms of a crisis so appropriate intervention can occur in a time-sensitive manner. In addition, myasthenia gravis patients should be made aware to be cautious of precipitating factors of a crisis, including but not limited to new beauty products.
PubMed: 38868287
DOI: 10.7759/cureus.60186 -
Central Pontine Myelinolysis: A Rare and Life-Threatening Adverse Effect of Clobazam and Quetiapine.Cureus May 2024Central pontine myelinolysis (CPM) is a rare neurological disorder characterized by demyelination within the central portion of the pons. While hyponatremia is a...
Central pontine myelinolysis (CPM) is a rare neurological disorder characterized by demyelination within the central portion of the pons. While hyponatremia is a well-known precipitating factor, other etiologies, including medication use, have been reported. We present a case of a 69-year-old male with a history of obsessive-compulsive disorder, stroke, and type 2 diabetes mellitus who developed confusion, altered sensorium, and weakness in all four limbs. An MRI brain imaging revealed characteristic findings suggestive of CPM. Despite normal serum sodium levels, discontinuation of clobazam and quetiapine, medications taken by the patient, led to clinical improvement. This case underscores the importance of considering medication-induced CPM in the differential diagnosis of patients presenting with neurological symptoms, even in the absence of electrolyte abnormalities.
PubMed: 38854288
DOI: 10.7759/cureus.60007 -
Industrial Psychiatry Journal 2024There is a dearth of research on risk factors of delirium among elderly inpatients in nonintensive low resource settings.
BACKGROUND
There is a dearth of research on risk factors of delirium among elderly inpatients in nonintensive low resource settings.
AIM
To determine the risk factors of delirium in elderly inpatients in a nonintensive care unit setting.
MATERIALS AND METHODS
Sixty two elderly patients with delirium (cases) and 62 patients without delirium (controls) were administered a semi-structured proforma with socio-demographic variables and putative predisposing and precipitating risk factors and the Vellore screening instrument for dementia.
RESULTS
On univariate analysis, factors such as past cognitive impairment, history of nocturnal confusion and delirium, diminished daily living activities, severe medical illness, history of psychiatric illness, presence of dementia, infection, fever above 100F, abnormal electrolytes abnormal RFT, leukocytes in urine, hypoxia, anticholinergics and benzodiazepines, emergency admission, use of physical restraints, bladder catheterization, more than routine investigations, intensive care unit admission, surgery, and duration of hospital stay more than 10 days were found to be significantly associated with delirium. On multivariate analysis with binary logistic regression, bladder catheterization (odds ratio [OR] = 13.85; confidence interval [CI] = 1.44-133.14), abnormal electrolytes (OR = 5.12; CI = 1.11-23.69), and hypoxia (OR = 75.52; CI = 4.64-1.134E3) were detected to be independently associated with delirium.
CONCLUSION
Acute modifiable rather than long-term factors were risk factors for delirium among the elderly. An awareness of modifiable risk factors has the potential of developing targeted interventions for the early mitigation of delirium.
PubMed: 38853788
DOI: 10.4103/ipj.ipj_16_23 -
Biomedicine & Pharmacotherapy =... Jul 2024Intracranial atherosclerotic stenosis (ICAS) is a pathological condition characterized by progressive narrowing or complete blockage of intracranial blood vessels caused... (Review)
Review
Intracranial atherosclerotic stenosis (ICAS) is a pathological condition characterized by progressive narrowing or complete blockage of intracranial blood vessels caused by plaque formation. This condition leads to reduced blood flow to the brain, resulting in cerebral ischemia and hypoxia. Ischemic stroke (IS) resulting from ICAS poses a significant global public health challenge, especially among East Asian populations. However, the underlying causes of the notable variations in prevalence among diverse populations, as well as the most effective strategies for preventing and treating the rupture and blockage of intracranial plaques, remain incompletely comprehended. Rupture of plaques, bleeding, and thrombosis serve as precipitating factors in the pathogenesis of luminal obstruction in intracranial arteries. Pericytes play a crucial role in the structure and function of blood vessels and face significant challenges in regulating the Vasa Vasorum (VV)and preventing intraplaque hemorrhage (IPH). This review aims to explore innovative therapeutic strategies that target the pathophysiological mechanisms of vulnerable plaques by modulating pericyte biological function. It also discusses the potential applications of pericytes in central nervous system (CNS) diseases and their prospects as a therapeutic intervention in the field of biological tissue engineering regeneration.
Topics: Pericytes; Humans; Animals; Intracranial Arteriosclerosis; Vasa Vasorum; Cerebral Arteries
PubMed: 38850658
DOI: 10.1016/j.biopha.2024.116870 -
The International Journal of Angiology... Jun 2024Venous thromboembolism (VTE) is a very frequent cardiovascular entity that encompasses deep vein thrombosis and pulmonary embolism (PE). This last entity represents a... (Review)
Review
Venous thromboembolism (VTE) is a very frequent cardiovascular entity that encompasses deep vein thrombosis and pulmonary embolism (PE). This last entity represents a major cause of cardiovascular morbidity and mortality. The incidence of PE and the rate of PE-related morbidity significantly increase with age, race, and underlying medical conditions, such as malignancy. Given the recent advances in diagnostic strategies and algorithms, patients can be risk assessed and treated promptly to avoid disease progression. Anticoagulation is the mainstay of treatment for acute PE that is not hemodynamically unstable. Direct oral anticoagulants, such as apixaban, rivaroxaban, or edoxaban, are currently the preferred agents for the treatment of patients who present with acute PE or for long-term treatment. Treatment duration should be continued for at least 3 months, and all patients should be assessed for extended duration of therapy based on the precipitating factors that led to the development of the VTE. Novel anticoagulant agents targeting factor XI/XIa are currently being investigated in phases 2 and 3 clinical trials, representing an attractive option in anticoagulation therapies in patients with VTE. For hemodynamically unstable patients, systemic thrombolysis is the treatment of choice, and it may also be of benefit-in reduced dose-for patients with intermediate to high risk who are at risk of hemodynamic collapse.
PubMed: 38846991
DOI: 10.1055/s-0044-1782537 -
International Journal of... Jun 2024Sleep quality often deteriorates with age, and insomnia among the elderly increases the risks of both physical and psychiatric disorders. To elucidate the mechanisms and...
Sleep quality often deteriorates with age, and insomnia among the elderly increases the risks of both physical and psychiatric disorders. To elucidate the mechanisms and identify useful diagnostic biomarkers for insomnia in the elderly, the current study investigated the associations of waking brain activity patterns with susceptibility to stress-induced insomnia (sleep reactivity) and dysfunctional beliefs about sleep, major factors precipitating and maintaining insomnia, respectively. Forty-five participants aged 60 years or older with insomnia completed self-reported measures assessing depression, anxiety, sleep quality, dysfunctional beliefs about sleep, and sleep reactivity. Participants were then examined by quantitative electroencephalography (qEEG) during wakefulness, and spectral analysis was conducted to examine associations of regional frequency band power with these insomnia-precipitating and -maintaining factors. Dysfunctional beliefs about sleep were significantly correlated with higher beta/high-beta frequency band powers, while sleep reactivity was correlated with higher theta and delta frequency band powers. These findings suggest that sleep reactivity of older adults is associated with widespread cortical deactivation leading to poor stress coping, while their dysfunctional beliefs about sleep are associated with hyperactivation which is related to cognitive processes. These associations suggest that cognitive inflexibility and maladaptive stress-coping contribute to insomnia among the elderly.
PubMed: 38844053
DOI: 10.1016/j.ijpsycho.2024.112373