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Therapeutic Potential of Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors in Liver Disease: Focus on Cirrhosis.
No full textCirrhosis, a progressive condition characterized by hepatic fibrosis and functional decline, remains a significant global health burden. Despite advancements in understanding its pathophysiology, effective therapies to halt or reverse progression are limited, especially in advanced stages. Cirrhosis decompensation represents an inflection point in the disease course, with a substantial increase in mortality. Ascites is the most common decompensating event, associated with significant morbidity and healthcare burden, making it a key target in the management of decompensated cirrhosis. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, widely used for type 2 diabetes mellitus, have demonstrated potential beyond glucose regulation. Evidence from clinical and preclinical studies suggests that SGLT2 inhibitors may improve hepatic parameters, reduce hepatic steatosis and fibrosis, and mitigate complications such as ascites. This review explores the multifaceted effects of SGLT2 inhibitors on cirrhosis, focusing on their mechanisms, clinical implications, and therapeutic potential in cirrhosis. By addressing current gaps in therapeutic strategies, SGLT2 inhibitors may represent a novel avenue for improving outcomes in patients with cirrhosis
Unexpected Complications: A Case of Imatinib-induced Serositis Leading to Pericardial and Recurrent Bilateral Pleural Effusions
No full textIntroduction: Imatinib, a tyrosine-kinase inhibitor used to treat chronic myelogenous leukemia (CML), is generally well-tolerated. However, it can cause serositis in less than 1% of individuals. Here, we present a case of imatinib-induced pericardial effusion with pre-tamponade physiology and bilateral pleural effusions. Case: A 72-year-old male with a history of stage 3 A lung adenocarcinoma, esophageal adenocarcinoma in remission, CML on imatinib since 2017, and a history of recurrent pleural effusions presented to the hospital with shortness of breath and cough. He was recently admitted with similar symptoms and required a right-sided chest tube placement for sizeable exudative pleural effusion with a negative cytology. He was offered VATS with pleural biopsy and pleurodesis, but he declined. This time, he was initially hypotensive (BP 90/66 mm Hg), tachycardic (heart rate 90 bpm), and afebrile. Decreased breath sounds were auscultated bilaterally. CBC showed a WBC count of 10,700 per microliter, hemoglobin 7.7 g/dl, troponin 59 ng/L, BNP 108 pg/ml, and lactic acid 2.1 mmol/l. A chest x-ray showed unchanged small pleural effusions. A CT chest showed small bilateral pleural effusions (more significant on the left) and a large pericardial effusion. An urgent echocardiogram showed massive circumferential pericardial effusion with the deepest pocket adjacent to the right ventricle measuring 2.1 cm and pre-tamponade physiology. Given the recurrence of pleural effusions and large pericardial effusion, there was concern for malignancy vs imatinib-induced serositis. Pericardiocentesis yielded approximately 290 mL of serosanguinous fluid, and fluid analysis revealed exudative characteristics, with cytology negative for malignancy. He also underwent left-sided VATS, pleural biopsy, and pleurodesis, with fluid analysis consistently showing exudative fluid with no malignancy. Oncology was consulted, and it was suspected that the patient\u27s recurrent pleural effusions and unremarkable pleural and pericardial fluid studies with negative biopsies were likely due to imatinib-induced serositis. Given this suspicion, imatinib was discontinued. His CML had been in remission since 2022. A onemonth follow-up showed no recurrence of effusion. Discussion: Imatinib-induced serositis is rare and presents as pleural/pericardial effusions. It has been reported in patients initiating therapy and in some studies up to 2 years after initiating imatinib. Our case is interesting because our patient has been on a stable imatinib regimen since 2017. Clinicians should consider this rare adverse effect in patients on long-term imatinib therapy
An update on gastrointestinal stromal tumors (GISTs) with a focus on extragastrointestinal stromal tumors (EGISTs).
No full textGastrointestinal stromal tumors (GISTs) originate from mesenchymal cells and account for ∼1% of primary malignant tumors in the digestive system. They are diagnosed based on characteristic immunohistochemical staining pattern, including CD117 and DOG1, as well as genetic analysis for mutations in the KIT and platelet-derived growth factor receptor α genes. Extragastrointestinal stromal tumors (EGISTs) share very similar morphology with GISTs but arise outside the gastrointestinal tract. The most common locations for EGISTs are the omentum, mesentery, retroperitoneum, and pancreas, followed by the liver, vagina, and prostate. The mean age of presentation of these tumors is in the sixth decade of life and tumor dimensions at different locations typically range from 7 to 15.8 cm. Most of these tumors are unifocal and of the spindle cell type. GISTs generally have a better prognosis than EGISTs, with cumulative 5-year survival rates of 85% for GISTs and 38%-60.9% for EGISTs. Among EGISTs, omental tumors have higher overall survival than mesenteric or retroperitoneal tumors. Additionally, age of \u3e60 years, male sex, larger tumor size, higher mitotic rate, and nuclear pleomorphism are associated with worse prognosis in EGISTs
Use of aspirin for chemoprevention in Lynch syndrome: A systematic review and meta-analysis.
No full textBackground: Lynch syndrome is the most common hereditary colorectal cancer (CRC) that is caused by germline mutations in mismatch repair genes. Previous studies have reported variable results regarding the role of aspirin as a chemopreventive agent in patients with hereditary colon cancer like Lynch syndrome. With this meta-analysis, we aimed to identify whether aspirin reduces the incidence of CRC in patients with Lynch syndrome. Methods: Following PRISMA guidelines, a systematic literature search was conducted in Pubmed, Embase and Clinicaltrials.gov from the date of inception to December 31, 2024 focusing on the use of aspirin in Lynch sydrome. After removing duplicates, 911 studies were primarily screened and the secondary screening yielded 4 studies, including one randomized controlled trial(RCT) and three cohort studies. Meta-analysis was performed for the calculation of Risk Ratio with 95% Confidence Interval utilizing Inverse Variance Random Effects model using Review Manager (version 5.4.1). Results: A total of 3437 patients with Lynch syndrome were included from all four studies with the mean age being 44 years and female gender being 56.4% (n = 1938). The most common mutations identified were MLH1 (39.4%) and MSH2 (39.3%). Former or current smoking was reported in 45% patients (n = 1157/2576). Patients who had aspirin exposure were 736 and patients without aspirin use were 2701. Out of 3437 patients, the total CRC cases reported were 1124 (32.7%). CRC was reported in 201 patients (27.3%) who used aspirin, compared to 923 patients(34%) who did not use aspirin. The risk ratio for CRC development in patients with use of aspirin, irrespective of duration, compared to patients without aspirin use was 1.16 [95% CI 0.79-1.70, Chi2= 26.38, p\u3c 0.00001, I2 = 89%], which shows no significant reduction in CRC with aspirin use. In addition, the risk ratio when aspirin use of at least 2 years was compared with non-aspirin users was 0.97 [95%CI 0.73-1.28, Chi2= 4.44, p = 0.11, I2= 55%], which shows no significant statistical difference between the two groups. Conclusions: Current National Comprehensive Cancer Network guidelines suggest considering the use of aspirin in Lynch syndrome based on evidence from the RCT that was included in our review. However, real-world application of aspirin remains limited due to a variety of factors, including uncertainty of its effectiveness and concern for potential side effects. Our study did not show a statistically significant benefit of aspirin use on development of CRC in Lynch syndrome patients possibly due to short duration of follow up and presence of confounding factors between CRC and non-CRC groups. Further well-designed RCTs are needed to address this gap
Trends in cardiovascular disease mortality among pancreatic cancer patients in the US (1999-2023): Uncovering hidden comorbidities and their impact
No full textBackground: Pancreatic cancer, a highly lethal malignancy, unequally impacts middle-aged populations and often coexists with cardiovascular disease (CVD), increasing mortality. Despite treatment advances, limited data exist on CVD-related deaths in pancreatic cancer patients. This study highlights 1999-2023 trends to uncover demographic disparities in the US for improving survival outcomes. Methods: We analyzed CDC WONDER death certificates (1999-2023) for adults aged ≥45 with pancreatic cancer (ICD-10: C25) and cardiovascular disease (ICD-10: I00-I99). Age-adjusted mortality rates (AAMR) per 100,000 were calculated, and JoinPoint regression was used to estimate annual percent change (APC) and average annual percent change (AAPC). Results: From 1999 to 2023, 235,585 deaths attributed to CVD and pancreatic cancer were reported. Overall, the AAMR rose from 7.4 (1999) to 9.6 (2023), with an AAPC of 1.21 (95% CI 1.07-1.35). Mortality remained stable until 2015 [APC 0.07, 95% CI = -0.96-1.45], slightly increased till 2018 [APC 1.56, 95% CI = -0.60-2.26], followed by a steep rise from 2015-2021 [APC 6.70∗, 95% CI = 4.68-7.97], and a progressive rise till 2023 [APC 1.78∗, 95% CI = 0.07-4.08]. AAMRs rose for both sexes, with males consistently higher than females [AAPC 1.48 (1.31-1.66) vs. 0.96 (0.83-1.08), respectively]. Males\u27 AAMRs rose from 8.6 (1999) to 11.5 (2023), while females\u27 rose from 6.5 to 7.9. Among racial groups, NH American Indians/Alaskan Natives showed the steepest rise (AAPC 2.43%), followed by NH Whites (1.54%), Hispanics (0.63%), NH Blacks/African Americans (0.59%), and NH Asians/Pacific Islanders (-0.79%). Regionally, the South had the highest AAPC (1.89%), followed by the Midwest (1.84%), West (1.50%), and Northeast (-0.06%). Urban areas consistently had higher AAMRs than rural areas (7.4 vs. 7.2). States in the 90th percentile for AAMRs included New York, California, Mississippi, and Nebraska. Conclusions: This analysis of CVD-related mortality in pancreatic cancer patients, reveals a significant rise in AAMRs, especially in males, NH American Indians, residents of urban and Southern US. The study emphasizes the integration of cardiovascular care into pancreatic cancer management for high-risk groups, requiring oncologist-cardiologist collaboration
Relationship Between Perceived Stress Level, Psychological Flexibility, Depression, and Anxiety in Patients with Acute Myocardial Infarction.
No full textEfficacy and safety of levetiracetam for pediatric convulsive status epilepticus in emergency settings: a systematic review and meta-analysis.
No full textBACKGROUND: Status epilepticus is one of the most commonly occuring emergencies among children across the world. Time is crucial in the treatment of SE, with increasing risk of long term adverse events and sequelae with delay in treatment or action of drugs. This systematic review and meta-analysis aims to compare levetiracetam, a drug known for its comparatively safer profile, with other routinely used drugs in pediatric SE like phenytoin, fosphenytoin and valproate.
METHODS: A comprehensive literature search was conducted across four databases from 1996 till November 2024. All original studies evaluating the efficacy of levetiracetam vis-a-vis other anti-seizure medications in pediatric children in an emergency setting were included in the study. Data analysis was conducted using RevMan software, using a random-effects model.
RESULTS: A total of fourteen studies, comprising a patient population of 2,473, were included for further quantitative analysis. No differences were noted between the drugs when comparing seizure termination and recurrence at 24 h. Levetiracetam notably reduced the time to cessation of seizures when compared to phenytoin or fosphenytoin (MD=-3.97, 5% CI [-6.18, -1.76], p = 0.0004) and length of ICU stay over phenytoin (MD = 0.77, 95% CI [0.54, 1.00], p \u3c 0.00001). A lower risk of adverse events was noted on use of levetiracetam over fosphenytoin (RR = 0.62, 95% CI [0.40, 0.96], p = 0.03); however risk of agitation was the least on use of phenytoin (RR = 3.90, 95% CI [1.42, 10.73], p = 0.008). Non significant differences in mortality rates were observed.
CONCLUSION: The study concludes better immediate effects of levetiracetam such as faster cessation of seizures. Levetiracetam was also suggested to stabilize patients faster, as implied by the lesser ICU stay and lower risk of adverse events. Further studies are needed to evaluate the efficacy of levetiracetam over other anti-seizure medications
Discovery of Breast Cancer Through Overlapping Symptoms of NMOSD and Anti-Ri Encephalitis: A blessing in disguise
No full textObjective: To report unusual presentation of Anti-Ri antibody associated encephalopathy mimicking neuromyelitis optica spectrum disorder (NMOSD), leading to diagnosis of breast cancer. Background: Anti-Ri is an anti-neuronal antibody targeting the NOVA antigen in the CNS. Anti-Ri-associated encephalitis presents variably, commonly as opsoclonus-myoclonus or axial/pancerebellar syndrome. It can mimic other neuro-demyelinating conditions like NMOSD. Treatment typically involves immunosuppression or addressing underlying malignancies. Design/Methods: Case Report Results: 65-year old female presented to hospital with 10 days of daytime sleepiness, left eyelid drooping, double vision, right sided drooling, and left arm and leg weakness. Examination revealed left sided ptosis, horizontal gaze palsy (right \u3e left), right lower motor neuron facial palsy, and 3/5 strength in left upper and lower extremities. Initial blood work was unremarkable. MRI Brain revealed prominent CSF sleeves along bilateral optic nerves suggestive of optic atrophy, T2 and FLAIR hyperintensities in subcortical and deep white matter of bilateral frontal and parietal regions, periaqueductal region, dorsal aspect of pons and medulla. Her presentation and MRI led to provisional diagnosis of NMOSD and she was started on high dose steroids without response. Serum anti-MOG and anti-NMO antibodies were negative. CSF studies showed increased total cell count (18 cells/mm3), normal glucose and protein. Anti-MOG, anti-NMO, neurotropic virus and autoimmune encephalitis panel were negative. Serum paraneoplastic panel resulted positive for Anti-Ri antibodies. PET CT revealedsuspicious nodule in left breast without metastasis. She was treated with intravenous immunoglobulin therapy resulting insignificant improvement. Ultrasound guided biopsy revealed infiltrating carcinoma requiring total mastectomy withlymphadenectomy. Later, she required chemotherapy for symptoms recurrence. Conclusions: Anti-Ri encephalitis is uncommon entity, which further directs investigation to underlying occult malignancy. It can haveoverlapping symptoms with NMOSD and poses a diagnostic dilemma, as in our case. A high index of suspicion for Anti-Riencephalitis is required to prevent tumor spread and enable prompt treatment
Emerging modalities for neuroprognostication in neonatal encephalopathy: harnessing the potential of artificial intelligence.
No full textNeonatal Encephalopathy (NE) from presumed hypoxic-ischemic encephalopathy (pHIE) is a leading cause of morbidity and mortality in infants worldwide. Recent advancements in HIE research have introduced promising tools for improved screening of high-risk infants, time to diagnosis, and accuracy of assessment of neurologic injury to guide management and predict outcomes, some of which integrate artificial intelligence (AI) and machine learning (ML). This review begins with an overview of AI/ML before examining emerging prognostic approaches for predicting outcomes in pHIE. It explores various modalities including placental and fetal biomarkers, gene expression, electroencephalography, brain magnetic resonance imaging and other advanced neuroimaging techniques, clinical video assessment tools, and transcranial magnetic stimulation paired with electromyography. Each of these approaches may come to play a crucial role in predicting outcomes in pHIE. We also discuss the application of AI/ML to enhance these emerging prognostic tools. While further validation is needed for widespread clinical adoption, these tools and their multimodal integration hold the potential to better leverage neuroplasticity windows of affected infants. IMPACT: This article provides an overview of placental pathology, biomarkers, gene expression, electroencephalography, motor assessments, brain imaging, and transcranial magnetic stimulation tools for long-term neurodevelopmental outcome prediction following neonatal encephalopathy, that lend themselves to augmentation by artificial intelligence/machine learning (AI/ML). Emerging AI/ML tools may create opportunities for enhanced prognostication through multimodal analyses
Assessing Clinical Improvement of Infants Hospitalized for Respiratory Syncytial Virus-Related Critical Illness.
No full textBACKGROUND: Pediatric respiratory syncytial virus (RSV)-related acute lower respiratory tract infection (LRTI) commonly requires hospitalization. The Clinical Progression Scale Pediatrics (CPS-Ped) measures level of respiratory support and degree of hypoxia across a range of disease severity, but it has not been applied in infants hospitalized with severe RSV-LRTI.
METHODS: We analyzed data from a prospective surveillance registry of infants hospitalized for RSV-related complications across 39 U.S. PICUs from October through December 2022. We assigned CPS-Ped (0=discharged home at respiratory baseline to 8=death) at admission, days 2-7,10, and 14. We identified predictors of clinical improvement (CPS-Ped≤2 or 3-point decrease) by day 7 using multivariable log-binomial regression models and estimated the sample size (80% power) to detect 15% between-group clinical improvement with CPS-Ped versus hospital length of stay (LOS).
RESULTS: Of 585 hospitalized infants, 138 (23.6%) received invasive mechanical ventilation (IMV). Of the 49 (8.4%) infants whose CPS-Ped score worsened by 2 points after admission, one died. Failure to clinically improve by day 7 occurred in 205 (35%) infants and was associated with age \u3c3 \u3emonths, prematurity, underlying respiratory condition, and IMV in the first 24 hours in the multivariable analysis. The estimated sample size per arm required for detecting a 15% clinical improvement in a potential study was 584 using CPS-Ped clinical improvement versus 2,031 for hospital LOS.
CONCLUSIONS: CPS-Ped can be used to capture a range of disease severity and track clinical improvement in infants who develop RSV-related critical illness and could be useful for evaluating therapeutic interventions for RSV