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Ivermectin has been found to inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication in vitro. It is unknown whether this inhibition of SARS-CoV-2 replication correlates with improved clinical outcomes. To assess the effectiveness and safety of ivermectin in hospitalized patients with COVID-19. A total of 286 patients with COVID-19 were included in the study. Univariate analysis of the primary mortality outcome and comparisons between treatment groups were determined. Logistic regression and propensity score matching (PSM) was used to adjust for confounders. Patients in the ivermectin group received 2 doses of Ivermectin at 200 µg/kg in addition to usual clinical care on hospital Days 1 and 3. The ivermectin group had a significantly higher length of hospital stay than the control group; however, this significance did not maintain on multivariable logistic regression analysis. The length of intensive care unit (ICU) stay and duration of mechanical ventilation were longer in the control group. However, a mortality benefit was not seen with ivermectin treatment before and after PSM (p values = 0.07 and 0.11, respectively). ICU admission, and intubation rate were not significantly different between the groups (p = 0.49, and p = 1.0, respectively). No differences were found between groups regarding the length of hospital stay, ICU admission, intubation rate, and in-hospital mortality.
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Tratamento Farmacológico da COVID-19 , COVID-19/mortalidade , Ivermectina/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva , Ivermectina/administração & dosagem , Tempo de Internação/estatística & dados numéricos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Estudos Prospectivos , Respiração Artificial , Provedores de Redes de Segurança , Adulto JovemRESUMO
Background: The age-dependent prognostic impact of KRAS status in metastatic colorectal cancer (mCRC) is unknown. Materials & Methods: We used the National Cancer Database to evaluate the survival by KRAS status for age-groups <50, 50-69 and ≥70, adjusting for relevant patient and tumor characteristics. Results: mCRC patients (n = 26,095; 33.5%) had KRAS status reported, and 11,338 of these patients (43.4%) had mutations in the KRAS gene. Patients with KRAS mutations had worse overall survival than wild-type KRAS patients. In age-groups <50 years (23 vs 29 months; p < 0.001) and 50-69 (21 vs 23.4 months; p < 0.001), KRAS mutations were significantly associated with worse survival, whereas in the ≥70-year age-group, there was no significant association (14 vs 14 months; p = 0.34). Conclusion: We conclude that the age of patients influences the prognostic value of KRAS mutation in metastatic colorectal cancer.
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Biomarcadores Tumorais , Neoplasias Colorretais/genética , Neoplasias Colorretais/mortalidade , Mutação , Proteínas Proto-Oncogênicas p21(ras)/genética , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/terapia , Terapia Combinada/métodos , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Resultado do TratamentoRESUMO
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. Immune checkpoint inhibitors (ICIs) have become the new reference standard in first-line HCC treatment, replacing tyrosine kinase inhibitors (TKIs) such as sorafenib. Many clinical trials with different combinations are already in development to validate novel immunotherapies for the treatment of patients with HCC. Adoptive cell therapy (ACT), also known as cellular immunotherapy, with chimeric antigen receptors (CAR) or gene-modified T cells expressing novel T cell receptors (TCR) may represent a promising alternative approach to modify the immune system to recognize tumor cells with better clinical outcomes. In this review, we briefly discuss the overview of ACT as a promising treatment modality in HCC, along with recent updates of ongoing clinical trials.
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BACKGROUND: While the incidence of cholangiocarcinoma is rising, little is known about young-onset disease. We compared clinical characteristics and outcomes between patients with young-onset cholangiocarcinoma, diagnosed between the ages of 18 and <50 years, and patients with typical-onset cholangiocarcinoma, diagnosed at age 50 years or greater. METHODS: We used the National Cancer Database to identify patients with young-onset cholangiocarcinoma (n = 2520) and typical-onset cholangiocarcinoma (n = 23,826). We compared the frequency of demographic and clinical characteristics between the two groups. We compared overall survival between the two groups using multivariable Cox regression analysis after adjusting for age, gender, race/ethnicity, comorbidity, facility type, tumor location, tumor stage, surgical status, and receipt of radiotherapy, chemotherapy and surgery. RESULTS: When compared to patients with typical-onset disease (median age 68 years), patients with young-onset cholangiocarcinoma (median age 44 years) were more likely to be non-White (35.0% vs. 27.4%, p < 0.01), and had lower overall comorbidity burden. Patients with young-onset disease had a greater proportion of intrahepatic cholangiocarcinoma (56.0% vs. 45.5%, p < 0.001) and stage IV disease (50.5% vs. 43.5%, p < 0.001). Younger patients were more likely than typical-onset patients to receive definitive surgery (30.9% vs. 25.0%, p < 0.001), radiation (27.7% vs. 19.6%, p < 0.001) and chemotherapy (73.1% vs. 50.1%, p < 0.001). In adjusted analyses, patients with young-onset disease had a 15% decreased risk of death, compared with patients with typical-onset disease (HR 0.85 [95% CI 0.80-0.89], p < 0.001). CONCLUSIONS: Patients with young-onset cholangiocarcinoma may represent a demographically and clinically distinct group from those with more typical-onset disease.
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Neoplasias dos Ductos Biliares , Colangiocarcinoma , Humanos , Adolescente , Colangiocarcinoma/epidemiologia , Colangiocarcinoma/terapia , Ductos Biliares Intra-Hepáticos/patologia , Neoplasias dos Ductos Biliares/epidemiologia , Neoplasias dos Ductos Biliares/terapia , Estudos RetrospectivosRESUMO
Background: Advanced hepatocellular carcinoma (HCC) generally has a dismal prognosis. Bone metastases from HCC are infrequent, with a poorer prognosis. However, the survival influencing factors are not yet well understood. Aim: The aim of the present study was to assess the clinical features and tumor characteristics of HCC patients with bone metastasis. Methods: A cohort of 170,576 adult patients with HCC was studied using the National Cancer Database (NCDB) spanning from 2010 to 2019, and within this group, 5285 patients (3.1%) were diagnosed with bone metastasis. We performed the Kaplan-Meier method to calculate the median overall survival (OS). We included demographics (age at diagnosis, gender, race, insurance status), comorbidity score, and treatment characteristics. Results: Of a total of 5285 HCC patients with bone metastasis, 86.2% were male and 61.2% were non-Hispanic white. Most patients (55.1%) were below 65, and 89% had a total Charlson-Deyo comorbidity score of under 3. Among patients with known tumor grade, 24.8% had well-differentiated tumors, and 36.1% had poorly differentiated tumors. Chemotherapy was administrated to 39.5% of patients. In univariate analysis, patients with well-differentiated tumors had better OS compared to poorly differentiated tumors (5.4 months vs 3.0 months, p = 0.001). Patients who received single or multiagent chemotherapy were significantly associated with improved OS compared to patients who did not receive chemotherapy (7.0 and 8.5 months vs 1.94 months, respectively). We also found mortality difference between age, comorbidity scores, facility types and race groups. Conclusion: In this cohort analysis of NCDB data, we found better OS in treatment receipt, lower tumor grade, younger age, non-Hispanic Black and Hispanic race, treatment at academic facility and lower comorbidity score in HCC patients with bone metastasis. The study results may have a consequential impact on the treatment decisions for HCC patients with bone metastasis.
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Race and ethnic backgrounds affect the disease characteristics and clinical outcomes in many cancers, including acute myeloid leukemia; however, the association of race/ethnicity on myelodysplastic syndrome (MDS) is still controversial. Therefore, we aimed to study the impact of race/ethnicity on the disease characteristics and survival outcomes in patients with MDS. Adult patients with MDS diagnosed in 2004-2016 were selected using the SEER database. Race/ethnicity was categorized as non-Hispanic White (NHW), non-Hispanic Black (NHB), and Hispanic. Hispanic and NHB patients had significantly lower incidence rate ratio (IRR) in age group ≥01 years (p < .001) compared to NHW; however, in the age group <50 years, NHB patients had significantly higher IRR with an increased incidence rate of 49%. NHB patients had better overall survival than Hispanic and NHW patients (p < .001), even after adjusting for confounding variables. MDS have significant differences in age at diagnosis, disease risk, and survival outcomes based on racial/ethnic backgrounds.
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Etnicidade , Síndromes Mielodisplásicas , Adulto , Negro ou Afro-Americano , Hispânico ou Latino , Humanos , Lactente , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/epidemiologia , Síndromes Mielodisplásicas/terapia , População BrancaRESUMO
PURPOSE: CNS relapse in patients with diffuse large B-cell lymphoma (DLBCL) is associated with poor prognosis with a median survival of about 2.5 months. Data demonstrating best prophylactic strategy remain controversial and need further definition. PATIENTS AND METHODS: We present data of 110 patients with DLBCL treated with standard systemic therapy divided into four groups based on primary CNS prophylaxis strategy and CNS International Prognostic Index (IPI) risk categories. We compared their 3-year CNS relapse rate and overall survival in each group. RESULTS: The CNS prophylaxis strategy consisted of intrathecal (IT) methotrexate (MTX) in group 1, high-dose (HD) MTX in group 2, combination IT and HD MTX in group 3, and IT and/or HD MTX with intensive chemotherapy in group 4. At 3 years, CNS relapse rate was 8.6% (4/46), 8.3% (1/12), 4.8% (2/42), and 18% (2/11) in groups 1-4 (P = .64), respectively. According to CNS IPI, the CNS relapse rate was 16.6%, 10.1%, and 0% in high-, intermediate-, and low-risk groups, respectively. The 3-year overall survival rate was 69%, 75%, 80%, and 45% in groups 1-4 (P = .71), respectively. CONCLUSION: Our study while did not find statistical significance did indicate a lower incidence of CNS relapse with the addition of systemic HD MTX to IT MTX in the high-risk DLBCL population.
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Neoplasias do Sistema Nervoso Central , Linfoma Difuso de Grandes Células B , Linfócitos B , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/prevenção & controle , Seguimentos , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Recidiva Local de Neoplasia/prevenção & controleRESUMO
Patients with cancer are a vulnerable population during the COVID-19 pandemic due to underlying immunosuppression, pre-existing comorbidities, and poor nutrition. There is a lack of data describing the disease course of cancer patients with COVID-19 disease. Therefore, we analyzed data from cancer patients with COVID-19 who were admitted to our hospital. Cancer patients were categorized into two groups as survivors and non-survivors of COVID-19. Among 68 cancer patients with COVID-19, 27% of patients were admitted to ICU, and 37% of the patients died. The median age was 72, and non-survivors were older than survivors (p = 0.001). Non-survivors had higher comorbidity scores, late-stage cancer, and worse ECOG performance status than survivors (all p values<0.005). Non-survivors also had significantly lower lymphocyte count and albumin level but higher lactate dehydrogenase, C-reactive protein, fibrinogen, troponin, and ferritin levels than survivors. On multivariable analysis, increased age and mechanical ventilation were associated with increased odds of death. We report no association between anti-cancer treatments and mortality from COVID-19 disease. In summary, cancer patients have higher mortality of COVID-19 infection than the general population. In addition to generally known risk factors, the high mortality rate in cancer patients with COVID-19 is associated with several cancer-specific factors.
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COVID-19/epidemiologia , COVID-19/etiologia , Neoplasias/virologia , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/mortalidade , COVID-19/terapia , Comorbidade , Feminino , Hospitais/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Neoplasias/mortalidade , Neoplasias/terapia , Respiração Artificial , Estudos Retrospectivos , Provedores de Redes de Segurança/estatística & dados numéricos , Estados Unidos/epidemiologia , Adulto JovemRESUMO
The World Health Organization nominated SARS-CoV-2 as the cause of the Coronavirus Disease 2019 (COVID-19) and has been granted as a pandemic. COVID-19 is an emerging threat due to the risk of microvascular, venous, and arterial thrombosis, thereby exacerbating organ injury and mortality. Although the exact mechanism of extensive thromboembolism and myocardial injury caused by SARS-CoV-2 is not illuminated, it is clear that COVID-19 related hypercoagulation increasing the fatality of the disease. Herein, we reported a patient with extensive biventricular thrombi along with the new-onset severe systolic dysfunction as an unusual catastrophic presentation of COVID-19. In our patient, there was both a right atrial "clot in transit" from his DVT as well as extensive muralized biventricular thrombus from severe global hypokinesis. We believe that the hypercoagulable state of his COVID-19 infection, along with severe systolic dysfunction, caused this unusual presentation. Although the hypercoagulable state of COVID-19 is well recognized, there have not been any reported cases of extensive de-novo intracardiac thrombus as of yet. We urge awareness of severe and potentially fatal extensive thrombosis and cardiac failure as the initial clinical presentation of possible SARS-CoV-2.
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The prevalence of primary liver cancer is rapidly rising all around the world. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. Unfortunately, the traditional treatment methods to cure HCC showed poor efficacy in patients who are not candidates for liver transplantation. Until recently, tyrosine kinase inhibitors (TKIs) were the front-line treatment for unresectable liver cancer. However, rapidly emerging new data has drastically changed the landscape of HCC treatment. The combination treatment of atezolizumab plus bevacizumab (immunotherapy plus anti-VEGF) was shown to provide superior outcomes and has become the new standard first-line treatment for unresectable or metastatic HCC. Currently, ongoing clinical trials with immune checkpoint blockade (ICB) have focused on assessing the benefit of antibodies against programmed cell death 1 (PD-1), programmed cell death-ligand 1 (PD-L1), and cytotoxic T-lymphocyte- associated antigen 4 (CTLA-4) as monotherapies or combination therapies in patients with HCC. In this review, we briefly discuss the mechanisms underlying various novel immune checkpoint blockade therapies and combination modalities along with recent/ongoing clinical trials which may generate innovative new treatment approaches with potential new FDA approvals for HCC treatment in the near future.
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Central nervous system (CNS) tuberculosis is a rare manifestation of all tuberculosis presentations. The incidence of brain tuberculoma is increasing in developed countries due to HIV infection and immigration from tuberculosis-endemic countries. Symptoms and radiologic findings of CNS tuberculosis can be non-specific and lead to misdiagnosis or mistreatment. Intracranial tuberculoma can present with a seizure, intracranial hypertension, or focal neurologic symptoms. In our case, the diagnosis was challenging between neurosarcoidosis and intracranial tuberculoma due to inconclusive results of stereotactic brain biopsy and clinical presentation. The pathology result of the open brain biopsy revealed non-caseating granuloma. Finally, we were able to diagnose intracranial tuberculoma following acid-fast bacilli culture results of open brain biopsy. This report highlights the importance of including intracranial tuberculoma in the differential diagnosis of cerebral space-occupying lesions, even in patients with negative laboratory findings of tuberculosis.
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Lactobacillus acidophilus is a rod-shaped, Gram-positive bacterium generally found in the normal flora of the oropharynx, gastrointestinal, and genitourinary tracts. It is commonly known as nonpathogen in the human body. Endocarditis due to Lactobacillus is rarely encountered and associated with impaired immunity. Splenic abscess is also an uncommon infection that classically results from endocarditis or another source of hematogenous seeding. Here, we present the case of bioprosthetic aortic valve endocarditis and associated splenic abscess caused by Lactobacillus acidophilus. The source of the Lactobacillus bacteremia should be investigated because of the risk of life-threatening conditions. Most of the time, identifying Lactobacillus species is challenging and can cause a delay in diagnosis and timely treatment. Especially in patients who have significant underlying clinical conditions, physicians should consider Lactobacillus species as a causative microorganism.
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Moyamoya disease (MMD) is a chronic cerebrovascular occlusive disease that is characterized by progressive bilateral stenosis of the terminal portion of the internal carotid artery and its main branches. Cerebrovascular events are the primary presenting symptoms and are related both to stenosis and occlusion of the ICAs and their main branches. Detection of bilateral stenosis by cerebral angiography is considered the gold standard, but computed tomography angiography (CTA) is also an acceptable method of diagnosis. In the current literature, there are no precise data on the incidence of moyamoya disease in Europe and the United States. Also, the pathogenesis of MMD remains obscure, and genetic factors and inflammation are the two most representative mechanisms. Here, we report the case of MMD in a 29-year-old African American female who presented with an ischemic stroke for the second time that manifested after pregnancy. This case is important to increase awareness of the probability of this rare disease in Western countries as well as to call attention to pregnancy's accelerating effects of MMD. Careful, long-term neurologic and radiologic follow-up is essential in adult patients with MMD to prevent additional stroke events and improve outcomes.
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Background: We studied the effect of race and ethnicity on disease characteristics and survival in gastrointestinal neuroendocrine tumors. Methods: The Surveillance, Epidemiology, and End Results database was used to select patients with non-pancreatic gastrointestinal neuroendocrine tumors diagnosed between 2004 and 2015. Trends in survival were evaluated among three groups: Hispanic, non-Hispanic White, and non-Hispanic Black. Kaplan-Meier and Cox regression methods were performed to calculate overall survival and cause-specific survival after adjusting for patient and tumor characteristics. Results: A total of 26,399 patients were included in the study: 65.1% were non-Hispanic White, 19.9% were non-Hispanic Black, and 15% were Hispanic. Non-Hispanic White patients were more likely to be male (50.0%, p < 0.001), older than 60 years (48.0%, p < 0.001), and present with metastatic disease (17.7%, p < 0.001). Non-Hispanic White patients had small intestine neuroendocrine tumors, while Hispanic and non-Hispanic Black patients had rectum neuroendocrine tumors as the most common primary site. Hispanic patients had better overall survival, while non-Hispanic Black patients had better cause-specific survival versus non-Hispanic White patients. This finding was confirmed on multivariable analysis where Hispanic patients had improved overall survival compared to non-Hispanic White patients (Hazard ratio (HR): 0.89 (0.81-0.97)), whereas non-Hispanic Black patients had better cause-specific survival compared to non-Hispanic White patients (HR: 0.89 (0.80-0.98)). Conclusions: Race/ethnicity is an independent prognostic factor in patients with gastrointestinal neuroendocrine tumors.
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BACKGROUND: We aimed to study the effect of socioeconomic differences and molecular characteristics on survival in patients with young-onset pancreatic neuroendocrine tumors (YOPNET) and typical-onset PNET (TOPNET). METHODS: We identified the patients with YOPNET (<50 years) and TOPNET (≥50 years) who underwent definitive surgery diagnosed between 2004 and 2016 using the National Cancer Database. We evaluated overall survival (OS) using the Kaplan-Meier and Cox regression methods before and after propensity score matching. A publicly available genomic dataset was used to compare mutation frequencies among the two groups. RESULTS: A total of 6259 patients with PNET were included, of which 27% were YOPNET. Patients with YOPNET were more likely to be Black, Hispanic, female, and have private insurance versus patients with TOPNET (all p < 0.001). Patients with YOPNET had a lower comorbidity score, but higher stage and tumor size (all p < 0.001). YOPNET was associated with a greater improved OS than TOPNET before and after propensity score matching (p < 0.001). On multivariable analysis, this survival difference persisted for YOPNET as an independent prognostic factor (unmatched p = 0.008; matched p = 0.01). For genomic analysis, patients with YOPNET had a lower rate of multiple endocrine neoplasia type-1 (MEN-1) mutation than patients with TOPNET (26% vs. 56%, p < 0.001). CONCLUSIONS: YOPNET represents a disease with distinct clinical features. Patients with YOPNET who underwent definitive surgery had better OS than patients with TOPNET despite having higher stage and tumor size. YOPNET also had lower rate of MEN-1 mutation.