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OBJECTIVE: Even though patients with sepsis and DIC have a higher mortality rate compared to those without DIC, screening for DIC is not currently part of sepsis management protocols. This may be due to a lack of literature on the frequency of DIC occurrence in sepsis patients, as well as the absence of evidence on the optimal DIC criteria to use for identifying DIC and predicting mortality among the five criteria available. To address this gap, this study investigates the predictive value of five different criteria for diagnosing DIC and its relationship to patient outcomes in our population of sepsis patients. METHODS: In the Medicine department of Aga Khan University Hospital, a retrospective observational study was conducted, enrolling all adult patients with International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) coding of sepsis and clinical suspicion of DIC between January 2018 and December 2020. To diagnose DIC, five different criteria were utilized, namely the International Society of Thrombosis and Hemostasis (ISTH), the Korean Society on Thrombosis and Hemostasis (KSTH), the Japanese Association for Acute Medicine (JAAM), the revised-JAAM (RJAAM), and the Japanese Ministry of Health and Welfare (JMHW). The study analyzed the sensitivity, specificity, negative predictive value, positive predictive value, and accuracy of these five criteria, as well as the overall prediction of mortality. RESULTS: Of 222 septic patients included in this study with clinical suspicion of DIC, 94.6% of patient had DIC according to KSTH criteria, followed by JAAM (69.4%), ISTH (64.0%), JMHW (53.2%) and lastly R-JAAM (48.6%). KSTH had sensitivity of 95.4% in diagnosing DIC and predicting mortality with a positive predictive value of 70% but specificity of 7.3% only. JAAM had sensitivity of 75.9%, positive predictive value of 75.9% with a specificity of 45.5%. ISTH had sensitivity of 69.4%, positive predictive value 75.3% and specificity of 48.5%. CONCLUSION: DIC can impose a significant burden on septic patients and its presence can lead to higher mortality rates. Early detection through screening for DIC in septic patients can potentially reduce mortality. However, it is necessary to identify the most appropriate diagnostic criteria for each population, as various criteria have demonstrated different performance in different populations. Establishing a gold standard for each population can aid in accurate diagnosis of DIC.
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Coagulação Intravascular Disseminada , Sepse , Trombose , Adulto , Humanos , Hemostasia , Valor Preditivo dos TestesRESUMO
Inflammatory conditions play part in the progression of malignancies, and markers signifying growth of these factors can indicate prognosis. Neutrophil-to-lymphocyte (NLR) is used as a marker of subclinical inflammation that may become an integral part of workup to indicate prognosis and associated pathology. This study aims to explore the association of NLR ratio with clinical characteristics, radiological assessment and staging, histopathology, and disease outcomes of breast cancer. A retrospective cohort study was conducted in a tertiary care center to include breast cancer patients that were diagnosed between January 2001 and December 2020. Data including tumor size, lymph nodes, metastasis, histological grading, ER/PR/HER2-neu status, molecular subtypes, clinical staging); nodal findings (sentinel and axillary); pathology from frozen section; and disease outcomes were assessed. Multivariable regression and Kaplan-Meier survival curves were employed to indicate the association of NLR with breast cancer features and disease-free survival. A total of 2050 patients had a median age of 50 years, median NLR levels of 2.14, most common pathology ductal followed by lobular, and most common site of metastasis being lungs followed by bones. Disease-free rate was 7.6%, and a recurrence rate of 1.8%, while 1.6% deaths were reported. NLR was found associated with age, treatment outcomes, tumor size, lymph nodes, metastasis and clinical staging. Other positive correlations were with Ki67 proliferation index, molecular subtypes, and tumor size on frozen section (at transverse and craniocaudal dimensions). Negative correlations were seen with estrogen and progesterone receptors. However, NLR was not found predictable of disease-free survival (P = .160). Significant predictors of disease-free survival were histological grading, ER, PR status, molecular subtype, and Ki67 proliferation index. NLR being a readily available marker has shown novel findings in its association with tumor staging, disease outcomes and characteristics of breast malignancy.
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Neoplasias da Mama , Humanos , Pessoa de Meia-Idade , Feminino , Neoplasias da Mama/patologia , Estudos Retrospectivos , Antígeno Ki-67 , Neutrófilos/patologia , Receptor ErbB-2 , Prognóstico , Estadiamento de Neoplasias , Linfócitos/patologia , Receptores de ProgesteronaRESUMO
The association between coronavirus disease 19 (COVID-19) and autoimmune disease has been mounting, and literature on COVID-19-induced flare-up of systemic lupus erythematosus (SLE) disease is lacking. We describe a case of lupus cerebritis triggered by COVID-19 in a young female with SLE, who presented with fluctuated mentation, psychomotor retardation, slow speech, and intermittent choreiform movement in the upper part of the body. She had a history of COVID-19 infection three weeks back. Her serum immunoglobulin G antibodies were positive against COVID-19. On examination, she had psychomotor agitation, intermittent choreiform movements of upper limbs, and poor speech. Brain magnetic resonance imaging revealed hyperintense signals in the white matter of both hemispheres, suggestive of lupus cerebritis secondary to COVID-19 infection and lack of any other identifiable risk factor. Management included methylprednisolone, prednisone, and olanzapine. The patient was also placed on monthly intravenous cyclophosphamide, and her condition started improving gradually.
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Pneumocystis pneumonia (PCP) is an opportunistic infection caused by Pneumocystis jirovecii. PCP due to immunosuppressive drugs is rarely reported in the literature. Herein we present a case of PCP in a 49-year-old patient who presented with progressive shortness of breath, dry cough, and low-grade fever. History revealed that he was taking prednisolone daily for his hyperactive airway disease. His temperature was 99oF, and he had bilateral crackles in the lungs with resonant wheezing. High-resolution computed tomography showed diffuse ground-glass haze and cystic lesions in the middle and upper zones of both lungs. He was commenced on intravenous ceftriaxone and methylprednisolone based on provisional diagnosis of interstitial pneumonia. However, his condition worsened. His human immunodeficiency virus (HIV) test was reactive, and his CD4+ count was 275 cells/mm3. Bronchoalveolar lavage revealed PCP by direct immunofluorescent assay. Additional serum testing revealed marked elevation of beta-D-glucan, consistent with PCP diagnosis due to glucocorticoid use. Trimethoprim-sulfamethoxazole and voriconazole were initiated, and his respiratory symptoms started improving. His respiratory condition improved on day 9, and he was discharged with follow-up.
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Sydenham chorea (SC) is common in childhood with extensive differential diagnoses, including inherited disease, autoimmunity, endocrine disorders, and infections. SC due to acute rheumatic fever (ARF) is rare. Herein, we present a case of SC in an eight-year-old child who presented with choreiform movements of her face and limbs, including facial grimacing, difficulty walking, and slurred speech. She also had a runny nose and odynophagia. She had two episodes of sore throat in the last two months, and her physical examination was unremarkable except for hypertrophic tonsils and generalized hypotonia. Throat and blood culture were negative for group A streptococcus. Antistreptolysin O titer was 1139 IU/mL, and anti-deoxyribonuclease B titer was 2100 IU/mL, suggesting a recent group A streptococcal infection. Magnetic resonance imaging (MRI) of the brain revealed hyperintense signals in the thalami and corpus striatum. Echocardiogram was normal with no evidence of carditis. She was diagnosed with ARF and was commenced on amoxicillin and valproic acid. Later on, she was started on IVIG due to the persistence of chorea. Her symptoms improved, and she was discharged a week later on oral haloperidol for the next ten days.
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Daratumumab (dara) belongs to a class of monoclonal antibodies that target CD38 receptors expressed on multiple myeloma (MM) cells. It was first approved for MM treatment in 2015. The efficacy and safety of dara have been reported in many studies. In this analysis, we assessed the outcome of dara addition to standard of care for transplant-eligible newly diagnosed (ND) MM. We conducted a comprehensive search using PubMed, ClinicalTrial.gov, and Embase. Out of 435 articles, we included two randomized clinical trials. We computed the odds ratio (OR) of response rates and risk ratio (RR) of adverse effects using Cochrane RevMan version 5.4. A total of 1,292 patients were enrolled in both trials. The patients were randomized into the control group and the dara group. The dara group included 647 patients and the control group included 645 patients. The CASSIOPEIA trial reported the outcomes using dara, bortezomib (V), thalidomide (T), and dexamethasone (d) versus VTd. The GRIFFIN trial underlined the efficacy of dara, lenalidomide (R), and Vd in the dara group versus RVd in the control group. A pooled analysis of included studies showed an increased overall response rate (OR: 1.60; 95% CI: 1.06-2.41; p = 0.02; I 2 = 65%), stringent complete response (OR: 1.59; 95% CI: 1.24-2.05; p = 0.03; I 2 = 0%), and negative status for minimal residual disease (OR: 2.47; 95% CI: 1.97-3.10; p < 0.01; I 2 = 66%) in the dara group as compared to the control group. However, an increased risk of neutropenia (RR: 1.80; 95% CI: 1.60-2.03; p < 0.01) and decreased risk of peripheral neuropathy (RR: 0.92; 95% CI: 0.86-0.99; p = 0.02; I 2 = 52%) were observed in the dara group. Dara addition to the standard of care regimen for transplant-eligible NDMM has promising outcomes with increased efficacy and safety profile and manageable toxicity.
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Patients with systemic lupus erythematosus (SLE) experience neuropsychiatric symptoms. The term neuropsychiatric SLE (NPSLE) is a generic term that refers to a series of neurological and psychiatric symptoms directly related to SLE. In approximately 30% of patients with neuropsychiatric symptoms, SLE is the primary cause (NPSLE), and symptoms manifest more frequently around SLE onset. Neurovascular and psychotic conditions can also lead to NPSLE. Pathogenesis of NPSLE is implicated in both neuroinflammatory and ischemic mechanisms, and it is associated with high morbidity and mortality. After diagnosing and assigning causality, NPSLE treatment is individualized according to the type of neuropsychiatric manifestations, type of the predominant pathway, activity of SLE, and severity of the clinical manifestations. There are many problems to be addressed with regards to the diagnosis and management of NPSLE. Controlled clinical trials provide limited guidance for management, and observational cohort studies support symptomatic, antithrombotic, and immunosuppressive agents. The purpose of this review was to provide a detailed and critical review of the literature on the pathophysiology, diagnosis, and treatment of NPSLE. This study aimed to identify the shortcoming in diagnostic biomarkers, novel therapies against NPSLE, and additional research needs.