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DNA Tumoral Circulante , Neoplasias Colorretais , Células Neoplásicas Circulantes , Humanos , DNA Tumoral Circulante/genética , Recidiva Local de Neoplasia , Neoplasias Colorretais/genética , Neoplasias Colorretais/terapia , Neoplasias Colorretais/patologia , Células Neoplásicas Circulantes/patologia , Doença Crônica , Biomarcadores Tumorais/genéticaRESUMO
BACKGROUND: Colorectal cancers are slowly developing cancers of which more than 95% are adenocarcinomas, beginning in the mucus-producing glands lining the colon and rectum. In Pakistan, colorectal carcinoma is ranked as the seventh most common malignancy in men and the ninth most common in women with a male to female ratio of 9 to 1. This study aimed at investigating Neutrophil to Lymphocyte Ratio (NLR) as a potential marker for predicting severity of disease in terms of tumour histological grade in patients with pre-operative colorectal adenocarcinoma. METHODS: Retrospective cross-sectional study design was adopted and this study was conducted at the Department of Pathology, Pakistan Institute of Medical Sciences Islamabad. Sixty patients of all age-groups and both genders, diagnosed as colorectal adenocarcinoma on histopathological examination of resected specimens, were selected by consecutive non-probability sampling. Separately, 60 healthy subjects, age and sex-matched, were selected as control. RESULTS: Results revealed that the most common age group was 41-60 years showing 29 cases (48%) followed by the age group 61-80 years with 17 cases (28%). The most common site was the rectum having 24 cases (40%) followed by the right hemicolon with 13 cases (21.7%). The mean of neutrophil to lymphocyte ratio rose in direct proportion to the grade of colorectal carcinoma, showing a mean value of 4.5 in well differentiated low grade carcinoma, 5.0 in moderately differentiated and 6.0 in high grade poorly differentiated carcinoma. All patients had higher total leukocyte count, higher absolute neutrophil count, higher total neutrophil percentage and higher NLR as compared to their normal healthy counterparts. CONCLUSIONS: It is concluded that the NLR is directly proportional to tumour grade so it can be used preoperatively to assess whether the tumour is advanced so that it can be dealt with accordingly. This ratio can also be used as an independent screening marker for colorectal carcinoma since it shows very low levels in normal colonic epithelium.
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Adenocarcinoma , Neoplasias Colorretais , Humanos , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Neutrófilos/patologia , Estudos Retrospectivos , Estudos Transversais , Linfócitos/patologia , Neoplasias Colorretais/diagnóstico , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Biomarcadores , Contagem de Linfócitos , PrognósticoRESUMO
There is increasing evidence regarding the role of various maintenance therapy (MT) strategies after initial induction to treat newly diagnosed transplant-ineligible patients with MM. We reviewed the literature on available regimens for patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM). Lenalidomide (R)-based regimens are still the front-line therapy, but there is an increasing use of bortezomib-based regimens. The MT regimen is mainly based on the initial induction regimen. MT has shown survival benefits compared with patients without maintenance therapy. The most common adverse effects of MT include anemia, neutropenia, thrombocytopenia, infections, and peripheral neuropathy. In conclusion, induction followed by maintenance based on lenalidomide, bortezomib, ixazomib, or daratumumab-based regimens has shown promising results. Therefore, it is essential to conduct more clinical trials to better understand the role of MT in the treatment of NDMM patients who are not candidates for autologous stem cell transplantation.
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Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bortezomib , Dexametasona , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Lenalidomida/uso terapêutico , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/tratamento farmacológico , Transplante AutólogoRESUMO
Background and objectives: In recent years, immune-checkpoint inhibitors (ICIs) particularly atezolizumab is on the rise in treating advanced malignancies. With its increased clinical use, various electrolyte abnormalities have been reported in the literature. In this review, we have addressed the question of significant electrolyte abnormalities associated with atezolizumab. Materials and methods: Following PRISMA guidelines, we performed a thorough literature search in four databases including PubMed, Cochrane Library, Embase, and Clinicaltrials.gov. We included only randomized controlled trials from 2010 till March 2021. After a comprehensive screening of 1587 articles, we selected 14 articles for our review and tabulated the results. Following MeSH terms were used: "electrolyte abnormalities", "immune checkpoint inhibitors", "atezolizumab". Results: Non-small cell lung cancer (n = 1270) and metastatic urothelial carcinoma (n = 1164) were the most common malignancies among 3160 patients. The most common electrolyte abnormality was hypomagnesemia (4.7%). Hyponatremia, hypophosphatemia, hypercalcemia and hypokalemia were found in 2.3%, 0.63%, 0.25% and 0.06% patients respectively. For patients taking atezolizumab, hypomagnesemia was most frequently found in non-small cell lung carcinoma patients (9.4%), while urothelial metastatic carcinoma patients most commonly had hyponatremia (5.15%). Hypokalemia though insignificant was observed only in patients with metastatic renal cell carcinoma (2.85%). Conclusion: Since the use of atezolizumab is on the rise for the treatment of various cancers, more studies need to be conducted to better understand its safety and toxicity profile.
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Cadmium sulphide (CdS) nanoparticles (NPs) were synthesized through hydrothermal route and characterized by UV-Vis spectroscopy, X-ray diffraction (XRD), Energy dispersive X-ray analysis, Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy and Thermo gravimetric analysis (TGA).The band gap of CdS nanoparticles was found to be 2.38 eV. CdS NPs are crystalline aggregates with hexagonal structure as shown by SEM and XRD analysis. TGA study revealed that the synthesized nanomaterials were very stable to temperature and only 6.54% total loss occurred during heating range (25 °C-600 °C).The CdS NPs were used for the first time against the degradation of Eosin B (EB) and Methyl green (MG) dyes in aqueous solution.The degradation of EB and MG over CdS nanocatalysts followed second order kinetics. The predicted activation energies for both the dyes' reactions were 61.1 kJ/mol and 32.11 kJ/mol, respectively. About 95% and 90% dye degradation was observed at the time interval of 160 minutes for EB and MG, respectively. High percent degradation of EB was observed at high pH (pH 0) while at low pH (pH 4) high percent degradation was found for MG dye. Maximum dye degradation was found at the optimal dose (0.03 g/L) of the catalyst and at low dye concentration. The rate of EB and MG dye degradation was found to increase with increase in temperature up to 45 °C. The recyclability study showed that CdS nanoparticles could be reused for the degradation of the given dyes. Good antibacterial activity against Staphylococcus aureus was shown by CdS NPs. From the biocompatibility it was confirmed that CdS NPS are bioincompatible compatible.
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Corantes , Verde de Metila , Compostos de Cádmio , Catálise , Corantes/química , Azul de Eosina I , Cinética , Sulfetos , Termodinâmica , Difração de Raios XRESUMO
INTRODUCTION: Oncolytic viruses are genetically engineered viruses that target myeloma-affected cells by detecting specific cell surface receptors (CD46, CD138), causing cell death by activating the signaling pathway to induce apoptosis or by immune-mediated cellular destruction. AREAS COVERED: This article summarizes oncolytic virotherapy advancements such as the therapeutic use of viruses by targeting cell surface proteins of myeloma cells as well as the carriers to deliver viruses to the target tissues safely. The major classes of viruses that have been studied for this include measles, myxoma, adenovirus, reovirus, vaccinia, vesicular-stomatitis virus, coxsackie, and others. The measles virus acts as oncolytic viral therapy by binding to the CD46 receptors on the myeloma cells to utilize its surface H protein. These H-protein and CD46 interactions lead to cellular syncytia formation resulting in cellular apoptosis. Vesicular-stomatitis virus acts by downregulation of anti-apoptotic factors (Mcl-2, BCL-2). Based upon the published literature searches till December 2020, we have summarized the data supporting the advances in viral oncolytic for the treatment of MM. EXPERT OPINION: Oncolytic virotherapy is an experimental approach in multiple myeloma (MM); many issues need to be addressed for safe viral delivery to the target tissue.
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Mieloma Múltiplo , Terapia Viral Oncolítica , Vírus Oncolíticos , Humanos , Mieloma Múltiplo/terapia , Terapia Viral Oncolítica/métodos , Vírus Oncolíticos/genéticaRESUMO
Dural venous sinus thrombosis (DVST) leading to subarachnoid hemorrhage (SAH) is rarely reported in the literature. A 25-year-old primigravida with a history of pre-eclampsia presented with sudden onset headache, confusion, and loss of consciousness. Examination revealed bilateral equivocal planters and bilateral papillary edema. MRI and magnetic resonance venography (MRV) showed the right sinus thrombosis with elements of SAH. The coagulation profile was unremarkable. She was commenced on low molecular weight heparin with periodic monitoring of her Glasgow Coma Scale (GCS). Her condition started improving gradually. Repeat MRI and MRV after 10 days showed resolution of thrombosis and SAH. She was discharged with follow-up, and she was doing well on her recent visit two weeks later.
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Testes de Coagulação Sanguínea , Teste para COVID-19/métodos , COVID-19/sangue , Testes Hematológicos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alanina Transaminase/sangue , Biomarcadores , Contagem de Células Sanguíneas , COVID-19/diagnóstico , COVID-19/epidemiologia , Teste de Ácido Nucleico para COVID-19 , Teste para COVID-19/economia , Estudos Transversais , Países em Desenvolvimento , Diagnóstico Precoce , Índices de Eritrócitos , Humanos , Linfopenia/sangue , Linfopenia/etiologia , Masculino , Pessoa de Meia-Idade , Paquistão/epidemiologia , Estudos Prospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , SARS-CoV-2 , Centros de Atenção Terciária , Adulto JovemRESUMO
Management of rare hematological disorders pose unique diagnostic and therapeutic challenges due to unusual occurrence and limited treatment options. We retrospectively identified 45 patients receiving matched related donor transplant for rare hematological disorders from 2006 to 2019. Patients were divided into two groups (1) malignant and (2) non malignant. The malignant disorder group included four patients while the nonmalignant group included 41 patients divided into immune dysregulation (n = 23), bone marrow failure (n = 10), metabolic (n = 5), and bleeding diathesis (n = 3). Twenty-six (57.8%) patients received myeloablative conditioning (MAC) and 16 (35.6%) received reduced intensity conditioning (RIC), while 3 (6.6%) patients with severe combined immunodeficiency received stem cell infusion alone without conditioning. The cumulative incidence (CI) of grade II-IV acute GVHD (aGVHD) was 39.1% (n = 18) and chronic GVHD (cGVHD) 15.2% (n = 7). There was no primary graft failure while CI of secondary graft failure was 9%. Overall survival (OS) and disease-free survival (DFS) was 82.2% and 77.8% respectively. Group wise OS was 75% in the malignant group, 82.6% in the immune dysregulation group, 80% in patients with metabolic disorders and bone marrow failure, while 100% in patients with bleeding diathesis. This retrospective analysis shows that hematopoietic stem cell transplant can be a feasible treatment option for rare hematological disorders.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Paquistão , Estudos Retrospectivos , Condicionamento Pré-TransplanteRESUMO
INTRODUCTION: The impact of direct-acting antiviral agents (DAAs) on the development of hepatocellular carcinoma (HCC) is controversial and a part of the scientific community believes it as a biased interpretation of data. Many studies have reported an aggressive pattern of HCC after DAA use. In this study, we attempted to assess the changes in the pattern of HCC after treatment with DAAs or PI (PEG, pegylated-interferon). METHODS: A total of 37 HCC patients after DAA treatment and 21 HCC patients after PI treatment were included. The diagnosis of HCC was made and information about demographics, HCC infiltrative pattern, portal vein thrombosis (PVT), time at initial presentation, Child-Turcotte-Pugh (CTP) score, and Barcelona Clinic Liver Cancer (BCLC) stage were compared in the two groups. RESULTS: The total number of male patients in the DAA group was 62% while either gender was almost equal in PI. The age group of 40-60 was more prevalent in the DAA group while the PI group comprised more patients who were above 60 years. Patients in the DAA group presented after 3.35 years on average while patients in the PI group presented after about seven years. Most of the patients presented with the CTP stage of A. That is true for both groups. For BCLC staging, most of the patients had stage C, which means multiple lesions. At the initial presentation, most of the patients presented with multifocal lesions. CONCLUSION: Our study found no significant difference in the initial presentation between both groups. However, HCC patients with prior DAA therapy presented early than those with PI therapy.
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Bertolotti's syndrome is a congenital condition characterized by the sacralization of the lower lumbar vertebrae or the lumbarization of the sacral vertebrae. The cause of pain in Bertolotti's syndrome is multifactorial. This lumbosacral transitional vertebra has a prevalence of 4% to 30%. Rarely, it is considered in the differential diagnosis of low back pain in young people. Therefore, every aspect of Bertolotti's syndrome needs to be meticulously addressed, and it should be included in the differential diagnosis of chronic back pain. Herein, we present a case of Bertolotti's syndrome presented with chronic lower back pain, confirmed on X-ray and magnetic resonance imaging (MRI). He was managed with analgesics and steroids injection with regular follow-up.
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Children with coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), usually present with symptoms of mild upper respiratory tract infection without developing any significant complications. However, this observation has been rendered incautious by hundreds of clinical cases from around the world that have depicted a less benign multisystem inflammatory illness mimicking Kawasaki disease in COVID-positive pediatric patients. Our study aimed at retrospectively reviewing the different features of Kawasaki disease-like illness in children suffering from COVID-19, including the complications, laboratory investigations, treatment strategies used during their hospital stay, and outcomes. We searched the electronic database of the two pediatric units of Mayo Hospital, Lahore, Pakistan, for children who had been admitted to the ward between April 2020 and July 2020 and were diagnosed with COVID-19. A total of 10 such pediatric cases were found, whose clinical details were then reviewed and the obtained data were presented in the form of tables and percentages. The median age was between 4 months to 11 years (mean: 6 years). Of the 10 patients, 8 (80%) were boys. Criteria for Kawasaki disease were met in all of them (100%), with a complete presentation in five (50%). Fever (100%), conjunctival and oral cavity changes (90%), and rash (80%) were the most common features. Seven (70%) patients required admission to a critical care unit, but no mortality occurred. This article can assist in understanding and dealing with Kawasaki disease-like manifestation of pediatric COVID-19 infection, especially in critical care settings, and its possible complications. It will help in a timely and appropriate decision-making regarding treatment and management of such cases.