5-EPIFAT trial protocol: a multi-center, randomized, placebo-controlled trial of the efficacy of pharmacotherapy for fatigue using methylphenidate, bupropion, ginseng, and amantadine in advanced cancer patients on active treatment.

BACKGROUND: Cancer-related fatigue (CRF) is still undertreated in most patients, as evidence for pharmacological treatments is limited and conflicting. Also, the efficacy of the pharmacological agents relative to each other is still unclear. Therefore, medications that may potentially contribute to improving CRF will be investigated in this head-to-head trial. Our main objective is to compare the efficacy of methylphenidate vs. bupropion vs. ginseng vs. amantadine vs. placebo in patients with advanced cancer. METHODS: The 5-EPIFAT study is a 5-arm, randomized, multi-blind, placebo-controlled, multicenter trial that will use a parallel-group design with an equal allocation ratio comparing the efficacy and safety of four medications (Methylphenidate vs. Bupropion vs. Ginseng vs. Amantadine) versus placebo for management of CRF. We will recruit 255 adult patients with advanced cancer who experience fatigue intensity ≥ 4 based on a 0-10 scale. The study period includes a 4-week intervention and a 4-week follow-up with repeated measurements over time. The primary outcome is the cancer-related fatigue level over time, which will be measured by the functional assessment of chronic illness therapy-fatigue (FACIT-F) scale. To evaluate safety, the secondary outcome is the symptomatic adverse events, which will be assessed using the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events in cancer clinical trials (PRO-CTCAE). Also, a subgroup analysis based on a decision tree-based machine learning algorithm will be employed for the clinical prediction of different agents in homogeneous subgroups. DISCUSSION: The findings of the 5-EPIFAT trial could be helpful to guide clinical decision-making, personalization treatment approach, design of future trials, as well as the development of CRF management guidelines. TRIAL REGISTRATION: IRCT.ir IRCT20150302021307N6. Registered on 13 May 2023.

A multicentric and nationwide predictive study role of T cell sub-population in the prevalence and prognosis of cryoglobulinemia among genotype 4 chronic hepatitis C patients.

The infection caused by the hepatitis C virus (HCV) is a significant global health concern. The prevailing genotype of HCV in Egypt is 4a, commonly referred to as GT-4a. A significant proportion exceeding 50% of patients infected with HCV experience extrahepatic manifestations (EHMs), encompassing a diverse range of clinical presentations. These manifestations, including essential mixed cryoglobulinemia (MC), can serve as initial and solitary indicators of the disease. The complete understanding of the pathogenesis of EHM remains unclear, with autoimmune phenomena being recognized as the primary causative factor. In this study, we examined the predictive significance of T-cell subpopulations in relation to the occurrence and prognosis of cryoglobulinemia in HCV patients. A total of 450 CHC genotype four treatment naïve patients were enrolled in this analytic cross-sectional study after thorough clinical, laboratory, and radiological examinations. All patients underwent laboratory investigations, including testing for cryoglobulin antibodies and measurements of CD4 and CD8 levels; two groups were described according to their test results: Group 1 consists of patients who have tested positive for cryoglobulin antibodies and Group 2 consists of patients who have tested negative for cryoglobulin antibodies. The exclusion criteria encompassed individuals with HIV infection or chronic HBV infection. Additionally, pelvi-abdominal ultrasonography was performed. Our study included 450 treatment naïve CHC patients (59% male, mean age 50.8 years). The patients were categorized according to their cryoglobulin antibodys test results into two groups: group A, CHC patients with cryoglobulin antibodies (Abs) negative (364 patients), and group B, CHC patients with cryoglobulin Ab positive (86 patients). Group B demonstrated a higher average age, elevated international normalized ratio, more prolonged duration of HCV infection, lower albumin, higher alanine aminotransferase, higher aspartate aminotransferase, higher bilirubin, lower CD8, lower CD4, and lower CD4:CD8 ratio. In contrast, 27 out of 86 (31.40%) patients in group B had symptoms; 85.8% had purpura and arthralgia, 74.3% had paresthesias, 86.7% had weakness, and 12.2% had non-Hodgkin's lymphoma. The levels of CD4 and CD8 were found to be decreased in chronic HCV patients with MC. T-cell subpopulation serves as a reliable indicator for assessing the prevalence and prognosis of MC in individuals with genotype 4 chronic hepatitis C. However, additional research is needed to further understand the development and spread of various emerging infectious diseases. Nevertheless, it is noteworthy that a critical threshold may exist beyond which EHM reaches a point of no return.

Pernicious Anemia Following COVID-19 Vaccination: A Report of Two Cases.

Since December 2019 and the global epidemic of COVID-19 different countries have focused on vaccines, and one of the inactivated produced vaccines was the Sinopharm COVID-19 vaccine. Some side effects of this vaccine were reported previously, including pain at the vaccination site, fatigue, lethargy, headache, and tenderness, which were more prevalent among individuals <49 years old. Herein, we reported two patients aged 45 and 51 years old. Both patients have different signs and symptoms after receiving the second dose of the vaccine. None had a history of chronic disease. On examination and following labs and other diagnostic investigations, we found megaloblastic anemia due to atrophic gastritis and low intrinsic factor. These cases showed an autoimmune side effect of the Sinopharm COVID-19 vaccine that was previously reported with an exact mechanism but other features called Covid Arm, Guillain-Barré syndrome, and thrombocytopenia. The mechanism of this reaction is unclear yet.

Hypokalemia as a responsible factor related with the severity of hepatic encephalopathy: a wide multination cross-sectional study.

Several precipitating factors of hepatic encephalopathy have been recognized and studied. Hepatic encephalopathy which is a frequent and grave complication of liver failure, is associated with multiple biochemical changes like high serum ammonia, mercaptan and phenol levels, low albumin levels and derangements in electrolytes. It is characterized by a range of neuronal and psychological aberrations mainly due to the inability of liver to metabolize different neurotoxic chemicals produced in the body. Hypokalemia is one of the most important findings in hepatic encephalopathy and postulated as a precipitating factor of the condition. The authors aimed to know the frequency of hypokalemia and its relation to the severity of hepatic encephalopathy. Methods: After taking approval from the hospital ethical review committee, a total of 5000 patients with hepatic encephalopathy were recruited by consecutive sampling. They were interviewed, examined and investigated for serum potassium levels and other precipitating factors of hepatic encephalopathy. Results: Total of 5000 patients including 3070 (61.4%) males and 1930 (38.6%) females, aging 13 years and above were studied. The frequency of hypokalemia was 78% (3900 patients). Relating the serum potassium level with the severity of hepatic encephalopathy, 1200 (60%) out of 2000 patients with serum potassium below 2.5 mEq/l were in grade 4 (40%) and 800 out of 2000 were in grade 3 encephalopathy. On the other hand, only 700 patients (6.4%) out 1100 with serum potassium above 3.4 mEq/l were in grade 4 encephalopathy. Conclusion: Hypokalemia is a frequent finding in patients with hepatic encephalopathy and found to be directly related to its severity.

Role of magnetic resonance imaging in assessment of acetabular and femoral version in developmental dysplasia of the hip.

Objective: To evaluate the role of magnetic resonance imaging (MRI) in the assessment of femoral and acetabular version in developmental dysplasia of the hip (DDH). Materials and Methods: This was a cross-sectional study of 20 consecutive patients with DDH (27 dysplastic hips) who were examined with MRI. In dysplastic and normal hips (DDH and comparison groups, respectively), we evaluated the following parameters: osseous acetabular anteversion (OAA); cartilaginous acetabular anteversion (CAA); femoral anteversion; osseous Mckibbin index (OMI); cartilaginous Mckibbin index (CMI); and the thickness of the anterior and posterior acetabular cartilage. Results: The OAA was significantly greater in the dysplastic hips. The CAA, femoral anteversion, OMI, and CMI did not differ significantly between the normal and dysplastic hips. In the DDH and comparison groups, the OAA was significantly lower than the CAA, the OMI was significantly lower than the CMI, and the posterior acetabular cartilage was significantly thicker than the anterior cartilage. Conclusion: Our findings confirm that MRI is a valuable tool for the assessment of femoral and acetabular version in DDH. Preoperative MRI evaluation has great potential to improve the planning of pelvic and femoral osteotomies.

Objetivo: Avaliar o papel da ressonância magnética (RM) na avaliação da versão femoral e acetabular na displasia do desenvolvimento do quadril (DDQ). Materiais e Métodos: Estudo transversal de 20 pacientes consecutivos com DDQ (27 quadris displásicos) que foram examinados com RM. Nos quadris displásicos e normais (grupos DDQ e comparação, respectivamente), avaliamos os seguintes parâmetros: anteversão acetabular óssea (AAO), anteversão acetabular cartilaginosa (AAC), anteversão femoral, índice de Mckibbin ósseo (IMO), índice de Mckibbin cartilaginoso (IMC) e espessura da cartilagem acetabular anterior e posterior. Resultados: A AAO foi significativamente maior nos quadris displásicos. A AAC, anteversão femoral, IMO e IMC não diferiram significativamente entre os quadris normais e displásicos. Nos grupos DDQ e comparação, a AAO foi significativamente menor que a AAC, o IMO foi significativamente menor que o IMC, e a cartilagem acetabular posterior foi significativamente mais espessa que a anterior. Conclusão: Nossos achados confirmam que a RM é uma ferramenta valiosa para a avaliação da versão femoral e acetabular na DDQ. A avaliação pré-operatória por RM tem grande potencial para melhorar o planejamento das osteotomias pélvicas e femorais.

Role of magnetic resonance imaging in assessment of acetabular and femoral version in developmental dysplasia of the hip / Papel da ressonância magnética na avaliação da versão acetabular e femoral na displasia do desenvolvimento do quadril

Abstract Objective: To evaluate the role of magnetic resonance imaging (MRI) in the assessment of femoral and acetabular version in developmental dysplasia of the hip (DDH). Materials and Methods: This was a cross-sectional study of 20 consecutive patients with DDH (27 dysplastic hips) who were examined with MRI. In dysplastic and normal hips (DDH and comparison groups, respectively), we evaluated the following parameters: osseous acetabular anteversion (OAA); cartilaginous acetabular anteversion (CAA); femoral anteversion; osseous Mckibbin index (OMI); cartilaginous Mckibbin index (CMI); and the thickness of the anterior and posterior acetabular cartilage. Results: The OAA was significantly greater in the dysplastic hips. The CAA, femoral anteversion, OMI, and CMI did not differ significantly between the normal and dysplastic hips. In the DDH and comparison groups, the OAA was significantly lower than the CAA, the OMI was significantly lower than the CMI, and the posterior acetabular cartilage was significantly thicker than the anterior cartilage. Conclusion: Our findings confirm that MRI is a valuable tool for the assessment of femoral and acetabular version in DDH. Preoperative MRI evaluation has great potential to improve the planning of pelvic and femoral osteotomies.

Resumo Objetivo: Avaliar o papel da ressonância magnética (RM) na avaliação da versão femoral e acetabular na displasia do desenvolvimento do quadril (DDQ). Materiais e Métodos: Estudo transversal de 20 pacientes consecutivos com DDQ (27 quadris displásicos) que foram examinados com RM. Nos quadris displásicos e normais (grupos DDQ e comparação, respectivamente), avaliamos os seguintes parâmetros: anteversão acetabular óssea (AAO), anteversão acetabular cartilaginosa (AAC), anteversão femoral, índice de Mckibbin ósseo (IMO), índice de Mckibbin cartilaginoso (IMC) e espessura da cartilagem acetabular anterior e posterior. Resultados: A AAO foi significativamente maior nos quadris displásicos. A AAC, anteversão femoral, IMO e IMC não diferiram significativamente entre os quadris normais e displásicos. Nos grupos DDQ e comparação, a AAO foi significativamente menor que a AAC, o IMO foi significativamente menor que o IMC, e a cartilagem acetabular posterior foi significativamente mais espessa que a anterior. Conclusão: Nossos achados confirmam que a RM é uma ferramenta valiosa para a avaliação da versão femoral e acetabular na DDQ. A avaliação pré-operatória por RM tem grande potencial para melhorar o planejamento das osteotomias pélvicas e femorais.

THE PREVALENCE OF CELIAC DISEASE IN PATIENTS WITH IRON-DEFICIENCY ANEMIA IN CENTER AND SOUTH AREA OF IRAN

Background - Celiac disease is an immune-mediated enteropathy due to a permanent sensitivity to gluten in genetically susceptible people. Iron-deficiency anemia is the most widely experienced anemia in humans. Iron-deficiency anemia additionally is a common extra intestinal manifestation of celiac disease. Objective - To investigate correlation between tTg levels and histological alterations and then to determine the prevalence of celiac disease in Center and South area patients of Iran with iron deficiency anemia. Methods - A total of 402 patients aged 12-78 years who presented with iron-deficiency anemia were included in this study. Hemoglobin, mean corpuscular volume and serum ferritin were determined. Venous blood samples for anti-tissue transglutaminase antibody immunoglobuline A and G were obtained from these patients. Upper gastrointestinal endoscopy was recommended to patients who had positive serology. Results - Of 402 patients with iron-deficiency anemia, 42 (10.4%) had positive serology for celiac disease. The small intestine biopsy of all patients with positive serology showed pathological changes (Marsh I, II & III). There was not significant difference in the mean hemoglobin level between iron-deficiency anemia patients with celiac disease and without celiac disease, duodenal biopsy results did not show significant relationship between the severity of pathological changes and levels of anti-tTG IgG (P -value: 0/869) but significant relationship was discovered between pathological changes and levels of anti-tTG IgA (P -value: 0/004). Conclusion - Screening of celiac disease by anti-tissue transglutaminase antibody should be completed as a routine investigation in patients with iron-deficiency anemia. Also physicians must consider celiac disease as a possible reason of anemia in all patients with iron deficiency anemia.

Contexto - A doença celíaca é uma enteropatia imunomediada, devido a uma sensibilidade permanente ao glúten em pessoas geneticamente suscetíveis. A anemia por deficiência de ferro é a anemia mais frequente em seres humanos e, além disso, é uma manifestação extra intestinal comum da doença celíaca. Objetivo - Investigar a correlação entre níveis de imunoglobulina de anticorpos anti-transglutaminase tissular A (anti-tTG IgA) e G (IgG anti-tTG) e alterações histológicas e, em seguida, determinar a prevalência de doença celíaca no Centro e Sul do Irã em pacientes com anemia por deficiência de ferro. Métodos - Foram incluídos neste estudo um total de 402 pacientes com idades entre 12-78 anos, que apresentavam anemia por deficiência de ferro. Hemoglobina, volume corpuscular médio e ferritina sérica foram determinados. Amostras de sangue venoso para imunoglobulina de anti-tTG IgA e IgG anti-tTG foram obtidas nestes pacientes. Endoscopia gastrointestinal foi recomendada para pacientes que tiveram sorologia positiva. Resultados - Dos 402 pacientes com anemia por deficiência de ferro, 42 (10,4%) tiveram sorologia positiva para doença celíaca. A biópsia do intestino delgado de todos os pacientes com sorologia positiva mostrou alterações patológicas (Marsh I, II e III). Não houve diferença significativa no nível de hemoglobina média entre os pacientes com deficiência de ferro com ou sem a doença celíaca. O resultado da biopsia duodenal não mostrou relação significativa entre a gravidade das alterações patológicas e níveis de IgG anti-tTG (P -valor: 0/869), mas descobriu-se relação significativa entre as alterações patológicas e níveis de anti-tTG IgA (P -valor: 0/004). Conclusão - A pesquisa de doença celíaca por dosagem de anticorpo anti-transglutaminase tissular deve ser completada como investigação de rotina em pacientes com anemia por deficiência de ferro. Os clínicos devem considerar a doença celíaca como um possível causa de anemia em todos os pacientes com anemia ferropriva.

THE PREVALENCE OF CELIAC DISEASE IN PATIENTS WITH IRON-DEFICIENCY ANEMIA IN CENTER AND SOUTH AREA OF IRAN.

BACKGROUND: Celiac disease is an immune-mediated enteropathy due to a permanent sensitivity to gluten in genetically susceptible people. Iron-deficiency anemia is the most widely experienced anemia in humans. Iron-deficiency anemia additionally is a common extra intestinal manifestation of celiac disease. OBJECTIVE: To investigate correlation between tTg levels and histological alterations and then to determine the prevalence of celiac disease in Center and South area patients of Iran with iron deficiency anemia. METHODS: A total of 402 patients aged 12-78 years who presented with iron-deficiency anemia were included in this study. Hemoglobin, mean corpuscular volume and serum ferritin were determined. Venous blood samples for anti-tissue transglutaminase antibody immunoglobuline A and G were obtained from these patients. Upper gastrointestinal endoscopy was recommended to patients who had positive serology. RESULTS: Of 402 patients with iron-deficiency anemia, 42 (10.4%) had positive serology for celiac disease. The small intestine biopsy of all patients with positive serology showed pathological changes (Marsh I, II & III). There was not significant difference in the mean hemoglobin level between iron-deficiency anemia patients with celiac disease and without celiac disease, duodenal biopsy results did not show significant relationship between the severity of pathological changes and levels of anti-tTG IgG (P -value: 0/869) but significant relationship was discovered between pathological changes and levels of anti-tTG IgA (P -value: 0/004). CONCLUSION: Screening of celiac disease by anti-tissue transglutaminase antibody should be completed as a routine investigation in patients with iron-deficiency anemia. Also physicians must consider celiac disease as a possible reason of anemia in all patients with iron deficiency anemia.