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Impact of Intravenous Busulfan Pharmacokinetics on Safety in Pediatric Patients who have undergone Hematopoietic Stem Cell Transplant

Published on: 3rd December, 2024

Introduction: Busulfan (Bu)-based regimens are crucial for myeloablative conditioning in pediatric allogeneic stem cell transplantation. Despite its efficacy, Intravenous Bu has a narrow therapeutic index and variable pharmacodynamics especially in children, heightening the risk of adverse events. This study explores Bu dosing and related organ toxicities in pediatric patients at a tertiary center in Saudi Arabia.Methodology: This retrospective study at King Fahad Specialist Hospital in Dammam (KFSH-D), Saudi Arabia, included pediatric patients (≤16 years) treated with intravenous Bu before bone marrow transplantation from 2010 to 2022. Pharmacokinetic dose adjustments were based on AUC targets of 900-1350 µMol-min. Descriptive measures included mean, Standard Deviation (SD), median, minimum-maximum values, counts, and percentages. Statistical analyses used Kruskal-Wallis, Chi-square, and Fisher’s exact tests. Ethical approval was obtained from KFSH-D.Results: We identified 44 pediatric patients who underwent Bu prior to HSCT. Mean age was 4.95 ± 2.49 years, with a female majority (56.8%). Primary diseases included Beta Thalassemia (34.09%), Neuroblastoma (29.55%) among others. There was no significant difference in the cohort’s demographic and clinical features of the cohort. Nonetheless, higher infections were found in the Low-AUC group (66.7%) compared to the Target-AUC (40.0%) and Higher-AUC groups (0.0%) (p = 0.015).Conclusion: This study emphasizes the need for therapeutic drug monitoring and individualized Bu dosing in pediatric HSCT to minimize toxicity and improve outcomes. Larger multicenter studies are recommended to refine dosing strategies and enhance the safety and efficacy of Bu-based regimens.
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The forgotten player in the surgical history

Published on: 13th May, 2019

OCLC Number/Unique Identifier: 8164026356

The research concerning a preventive treatment of an osteoporitic femoral neck fracture started in 1990 because the surgical procedure of unstable femoral neck fractures is difficult. After effects are frequent and their number will increase in the next decade. The goal is to reinforce the femur with a biomaterial acting as a bone graft. Natural coral is bioresorbable and biocompatible. It acts as an autofocus bone graft for reconstruction of either cortex or cancellous bone and increases their mechanical resistance. This work shows evidence of new bone formation in an osteoporotic unbroken femoral neck femur. Consequently, the preventive surgical treatment of osteoporosis should be taken in consideration [1]. The purpose of this work is to show the results on the mineralization of the cancellous bone of an upper femoral metaphyses when a natural biomaterial is set in an unbroken osteoporotic femoral neck. Summary: Mrs. L is an 84 years old lady. Her osteoporotic unbroken right hip was grafted preventively with a biomaterial in order to prevent the high risk of break in case of fall. The biomaterial used is beads of natural coral. The reasons of this preventive treatment is discussed, as well as the choice of the biomaterial. The results are shown including a two years follow up. Brief History: Before going further, few words of history. Three centuries BC, an Aristote’s follower, Théophraste thinks that Natural coral is a petrified plant. For Ovide natural coral is a soft alga air-hardening. Al Biruni classes it among animals, because that respond to touch. At the beginning of the XVIIth century, Marsigli thinks that they are flowers which open out there in aquarium. The French Jean-André Peyssonnel, a young naturalist, says as Biruni, that in fact, corals are animals. At last, Buffon claims: These marine plants, were classified first in the rank of minerals, then in those of plants, and finally in that of animals. Natural coral is obviously an animal. After the Second World War, coral samples were analyzed by American scientists. Among 800 corail species, 3 where specially analyzed: Acropora, Porites and Libophylia. Mrs Nane Guillemin did in France her PHD on natural coral and with her team made a complete fundamental analysis (physical, chemical and biological properties) of the material, while the American scientists worked on the chemical bone’s properties. In France, Pr Ohayoun and his team worked on the surgical application in the dental field, Dr. Yves Cirotteau in the orthopedic surgery, specifically for osteoporotic disease and for the traumatologic field
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Precision and personalized vaccines needed to face COVID-19 pandemic

Published on: 28th April, 2021

OCLC Number/Unique Identifier: 9028054428

Among the abounding lessons we learned from the SARS-C0V-2 pandemic is the uttermost determinant that people are not equal before the severity of COVID-19. Indeed, the disease course differs with age, gender, ethnicity, underlying clinical conditions and virus variants. Other diseases modifying factors are associated with genetic traits such as those driving the immune response, the blood groups, the coagulation system and the ACE2 receptor variants [1-4].
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Myxedema coma in COVID-19

Published on: 31st July, 2021

OCLC Number/Unique Identifier: 9146322981

SARS-CoV-2 infection is associated with thyroid disorders. It has been reported that myxedema coma (MC) can be complicated with COVID-19. COVID-19-related thyroid disorders consist of a broad spectrum of thyroid dysfunction, from thyrotoxicosis to decompensated hypothyroidism. It is possible that both primary and central thyroid disorders are induced by COVID-19 due to systemic inflammatory and immune responses. We experienced two cases in which patients with COVID-19 developed MC with central hypothyroidism. It is likely that MC affected the severity of COVID-19. It is necessary to consider the existence of MC during SARS-CoV-2 infection. We propose the potential mechanisms.
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Durable Response to Pembrolizumab and Lenvatinib in a Patient with Chemotherapy-refractory Cholangiocarcinoma

Published on: 18th July, 2024

Cholangiocarcinoma (CCA), a rare malignancy originating from bile duct epithelial cells, often presents a challenging prognosis due to its rarity, delayed diagnosis, and early recurrence post-curative-intent treatments. Additional complexities include difficulties in achieving R0 resection during surgical intervention and the lack of effective second-line treatments following the failure of first-line regimens, particularly in unresectable advanced cases.In this case study, we demonstrate a durable response to a combination regimen of pembrolizumab and lenvatinib in a patient with distal CCA. Despite the regimen’s interim median Progression-Free Survival (PFS) of 6.1 months (95% CI, 2.1-6.4), our patient achieved a clinical and radiological PFS of approximately two years. The underlying mechanisms, potentially involving the upregulation of immune response pathways through undisclosed means or influenced by lenvatinib’s activation of T cells, might augment the sensitivity to PD-1 antibodies like pembrolizumab, contributing to the patient’s sustained response over two years.This case also highlights the significance of the patient’s initial good health condition, multidisciplinary care, and the potential impact of molecular subtyping on treatment selection in a patient with distal CCA who underwent numerous diagnostic procedures, intricate surgical interventions, and subsequent treatment regimens over seven years. Additionally, we underscore significant landmark trials and emerging combination therapies, including chemotherapies, immunotherapy, and targeted treatments in this report.
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Association between clinical forms of Leprosy and contacts with the vaccination state with BCG in five endemic municipalities in the Brazilian Amazon

Published on: 19th July, 2022

OCLC Number/Unique Identifier: 9575035083

Introduction: The World Health Organization (WHO) strategy for leprosy control from 2021 to 2030 focuses on interrupting transmission, reducing autochthonous cases to zero, and using a safe and effective vaccine and chemoprophylaxis. In 2020, 127,396 new cases were registered in the world, 19,195 new cases in the Americas, and, of these, 17,979 cases in Brazil, about 93.66% of the total in the Americas. Brazil is classified as a country with a high burden of the disease, occupying the 2nd place in the world, behind only India (WHO, 2020). Análise do período de 2010-2015 em publicação recente9, apresenta as seguintes cidades no estado do Pará nas quais se observou maiores taxas de incidência (detecção): Marituba, Belém, Marabá, Parauapebas e Altamira [9]. Material and method: This is an analytical retrospective study carried out in a database - Epi-Info resulting from records of Surveillance and Seroprevalence actions in five endemic municipalities for leprosy located in the Southeast and West of Pará. The following variables were analyzed: age, sex, Clinical Classification, vaccination status with BCG, and the result of the search for IgM antibodies against PGL-1 of Mycobacterium leprae by the “In house” ELISA technique. Results: We evaluated 1551 records examined in the laboratory from 2014 to 2016, which were classified into 123 Multibacillary -MB patients (123/1551 = 7.93%); 71 Paucibacillary-PB patients (71/1551 = 4.57%); 451 Intradomicilliary Consanguineous Contacts - CCOSI (451/1551 = 29.07%) and 906 Non Consanguineous Contacts - CNCOS (906/1551 = 58.41%). 57 MB patients (13.47%), 13 PB patients (3.07%), 133 CCOSI (31.44%) and 220 CNCOS (52.00%) were positive for PGL-1. The correlation of the Classification with the vaccination status showed 57 MB patients without any BCG (57/125 = 45.6%) and only 3 patients with two doses of BCG (3/125 = 2.4%); 17 PB patients without any dose of BCG (17/69 = 24.63%); 80 CCOSI without any BCG (80/455 = 17.58%) and 171 CNCOS (171/906 = 18.87%). The odds ratio (OR) in the analysis between unvaccinated MB patients compared to CCOSI was statistically significant (OR = 14.25; p ˂ 0.0001). The study shows the importance of using the BCG vaccine in healthy contacts of patients with leprosy, as it shows the probability of unvaccinated individuals being 14.25 times more likely to become ill with Multibacillary forms compared to CCOSI. In addition, the BCG vaccine has been in use for 80 years and is the only vaccine that we can use in leprosy control programs. Conclusion: Although the leprosy epidemiological data analyzed recently (2010 - 2015) show a downward trend in the main indicators in Pará, such as the detection of new cases and prevalence, the endemic municipalities are still classified as hyperendemic for the population under 15 years of age and This proves that Surveillance is essential, as well as BCG vaccination according to the Ministry of Health Standards.
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Atherogenic risk assessment of naive HIV-infected patients attending Infectious Diseases Service of Kinshasa University Teaching Hospital, Democratic Republic of the Congo (DRC)

Published on: 13th October, 2020

OCLC Number/Unique Identifier: 8689021635

Background and aim: Metabolic abnormalities are common in HIV/AIDS. Increasingly, lipid ratios are used as screening tools for dyslipidaemia in these medical conditions. The aim of this study was to assess the ability of 4 lipid ratios to predict cardiovascular risks. Methods: This is a cross-sectional and analytical study included 105 HIV+ patients followed in Kinshasa University Teaching Hospital (KUTH). Four indices [Atherogenic Index of Plasma (AIP), Castelli Risk Index (CRI) I and II, Atherogenic coefficient (AC)] were compared. Statistical analyzis consisted of measuring frequencies and means, Student’s t-tests, ANOVA and Ficher’s exact test, and the calculation of the Kappa value. Results: Lipid ratios predicted respectively the risk in 62% (AIP), 28.6% (CRI-I) and 23.8% (CRI-II). CRI-I and II were elevated, especially in women. The AIP appeared to be a better predictor than CRI-I and II to assess dyslipidaemia in general and the high-risk frequency. The cholesterol detected risk in 66.7% (Low HDL-C), 50% (High LDL-C), 38.9% (High TC and/or TG). The atherogenic risk was higher with age, advanced WHO stage, HIV-TB, HBV-HCV co-infections, smoking and alcohol intake. Haemoglobin (Hb) and CD4 counts were low when the risk was high. Age ≥ 50 years, stage 4 (WHO), CD4s+ ≤ 200 cells/µL were independent factors associated with atherogenic risk. Conclusion: Lipid ratios can be used as reliable tools for assessing cardiovascular risk of naïve HIV-infected patients who received HAART.
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Pomaded and unctuous- spindle cell lipoma

Published on: 17th March, 2023

Spindle cell lipoma and pleomorphic lipoma emerge as benign, adipocytic neoplasms representing a morphologic continuum of a singular neoplasm. In addition to myofibroblastoma and cellular angiofibroma, spindle cell lipoma or pleomorphic lipoma configures as a constituent of chromosome 13q/RB1 family of tumors. Initially scripted by Enzinger and Harvey in 1975 with an obsolete terminology of dendritic fibromyxolipoma, aforesaid adipocytic neoplasms articulate an estimated 1.5% of lipomatous tumors. In contrast to conventional lipoma, spindle cell lipoma or pleomorphic lipoma is an uncommonly discerned variant, demonstrating a proportion of 1: 60.
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Success, Survival and Prognostic Factors in Implant Prosthesis: Experimental Study

Published on: 19th December, 2023

The primary objective of this study was to detect the success and short-term survival rate of dental implant prosthetic therapy. The valuation of a possible relationship between the general and local clinical conditions of the patients (presence of risk factors and type of dental implant-supported prosthesis) and the satisfaction perceived by the patient, with success and survival of implant devices was investigated.The sample trial consisted of 23 patients, for a total of 50 dental implants supporting a prosthetic therapy. Preliminarily, an analysis of averages and frequencies of the anamnestic data was presented, as numbers and percentages. The implant success rate was calculated by assessing whether the implants fulfilled the success criteria defined by the Pisa Consensus Conference. The ANOVA test was used to check whether there was an association between the success of the implant device, the anamnestic data collected, and the type of prosthesis supported by the implants. Finally, the survival rate was calculated using the Kaplan - Meier method.The 2-year success rate of 50 implants was assessed at 98%. The 2-year survival rate was 97%. Finally, sex, age, compensated diabetes, a smaller and equal number of cigarettes per day (10 per day), the BOP, and the type of titanium dental implants supported by prosthesis, do not determine a change in success and are therefore not adequate parameters to predict the outcome of implant success. Following the results obtained, it is appropriate to continue the research by expanding the clinical observation times in order to obtain more solid scientific and clinical evidence.
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An unmistakable tumour of the tongue

Published on: 11th November, 2022

A 37-year-old woman suffered from a painful and swelling lesion of the base of the tongue, with no history of smoking or medical history of tumours.
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