A Comparison Between MRIT2 and NT-ProBNP in Early Detection of Heart Diseases in Thalassemia Major Patients: A Cross-Sectional Study

One of the most common causes of mortality in major thalassemia is cardiac complications. Despite existence of several methods for diagnosis of cardiac complications in thalassemia, this sequel persists as a major problem in these patients. The aim of this study is to compare the level of serum NT-ProBNP and cardiac MRI T2* in early detection and treatment of cardiac disorders in beta thalassemia major patients. 35 major thalassemic patients on regular transfusion were selected in our center from 2013 to 2014. All of the patients were at least 8 years old. NT-ProBNP and MRIT2* analyses were carried out for these patients, and consequently the findings were compared together and analyzed. There is a strong correlation between NT-ProBNP and MRIT2* (p value < 0.001) in early detection of cardiac disorders. NT-ProBNP is an important marker for diagnosis of cardiac complications before emergence of heart failure in thalassemic patients. Given the findings of this study, it is recommended that this marker be used on a regular basis for thalassemic patients on regular transfusion.     

Porcine xenograft biosynthetic wound dressings for the management of postoperative Mohs wounds

Cadaveric allografts and a large variety of other biologic dressings have been reported as being useful for the postoperative management of Mohs micrographic surgery (MMS) wounds. Although the use of porcine xenografts for the immediate postoperative management of these wounds is known, their use has not been detailed in the dermatology literature. A case series of 15 consecutive Mohs micrographic surgery patients (mean age = 74.9 years, range = 49 to 89 years) with wounds initially managed with porcine xenografts is described. Porcine xenografts were useful in a variety of clinical settings following MMS. These included: (1) wound management when tumor margins were indeterminate pending additional dermatopathology studies and (2) wound management when there are issues such as through and through nasal defects involving the mucosa, large wound depth, exposed cartilage and or bone, or patient medical comorbidities that delay or prevent plans for immediate wound reconstruction. Future controlled studies of biologic dressings are needed to determine which options are best for micrographic surgery wounds. Comparisons should also include the traditional option of second intention healing without biologic dressings.     

Influence of drying conditions of zirconium molybdate gel on performance of Tc gel generator

^99mTc can be produced from ⁹⁹Mo/^99mTc gel generators. These gels are part of the generator and the ⁹⁹Mo/^99mTc gel generator performance is directly related with gel structure. In this work a series of zirconium molybdate gels have been synthesized and dried under different conditions and characterized using thermal analysis (TGA, DTA), SEM, XRD and porosity measurements. It is found that the water content of the gel determines the structure porosity which allows the diffusion of the ^99mTcO₄⁻ ions inside the gel and was directly connected with performance of the ⁹⁹Mo/^99mTc gel generators. Drying conditions of the gel is as an important factor that influence water content and physical–chemical properties of this gel and must be carefully studied to optimize the properties of the gel generators.     

Role of frailty in prediction of hospitalized older adult patient’s outcomes: a prospective study

Background/aim Frailty is associated with an increased risk of negative short-term and long-term hospital outcomes. This study aimed to evaluate the role of frailty in predicting readmission, length of stay, and quality of life in the hospitalized older adults.Materials and methods This observational study was conducted at Ziaiyan Hospital, Tehran, Iran. In total, 304 participants (65–85 years), were enrolled through the inclusion criteria from August to December 2019. The frailty index (FI) was assessed by the minimum data set-home care. Readmission was obtained through telephone interviews. The length of stay was gathered by the patient’s hospital records, and the EuroQol questionnaire was used for assessing the quality of life. Data were collected by a researcher nurse at the admission time, 30, 60, and 90 days after discharge. The logistic regression model and repeated measures ANOVA were employed to analyze the association between frailty and outcomes.ResultsAccording to FI, 102 (33.55%) participants were pre-frail, whereas 35 (11.51%) were frail. In the fully-adjusted model for readmission, the pre-frail participants had a higher risk of readmission at the hospital in comparison with the nonfrail and frail groups (OR = 1.88, 95% CI = 1.90–3.26), and also for GP visits, frail patients showed nearly significant differences (OR = 2.45, 95% CI = 0.99–6.06) but there were no differences between frail and pre-frail patients in readmissions in the emergency ward. In a fully-adjusted prolonged stay model, pre-frail patients had a higher probability to stay longer in hospital (OR = 2.28, 95% CI: 1.24–4.18). The fully-adjusted model for QoL showed, frail patients were more prone to the declined levels of QoL in comparison with pre-frail patients (OR = 10.77, 95% CI: 3.97–29.18).ConclusionsThe findings indicated that frailty worsened negative outcomes and declined QoL. Early diagnosis in hospital settings could be beneficial for designing optimal care plans for the frail and pre-frail patients.     

Bromodomain inhibition overcomes treatment resistance in distinct molecular subtypes of melanoma

Therapy of BRAF-mutant melanoma with selective inhibitors of BRAF (BRAFi) and MEK (MEKi) represents a major clinical advance but acquired resistance to therapy has emerged as a key obstacle. To date, no clinical approaches successfully resensitize to BRAF/MEK inhibition. Here, we develop a therapeutic strategy for melanoma using bromosporine, a bromodomain inhibitor. Bromosporine (bromo) monotherapy produced significant anti-tumor effects against established melanoma cell lines and patient-derived xenografts (PDXs). Combinatorial therapy involving bromosporine and cobimetinib (bromo/cobi) showed synergistic anti-tumor effects in multiple BRAFi-resistant PDX models. The bromo/cobi combination was superior in vivo to standard BRAFi/MEKi therapy in the treatment-naive BRAF-mutant setting and to MEKi alone in the setting of immunotherapy-resistant NRAS- and NF1-mutant melanoma. RNA sequencing of xenografts treated with bromo/cobi revealed profound down-regulation of genes critical to cell division and mitotic progression. Bromo/cobi treatment resulted in marked DNA damage and cell-cycle arrest, resulting in induction of apoptosis. These studies introduce bromodomain inhibition, alone or combined with agents targeting the mitogen activated protein kinase pathway, as a rational therapeutic approach for melanoma refractory to standard targeted or immunotherapeutic approaches.

Melanoma is the fifth most common malignancy in the Unites States, with an estimated 106,110 new cases in 2021 (1). The death toll attributed to melanoma has decreased sharply, owing in part to the revolution that has taken place in the therapy of advanced disease, with significant advances both in immunotherapeutic and targeted interventions. In the realm of targeted therapy, the efficacy of small molecule inhibitors targeting mutant BRAF in metastatic melanoma (2, 3) represented a landmark in the targeted therapy of cancer. Subsequently, the combination of BRAF and MEK inhibition resulted in increased response rates and prolonged survival (4–6). More recently, durable responses have been reported with BRAF/MEK-targeted therapy (7). However, despite these clear improvements in patient outcome, many patients eventually progress. As a result, the development of acquired resistance to targeted agents constitutes a significant clinical obstacle. While numerous mechanisms of resistance to targeted therapy have been described (8), many of these mechanisms result in reactivation of the mitogen activated protein kinase (MAPK) pathway in which BRAF operates (9, 10). Therefore, new therapeutic approaches will be required to increase the proportion of responding patients, the durability of the responses observed, and to resensitize melanoma cells to BRAF inhibitors upon the development of acquired resistance. To date, few effective targets for combinatorial therapy with BRAF inhibitors (beyond MEK) have been identified, and none that have proved superior to the BRAFi/MEKi combination.Previously, we identified an important role for the BPTF gene in melanoma progression, and as a potential therapeutic target (11). BPTF promotes melanoma progression by activating a cascade of gene expression including ERK, BCL2, and BCL-XL, resulting in promotion of cell-cycle progression and suppression of apoptosis. BPTF gene silencing resulted in abrogation of the proliferative and metastatic potential of melanoma cells and in sensitization to BRAF inhibition (11).Recently, bromodomain inhibition has emerged as a novel approach to cancer therapy. Bromodomains are protein motifs that bind to acetylated lysine residues on histones, with a critical role in chromatin remodeling (12, 13). The development of ligands targeting the BET (bromodomain and extracellular-terminal) family member BRD4 (14) demonstrated the potential of small molecule inhibition of the bromodomain-acetyl-lysine interaction and is being pursued actively in the clinical arena. However, BET family bromodomains do not share significant sequence homology with that of BPTF (15), indicating that distinct inhibitors will be required to effectively target BPTF. Collectively, these observations suggest the potential utility of a bromodomain inhibitor, alone or in combination with MAPK pathway inhibition, as a rational therapeutic strategy for melanoma, which represents the focus of the current analysis.