Challenges and opportunities for access to Advanced Therapy Medicinal Products in Brazil.

Background Aims: The marketing authorization of Advanced Therapy Medicinal Products (ATMPs) in Brazil is recent. The features of these therapies impose specialized regulatory action and are consequently challenging for developers. The goal of this study was to identify the industry's experience in clinical development, marketing authorization and access to ATMPs through the Unified Health System (SUS, acronym in Portuguese), from a regulatory perspective.

International recommendations for screening and preventative practices for long-term survivors of transplantation and cellular therapy: a 2023 update.

As hematopoietic cell transplantation (HCT) and cellular therapy expand to new indications and international access improves, the volume of HCT performed annually continues to rise. Parallel improvements in HCT techniques and supportive care entails more patients surviving long-term, creating further emphasis on survivorship needs. Survivors are at risk for developing late complications secondary to pre-, peri- and post-transplant exposures and other underlying risk-factors.

International Recommendations for Screening and Preventative Practices for Long-Term Survivors of Transplantation and Cellular Therapy: A 2023 Update.

As hematopoietic cell transplantation (HCT) and cellular therapy expand to new indications and international access improves, the number of HCTs performed annually continues to rise. Parallel improvements in HCT techniques and supportive care entails more patients surviving long term, creating further emphasis on survivorship needs. Survivors are at risk for developing late complications secondary to pretransplantation, peritransplantation, and post-transplantation exposures and other underlying risk factors.

Splenic irradiation for myelofibrosis prior to hematopoietic cell transplantation: A global collaborative analysis.

Splenomegaly is the clinical hallmark of myelofibrosis. Splenomegaly at the time of allogeneic hematopoietic cell transplantation (HCT) is associated with graft failure and poor graft function. Strategies to reduce spleen size before HCT especially after failure to Janus kinase (JAK) inhibition represent unmet clinical needs in the field.

Cocaine and Volatile Nitrite-Induced Methemoglobinemia; a Case Report and Treatment Approach Review.

Cyanosis is typically a sign of a potentially life-threatening condition in the emergency department and requires immediate workup and treatment. This case report highlights the diagnostic reasoning and clinical approach to cocaine- and volatile nitrite-induced methemoglobinemia (MHG). MHG is a rare, life-threatening cause of cyanosis.

Evaluation of right ventricular function during liver transplantation with transesophageal echocardiography.

Background: The pathophysiology of advanced liver cirrhosis may induce alterations in the circulatory system that may be challenging for the anesthesiologist to manage intraoperatively, and perioperative cardiovascular events are associated with worse outcomes in cirrhotic patients undergoing liver transplantation. It remains controversial whether right ventricular function is impaired during this procedure. Studies using transesophageal echocardiography for quantitative analysis of the right ventricle remain scarce in this setting, yielding conflicting results.

Economic analysis of the different endodontic instrumentation techniques used in the Unified Health System.

Background: To assess the financial impact of incorporating a new (reciprocal) technology into endodontic treatments in the public health system (SUS).

Methods: This was a economic evaluation study (comparing the 3 different endodontic instrumentation techniques-manual, rotary and reciprocating), allocative efficiency analysis to optimize existing resources in the SUS, and financial contribution impact analysis of incorporation of a new technology. Thirty-one (31) 12 years-old volunteers were evaluated.

Landscape of Brazilian research and development public funding in advanced therapies: lessons learned and a roadmap for middle-income economies.

Background Aims: Advanced therapy medicinal products (ATMPs) have reached the forefront of biotechnological innovation, partly due to public funders' efforts in the early stages of research and development (R&D). Data on investment in R&D of ATMPs are recognized as scarce, particularly in developing countries. Because of the numerous peculiarities of the Brazilian health system and the science and technology (S&T) system, the country is a good example for the evaluation of public investments in R&D of ATMPs.

Computed tomography on lung cancer screening is useful for adjuvant comorbidity diagnosis in developing countries.

Purpose: The aim of this study was to analyse and quantify the prevalence of six comorbidities from lung cancer screening (LCS) on computed tomography (CT) scans of patients from developing countries.

Methods: For this retrospective study, low-dose CT scans (n=775) were examined from patients who underwent LCS in a tertiary hospital between 2016 and 2020. An age- and sex-matched control group was obtained for comparison (n=370).

The Difficult Decision Not to Prescribe Artificial Nutrition by Health Professionals and Family: Bioethical Aspects.

Introduction: Bioethics and nutrition are essential issues in end of life, advanced dementia, life-sustaining therapies, permanent vegetative status, and unacceptably minimal quality of life. Even though artificially administered nutrition (AAN), for this type of health condition, does not improve quality of life and extension of life, and there is evidence of complications (pulmonary and gastrointestinal), it has been used frequently. It had been easier considering cardiopulmonary resuscitation as an ineffective treatment than AAN for a healthy team and/or family.

Aryl hydrocarbon receptor (AhR) activation contributes to high-fat diet-induced vascular dysfunction.

Background And Purpose: Metabolic and vascular dysfunction are common features of obesity. Aryl hydrocarbon receptor (AhR) regulates lipid metabolism and vascular homeostasis, but whether vascular AhR are activated in obesity or have a protective and/or harmful effects on vascular function in obesity are unknown. Our study addresses whether AhR activation contributes to obesity-associated vascular dysfunction and the mechanisms involved in these AhR effects.

Omidubicel vs standard myeloablative umbilical cord blood transplantation: results of a phase 3 randomized study.

Omidubicel is an ex vivo expanded hematopoietic progenitor cell and nonexpanded myeloid and lymphoid cell product derived from a single umbilical cord blood unit. We report results of a phase 3 trial to evaluate the efficacy of omidubicel compared with standard umbilical cord blood transplantation (UCBT). Between January 2017 and January 2020, 125 patients age 13 to 65 years with hematologic malignancies were randomly assigned to omidubicel vs standard UCBT.

Association between leukocyte telomere length and sex by quantile regression analysis.

Introduction: Telomere length (TL) is a biomarker of cellular proliferative history. In healthy individuals, leukocyte TL shortens with age and associates with the lifespan of men and women. However, most of studies had used linear regression models to address the association of the TL attrition, aging and sex.

Expanding the horizons of clinical applications of proximal humerus locking plates in the lower extremities: A technical note.

Pre-contoured anatomical locking plates were designed to address the clinical need of fixing small epiphyseal segments with a larger number of screws. Those plates match the contour and shape of a variety of bones allowing for optimal buttress properties. The aim of this manuscript is to highlight the benefits of applying proximal humerus locking plates in the fixation of lower extremity bones.

Tumor Growth Rate to Predict the Outcome of Patients with Neuroendocrine Tumors: Performance and Sources of Variability.

Introduction: Tumor growth rate (TGR), percentage of change in tumor volume/month, has been previously identified as an early radiological biomarker for treatment monitoring in neuroendocrine tumor (NET) patients. We assessed the performance and reproducibility of TGR at 3 months (TGR3m) as a predictor factor of progression-free survival (PFS), including the impact of imaging method and reader variability.

Methods: Baseline and 3-month (±1 month) CT/MRI images from patients with advanced, grade 1-2 NETs were retrospectively reviewed by 2 readers.

Fluid Overload and Risk of Mortality in Critically Ill Patients.

Background: Fluid overload (FO) is a condition present in critical care units, and it is associated with clinical complications and worse outcomes for severe patients.

Objective: The aim of this study was to verify if FO is a risk factor for mortality in critically ill patients.

Methods: Retrospective study performed in a Brazilian intensive care unit, from January to March 2016, with patients older than 18 years and hospitalized for more than 24 hours.

Tumor Growth Rate as a Validated Early Radiological Biomarker Able to Reflect Treatment-Induced Changes in Neuroendocrine Tumors: The GREPONET-2 Study.

Purpose: Tumor growth rate (TGR) represents the percentage change in tumor volume per month (%/m). Previous results from the GREPONET study showed that TGR measured after 3 months (TGR) of starting systemic treatment (ST) or watch and wait (WW) was an early biomarker predicting progression-free survival (PFS) in neuroendocrine tumors (NET).

Experimental Design: Patients from 7 centers with advanced grade (G) 1/2 NETs from the pancreas (P)/small bowel (SB) initiating ST/WW were eligible.

Value of Tumor Growth Rate (TGR) as an Early Biomarker Predictor of Patients' Outcome in Neuroendocrine Tumors (NET)-The GREPONET Study.

Introduction: Tumor growth rate (TGR; percent size change per month [%/m]) is postulated to be an early radiological biomarker to overcome limitations of RECIST. This study aimed to assess the impact of TGR in neuroendocrine tumors (NETs) and potential clinical and therapeutic applications.

Materials And Methods: Patients (pts) with advanced grade (G) 1/2 NETs from the pancreas or small bowel initiating systemic treatment (ST) or watch and wait (WW) were eligible.

Screening: Actual trends on PSA marker. When, who, how?

Prostate cancer (PCa) is the most common non-skin malignancy among men world-wide. PCa incidence is higher among African American (AA) menin comparison to the white population. Men with a previous history of PCa in first-line relatives carry also an increased risk for this disease.

Worst outcomes according to RAS mutation variants: an analysis in patients with metastatic colorectal adenocarcinoma.

Purpose: Over 50% of metastatic colorectal cancers harbor RAS mutations. It is unclear if different mutation variants have an impact on survival. The purpose of this study was to evaluate the impact of these mutations on colorectal cancer survival.

Kidney-derived c-kit progenitor/stem cells contribute to podocyte recovery in a model of acute proteinuria.

Kidney-derived c-kit cells exhibit progenitor/stem cell properties and can regenerate epithelial tubular cells following ischemia-reperfusion injury in rats. We therefore investigated whether c-kit progenitor/stem cells contribute to podocyte repair in a rat model of acute proteinuria induced by puromycin aminonucleoside (PAN), the experimental prototype of human minimal change disease and early stages of focal and segmental glomerulosclerosis. We found that c-kit progenitor/stem cells accelerated kidney recovery by improving foot process effacement (foot process width was lower in c-kit group vs saline treated animals, P = 0.

Constitutive Activation of the Nutrient Sensor mTORC1 in Myeloid Cells Induced by Tsc1 Deletion Protects Mice from Diet-Induced Obesity.

Scope: To test whether myeloid cells Tsc1 deletion and therefore constitutive activation of the nutrient sensor mTORC1 protects from high-fat diet (HFD)-induced obesity, glucose intolerance, and adipose tissue inflammation.

Methods And Results: Mice with Tsc1 deletion in myeloid cells (MTsc1KO) and littermate controls (MTsc1WT) were fed with HFD for 8 weeks and evaluated for body weight, glucose homeostasis, and adipose tissue inflammation. MTsc1KO mice were protected from HFD-induced obesity and glucose intolerance.

Immunophenotyping of Monocytes During Human Sepsis Shows Impairment in Antigen Presentation: A Shift Toward Nonclassical Differentiation and Upregulation of FCγRi-Receptor.

Monocytes and macrophages are pivotal in the host response to sepsis, recognizing the infecting microorganism and triggering an inflammatory response. These functions are, at least in part, modulated by the expression of cell surface receptors. We aimed to characterize the monocyte phenotype from septic patients during an ongoing sepsis process and its association with clinical outcomes.