Lenalidomide or Thalidomide for Transplant-Ineligible Patients With Newly Diagnosed Multiple Myeloma? An Overview of Systematic Reviews.

OBJECTIVES: To present an overview of evidence of efficacy, safety, and health-related quality of life of lenalidomide or thalidomide for transplant-ineligible multiple myeloma. METHODS: A literature search was performed in 5 databases until July 2022. We included systematic reviews with network meta-analyses of randomized controlled trials on the use of lenalidomide compared with thalidomide for transplant-ineligible multiple myeloma. The A Measurement Tool to Assess Systematic Reviews 2 was used to appraise the quality of included reviews. The results were focused on the lenalidomide + dexamethasone until disease progression (RDc) versus thalidomide + dexamethasone until disease progression (TDc) and induction with melphalan + prednisone + lenalidomide, followed by maintenance with lenalidomide (MPR-R) versus induction with melphalan + prednisone + thalidomide, followed by maintenance with thalidomide (MPT-T) regimens. RESULTS: Nine studies were included. Only 1 study did not show any weakness in critical domains of A Measurement Tool to Assess Systematic Reviews 2. For overall survival, RDc proved to be superior to TDc; however, no study showed significant difference between MPR-R and MPT-T. For progression-free survival, 2 of 3 studies showed that RDc is better than TDc; however, no difference between MPR-R and MPT-T was found. Regarding safety, these lenalidomide-based regimens had a lower risk for neurologic adverse events, with an increased risk of hematologic adverse events. No health-related quality of life meta-analyses were found. CONCLUSIONS: These findings suggest that, in terms of efficacy and safety, lenalidomide-based regimen is a good option for treatment of transplant-ineligible multiple myeloma in the public health system of Brazil, especially for those patients who develop severe neuropathy with thalidomide.

Clinical networking results in continuous improvement of the outcome of patients with acute promyelocytic leukemia.

The introduction of all-trans retinoic acid (ATRA) combined with anthracyclines has significantly improved the outcomes for patients with acute promyelocytic leukemia (APL), and this strategy remains the standard of care in countries where arsenic trioxide is not affordable. However, data from national registries and real-world databases indicate that low- and middle-income countries (LMIC) still face disappointing results, mainly due to high induction mortality and suboptimal management of complications. The American Society of Hematology established the International Consortium on Acute Leukemias (ICAL) to address this challenge through international clinical networking. Here, we present the findings from the ICAPL study involving 806 patients with APL recruited in Brazil, Chile, Paraguay, Peru, and Uruguay. The induction mortality rate has decreased to 14.6% compared to the pre-ICAL rate of 32%. Multivariable logistic regression analysis revealed as factors associated with induction death: age ≥ 40 years, ECOG = 3, high-risk status based on the PETHEMA/GIMEMA classification, albumin level ≤ 3.5 g/dL, bcr3 PML/RARA isoform, the interval between presenting symptoms to diagnosis exceeding 48 hours, and the occurrence of central nervous system and pulmonary bleeding. With a median follow-up of 53 months, the estimated 4-year overall survival (OS) rate is 81%, the 4-year disease-free survival (DFS) rate is 80%, and the 4-year cumulative incidence of relapse (CIR) rate is 15%. These results parallel those observed in studies conducted in high-income countries, highlighting the long-term effectiveness of developing clinical networks to improve clinical care and infrastructure in LMIC.

Cephalometric Evaluation in Patients with Obstructive Sleep Apnea undergoing Lateral Pharyngoplasty.

Introduction Lateral pharyngoplasty (LP) has shown promising results. Craniofacial deformity reduces the pharyngeal space, contributing to the etiopathogenesis. The analysis of craniofacial features can be performed using cephalometry. Objective To verify if craniofacial deformity is associated with worse polysomnographic data in patients with obstructive sleep apnea (OSA), and to verify if the preoperative cephalometric parameters can interfere with the surgical success of the LP. Methods The study included 21 patients with OSA aged between 18 and 65 years who underwent LP in a university hospital from 2015 to 2019. Polysomnography was performed postoperatively, after a minimum period of 6 months from the surgical procedure. In addition, a cephalometric evaluation was performed to assess craniofacial deformity, and to correlate it with the polysomnographic results. Results The mean and median of all polysomnographic respiratory parameters improved postoperatively, especially the apnea-hypopnea index (AHI), which went from 40.15 to 16.60 events per hour ( p = 0.001). Of the 21 patients, 15 showed improvements in the AHI postoperatively. As for the cephalometric evaluations, we found that the longer the distance between the hyoid bone and the mandibular plane, the greater the patient's preoperative AHI ( p = 0.011). When assessing whether cephalometric changes related to craniofacial deformities influence the surgical outcome of LP, no correlation was found for any cephalometric measurement. Conclusion The longer the distance between the hyoid bone and the mandibular plane, the greater the preoperative AHI, and LP was an effective OSA treatment. Cephalometric variables are not able to modify or determine the success of LP in apneic patients in the population assessed.

Relationship between OSA pathophysiological phenotypes and treatment response to mandibular advancement devices: a pilot study.

STUDY OBJECTIVES: To assess whether critical pathophysiological phenotypes predict treatment response in patients with obstructive sleep apnea (OSA) using a mandibular advancement device (MAD). METHODS: Thirty-one OSA patients were treated with a MAD. Individuals were categorized and graded into four pathophysiological phenotypes based on polysomnographic features (anatomical, ventilatory control, arousal threshold and muscle responsiveness). Morphoanthropometric data were additionally assessed. Patients were classified as responders or nonresponders. Associations between polysomnographic phenotypes and treatment response were documented, as was morphoanthropometric data and their impact on therapeutic success. RESULTS: There was a male predominance (64.5%), with a median age of 49 years (25p:40; 75p:55), BMI=27.4 kg/m2 (26; 28.8) and apnea-hypopnea index (AHI) of 18.2 (25p:11.7; 75p: 27.6). The majority of patients treated with a MAD (58%) were good responders (68.0% mild and moderate versus 16.7% severe). Treatment response was associated with shorter intermolar and interpremolar distances in the lower arch (p = 0.0092 and 0.0129). Rapid eye movement sleep AHI (REMAHI) and MAD-related treatment response were inversely correlated (p = 0.0013). Favorable anatomical (p = 0.0339) and low muscle response (p = 0.0447) phenotypes were correlated with outcomes. CONCLUSIONS: According to our results, a favorable response occurred in a better 'anatomical phenotype' and in the worse 'muscular responsiveness phenotype' according to polysomnographic data. Furthermore, other favorable predictors, such as a REMAHI <16 and a smaller distance between lower molars and premolars, were found. These findings indicate that clinical and polysomnographic aspects can discriminate phenotypes that may guide decisions on MAD treatment for OSA.

Robust 3D breast reconstruction based on monocular images and artificial intelligence for robotic guided oncological interventions.

Breast cancer is a global public health concern. For women with suspicious breast lesions, the current diagnosis requires a biopsy, which is usually guided by ultrasound (US). However, this process is challenging due to the low quality of the US image and the complexity of dealing with the US probe and the surgical needle simultaneously, making it largely reliant on the surgeon's expertise. Some previous works employing collaborative robots emerged to improve the precision of biopsy interventions, providing an easier, safer, and more ergonomic procedure. However, for these equipment to be able to navigate around the breast autonomously, 3D breast reconstruction needs to be available. The accuracy of these systems still needs to improve, with the 3D reconstruction of the breast being one of the biggest focuses of errors. The main objective of this work is to develop a method to obtain a robust 3D reconstruction of the patient's breast, based on RGB monocular images, which later can be used to compute the robot's trajectories for the biopsy. To this end, depth estimation techniques will be developed, based on a deep learning architecture constituted by a CNN, LSTM, and MLP, to generate depth maps capable of being converted into point clouds. After merging several from multiple points of view, it is possible to generate a real-time reconstruction of the breast as a mesh. The development and validation of our method was performed using a previously described synthetic dataset. Hence, this procedure takes RGB images and the cameras' position and outputs the breasts' meshes. It has a mean error of 3.9 mm and a standard deviation of 1.2 mm. The final results attest to the ability of this methodology to predict the breast's shape and size using monocular images.Clinical Relevance- This work proposes a method based on artificial intelligence and monocular RGB images to obtain the breast's volume during robotic guided breast biopsies, improving their execution and safety.

A concept for integrated care pathways for atopic dermatitis-A GA2 LEN ADCARE initiative.

INTRODUCTION: The integrated care pathways for atopic dermatitis (AD-ICPs) aim to bridge the gap between existing AD treatment evidence-based guidelines and expert opinion based on daily practice by offering a structured multidisciplinary plan for patient management of AD. ICPs have the potential to enhance guideline recommendations by combining interventions and aspects from different guidelines, integrating quality assurance, and describing co-ordination of care. Most importantly, patients can enter the ICPs at any level depending on AD severity, resources available in their country, and economic factors such as differences in insurance reimbursement systems. METHODS: The GA2 LEN ADCARE network and partners as well as all stakeholders, abbreviated as the AD-ICPs working group, were involved in the discussion and preparation of the AD ICPs during a series of subgroup workshops and meetings in years 2020 and 2021, after which the document was circulated within all GAL2 EN ADCARE centres. RESULTS: The AD-ICPs outline the diagnostic procedures, possible co-morbidities, different available treatment options including differential approaches for the pediatric population, and the role of the pharmacists and other stakeholders, as well as remaining unmet needs in the management of AD. CONCLUSION: The AD-ICPs provide a multidisciplinary plan for improved diagnosis, treatment, and patient feedback in AD management, as well as addressing critical unmet needs, including improved access to care, training specialists, implementation of educational programs, assessment on the impact of climate change, and fostering a personalised treatment approach. By focusing on these key areas, the initiative aims to pave the way for a brighter future in the management of AD.

The landscape of hematology research in Brazil: an analysis of data from citation databases

ABSTRACT Introduction: Scientometrics is the field concerned with measuring and analyzing academic literature, using specific metrics and data from bibliometric databases. Hematology is a broad area of science and medicine, from which several landmark scientific discoveries have emerged. Objective: The aim of this report is to provide a snapshot of the landscape of hematology research in Brazil, based on a comprehensive analysis of published studies in hematology whose authors were affiliated to Brazilian institutions from 1980 to 2020. Method: Articles, reviews and letters to the editor with at least one author affiliated to a Brazilian institution were retrieved from Incytes/Web of Science or Scopus databases. Importantly, only papers classified in the subject area "Hematology" by the embedded algorithms of each database were included. Results: Considering all published papers, Brazil is in the 22nd position, contributing with around 1.1% of papers in this period. A clear and sustained increase in publication output can be observed from the early 1990's to the present moment. Publicly-funded higher education institutions were the main contributors to the development and consolidation of the hematology scientific community, which has grown in diversity, with an increasing number of contributions from private institutions. In regard to funding, public agencies have been and remain by large as the most important funder of research in hematology in Brazil. Conclusion: We suggest that continuous monitoring of the temporal trends of some of the data compiled in our report could potentially contribute to a clearer picture of the development of hematology research in Brazil.

Career paths and workforce diversity in hematology: A cross-sectional study of a 35-year alumni cohort from an academic residency program in Brazil

ABSTRACT Introduction: Although not mandatory, medical residency has become a sine qua non condition for practicing in most medical specialties in Brazil. Residency programs are hosted mainly by university accredited academic centers and hospitals in the national public healthcare system, under guidance and accreditation by a national commission. Despite the importance of these programs for the development of the hematology workforce, few studies have addressed their characteristics and impact on society. Methods: We performed a comprehensive cross-sectional survey of a 35-year alumni cohort from a hematology academic residency program in Brazil. Results: In total, 86/98 (87.8%) responded to the survey. The mean age at residency completion was 28.5 years, 60.5% of the alumni were women and sixty-four (74.4%) self-declared their skin color as white. Higher rates of parental education attainment and low rates of trainee financial dependence were observed and these patterns were stable over time. While the proportion of trainees from other states increased steadily, the number of hematologists practicing in other states remained stable. Approximately half of the alumni worked both in the private and public sectors, mainly in malignant hematology and in outpatient clinics. Twenty-five percent of the alumni reported prior leadership and teaching positions, mainly as directors of transfusion services. Conclusion: Our results provide data that can be potentially useful for policymakers and curricular development in the planning of strategies concerning the future workforce of hematologists.

Combination of Naltrexone and Isotretinoin for the Treatment of Darier Disease.

Darier disease (DD) is an autosomal-dominant genodermatosis in which mutations in the ATP2A2 gene result in impaired intercellular adhesion and epidermal blistering. Treatment options usually rely on systemic retinoids, but a refractory disease is still a therapeutical challenge. Given the similarity of DD pathogenesis with Hailey-Hailey disease, concomitant treatment with low-dose-naltrexone (LDN) has been proposed. We present the case of a 34-year-old woman with a 20-year history of severe, biopsy-proven DD, previously treated with several unsuccessful topical and systemic treatments, including oral isotretinoin, cyclosporine, doxycycline, methotrexate, acitretin, and subcutaneous adalimumab. At presentation, she had widespread keratotic, crusted, brown papules on her trunk and proximal extremities. Treatment with oral LDN (4.5 mg/day in manipulated tablets) was then initiated while maintaining the current isotretinoin therapy. After three months, there was a nearly complete clearance of the lesions, and no adverse effects were reported.

Effectiveness of the peripherally inserted central catheter for hematopoietic stem cell transplantation: a systematic review protocol

OBJECTIVE: to assess the effectiveness and safety of the peripherally inserted central catheter for hematopoietic stem cell transplantation. METHOD: this review will follow the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, and the search steps will be presented through the flow diagram. The search strategy aims to locate both published and unpublished studies. No time or language restrictions will be applied. The review will consider experimental and observational studies that include adult and pediatric patients undergoing hematopoietic stem cell transplantation. Patients using peripherally inserted central catheters will be compared with those using other central catheters.

The landscape of hematology research in Brazil: an analysis of data from citation databases.

INTRODUCTION: Scientometrics is the field concerned with measuring and analyzing academic literature, using specific metrics and data from bibliometric databases. Hematology is a broad area of science and medicine, from which several landmark scientific discoveries have emerged. OBJECTIVE: The aim of this report is to provide a snapshot of the landscape of hematology research in Brazil, based on a comprehensive analysis of published studies in hematology whose authors were affiliated to Brazilian institutions from 1980 to 2020. METHOD: Articles, reviews and letters to the editor with at least one author affiliated to a Brazilian institution were retrieved from Incytes/Web of Science or Scopus databases. Importantly, only papers classified in the subject area "Hematology" by the embedded algorithms of each database were included. RESULTS: Considering all published papers, Brazil is in the 22nd position, contributing with around 1.1% of papers in this period. A clear and sustained increase in publication output can be observed from the early 1990's to the present moment. Publicly-funded higher education institutions were the main contributors to the development and consolidation of the hematology scientific community, which has grown in diversity, with an increasing number of contributions from private institutions. In regard to funding, public agencies have been and remain by large as the most important funder of research in hematology in Brazil. CONCLUSION: We suggest that continuous monitoring of the temporal trends of some of the data compiled in our report could potentially contribute to a clearer picture of the development of hematology research in Brazil.

Career paths and workforce diversity in hematology: A cross-sectional study of a 35-year alumni cohort from an academic residency program in Brazil.

INTRODUCTION: Although not mandatory, medical residency has become a sine qua non condition for practicing in most medical specialties in Brazil. Residency programs are hosted mainly by university accredited academic centers and hospitals in the national public healthcare system, under guidance and accreditation by a national commission. Despite the importance of these programs for the development of the hematology workforce, few studies have addressed their characteristics and impact on society. METHODS: We performed a comprehensive cross-sectional survey of a 35-year alumni cohort from a hematology academic residency program in Brazil. RESULTS: In total, 86/98 (87.8%) responded to the survey. The mean age at residency completion was 28.5 years, 60.5% of the alumni were women and sixty-four (74.4%) self-declared their skin color as white. Higher rates of parental education attainment and low rates of trainee financial dependence were observed and these patterns were stable over time. While the proportion of trainees from other states increased steadily, the number of hematologists practicing in other states remained stable. Approximately half of the alumni worked both in the private and public sectors, mainly in malignant hematology and in outpatient clinics. Twenty-five percent of the alumni reported prior leadership and teaching positions, mainly as directors of transfusion services. CONCLUSION: Our results provide data that can be potentially useful for policymakers and curricular development in the planning of strategies concerning the future workforce of hematologists.

Lateral pharyngoplasty: polysomnographic results and phenotype-based analysis of OSA.

PURPOSE: There are several surgical treatments for obstructive sleep apnea (OSA) including lateral pharyngoplasty (LP) have yielded promising results, clearly improving symptoms of the disease. However, there are few publications in relation to polysomnographic (PSG) results, and patient selection remains a challenge. There are currently four pathophysiological phenotypes for OSA: anatomical, low arousal threshold, ventilatory instability, and poor muscle response. This study sought to evaluate the PSG results of LP and to verify whether the phenotypic profile is predictive of surgical success. METHODS: This was an observational, retrospective, cross-sectional study that analyzed the PSG results (pre-surgical and at least 6 months after surgery) of patients treated with Cahali's LP. To assess phenotypes, the following variables of interest (obtained from the pre-operative PSG) were used: apnea-hypopnea index (AHI) during REM sleep (AHIrem), percentage of hypopneas in the AHI, number of central or mixed apneas, and AHIrem and non-REM AHI ratio. RESULTS: Of 46 patients, it was possible to evaluate the phenotype in 28 patients. There were significant differences in the AHI values, ranging from 37.5 (20.8-49.7) to 10.3 (2.3-33.0) (p < 0.001). The minimum oxyhemoglobin saturation ranged from 78 ± 11 to 83 ± 8 p = 0.008. The time with oxyhemoglobin saturation < 90% ranged from 3.6 min (0.5-9.1) to 0.0 (0.0-1.5) p = 0.031. An AHIrem of < 20 events/h showed a positive correlation with surgical success. CONCLUSION: LP is efficient for the treatment of OSA, yielding significant improvement in all respiratory parameters evaluated by PSG. A pre-operative AHIrem of < 20 events/h was associated with surgical success. Other variables of interest for determining the phenotypes were not predictors of surgical success.

The Impact of Clinical and Craniofacial Changes on the Surgical Outcomes of Lateral Pharyngoplasty in the Treatment of Obstructive Sleep Apnea.

Objective To verify if maxillomandibular retrusion, obesity, and increased neck circumference are factors of worse surgical prognosis for lateral pharyngoplasty in apneic patients. Materials and Methods We evaluated 53 patients with obstructive sleep apnea who underwent lateral pharyngoplasty. Clinical evaluation was performed before the surgical procedure and included the measurement of body mass index (BMI) in kg/m 2 , neck circumference in centimeters, and a clinical evaluation of the facial profile obtained through the natural position of the oriented head. The polysomnographic evaluation was performed with at a minimum of 6 months after surgery, and polysomnographic results were correlated with the preoperative clinical data. Results The mean age of the patients was 38.8 years; the mean BMI was of 29.28kg/m 2 , and 84.9% of the sample was composed of men and 15.1% of women. There was a significant reduction in the mean value of the main respiratory parameters verified by polysomnography, such as apnea-hypopnea index (AHI) from 31.60 events per hour to 8.15 ( p < 0.001); NadirO 2 went from 81% to 85% ( p = 0.002) and mean oxyhemoglobin saturation from 94% to 95% ( p = 0.024). It was also observed that the greater the maxillomandibular retrusion, the lower the mean reduction of the AHI after surgery. The increase in neck circumference proved to be a factor associated with the surgical outcome, and for each 1-cm decrease in the neck circumference, the chance of surgical success increased 1.2-fold. Conclusion Lateral pharyngoplasty is an efficient surgical obstructive sleep apnea treatment. The lower the neck circumference measurement, the greater the chances of surgical success, and clinically evaluated maxillomandibular retrusion can reduce the magnitude of improvement in respiratory parameters after lateral pharyngoplasty in apneic patients.

Impaired repair properties of endothelial colony-forming cells in patients with granulomatosis with polyangiitis.

In patients with ANCA-associated vasculitis, interactions between neutrophils and endothelial cells cause endothelial damage and imbalance. Endothelial colony-forming cells (ECFCs) represent a cellular population of the endothelial lineage with proliferative capacity and vasoreparative properties. This study aimed to evaluate the angiogenic capacity of ECFCs of patients with granulomatosis with polyangiitis (GPA). The ECFCs of 13 patients with PR3-positive GPA and 14 healthy controls were isolated and characterized using fluorescence-activated cell sorting, capillary tube formation measurement, scratching assays and migration assays with and without plasma stimulation. Furthermore, three patients with active disease underwent post-treatment recollection of ECFCs for longitudinal evaluation. The ECFCs from the patients and controls showed similar capillary structure formation. However, the ECFCs from the patients with inactive GPA exhibited early losses of angiogenic capacity. Impairments in the migration capacities of the ECFCs were also observed in patients with GPA and controls (12th h, p = 0.05). Incubation of ECFCs from patients with GPA in remission with plasma from healthy controls significantly decreased migration capacity (p = 0.0001). Longitudinal analysis revealed that treatment significantly lowered ECFC migration rates. This study revealed that ECFCs from the patients with PR3-positive GPA in remission demonstrated early losses of tube formation and reduced migration capacity compared to those of the healthy controls, suggesting impairment of endothelial function.

Using Antigen Expression of Leukemic Cells for a Fast Screening of Acute Promyelocytic Leukemia by Flow Cytometry.

(1) Background: Acute promyelocytic leukemia is curable, but bleeding complications still provoke a high early mortality. Therefore, a fast diagnosis is needed for timely starting treatment. We developed a diagnostic algorithm using flow cytometric features for discrimination between acute promyelocytic leukemia (APL) and other types of acute myeloid leukemias (AML). (2) Methods: we analyzed newly diagnosed AMLs where immunophenotyping was performed at diagnosis by an 8-color protocol. The mean fluorescence intensity (MFI) of each antigen used was assessed, and those best separating APL from other types of AML were obtained by a discriminant analysis. Phenotypic characteristics of myeloblasts of normal bone marrow were used as controls. (3) Results: 24 cases of APL and 56 cases of other primary AMLs entered the study. Among non-APL AMLs, 4 had fms-related tyrosine kinase 3 gene internal tandem duplications (FLT3-ITD) mutation, 2 had nucleophosmin (NPM1) and 10 had both mutations. SSC (p < 0.0001), HLA-DR (p < 0.0001), CD13 (p = 0.001), CD64 (p = 0.004) and CD33 (p = 0.002) were differentially expressed, but this was not the case for CD34 (50% of non-APLs had a low expression). In the discriminant analysis, the best differentiation was achieved with SSC and HLA-DR discriminating 91.25% of the patients. (4) Conclusion: MFC could differentiate APL from non-APL AML in the majority of the cases.