Hairy cell leukemia with isolated bone lesions.

Key Clinical Message: 18F-FDG PET/CT has clinical relevance in HCL at diagnosis and for the follow-up of patients treated, especially in case of atypical presentations such as bone involvements (which are probably underestimated) and poor bone marrow infiltration. Abstract: Bone lesions are rarely reported in Hairy Cell Leukemia (HCL). We report two BRAFV600E mutated HCL patients presented bone lesions at foreground, poor bone marrow involvement, and the important role 18F-FDG PET/CT played in their management. We discuss the crucial role that 18F-FDG PET/CT could play in HCL routine practice.

Hodgkin lymphoma and female fertility: a multicenter study in women treated with doxorubicin, bleomycin, vinblastine, and dacarbazine.

Preservation of fertility has become a growing concern in young females with Hodgkin lymphoma (HL). However, the rate of pregnancy after the current most frequently prescribed ABVD (doxorubicin [Adriamycin], bleomycin, vinblastine, and darcarbazine) chemotherapy for HL has rarely been studied. In this study, we aim to determine the impact of ABVD on the fertility of women treated for HL. We conducted a noninterventional, multicenter study of female patients of childbearing age who were treated for HL. Two healthy apparied women nonexposed to chemotherapy (our controls) were assigned for each patient. Fertility was assessed by the number of pregnancies and births after HL treatment. Sixty-seven patients were included. The median age at diagnosis was 24.4 years (range, 16-43). HL was a localized disease for 68.7%. Of all the patients, 53.7% started at least 1 pregnancy after treatment vs 54.5% of the controls (P = .92). Of all the patients who desired children, 81% had at least 1 pregnancy. Patients treated with ABVD did not have a longer median time to pregnancy (4.8 years in the group of patients and 6.8 years for controls). Across patients, there were 58 pregnancies and 48 births (ratio, 1:2) and 136 pregnancies and 104 births (ratio, 1:3) for the control cohort. No increase in obstetric or neonatal complications has been reported in HL in our study. The number of pregnancies, births, and the time to start a pregnancy in young women treated with ABVD for HL is not different from that of controls. Therefore, females with HL treated with ABVD should be reassured regarding fertility.

Force-velocity relationship in Paralympic powerlifting: two or multiple-point methods to determine a maximum repetition.

BACKGROUND: Due to the absence of evidence in the literature on Paralympic Powerlifting the present study investigated various methods to assess bench press maximum repetition and the way each method influences the measurement of minimum velocity limit (MVT), load at zero velocity (LD0), and force-velocity (FV). OBJECTIVE: To evaluate the precision of the multi-point method using proximal loads (40, 50, 60, 70, 80, and 90% of one repetition maximum; 1RM) compared to the four-point method (50, 60, 70, and 80% of 1RM) and the two-point method using distant loads (40 and 80% and 50 and 80% of 1RM) in in the MVT, LD0, and FV, in bench press performed by Paralympic Powerlifters (PP). METHODS: To accomplish this, 15 male elite PP athletes participated in the study (age: 27.7 ± 5.7 years; BM: 74.0 ± 19.5 kg). All participants performed an adapted bench press test (free weight) with 6 loads (40, 50, 60, 70, 80, and 90% 1RM), 4 loads (50, 60, 70, and 80% 1RM), and 2 loads (40-80% and 50-80% 1RM). The 1RM predictions were made by MVT, LD0, and FV. RESULTS: The main results indicated that the multiple (4 and 6) pointsmethod provides good results in the MVT (R2 = 0.482), the LD0 (R2 = 0.614), and the FV (R2 = 0.508). The two-point method (50-80%) showed a higher mean in MVT [1268.2 ± 502.0 N; ICC95% 0.76 (0.31-0.92)], in LD0 [1504.1 ± 597.3 N; 0.63 (0.17-0.86)], and in FV [1479.2 ± 636.0 N; 0.60 (0.10-0.86)]. CONCLUSION: The multiple-point method (4 and 6 points) and the two-point method (40-80%) using the MVT, LD0, and FV all showed a good ability to predict bench press 1RM in PP.

Smoldering multiple myeloma: biology, clinical manifestations and management.

Smoldering multiple myeloma (SMM) is a heterogeneous group of asymptomatic plasma cell disorder characterized by the presence of monoclonal protein ≥ 30 g/L and/or 10-60% of bone marrow plasma cells and no evidence of SLiM-CRAB criteria according to the 2014 International Myeloma Working Group (IMWG) recommendations. Once the effort to reclassify SMM with active disease as MM requiring treatment was completed, the need to redefine new high-risk SMM arose. The 20/2/20 and the IMWG risk model with the add-on high-risk cytogenetic abnormalities allow to identify high-risk SMM with 50% risk of progression to MM within 2 years, and therefore might help to propose a better therapeutic approach, either with the goal to « cure ¼ by profoundly debulk the MM with aggressive therapies, or alternatively to restore the immune surveillance like a « delay ¼ strategy with immune-based therapies. The debate is still ongoing but clearly challenges the watch-and-wait standard of care.

Analysis of Pacing Strategies in AMRAP, EMOM, and FOR TIME Training Models during "Cross" Modalities.

Empirically, it is widely discussed in "Cross" modalities that the pacing strategy developed by an athlete or trainee has a significant impact on the endurance performance in a WOD in the AMRAP, EMOM, or FOR TIME model. We can observe at least six pacing strategies adopted during the cyclical modalities in the endurance performance in the scientific literature. However, besides these modalities, exercises of acyclical modalities of weightlifting and gymnastics are performed in the "Cross" modalities. These exercises may not allow the same pacing strategies adopted during cyclic modalities' movements due to their motor characteristics and different intensity and level of effort imposed to perform the motor gesture. In addition to the intensity and level of effort that are generally unknown to the coach and athlete of the "Cross" modalities, another factor that can influence the adoption of a pacing strategy during a WOD in the AMRAP, EMOM, or FOR TIME model is the task endpoint knowledge, which varies according to the training model used. Thus, our objective was to evaluate situations in which these factors can influence the pacing strategies adopted in a self-regulated task with cyclic and acyclic modalities movements during an endurance workout in the AMRAP, EMOM, and FOR TIME model. Given the scarcity of studies in the scientific literature and the increasing discussion of this topic within the "Cross" modalities, this manuscript can help scientists and coaches better orient their research problems or training programs and analyze and interpret new findings more accurately.

Novel Non-Immunologic Agents for Relapsed and Refractory Multiple Myeloma: A Review Article.

Novel treatments are needed to address the lack of options for patients with relapsed or refractory multiple myeloma. Even though immunotherapy-based treatments have revolutionized the field in recent years, offering new opportunities for patients, there is still no curative therapy. Thus, non-immunologic agents, which have proven effective for decades, are still central to the treatment of multiple myeloma, especially for advanced disease. Building on their efficacy in myeloma, the development of proteasome inhibitors and immunomodulatory drugs has been pursued, and has led to the emergence of a novel generation of agents (e.g., carfilzomib, ixazomib, pomalidomide). The use of alkylating agents is decreasing in most treatment regimens, but melflufen, a peptide-conjugated alkylator with a completely new mechanism of action, offers interesting opportunities. Moreover, with the identification of novel targets, new drug classes have entered the myeloma armamentarium, such as XPO1 inhibitors (selinexor), HDAC inhibitors (panobinostat), and anti-BCL-2 agents (venetoclax). New pathways are still being explored, especially the possibility of a mutation-driven strategy, as biomarkers and targeted treatments are increasing. Though multiple myeloma is still considered incurable, the treatment options are expanding and are progressively becoming more diverse, largely because of the continuous development of non-immunologic agents.

Waldenström macroglobulinemia and relationship to immune deficiency.

Primary or secondary immune deficiency (ID) is a risk factor, although rare, to develop Waldenström macroglobulinemia (WM). We aimed to better understand the incidence of this occurrence in the real-life and the outcome of either entity. We conducted a review of 194 WM in the Poitou-Charentes registry and identified 7 (3.6%) with a prior history of ID. Across the 7 WM with ID, 4 progressed to active WM disease and required treatment for WM with a median time between WM diagnosis and the first treatment of 1.5 years (range 0-3). The median time from ID to WM occurrence was 8 years (1-18). WM could develop from ID, although a rare event. Our first action was to systematically decrease immunosuppression with long-term control of ID. Half of indolent WM remained indolent despite ID and for remaining WM none appeared of poor risk WM.

Three Drug Combinations in the Treatment of Fit Elderly Multiple Myeloma Patients.

The multiple myeloma (MM) non transplant eligible (NTE) population is growing in line with the aging of the population in Western countries. Historically, this population has been known for having a greater risk of treatment related toxicity, and therefore drug development was slow and rather oriented towards the improvement of safety profile than the optimization of disease control. However, NTE MM patients, at least for the fit/non frail patients in recent years, seemed to have benefited more from a less palliative care to improve the depth of response and then prolong survival. NTE MM being a quite heterogeneous population, there are still a number of groups of patients that are in need of more efficient therapy, avoiding unnecessary toxicity, particularly for the frail patients. The use of triplet regimen with a melphalan-prednisone (MP) backbone has long been the standard of care for NTE MM, often dedicated to non-frail patients. New standards of care, triplet, and even quadruplet combinations, are emerging on the basis of the MP backbone but also on the more recently approved lenalidomide-dexamethasone (Rd) backbone. These developments were largely possible in line with the development of antibody-based immunotherapies (IT) in MM. The objective to improve outcomes with an acceptable safety profile will see other key therapeutic developments such as the dropping of dexamethasone early in the disease course or various attempts to allow permanent treatment discontinuation with a prolonged disease control. In that context, it is possible that immunomonitoring, minimal residual disease (MRD), and genomic risk-adaptation will become key elements of the treatment decisions on triplet-based regimens.

Multiple Myeloma: An Overview of the Current and Novel Therapeutic Approaches in 2020.

The survival rate of multiple myeloma (MM) patients has drastically increased recently as a result of the wide treatment options now available. Younger patients truly benefit from these innovations as they can support more intensive treatment, such as autologous stem cell transplant or multiple drug association (triplet, quadruplet). The emergence of immunotherapy allowed new combinations principally based on monoclonal anti-CD38 antibodies for these patients. Still, the optimal induction treatment has not been found yet. While consolidation is still debated, maintenance treatment is now well acknowledged to prolong survival. Lenalidomide monotherapy is the only drug approved in that setting, but many innovations are expected. Older patients, now logically named not transplant-eligible, also took advantage of these breakthrough innovations as most of the recent drugs have a more acceptable safety profile than previous cytotoxic agents. For this heterogenous subgroup, geriatric assessment has become an essential tool to identify frail patients and provide tailored strategies. At relapse, options are now numerous, especially for patients who were not treated with lenalidomide, or not refractory at least. Concerning lenalidomide refractory patients, approved combinations are lacking, but many trials are ongoing to fill that space. Moreover, innovative therapeutics are increasingly being developed with modern immunotherapy, such as chimeric antigen receptor T-cells (CAR-T cells), bispecific antibodies, or antibody-drug conjugates. For now, these treatments are usually reserved to heavily pre-treated patients with a poor outcome. MM drug classes have tremendously extended from historical alkylating agents to current dominant associations with proteasome inhibitors, immunomodulatory agents, and monoclonal anti-CD38/anti SLAMF7 antibodies. Plus, in only a couple of years, several new classes will enter the MM armamentarium, such as cereblon E3 ligase modulators (CELMoDs), selective inhibitors of nuclear export, and peptide-drug conjugates. Among the questions that will need to be answered in the years to come is the position of these new treatments in the therapeutic strategy, as well as the role of minimal residual disease-driven strategies which will be a key issue to elucidate. Through this review, we chose to enumerate and comment on the most recent advances in MM therapeutics which have undergone major transformations over the past decade.

The Role of Immunotherapy in Non-transplant Eligible Multiple Myeloma.

As the global population is aging and survival in multiple myeloma (MM) is increasing, treating older MM patients, redefined as non-transplant eligible (NTE), is becoming more frequent. Yet, treating these patients remains a real challenge especially because of a marked heterogeneity in the population and an increased susceptibility to treatment toxicity. Indeed, the balance between efficacy and safety must be considered at all time throughout the treatment history for these patients. Therefore, younger and older patients were historically treated in a very different way, even though the safety profile of most anti-myeloma drugs has drastically improved over the years. The emergence of immunotherapy (IT) has largely widened the therapeutic options available in MM and above all has allowed a therapy at optimal dose, and therefore optimal activity, for all patients independently of their frailty features, with no increase in safety issues. Among the novel anti-myeloma IT-based agents, anti-CD38 monoclonal antibodies (mAbs) are now becoming the new backbone of treatment for NTE patients, in association with lenalidomide and dexamethasone. Moreover, several new IT-based drugs are currently being developed and investigated either alone or in association; such as new anti-CD38 mAbs, anti-CD38 mAbs with many different combinations, but also the CAR-T cells, bispecific T-cell engager (BiTEs), or antibody drug conjugate (ADC) targeting BCMA. One would expect that immunotherapy will ultimately change and even transform the MM landscape, even for elderly patients. Immunotherapy represents a shift in treatment paradigm in MM as it provides truly efficient drugs with a very favorable safety profile.

Cross modalities: are the AMRAP, RFT and EMOM models applicable to health? / Modalidades Cross: Os Modelos AMRAP, RFT e EMOM são aplicáveis no contexto da Saúde?

Abstract Currently, training models based on the maximum number of repetitions/rounds or on the execution of a proposed task in the shortest possible time have been gaining ground among Physical Education professionals. However, in our opinion, these models have significant drawbacks that oppose their use in the health context. Thus, we provide an analysis of the problems related to the control and magnitude of the training load (volume and intensity), distribution, duration, and characteristics of the recovery intervals and, of course, the intra-session density. This analysis was made without having measured each of these proposals directly. It is based on the reflection of the dynamics of the efforts made and potential fatigue generated. We hope to be able to verify and provide accurate and reliable data that may support and confirm the hypothesis generated through this analysis.

Resumo Atualmente, os modelos de treinamento em que são executados o número máximo de repetições/rounds ou se completa a tarefa proposta no menor tempo possível têm sido muito utilizados por grande parte dos profissionais de Educação Física. Contudo, ao nosso ver, tais modelos possuem importantes inconvenientes que contrapõem sua utilização dentro do contexto da saúde. Assim, nós fornecemos uma análise dos problemas relacionados ao controle da magnitude da carga de treinamento (volume e intensidade), a distribuição, duração e características das recuperações e, logicamente, da densidade intra-sessão. Esta análise foi realizada sem ter medido diretamente cada uma dessas propostas e se baseia na lógica da dinâmica dos esforços realizados e da potencial fadiga gerada.Em breve, esperamos poder verificar e fornecer os dados específicos para confirmar esta análise.

Phase I dose-escalation study of F50067, a humanized anti-CXCR4 monoclonal antibody alone and in combination with lenalidomide and low-dose dexamethasone, in relapsed or refractory multiple myeloma.

PURPOSE: Multiple myeloma (MM) remains an incurable disease as tumor cells ultimately resist to all available drugs. Homing of tumor cells to the bone marrow microenvironment, involving especially the CXCR4/SDF-1 axis, allows them to survive, proliferate and resist to therapy. F50067, a humanized anti-CXCR4 IgG1 antibody, has promising preclinical activity in MM.We present a phase I multicenter escalation study in relapsed/refractory MM (RRMM) to determine the maximum tolerated dose (MTD) for F50067 alone and in combination with lenalidomide and low dose dexamethasone (Len-Dex). EXPERIMENTAL DESIGN: 14 end-stage RRMM patients received F50067 single agent (n = 10) or in combination with Len-Dex (n = 4). RESULTS: One dose-limiting toxicity was observed, a grade 4 neutropenia lasting more than 7 days in combination arm. MTD could not be established. Thrombocytopenia was observed in 100% and neutropenia in 92.9% of patients with no cases of febrile neutropenia and no severe bleeding or hematoma. Non-hematological adverse events were of mild to moderate severity.Nine patients (6 in single arm and 3 in combination arm) were evaluable for response, with 66.7% overall response rate (≥PR) in combination arm, and 33.3% of disease control (≥SD) in single agent arm. At the time of study termination, 55.6% had progressed. CONCLUSION: This study suggests that egression of tumor cells to the blood stream can represent a novel therapeutic strategy for MM. However, because of significant hematological toxicity, this study had to be discontinued. Further studies are needed to validate the feasibility of this approach in clinical practice.

Tuberculous anal fistulas--prevalence and clinical features in an endemic area.

INTRODUCTION: The aim of this study was to determine the prevalence of tuberculosis (TB) in anal fistulas at a referral hospital in Cape Town, and to document the clinical features and course of patients with tuberculous anal fistulas. PATIENTS AND METHODS: This was a prospective study of all patients who underwent surgery for anal fistulas at the Colorectal Surgery Unit at Groote Schuur Hospital, Cape Town, from 2004 to 2006. Tissue was submitted for histopathological examination, Ziehl-Neelsen (ZN) staining and TB culture. The patients with proven TB were followed up until January 2008. RESULTS: During the 3-year study period, 117 operations were performed on 96 patients. TB was diagnosed in 7 of the 96 patients (7.3%). In 5 of these 7 cases, the diagnosis of TB could be proven on histological examination and ZN staining, while in 2 cases the diagnosis could only be made on TB culture. None of the 7 patients had systemic features suggestive of TB, and only 1 had evidence of TB on a chest radiograph, Five patients were HIV-negative, and 2 declined testing. After a median follow-up of 2 years, 5 of 7 patients had evidence of recurrent or persistent fistulas, despite having completed 6 months of TB treatment. CONCLUSION: At a referral hospital in an endemic area, TB was present in 7.3% of anal fistulas. Histopathological examination including ZN staining was inadequate to make the diagnosis in a third of these patients. Tissue from anal fistulas should therefore routinely be sent for TB culture as well as histopathological examination and ZN staining in areas where TB is prevalent.