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B-cell maturation antigen (BCMA) has emerged as a promising immunotherapeutic target in multiple myeloma (MM) management, with the successive approval of antibody-drug conjugates, bispecific antibodies, and chimeric antigen receptor T-cell therapies directed to this membrane receptor. Soluble BCMA (sBCMA), a truncated version produced through gamma-secretase cleavage, can be quantified in serum/plasma samples from patients with MM via electrochemiluminescence, fluorescence, or enzyme-linked immunosorbent assays, as well as through mass spectrometry-based proteomics. Besides its short serum half-life and independence from kidney function, sBCMA represents a reliable and convenient tool for MM monitoring in patients with nonsecretory or oligosecretory disease. Numerous studies have suggested a potential utility of this bioanalyte in the risk stratification of premalignant plasma cell disorders, diagnosis and prognostication of MM, and response evaluation following anti-myeloma therapies. In short, sBCMA might be the "Swiss army knife" of MM laboratory testing, but is it ready for prime time?
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Anticorpos Biespecíficos , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/patologia , Antígeno de Maturação de Linfócitos B , Imunoterapia Adotiva , Anticorpos Biespecíficos/uso terapêutico , Secretases da Proteína Precursora do AmiloideRESUMO
Thrombosis represents a frequent and potentially severe complication in individuals diagnosed with multiple myeloma (MM). These events can be driven by both the disease as well as the therapies themselves. Overall, available evidence is inconclusive about the differential thrombogenicity of carfilzomib/lenalidomide/dexamethasone (KRd) and bortezomib/lenalidomide/dexamethasone (VRd). This meta-analysis compares the risk for venous thromboembolism (VTE; including deep venous thrombosis and pulmonary embolism) and arterial thromboembolism (ATE; including myocardial infarction and ischemic stroke) with KRd versus VRd as primary therapy for newly diagnosed MM (NDMM). Out of 510 studies identified after deduplication, one randomized controlled trial and five retrospective cohort studies were included. We analyzed 2304 patients (VRd: 1380; KRd: 924) for VTE events and 2179 patients (VRd: 1316; KRd: 863) for ATE events. Lower rates of VTE were observed in the VRd group when compared with the KRd group (6.16% vs. 8.87%; odds ratio [OR], 0.53; 95% confidence interval [CI], 0.32-0.88; p = .01). Both treatment groups exhibited minimal ATE incidence, with no significant difference between them (0.91% vs. 1.16%; OR, 1.01; 95% CI, 0.24-4.20; p = .99). In view of potential biases from retrospective studies, heterogeneity of baseline population characteristics, and limited access to patient-level data (e.g., VTE risk stratification and type of thromboprophylaxis regimen used) inherent to this meta-analysis, additional research is warranted to further validate our findings and refine strategies for thrombosis prevention in MM.
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Protocolos de Quimioterapia Combinada Antineoplásica , Bortezomib , Dexametasona , Lenalidomida , Mieloma Múltiplo , Oligopeptídeos , Humanos , Mieloma Múltiplo/tratamento farmacológico , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Dexametasona/uso terapêutico , Oligopeptídeos/administração & dosagem , Oligopeptídeos/efeitos adversos , Oligopeptídeos/uso terapêutico , Bortezomib/administração & dosagem , Bortezomib/efeitos adversos , Bortezomib/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Lenalidomida/administração & dosagem , Lenalidomida/efeitos adversos , Tromboembolia/prevenção & controle , Tromboembolia/epidemiologia , Tromboembolia/etiologia , Tromboembolia/induzido quimicamente , Tromboembolia Venosa/prevenção & controle , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/induzido quimicamenteRESUMO
In view of the increasing data evaluating carfilzomib-based induction for newly-diagnosed multiple myeloma (NDMM), we conducted a systematic review and meta-analysis comparing the efficacy of carfilzomib/lenalidomide/dexamethasone (KRd) versus bortezomib/lenalidomide/dexamethasone (VRd). Three studies totaling 1597 patients (50% KRd-treated, 50% VRd-treated) were included. Despite similar survival outcomes and overall response rate compared with the VRd arm, KRd-treated subjects showed higher odds of achieving complete responses and measurable residual disease negativity. Among patients with high-risk cytogenetics (n = 348), KRd was associated with significant improvement in progression-free survival (HR = 0.70; 95% CI = 0.50-0.97; p = .03; I2 = 0%), suggesting carfilzomib-based induction may be preferable in this NDMM subpopulation.
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Protocolos de Quimioterapia Combinada Antineoplásica , Bortezomib , Dexametasona , Lenalidomida , Mieloma Múltiplo , Oligopeptídeos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/mortalidade , Humanos , Lenalidomida/administração & dosagem , Lenalidomida/uso terapêutico , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Oligopeptídeos/administração & dosagem , Oligopeptídeos/uso terapêutico , Bortezomib/administração & dosagem , Bortezomib/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Intervalo Livre de Progressão , Resultado do TratamentoRESUMO
Patients with multiple myeloma (MM) are at an elevated risk of venous thromboembolism (VTE), which is further increased for those undergoing anti-myeloma therapy. Current guidelines suggest low-dose direct oral anticoagulants (DOACs) as an alternative to aspirin for primary thromboprophylaxis in this population, but data comparing these two therapies are limited. We performed a systematic review and meta-analysis to compare DOACs with aspirin for primary thromboprophylaxis in individuals undergoing outpatient anti-myeloma therapy. Studies were selected when comparing DOACs versus aspirin for thrombotic and haemorrhagic outcomes. We included 10 randomised controlled trials and observational studies comprising 1026 patients with MM who received primary thromboprophylaxis with DOACs (n = 337) or aspirin (n = 689). DOAC thromboprophylaxis was associated with a significantly lower incidence of VTE compared with aspirin (OR 0.33; 95% CI 0.16-0.68; p < 0.001). Major, clinically relevant non-major and minor bleeding event rates did not differ significantly between groups. Overall, our meta-analysis suggests that DOACs may be a preferable option to aspirin for the prevention of MM-related thrombosis. However, these results should be interpreted in the context of heterogeneous baseline population characteristics and potential bias from including observational studies. Further research is needed to evaluate the optimal thromboprophylaxis strategy, particularly in high-risk individuals.
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BACKGROUND: Colorectal carcinoma (CRC) is widely treated by chemotherapy based on an intensely neurotoxic drug: oxaliplatin (OXL). We objective to evaluate prospectively the orofacial neurotoxicity during FLOX (fluorouracil + leucovorin + OXL) chemotherapy. METHODS: So, 46 patients with CRC were prospectively evaluated during FLOX chemotherapy by 3 cycles (C) of 6 weeks (W) each. We weekly applied the orofacial section of the Acute and Chronic Neuropathy Questionnaire of Common Toxicity Criteria for Adverse Events of the National Cancer Institute of the United States of America (Oxaliplatin-specific neurotoxicity scale). Patients were asked the following concerning the severity (scores 0-5) of orofacial symptoms: jaw pain, eyelids drooping, throat discomfort, ear pain, tingling in mouth, difficulty with speech, burning or discomfort of the eyes, loss of any vision, feeling shock/pain down back and problems breathing. We summed the scores (0-50) and evaluated the clinicopathological data. Friedman/Dunn, Chi square and multinomial regression logistic tests were used (SPSS 20.0, p < 0.05). RESULTS: There was a significant increase in sum of orofacial neurotoxicity from baseline to C1.W3, C2.W1 and C3.W5 (p < 0.001) due increase in scores of jaw pain (p < 0.001), eyelids drooping (p = 0.034), throat discomfort (p < 0.001), ear pain (p = 0.034), tingling in mouth (p = 0.015), burning/discomfort of your eyes (p < 0.001), loss of any vision (p < 0.001), feeling shock/pain down back (p < 0.001), problems with breathing (p = 0.045), but not difficulty with speech (p = 0.087). Women (p = 0.021) and young patients (p = 0.027) had significant higher prevalence of orofacial neurotoxicity. CONCLUSIONS: FLOX-related orofacial neurotoxicity begins acutely and remains long term with increased incidence in women and younger patients.
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Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Síndromes Neurotóxicas/etiologia , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/patologia , Face , Feminino , Fluoruracila/administração & dosagem , Humanos , Incidência , Leucovorina/administração & dosagem , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Boca/efeitos dos fármacos , Síndromes Neurotóxicas/epidemiologia , Oxaliplatina/administração & dosagem , Doenças do Sistema Nervoso Periférico/epidemiologia , Estudos ProspectivosRESUMO
STUDY OBJECTIVE: Insufficient penile skin is common during vaginoplasty for male-to-female transition. This issue may be compensated by a scrotal skin flap, with the drawback of hair growth [1]. In recent studies, Nile tilapia skin was successfully used for the surgical management of Mayer-Rokitansky-Küster-Hauser syndrome [2,3] and vaginal stenosis [4,5]. This study aims to describe a novel technique for primary vaginoplasty in male-to-female gender-affirming surgery using Nile tilapia skin as a biocompatible graft to ensure adequate vaginal depth. DESIGN: Stepwise demonstration of the procedure with narrated video footage. SETTING: Transgender health clinic. INTERVENTIONS: A 29-year-old patient with gender dysphoria was referred to our office because of a desire for gender-affirming surgery. A physical examination revealed normal male genitalia with a 14-cm-long penis. Before surgery, approval from the institutional review board and written permission from the patient were obtained. After orchiectomy, penile disassembly, perineal dissection, and urethroplasty were performed, and a hollow Nile tilapia skin mold was prepared and sutured to the distal edge of the remaining penile skin. This structure was inverted, covering the newly created canal. The neocavity was then filled with a handmade inflatable vaginal mold, held in place by sutures in the labia majora. Finally, labiaplasty and clitoroplasty were conducted. After 7 days, the inflatable mold was removed, and the use of progressively larger dilators was initiated. After 3 weeks, a neovagina that was 16 cm long and able to accommodate the width of 2 fingers was detected. At that time, the Nile tilapia skin was completely reabsorbed into the neovaginal mucosa. There were no complications in the early postsurgical period. CONCLUSION: Nile tilapia skin, a safe, low-cost, and easy-to-use biocompatible material, may be an alternative option to scrotal skin grafts for neovaginal augmentation in primary vaginoplasty for male-to-female gender transition. However, further studies are needed to confirm this assertive.
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Ciclídeos , Disforia de Gênero/cirurgia , Cirurgia de Readequação Sexual/métodos , Transplante de Pele/métodos , Estruturas Criadas Cirurgicamente , Adulto , Animais , Materiais Biocompatíveis/uso terapêutico , Brasil , Feminino , Procedimentos Cirúrgicos em Ginecologia/métodos , Humanos , Masculino , Orquiectomia , Pênis/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Transplante de Pele/veterinária , Retalhos Cirúrgicos/cirurgia , Transplante Heterólogo , Transplante Heterotópico , Transexualidade/cirurgia , Vagina/cirurgiaRESUMO
Mayer-Rokitansky-Küster-Hauser syndrome is the second most common cause of primary amenorrhea, trailing only to gonadal dysgenesis. Neovaginoplasty is an appropriate treatment option for patients who have failed dilation therapy. Several biomaterials have been used in this procedure, including peritoneum, amnion, skin grafts, and myocutaneous flaps. Nile Tilapia Fish Skin has noninfectious microbiota, morphologic structure comparable to human skin, and high in vivo bioresorption. In addition, it showed good outcomes when used as a xenograft for burn treatment. Thus, we suggest it as a new biologic graft for vaginal agenesis management. In this descriptive study, neovaginoplasty using Nile Tilapia Fish Skin offered 3 patients an anatomic and functional neovagina via a simple method with potential long-term effectiveness. When postsurgical dilation was performed correctly, a vaginal length greater than 6 cm was maintained at 180 days follow-up. Histologic and immunohistochemical analyses revealed the presence of stratified squamous epithelium with high expression of cytokeratins and fibroblast growth factor, matching the characteristics of normal adult vaginal tissue. We believe that further studies will show Nile Tilapia Fish Skin to be a relevant option in the therapeutic arsenal of Mayer-Rokitansky-Küster-Hauser syndrome.
Assuntos
Transtornos 46, XX do Desenvolvimento Sexual/cirurgia , Ciclídeos , Anormalidades Congênitas/cirurgia , Ductos Paramesonéfricos/anormalidades , Procedimentos de Cirurgia Plástica/métodos , Transplante de Pele/métodos , Vagina/anormalidades , Administração Intravaginal , Adolescente , Adulto , Animais , Produtos Biológicos/uso terapêutico , Brasil , Dilatação/métodos , Feminino , Humanos , Ductos Paramesonéfricos/cirurgia , Procedimentos de Cirurgia Plástica/efeitos adversos , Transplante de Pele/efeitos adversos , Retalhos Cirúrgicos , Transplante Heterólogo/efeitos adversos , Transplante Heterólogo/métodos , Transplante Heterotópico/efeitos adversos , Transplante Heterotópico/métodos , Resultado do Tratamento , Vagina/cirurgia , Adulto JovemRESUMO
Despite a considerable decrease in its incidence worldwide, burns remain the fourth most common type of trauma. The majority of burns are small, with 75% of injuries treated on an outpatient basis. Tilapia skin, as a biological material, has been suggested as an option for the management of burn wounds. After good results were obtained with the use of a glycerolised version of tilapia skin in burned children and adults, it was hypothesised that similar outcomes could be achieved with the use of a lyophilised version of tilapia skin. We report the case of a 33-year-old female patient with scalds to the upper abdomen, and both breasts, arms and forearms. Involvement of 10% of total body surface area with superficial partial thickness burns was calculated. The good adherence of tilapia skin to the wound bed, a 10-day period for complete re-epithelialisation of the wounds and the absence of side effects suggested that the lyophilised version of tilapia skin is effective for burn treatment. Compared with glycerolisation, lyophilisation is thought to permit extended storage of sterile tissue and decreased costs related to distribution and transport, but further studies are needed to confirm this.
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Curativos Biológicos , Queimaduras/terapia , Xenoenxertos , Tilápia , Adulto , Animais , Brasil , Feminino , Humanos , Reepitelização , Lesões dos Tecidos Moles , Transplante Heterólogo , Resultado do Tratamento , CicatrizaçãoRESUMO
B-cell-maturation-antigen (BCMA)-directed therapies are highly active for multiple myeloma, but infections are emerging as a major challenge. In this retrospective, single-center analysis we evaluated infectious complications after BCMA-targeted chimeric-antigen-receptor T-cell therapy (CAR-T), bispecific-antibodies (BsAb) and antibody-drug-conjugates (ADC). The primary endpoint was severe (grade ≥ 3) infection incidence. Amongst 256 patients, 92 received CAR-T, 55 BsAb and 109 ADC. The incidence of severe infections was higher with BsAb (40%) than CAR-T (26%) or ADC (8%), including grade 5 infections (7% vs 0% vs 0%, respectively). Comparing T-cell redirecting therapies, the incidence rate of severe infections was significantly lower with CAR-T compared to BsAb at 1-year (incidence-rate-ratio [IRR] = 0.43, 95%CI 0.25-0.76, P = 0.004). During periods of treatment-emergent hypogammaglobulinemia, BsAb recipients had higher infection rates (IRR:2.27, 1.31-3.98, P = 0.004) and time to severe infection (HR 2.04, 1.05-3.96, P = 0.036) than their CAR-T counterparts. During periods of non-neutropenia, CAR-T recipients had a lower risk (HR 0.44, 95%CI 0.21-0.93, P = 0.032) and incidence rate (IRR:0.32, 95% 0.17-0.59, P < 0.001) of severe infections than BsAb. In conclusion, we observed an overall higher and more persistent risk of severe infections with BsAb. Our results also suggest a higher infection risk during periods of hypogammaglobulinemia with BsAb, and with neutropenia in CAR-T recipients.
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B-cell-maturation-antigen (BCMA)-directed therapies are highly active for multiple myeloma, but infections are emerging as a major challenge. In this retrospective, single-center analysis we evaluated infectious complications after BCMA-targeted chimeric-antigen-receptor T-cell therapy (CAR-T), bispecific-antibodies (BsAb) and antibody-drug-conjugates (ADC). The primary endpoint was severe (grade ≥3) infection incidence. Amongst 256 patients, 92 received CAR-T, 55 BsAb and 109 ADC. The incidence of severe infections was higher with BsAb (40%) than CAR-T (26%) or ADC (8%), including grade 5 infections (7% vs 0% vs 0%, respectively). Comparing T-cell redirecting therapies, the incidence rate of severe infections was significantly lower with CAR-T compared to BsAb at 1-year (incidence-rate-ratio [IRR] = 0.43, 95%CI 0.25-0.76, P = 0.004). During periods of treatment-emergent hypogammaglobulinemia, BsAb recipients had higher infection rates (IRR:2.27, 1.31-3.98, P = 0.004) and time to severe infection (HR 2.04, 1.05-3.96, P = 0.036) than their CAR-T counterparts. During periods of non-neutropenia, CAR-T recipients had a lower risk (HR 0.44, 95%CI 0.21-0.93, P = 0.032) and incidence rate (IRR:0.32, 95% 0.17-0.59, P < 0.001) of severe infections than BsAb. In conclusion, we observed an overall higher and more persistent risk of severe infections with BsAb. Our results also suggest a higher infection risk during periods of hypogammaglobulinemia with BsAb, and with neutropenia in CAR-T recipients.
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Antígeno de Maturação de Linfócitos B , Imunoterapia Adotiva , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/terapia , Antígeno de Maturação de Linfócitos B/imunologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Imunoterapia Adotiva/efeitos adversos , Adulto , Infecções/etiologia , Infecções/epidemiologia , Anticorpos Biespecíficos/uso terapêutico , Anticorpos Biespecíficos/efeitos adversos , Idoso de 80 Anos ou mais , Incidência , Imunoconjugados/uso terapêutico , Imunoconjugados/efeitos adversosRESUMO
Despite being the mainstay of management for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), there is limited data regarding the impact of tocilizumab (TCZ) and corticosteroids (CCS) on chimeric antigen receptor (CAR) T-cell efficacy in multiple myeloma (MM). The present study aims to evaluate the prognostic impact of these immunosuppressants in recipients of BCMA- or GPRC5D-directed CAR T cells for relapsed/refractory MM. Our retrospective cohort involved patients treated with commercial or investigational autologous CAR T-cell products at a single institution from March 2017-March 2023. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall response rate (ORR), complete response rate (CRR), and overall survival (OS). In total, 101 patients (91% treated with anti-BCMA CAR T cells and 9% treated with anti-GPRC5D CAR T cells) were analyzed. Within 30 days post-infusion, 34% received CCS and 49% received TCZ for CRS/ICANS management. At a median follow-up of 27.4 months, no significant difference in PFS was observed between CCS and non-CCS groups (log-rank p = 0.35) or between TCZ and non-TCZ groups (log-rank p = 0.69). ORR, CRR, and OS were also comparable between evaluated groups. In our multivariable model, administering CCS with/without TCZ for CRS/ICANS management did not independently influence PFS (HR, 0.74; 95% CI, 0.36-1.51). These findings suggest that, among patients with relapsed/refractory MM, the timely and appropriate use of CCS or TCZ for mitigating immune-mediated toxicities does not appear to impact the antitumor activity and long-term outcomes of CAR T-cell therapy.
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Corticosteroides , Anticorpos Monoclonais Humanizados , Imunoterapia Adotiva , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/terapia , Mieloma Múltiplo/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Anticorpos Monoclonais Humanizados/uso terapêutico , Idoso , Imunoterapia Adotiva/efeitos adversos , Imunoterapia Adotiva/métodos , Estudos Retrospectivos , Prognóstico , Corticosteroides/uso terapêutico , Adulto , Receptores de Antígenos Quiméricos/uso terapêutico , Idoso de 80 Anos ou maisRESUMO
The emergence of chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of hematologic malignancies, including multiple myeloma (MM). Two BCMA-directed CAR T-cell products - idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel) - have received US Food and Drug Administration (FDA) approval for patients with relapsed/refractory MM who underwent four or more prior lines of therapy (including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody). Despite producing unprecedented response rates in an otherwise difficult to treat patient population, CAR T-cell therapies are commonly associated with immune-related adverse events (e.g., cytokine release syndrome and neurotoxicity), cytopenias, and infections. Moreover, many patients continue to exhibit relapse post-treatment, with resistance mechanisms yet to be fully understood. Ongoing basic, translational, and clinical research efforts are poised to generate deeper insights into the optimal utilization of these therapies, improve their efficacy, minimize associated toxicity, and identify new target antigens in patients with MM.
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Neoplasias Hematológicas , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/terapia , Imunoterapia Adotiva/efeitos adversos , Recidiva Local de Neoplasia , AntiviraisRESUMO
From the 1960s to the early 2000s, alkylating agents (e.g., melphalan, cyclophosphamide, and bendamustine) remained a key component of standard therapy for newly-diagnosed or relapsed/refractory multiple myeloma (MM). Later on, their associated toxicities (including second primary malignancies) and the unprecedented efficacy of novel therapies have led clinicians to increasingly consider alkylator-free approaches. Meanwhile, new alkylating agents (e.g., melflufen) and new applications of old alkylators (e.g., lymphodepletion before chimeric antigen receptor T-cell [CAR-T] therapy) have emerged in recent years. Given the expanding use of antigen-directed modalities (e.g., monoclonal antibodies, bispecific antibodies, and CAR-T therapy), this review explores the current and future role of alkylating agents in different treatment settings (e.g., induction, consolidation, stem cell mobilization, pre-transplant conditioning, salvage, bridging, and lymphodepleting chemotherapy) to ellucidate the role of alkylator-based regimens in modern-day MM management.
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Mieloma Múltiplo , Receptores de Antígenos Quiméricos , Humanos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/diagnóstico , Alquilantes/uso terapêutico , Ciclofosfamida , Cloridrato de Bendamustina/uso terapêuticoRESUMO
INTRODUCTION: Despite major advances in surveillance and management, advanced cholangiocarcinoma (CCA) still carries a dismal prognosis. In recent years, several actionable genomic alterations in pancreatobiliary malignancies have been identified. For instance, homologous recombination deficiency (HRD) has been considered a predictive biomarker of clinical response to platinum and poly (ADP-ribose) polymerase (PARP) inhibitors. CASE REPORT: A 53-year-old man with a stage 3 (T4N0M0) BRCA2-mutant CCA developed intolerable toxicity after 44 cycles of gemcitabine/cisplatin. In light of his HRD positivity, treatment was switched to single-agent olaparib. The patient showed a partial radiological response, which was maintained after 8 months of olaparib discontinuation (progression-free survival >36 months). CONCLUSION: Given the durable response observed, olaparib can be a valuable therapeutic tool in BRCA-mutant CCAs. Ongoing and future clinical trials are needed to confirm the role of PARP inhibition in similar patients and to define the clinicopathological and molecular profile of the individuals most likely to benefit.
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Neoplasias dos Ductos Biliares , Tumor de Klatskin , Neoplasias Ovarianas , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Inibidores de Poli(ADP-Ribose) Polimerases/efeitos adversos , Tumor de Klatskin/tratamento farmacológico , Neoplasias Ovarianas/patologia , Poli(ADP-Ribose) Polimerases/genética , Poli(ADP-Ribose) Polimerases/uso terapêutico , Neoplasias dos Ductos Biliares/tratamento farmacológico , Neoplasias dos Ductos Biliares/genética , Ductos Biliares Intra-Hepáticos/patologia , Mutação , Células Germinativas/patologia , Proteína BRCA2/genéticaRESUMO
Immunomodulatory drugs (IMiDs) have become an integral part of therapy for both newly diagnosed and relapsed/refractory multiple myeloma (RRMM). IMiDs bind to cereblon, leading to the degradation of proteins involved in B-cell survival and proliferation. Thalidomide, a first-generation IMiD, has little to no myelosuppressive potential, negligible renal clearance, and long-proven anti-myeloma activity. However, thalidomide's adverse effects (e.g., somnolence, constipation, and peripheral neuropathy) and the advent of more potent therapeutic options has led to the drug being less frequently used in many countries, including the US and Canada. Newer-generation IMiDs, such as lenalidomide and pomalidomide, are utilized far more frequently. In numerous previous trials, salvage therapy with thalidomide (50-200 mg/day) plus corticosteroids (with or without selected cytotoxic or targeted agents) has been shown to be effective and well-tolerated in the RRMM setting. Hence, thalidomide-based regimens remain important alternatives for heavily pretreated patients, especially for those who have no access to novel therapies and/or are not eligible for their use (due to renal failure, high-grade myelosuppression, or significant comorbidities). Ongoing and future trials may provide further insights into the current role of thalidomide, especially by comparing thalidomide-containing regimens with protocols based on newer-generation IMiDs and by investigating thalidomide's association with novel therapies (e.g., antibody-drug conjugates, bispecific antibodies, and chimeric antigen receptor T cells).
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Antineoplásicos , Mieloma Múltiplo , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Humanos , Fatores Imunológicos/efeitos adversos , Lenalidomida/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Terapia de Salvação , Talidomida/efeitos adversosRESUMO
INTRODUCTION: Coronavirus disease 2019 (COVID-19) may present with extrapulmonary manifestations, including hematologic changes. Previous studies suggest that severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) can interact with the renin-angiotensin system, ultimately causing increased production of angiotensin II. By reporting the cases of previously healthy young adults diagnosed with a hematologic malignancy after experiencing COVID-19, we raise the hypothesis that the SARS-Cov-2 infection could act as a trigger for leukemogenesis in predisposed individuals. METHODS: This was a case series performed through extraction of relevant clinical information from the medical records of three patients admitted to our Hematology unit between August 2020 and September 2020. MAIN RESULTS: Considering the relatively rapid development of cytopenias following recovery from COVID-19, it cannot be ruled out that SARS-Cov-2 played a role in leukemogenesis in those patients. Based on previous in vitro studies, the renin-angiotensin system imbalance induced by SARS-CoV-2 could potentially promote in vivo leukemogenesis through several mechanisms. CONCLUSION: Despite the advances in pathophysiological and clinical characterization of COVID-19, the consequences of the pandemic to the incidence of hematologic diseases are still to be elucidated. In this context, future dissection of the status of the local bone marrow renin-angiotensin system in leukemogenesis is a clinically relevant basic research area.
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Despite recent advances in treatment and surveillance, metastatic melanoma still carries a poor prognosis. Large/giant congenital melanocytic nevi (CMNs) constitute a known risk factor for the condition, with the greatest risk for malignant transformation thought to be during childhood (median age at diagnosis of 3 years in a previous cohort). Herein, we present the case of a 30-year-old male who, after undergoing multiple excision/grafting procedures for a giant CMN as a child, was diagnosed with an NRAS-mutant, MDM2-amplified metastatic melanoma more than 20 years later. Response to ipilimumab/nivolumab immunotherapy, cisplatin/vinblastine/temozolomide chemotherapy, and nivolumab/relatlimab immunotherapy was poor. This case highlights the importance of lifetime monitoring with once-yearly dermatological examination (including lymph node palpation) in large/giant CMN patients, as well as the need for further clinical trials evaluating novel therapies for NRAS-mutant melanoma.
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AIM: In the Roux-en-Y gastric bypass technique, classic laparoscopic surgical retractors are usually rigid, require an additional incision for its installation, or must be handled by an assistant during the surgical procedure, involving a risk of liver injury. The aim of this study was to evaluate and validate a technique of the esophagogastric junction exposure obtained by the flexible liver retractor in bariatric surgery, comparing its efficacy with the retractor classically used for this purpose. METHODS: This study was performed as a randomized, open, prospective, controlled, and comparative design in patients with medical indications of bariatric surgery. The subjects were distributed in the classic (control) and flexible (test) retractor groups. RESULTS: A total of 100 patients (n=50 control group, n=50 test group) were included. No statistically significant difference was observed in the mean duration of surgery. Regarding visibility, 100% of the patients in the flexible retractor group demonstrated an optimal visibility level, although without statistical significance concerning the classic retractor group (94%). Invariably, carrying a trocar was necessary when using the classic retractor. CONCLUSIONS: The flexible liver retractor is safe, effective, ergonomic, and inexpensive. Furthermore, it presented a satisfactory aesthetic profile, and the use of specific instruments, new adaptation curve, and training for its handling were not required.
OBJETIVOS: Os afastadores clássicos de cirurgia laparoscópica são geralmente rígidos, necessitando de uma incisão adicional para sua instalação ou de um auxiliar para manuseio durante o ato cirúrgico e ainda, podem envolvem risco de injúria hepática. Avaliar e validar uma técnica de exposição da junção esofagogástrica obtida pelo afastador flexível de fígado em cirurgia bariátrica comparando sua eficácia com a de afastador classicamente utilizado para este fim. MÉTODOS: Tratou-se de um estudo prospectivo, aberto, controlado e comparativo em pacientes com indicação de cirurgia, distribuídos de forma randomizada em dois grupos: clássico (controle) e afastador flexível (teste). RESULTADOS: Foram incluídos 100 pacientes (n=50 grupo controle, n=50 grupo teste), sem diferença estatística na distribuição por idade e por morbidades, havendo diferença estatística somente no gênero (grupo controle obteve proporção maior de homens, p=0,020). Em relação ao tempo médio de realização das operações, não foi constatada diferença estatística. No quesito visibilidade, verificou-se que 100% dos pacientes do grupo afastador flexível obteve nível de visibilidade ótima, porém sem significância estatística com relação ao grupo clássico (94%). Invariavelmente, foi necessário um portal a mais de trocarte quando do uso do afastador clássico. CONCLUSÃO: O afastador flexível de fígado demonstrou-se seguro, eficaz, ergonômico, de baixo custo, de perfil estético satisfatório, não requerendo instrumental específico para uso ou nova curva de adaptação e aprendizado para manuseio.
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Cirurgia Bariátrica , Derivação Gástrica , Obesidade Mórbida , Junção Esofagogástrica/cirurgia , Humanos , Estudos ProspectivosRESUMO
BACKGROUND: In a phase II study comparing Nile tilapia fish skin to silver sulfadiazine cream for outpatient management of superficial partial-thickness burns, the fish skin decreased reepithelialization time (average reduction, 1.43 days), dressing changes (average reduction, 3.72 dressings), and visual analogue scale pain scores. The present study aimed to further evaluate Nile tilapia fish skin efficacy for superficial partial-thickness burns. Unlike silver sulfadiazine cream, the fish skin has good adherence to the wound bed, which may prevent infections and decrease need for dressing changes. Thus, it could be a low-cost alternative to hasten healing and improve pain of burn patients. METHODS: A phase III randomized controlled trial was conducted from April of 2017 to October of 2018 in Fortaleza, Brazil, and included 115 outpatients aged 18 to 70 years with superficial partial-thickness burns affecting 15 percent or less of body surface area and no previous treatment. Fifty-seven patients were treated with the glycerolized fish skin and 58 with silver sulfadiazine cream 1%. Primary outcomes were reepithelialization time, number of dressings, treatment-related costs, and pain intensity, assessed by means of visual analogue scale, Electronic von Frey, Burns Specific Pain Anxiety Scale, and analgesic use. Patients were evaluated every 48 hours. RESULTS: Patients treated with fish skin required fewer days for reepithelialization (9.7 ± 0.6 days versus 10.2 ± 0.9 days; p = 0.001) and fewer dressings (1.6 ± 0.7 versus 4.9 ± 0.5; p < 0.001). They also had decreased analgesic needs and visual analogue scale, Burns Specific Pain Anxiety Scale, and Electronic von Frey measurements. Finally, fish skin use reduced the final average treatment-related cost per patient by 42.1 percent. CONCLUSION: By hastening reepithelialization, improving burn-related pain, and decreasing treatment-related costs, Nile tilapia fish skin could benefit the resource-poor public health systems of developing countries. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.
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Bandagens , Queimaduras/terapia , Ciclídeos , Custos de Cuidados de Saúde , Dor/prevenção & controle , Pele/lesões , Adolescente , Adulto , Idoso , Animais , Queimaduras/complicações , Feminino , Humanos , Escala de Gravidade do Ferimento , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Estudos Prospectivos , Adulto JovemRESUMO
OBJECTIVES: This study aims at evaluating whether subjective donor deferral (SDD) has the potential for increasing blood transfusion safety. BACKGROUND: Appropriate donor selection via clinical and serologic screening is necessary to prevent transfusion-transmissible infections (TTIs). One additional strategy adopted by some Brazilian blood transfusion centers (BTCs) is the rejection of a donation by the pre-donation interviewer based on subjective factors. METHODS/MATERIALS: We conducted a STROBE-guided cross-sectional study including 105 005 prospective donors who presented to our BTC between 1 January 2013, and 31 December 2015. Donors were evaluated for age, gender, education level, donation type and history, confidential unit exclusion, SDD, and results of serologic screening for TTIs. RESULTS: Even after controlling for potential confounding variables, subjectively deferred donors were more likely to have at least one reactive serology in the standard screening (OR: 2.80; 95% CI: 2.13-3.69; P < .001). They also had a higher risk for testing positive for syphilis (OR: 4.47; 95% CI: 3.05-6.55; P < .001), hepatitis B (OR: 5.69; 95% CI: 2.48-13.08; P < .001), and HIV (OR: 6.14; 95% CI: 3.22-11.69; P < .001). CONCLUSIONS: Routine implementation of SDD in donor selection may be an effective additional measure to avoid TTIs, highlighting the importance of interviewer experience, perspicacity, and face-to-face contact with donors for blood safety assurance.