RESUMO
The incidence of melanoma, the most lethal form of skin cancer, has increased due to ultraviolet exposure. The treatment of advanced melanoma, particularly metastatic cases, remains challenging with poor outcomes. Targeted therapies involving BRAF/MEK inhibitors and immunotherapy based on anti-PD1/anti-CTLA4 antibodies have achieved long-term survival rates of approximately 50% for patients with advanced melanoma. However, therapy resistance and inadequate treatment response continue to hinder further breakthroughs in treatments that increase survival rates. This review provides an introduction to the molecular-level pathogenesis of melanoma and offers an overview of current treatment options and their limitations. Cells can die by either accidental or regulated cell death (RCD). RCD is an orderly cell death controlled by a variety of macromolecules to maintain the stability of the internal environment. Since the uncontrolled proliferation of tumor cells requires evasion of RCD programs, inducing the RCD of melanoma cells may be a treatment strategy. This review summarizes studies on various types of nonapoptotic RCDs, such as autophagy-dependent cell death, necroptosis, ferroptosis, pyroptosis, and the recently discovered cuproptosis, in the context of melanoma. The relationships between these RCDs and melanoma are examined, and the interplay between these RCDs and immunotherapy or targeted therapy in patients with melanoma is discussed. Given the findings demonstrating melanoma cell death in response to different stimuli associated with these RCDs, the induction of RCD shows promise as an integral component of treatment strategies for melanoma.
RESUMO
BACKGROUND: Blood transfusion (BT) may be associated with an increased risk of thromboembolism. The associations between transfusion reactions (TRs) during BTs and potential risk factors for the development of thromboembolism in patients underwent blood transfusion have not been analyzed. Therefore, this study aimed to compare risk factors associated with the development of venous thromboembolism (VTE) or pulmonary embolism (PE) between patients underwent blood transfusion with and without TRs. STUDY DESIGNS AND METHODS: The retrospective study was conducted between April 1, 2017, and March 31, 2020, at a medical center in Taiwan. Blood-transfused patients were grouped into two cohorts as follows: those who experienced TRs and those who did not experience TRs. Both cohorts were subjected to follow-up until March 31, 2021. The endpoints for both groups were the occurrence of VTE or PE or the date of March 31, 2021. To investigate between-cohort risk differences, a Kaplan-Meier survival analysis and multiple Cox proportional hazard model was used. RESULTS: A total of 10,759 patients underwent 59,385 transfusion procedures, with 703 patients in the TR group, and 10,056 patients in the non-TR group. The risk of VTE or PE was twice as high in the TR group than in the non-TR group (adjusted hazard ratio 2.53, 95% confidence interval 1.49-4.29, p = .001). Meanwhile, age, female sex, transfusion frequency increment, and being nondiabetic was associated with an increased risk of developing thromboembolism. CONCLUSION: TRs are associated with increased long-term thromboembolism risk in patients underwent blood transfusion. It is imperative for clinicians to acknowledge this and maintain rigorous follow-up.
Assuntos
Reação Transfusional , Tromboembolia Venosa , Humanos , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Reação Transfusional/epidemiologia , Fatores de Risco , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/epidemiologia , Embolia Pulmonar/etiologia , Embolia Pulmonar/epidemiologia , Adulto , Taiwan/epidemiologia , Modelos de Riscos Proporcionais , Tromboembolia/etiologia , Tromboembolia/epidemiologia , Estimativa de Kaplan-Meier , Transfusão de SangueRESUMO
OBJECTIVE: To assess the spectrum of patients who developed recurrent acute transfusion reactions (TRs) and to characterize these recurrent TRs. METHODS: This retrospective study included patients who developed ≥2 acute TRs between April 2017 and March 2020 in a tertiary medical centre. RESULTS: Among 216 TRs that occurred after 2024 transfusions in 87 patients, 66 (75.9%) patients reported a history of transfusions before the first TR and 70 (80.5%) patients received further transfusions after the last TR; with the same type of TR and reaction to the same type of blood product observed in 59 (67.8%) patients and 56 (64.4%) patients, respectively. TRs were most commonly associated with packed red blood cell (PRBC) transfusions and a febrile non-haemolytic transfusion reaction (FNHTR) was the most common type of TR. However, leukocyte reduced (LR) PRBCs were less common than LR platelets among transfusions with TR (22.7% [27/119] versus 75.0% [57/76], respectively) and premedication was prescribed before 196 of 216 (90.7%) transfusions with TR. CONCLUSION: Most patients with recurrent TRs received repeated transfusions in addition to transfusions with TR. Instead of considering premedication, an increase in the use of LR might be the strategy to reduce the recurrence of TR.
Assuntos
Transfusão de Sangue , Reação Transfusional , Humanos , Estudos Retrospectivos , Transfusão de Eritrócitos/efeitos adversos , PacientesRESUMO
INTRODUCTION: Malignant germ cell tumors (MGCTs) can develop either extracranially or intracranially. Growing teratoma syndrome (GTS) may develop in these patients following chemotherapy. Reports on the clinical characteristics and outcomes of GTS in children with MGCTs are limited. METHODS: We retrospectively collected the data, including the clinical characteristics and outcomes of five patients in our series and 93 pediatric patients selected through a literature review of MGCTs. This study aimed to analyze survival outcomes and risk factors for subsequent events in pediatric patients with MGCTs developing GTS. RESULTS: The sex ratio was 1.09 (male/female). In total, 52 patients (53.1%) had intracranial MGCTs. Compared with patients with extracranial GCTs, those with intracranial GCTs were younger, predominantly boys, had shorter intervals between MGCT and GTS, and had GTS mostly occurring over the initial site (all p < 0.001). Ninety-five patients (96.9%) were alive. However, GTS recurrence (n = 14), GTS progression (n = 9), and MGCT recurrence (n = 19) caused a substantial decrease in event-free survival (EFS). Multivariate analyses showed that the only significant risk factors for these events were incomplete GTS resection and different locations of GCT and GTS. Patients without any risk had a 5-year EFS of 78.8% ± 7.8%, whereas those with either risk had 41.7% ± 10.2% (p < 0.001). CONCLUSION: For patients with high-risk features, every effort should be made to closely monitor, completely remove, and pathologically prove any newly developed mass to guide relevant treatment. Further studies incorporating the risk factors into treatment strategies may be required to optimize adjuvant therapy.
Assuntos
Neoplasias Embrionárias de Células Germinativas , Teratoma , Neoplasias Testiculares , Humanos , Criança , Masculino , Feminino , Teratoma/patologia , Teratoma/cirurgia , Estudos Retrospectivos , Neoplasias Embrionárias de Células Germinativas/terapia , SíndromeRESUMO
BACKGROUND: CBT is a potentially effective treatment for anxiety disorders following TBI; however, empirical evidence has mainly come from clients with mild TBI. This paper describes a CBT-based anxiety treatment programme adapted for clients with more severe injuries. Two case studies are provided to illustrate the implementation of the programme, as a step toward larger scale testing of the programme's feasibility. METHODS AND PROCEDURES: A manualised adapted CBT treatment manual was used to deliver CBT in a standardised manner to two clients, one with severe and one with moderate TBI. Outcome was evaluated using a single-subject design with repeated measures of anxiety, mood and coping style at pre- and post-CBT. RESULTS: The two clients demonstrated positive treatment response on either a measure of anxiety or a continuous measure of distress. Although neither demonstrated a clinically significant change according to the primary outcome measure (Hospital Anxiety and Depression Scale), they showed significant change in at least one corroborated measure of anxiety. CONCLUSIONS: This study suggests the potential utility of the adapted CBT programme for clients with moderate-severe TBI. Limitations of the single case studies were discussed, while noting how they would be addressed in a follow-up randomised controlled trial.
Assuntos
Transtornos de Ansiedade/terapia , Lesões Encefálicas/psicologia , Terapia Cognitivo-Comportamental , Adulto , Transtornos de Ansiedade/etiologia , Terapia Cognitivo-Comportamental/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Inquéritos e Questionários , Resultado do TratamentoRESUMO
Although cognitive-behavioural therapy (CBT) is the treatment of choice for anxiety, its delivery needs to be adapted for individuals with traumatic brain injury (TBI). It also requires clients' active engagement for maximum benefit. This study was a pilot randomised controlled trial involving an anxiety treatment programme adapted for people with TBI, based on CBT and motivational interviewing (MI). Twenty-seven participants with moderate/severe TBI (aged 21-73 years, 78% males) recruited from a brain injury rehabilitation hospital were randomly allocated to receive MI + CBT (n = 9), non-directive counselling (NDC) + CBT (n = 10) and treatment-as-usual (TAU) (n = 8). CBT and MI were manualised and delivered in 12 weekly individual sessions. Primary outcome was self-reported anxiety symptoms assessed at baseline, at the end of NDC/MI and immediately following CBT. Assessment was conducted by assessors blinded to group assignment. Intention-to-treat analyses showed that the two active treatment groups demonstrated significantly greater anxiety reduction than TAU. Participants receiving MI showed greater response to CBT, in terms of reduction in anxiety, stress and non-productive coping, compared to participants who received NDC. The results provided preliminary support for the adapted CBT programme, and the potential utility of MI as treatment prelude. Longer follow-up data are required to evaluate the maintenance of treatment effects.
Assuntos
Ansiedade/terapia , Lesões Encefálicas/terapia , Terapia Cognitivo-Comportamental/métodos , Entrevista Motivacional/métodos , Adulto , Idoso , Ansiedade/complicações , Ansiedade/psicologia , Lesões Encefálicas/complicações , Lesões Encefálicas/psicologia , Aconselhamento/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos/estatística & dados numéricos , Cooperação do Paciente/estatística & dados numéricos , Projetos Piloto , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , AutorrelatoRESUMO
A brief preparatory programme, based on the principles of motivational interviewing (MI), was developed as a way of engaging clients with traumatic brain injury (TBI) and preparing them for a cognitive behaviour therapy (CBT) programme for anxiety. The MI + CBT programme was delivered to a male client in his early 40s with severe TBI at four months post-injury, using a single-subject design with repeated measures pre- and post-treatment. The client received three sessions of manualised MI, followed by nine sessions of CBT. The MI sessions focused on helping the client to develop more realistic goals and supporting his self-efficacy about his ability to cope with anxiety. Specific strategies were used to accommodate the client's cognitive limitations, such as the use of personally meaningful metaphors and role plays. Re-assessments were conducted at the end of MI, CBT and nine weeks post-treatment, using a semi-structured clinical interview and self-report measures of anxiety, mood and change expectancy. The client showed significant improvement in anxiety following treatment and a significant reduction in subjective units of distress (SUDS) between the MI and CBT phases. The results suggest the potential utility of MI in people with TBI, and the need to evaluate treatment protocols in a controlled trial.
Assuntos
Ansiedade/terapia , Lesões Encefálicas/terapia , Terapia Cognitivo-Comportamental/métodos , Entrevista Motivacional/métodos , Adulto , Ansiedade/complicações , Ansiedade/psicologia , Lesões Encefálicas/complicações , Lesões Encefálicas/psicologia , Humanos , Masculino , Avaliação de Processos e Resultados em Cuidados de Saúde/métodos , Avaliação de Processos e Resultados em Cuidados de Saúde/estatística & dados numéricos , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , AutorrelatoRESUMO
Mastocytosis is a rare disorder affecting both children and adults by gathering of functionally defective mast cells in the body's tissues. The World Health Organization (WHO) classified mastocytosis into cutaneous mastocytosis, systemic mastocytosis (SM), and mast cell sarcoma (MCS). We hereby present a case of retroperitoneal MCS with concurrent systemic mastocytosis and an undisclosed associated hematological neoplasm (SM-undisclosed AHN). The diagnosis of MCS and SM was made after the second biopsy over retroperitoneal mass, lymph node, and ovary for rapidly progressive disease with the presentation of unexplained recurrent flushing, palpitation, and shock, in addition to abdominal pain. A clonal myeloid neoplasm was also suspected by the karyotype and hemogram data. Unfortunately, the patient succumbed to the disease quickly. Apart from this unique case, the previously reported cases of SM with MCS in the literature were also reviewed.
RESUMO
A 10-year-old boy who had been treated for acute lymphoblastic leukemia presented with persistent numbness of the left big toe and progressive pain of the ipsilateral lower leg. He had received allogeneic bone marrow transplantation 3 months after a testicular relapse. He was in hematologic remission at admission but as progressive swelling of his left leg continued, bone marrow relapse developed. A muscle biopsy revealed leukemic infiltrates in the surrounding muscles of the left sciatic nerve, and swelling of the nerve was found on a magnetic resonance imaging scan. His symptoms/signs subsided soon after reinduction chemotherapy. Unfortunately, he didn't survive because of a fungal sepsis that developed during the neutropenic state. This case represents a rare neurologic complication of what is currently an uncommon presentation for relapse of acute lymphoblastic leukemia, with acute sciatica and without coexisting epidural or leptomeningeal leukemia.
Assuntos
Infiltração Leucêmica/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Ciática/etiologia , Doença Aguda , Criança , Humanos , Perna (Membro)/patologia , Imageamento por Ressonância Magnética , Masculino , Músculo Esquelético/lesões , Músculo Esquelético/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Recidiva , Nervo Isquiático/patologia , Ciática/diagnósticoRESUMO
The incidence of multifocal atrial tachycardia (MAT) is very low and accounts for less than 1% of supraventricular tachycardia in infants and children. In this report, the clinical characteristics, medical treatment and outcome of MAT in 2 children are described. The first patient presented with tachycardia and respiratory failure since the day after birth. First, he received amiodarone, propranolol, and digoxin and then amiodarone alone. The heart rhythm converted to sinus rhythm 2 weeks after hospitalization. Although nonsustained MAT was occasionally observed when the infant suffered from pulmonary infection, the frequency of recurrent MAT decreased as the infant grew up. The second patient was a 5-year-old girl. She had congenital heart disease with double outlets of right ventricle (DORV), patent ductus arteriosus, coarctation of aorta, and ventricular and atrial septal defects. She underwent total correction at the age of 4 years. MAT was noted 3 months after the operation with the presentation of congestive heart failure. The heart rate slowed down and returned to normal sinus rhythm within several hours after amiodarone use. The symptoms and signs of congestive heart failure also disappeared. The patient took amiodarone regularly, and no tachycardia was detected during the follow-up period. MAT is considered to be a relatively benign arrhythmia with likely good outcome if there is no severe underlying illness. It can be well controlled under appropriate drugs, and a long period of follow-up is suggested. If pharmacologic intervention is required, we suggest that amiodarone may be an excellent choice.
Assuntos
Taquicardia/tratamento farmacológico , Amiodarona/uso terapêutico , Pré-Escolar , Eletrocardiografia , Frequência Cardíaca , Humanos , Lactente , Masculino , Taquicardia/complicações , Taquicardia/diagnósticoRESUMO
Pediatric oncology/hematology patients, especially those with acute lymphoblastic leukemia (ALL), often undergo repeated painful invasive procedures. Deep sedation, mandatory for these procedures in young children, can reduce patient anxiety and get their compliance during procedures. This study assessed clinical experience of employing methohexital or thiamylal with midazolam as sedative for elective invasive procedures in children with ALL. Between November 1997 and March 2004, 20 out of 33 ALL children received deep sedation after evaluation, mainly because of relatively young age (mean age 4.60 +/- 2.03 years). A total of 176 procedures were done, with 139 being intrathecal therapy. There were 98 and 78 procedures for the methohexital and thiamylal groups, respectively. The average dosages to complete the procedures were 2.2 +/- 1.2 mg/kg for methohexital and 3.4 +/- 2.1 mg/kg for thiamylal. One out of the 176 procedures was failed due to bradycardia, hypotension and cyanosis, in the methohexital group. Otherwise, no significant adverse events were found. Increased heart rate (HR) during stable blood pressure (BP) was observed in both groups. In conclusion, under careful monitoring and performed by experienced practitioners, the application of methohexital or thiamylal combined with midazolam to achieve deep sedation for invasive procedures in young children with ALL is safe.
Assuntos
Hipnóticos e Sedativos/farmacologia , Metoexital/farmacologia , Midazolam/administração & dosagem , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Tiamilal/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Criança , Pré-Escolar , Eletrocardiografia , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Lactente , Masculino , Estudos RetrospectivosAssuntos
Quimerismo , Sangue Fetal/transplante , Doadores de Tecidos , Adolescente , Humanos , Cinética , Masculino , Fatores de TempoRESUMO
PURPOSE: In a pilot randomized controlled trial, we investigated the effectiveness of a 12-weekly anxiety treatment programme adapted for individuals with moderate-severe TBI, based on cognitive behaviour therapy (CBT) and Motivational Interviewing (MI). The current study explored the variables associated with treatment response and group differences in change expectancy and working alliance. METHODS: Twenty-seven participants recruited from a brain injury rehabilitation hospital were randomly assigned to MI + CBT, non-directive counselling (NDC) + CBT and treatment-as-usual and assessors were blinded to treatment conditions. Correlation and multiple regression were used to examine the association between reduction in anxiety ratings and a number of clinical, injury and cognitive variables. Random effects regression was used to examine group difference in changes in working alliance and expectancy. RESULTS: There was a trend suggesting that greater injury severity may be predictive of poorer response to CBT and injury severity was significantly related to memory functioning. Participants receiving MI pre-treatment showed a greater increase in change expectancy at the end of CBT and at follow-up, but not at the end of MI. CONCLUSIONS: There is a need to further investigate the effectiveness of treatment for individuals with different injury severity and to explore the relationship between change expectancy and treatment outcome.
Assuntos
Transtornos de Ansiedade/terapia , Lesões Encefálicas/terapia , Terapia Cognitivo-Comportamental/métodos , Aconselhamento , Motivação , Adolescente , Adulto , Idoso , Transtornos de Ansiedade/psicologia , Lesões Encefálicas/reabilitação , Feminino , Seguimentos , Humanos , Entrevista Psicológica , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto JovemRESUMO
We report the case of a 4-year-old boy with acute lymphoblastic leukemia in high-risk group who suffered from generalized tonic-colonic seizure evolving into status epilepticus, and subsequent left hemiparesis during his first reinduction chemotherapy, consisting of dexamethasone, vincristine, l-asparaginase, and epirubicin. Superior sagittal sinus and cerebral venous thrombosis, predominantly in right side, were proved by brain magnetic resonance imaging. After aggressive treatment with low-molecular weight heparin (LMWH), left hemiparesis improved in 1 week. And he was fully ambulatory 3 weeks later. The second cycle of reinduction chemotherapy was conducted smoothly with the concomitant use of LMWH. This case illustrates the strong correlation of the rare thrombotic complication, superior sagittal sinus thrombosis, and hypercoagulable status secondary to combination use of l-asparaginase and corticosteroid. Early and vigilant recognition of superior sagittal sinus thrombosis and prompt anticoagulation with LMWH may prevent further neurological damage.
Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Trombose do Seio Sagital/etiologia , Asparaginase/efeitos adversos , Pré-Escolar , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Trombose do Seio Sagital/tratamento farmacológicoRESUMO
In this study, we reported the outcomes of hematopoietic stem cell transplantation (HSCT) as a treatment modality for pediatric patients admitted over the past 20 years in a single institute. From January 1989 to January 2007, 26 patients with a median age of 8 years underwent 14 matched sibling donor (MSD) and 12 alternative donor (AD) transplantations. Two patients received second transplantation successfully after primary graft failure and late graft rejection. Two patients who received transplantation from matched unrelated donors (MUD) died of sepsis, and one of them also had a graft failure at death. The overall 5-year survival rate was 92.1%: 83.3% for AD transplantation and 100% for MSD transplantation. Grade II acute graft versus host disease (GVHD) developed in 3 patients, and extensive chronic GVHD developed in 2 patients. An interval of more than 6 months from diagnosis to transplantation was the major poor prognostic factor for our patients' survival. Thus, in our experience, HSCT from a MSD remains the first choice of treatment for pediatric patients with severe aplastic anemia. For patients without MSD, transplantation from an AD can also result in long-term survival. Earlier transplantation after diagnosis can also result in better outcomes.
Assuntos
Anemia Aplástica/mortalidade , Anemia Aplástica/terapia , Transplante de Células-Tronco Hematopoéticas/mortalidade , Histocompatibilidade , Doadores de Tecidos/estatística & dados numéricos , Adolescente , Criança , Pré-Escolar , Feminino , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/mortalidade , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Prognóstico , Índice de Gravidade de Doença , Irmãos , Resultado do TratamentoRESUMO
We report a case of treatment-related acute myeloid leukemia (t-AML) in a 16-year-old male following treatment for osteosarcoma (OS). He had been treated with a protocol comprising neoadjuvant chemotherapy, definitive surgery with wide excision and adjuvant chemotherapy for OS. Four months after completion of the treatment, a routine hemogram showed hyperleukocytosis with 90% blasts. Bone marrow aspirate and a chromosomal analysis disclosed acute myeloid leukemia (AML), M5b with 46, XY, t(11;19)(q23;p13.3). The t-AML was characterized by early development (just 4 months after completion of chemotherapy for OS) and generalized leukemia cutis. The patient received an alkylating agent (ifosfamide) and DNA topoisomerase II-targeted drugs (etoposide and doxorubicin). In terms of latency, cytogenetics, and presentation, DNA topoisomerase II-targeted drug-related leukemia seemed likely for this patient. Clinically, his leukemia cutis had developed during a nadir in white blood cell count after the first induction of chemotherapy for AML. The rapid progression and its refractoriness to chemotherapy were poor prognostic signs.
Assuntos
Neoplasias Ósseas/tratamento farmacológico , Leucemia Mieloide Aguda/etiologia , Segunda Neoplasia Primária/etiologia , Osteossarcoma/tratamento farmacológico , Adolescente , Antineoplásicos Alquilantes/efeitos adversos , Humanos , Masculino , Inibidores da Topoisomerase IIRESUMO
BACKGROUND: The incidence of osteosarcoma peaks in adolescence and is much lower in preadolescence. However, reports on its clinical features in preadolescent patients are conflicting. In this study, we attempted to assess the differences in clinical appearance and prognosis of the malignancy between preadolescent and adolescent patients. METHODS: Between January 1980 and January 2006, 13 preadolescent and 58 adolescent patients with high-grade osteosarcoma were treated at our institute, and their medical records were reviewed and compared. RESULTS: The sex distribution, primary metastasis rate, pathologic fracture, histologic type, primary tumor location, and percentage of high alkaline phosphatase level were not different between the 2 groups. Poor responders (tumor necrosis rate < 90%) were more common in the preadolescent group (80% vs. 43%, p = 0.035). Overall survival rates in the preadolescent and adolescent groups were 51.3% and 56.4%, respectively (p = 0.735). In patients without primary metastasis, the 5-year overall survival rates were 60.6% and 66.7% for 11 preadolescents and 39 adolescents, respectively (p = 0.925). CONCLUSION: Considering the common findings in both groups, we suggest that preadolescent patients should be treated with the same regimen as that used for adolescent patients.