RESUMO
Despite the various parenchymal presentation of coronavirus disease 2019 (COVID-19) pneumonia, the involvement of the vascular component, the reduction of perfusion in noninjured part of the lung and secondary right to left shunt play an important role in the genesis of the respiratory insufficiency. We present the case of a 72-year-old woman admitted to Livorno Hospital for severe respiratory insufficiency due to SARS-CoV-2 infection unresponsive to noninvasive in whom administration of nebulized phosphodiesterase 3 (PDE3) inhibitor enoximone was able to improve oxygenation avoiding tracheal intubation. Intravenous infusions of phosphodiesterase inhibitors are commonly used as pulmonary vasodilators in the management of pulmonary hypertension. This is the first case showing that inhaled route administration of PDE3 inhibitor enoximone could be important in the management of COVID-19 hypoxemia, to restore perfusion in noninjured part of the lung, improving oxygenation and avoiding risks of systemic infusion.
Assuntos
Tratamento Farmacológico da COVID-19 , Enoximona/administração & dosagem , Hipóxia/tratamento farmacológico , Pulmão/irrigação sanguínea , Inibidores da Fosfodiesterase 3/administração & dosagem , Circulação Pulmonar/efeitos dos fármacos , Administração por Inalação , Aerossóis , Idoso , COVID-19/fisiopatologia , COVID-19/virologia , Feminino , Humanos , Hipóxia/fisiopatologia , Hipóxia/virologia , Nebulizadores e Vaporizadores , Resultado do TratamentoRESUMO
The introduction of highly active antiretroviral therapy (HAART) has changed dramatically the landscape of HIV disease. Deaths from AIDS-related diseases have been reduced by 75% since protease inhibitor therapy and combination antiretroviral therapy came into use in late 1995. While KS is declining, the situation for non-Hodgkin's lymphoma is more complex with a reduced incidence of primary central nervous system lymphoma, but a relatively stability in the number of patients developing systemic NHL. AIDS related NHL appears not to be markedly decreased by the introduction of HAART and it is the greatest therapeutic challenge in the area of AIDS oncology. The emphasis has now shifted to cure while maintaining vigilance regarding the unique vulnerability of HIV-infected hosts. Furthermore, also for the prolongation of the survival expectancy of these patients, other non AIDS-defining tumors, such as Hodgkin's disease, anal and head and neck, lung and testicular cancer, and melanoma have been recently reported with increased frequency in patients with HIV infection.
Assuntos
Síndrome da Imunodeficiência Adquirida/complicações , Doença de Hodgkin/epidemiologia , Neoplasias/epidemiologia , Neoplasias/terapia , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Terapia Antirretroviral de Alta Atividade , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Doença de Hodgkin/genética , Humanos , Linfoma Relacionado a AIDS/tratamento farmacológico , Linfoma Relacionado a AIDS/genética , Neoplasias/genética , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/prevenção & controleRESUMO
BACKGROUND: Primary effusion lymphoma (PEL) represents a peculiar lymphoma infected with human herpesvirus 8 (HHV-8) and occurs predominantly in human immunodeficiency virus (HIV)-infected patients. The aim of the present study was to evaluate the immunologic and virological parameters, including HHV-8 viremia, of 5 HIV-infected patients with PEL whose disease was diagnosed and treated at our institute. METHODS: Five patients were enrolled in the study. Biological parameters, such as latent and lytic HHV-8 antigen levels, plasma HHV-8 load, Epstein-Barr virus plasma DNA load, HIV-1 load, and CD4 cell count, were assessed before treatment, during therapy, and at follow-up. RESULTS: Four patients were treated with chemotherapy and highly active antiretroviral therapy (HAART), and 1 was treated with HAART alone; 3 of 5 patients reached complete remission. HHV-8 could be detected before the initiation of therapy in plasma from all patients analyzed. HHV-8 levels decreased after therapy in 4 patients. During the whole observation period, plasma HHV-8 load showed a statistically significant inverse correlation with CD4 cell count but no significant correlation with HIV load and response to therapy. CONCLUSIONS: Our analysis demonstrates that HHV-8 can be detected in the plasma at the onset of PEL; its prognostic role needs to be explored. CD4 cell count seems to be the most important indicator of progression of PEL.
Assuntos
Terapia Antirretroviral de Alta Atividade , Infecções por HIV/imunologia , Infecções por HIV/virologia , Linfoma não Hodgkin/etiologia , Adulto , Fármacos Anti-HIV , Contagem de Linfócito CD4 , Progressão da Doença , Feminino , Regulação Viral da Expressão Gênica , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Herpesvirus Humano 8 , Humanos , Linfoma não Hodgkin/virologia , Masculino , Carga Viral , Proteínas Virais/metabolismo , ViremiaRESUMO
PURPOSE: To describe the clinical features and outcome of HIV-associated primary effusion lymphoma (PEL) and to compare them with those of the other HIV-associated non-Hodgkin's lymphomas (NHLs). PATIENTS AND METHODS: From April 1987 to June 2002, 277 patients with HIV infection and systemic NHL were diagnosed and treated in our institution. Clinical features and outcome of PEL patients were compared with the features and outcomes of 162 patients belonging to the following histologic subtypes: plasmoblastic lymphoma of oral cavity (PBLOC, n = 11), immunoblastic lymphoma (IBL, n = 76), and centroblastic B-cell lymphoma (CBCL, n = 75). RESULTS: Among the 277 NHL patients, PEL was diagnosed in 11 patients (4%). Eight of 11 patients were treated with a cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-like regimen. Complete remission was reached in 42% of patients, with a median survival time of 6 months. When the clinical features and outcome of 11 PEL patients were compared with the other three groups of patients affected by NHL, at the onset of the disease, no statistically significant differences were observed in demographic data, CD4 absolute number, HIV viremia plasma levels, and clinical characteristics. When we compared the outcome of PEL patients with the CBCL group, a statistically significant worse outcome was observed; however, the clinical outcome of PEL patients was not significantly different from the outcome observed in the other two groups (PBLOC and IBL groups). CONCLUSION: PEL is a rare HIV-associated NHL type occurring as a late manifestation of HIV infection with a poor clinical outcome and a shorter overall survival compared with CBCL patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Infecções por HIV , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/epidemiologia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Humanos , Itália/epidemiologia , Linfoma não Hodgkin/mortalidade , Linfoma não Hodgkin/patologia , Masculino , Prontuários Médicos , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Vincristina/administração & dosagemRESUMO
Although the majority of head and neck cancers occur between the fifth and sixth decade, their onset in patients older than 60 years is not a rare event. A peculiar characteristic of almost all case series is the lower prevalence of radical treatments among elderly as compared to younger patients, in particular surgery and combined treatment of surgery plus radiation therapy or chemotherapy and radiation therapy. Radiotherapy is a feasible treatment in elderly patients, also in very advanced age groups and, in the era of organ preservation, chemotherapy combined with RT has a paramount importance. Therapeutical planning must be based not only on tumor characteristics, but also on the physiological, rather than the chronological age the patient. The main clinical problem is, therefore, the selection of patients to be administered anticancer treatment. In patients aged 70 or older, complete geriatric assessment and a multidisciplinary approach are the crucial points.
Assuntos
Neoplasias de Cabeça e Pescoço/terapia , Idoso , Terapia Combinada , Humanos , Pessoa de Meia-IdadeRESUMO
We compared the clinical characteristics and outcomes of 100 patients with human immunodeficiency virus (HIV)-associated non-Hodgkin lymphoma (NHL; HIV-NHL) treated in the highly active antiretroviral therapy era with those of 82 HIV-negative patients with aggressive NHL. The 3-year overall survival (OS) was 37% among patients with HIV-NHL and 74% among HIV-negative patients with NHL (P<.0001). However, the response-adjusted OS was similar in the 2 groups (hazard ratio, 1.4 for HIV-infected patients vs. 1 for HIV-negative patients; P=.24). Therefore, the achievement of complete remission should be the main goal in the treatment of patients with HIV-NHL.
Assuntos
Infecções por HIV/complicações , Linfoma Relacionado a AIDS/mortalidade , Linfoma não Hodgkin/mortalidade , Adolescente , Adulto , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Feminino , HIV , Infecções por HIV/tratamento farmacológico , Humanos , Linfoma Relacionado a AIDS/complicações , Linfoma não Hodgkin/complicações , Masculino , Pessoa de Meia-IdadeRESUMO
We evaluated the replication and resistance patterns of human immunodeficiency virus (HIV) strains recovered from HIV-infected patients with non-Hodgkin lymphoma (NHL) who were receiving chemotherapy (CT) concomitant with highly active antiretroviral therapy (HAART). We analyzed virological response to HAART in 35 patients with HIV and NHL who were treated with a cyclophosphamide-doxorubicin-vincristine-prednisone chemotherapy regimen and HAART and the virological response in 26 HIV-infected patients with CD20 cell-positive NHL who were treated with rituximab and cyclophosphamide-doxorubin-etoposide therapy. Genotype and virtual phenotype analyses were performed at baseline and when virological failure occurred. Only 9 patients met the criteria for virological failure. Genotype and virtual phenotype analyses demonstrated that, during CT administration, new mutations might occur, but there were no significant changes in the preexisting resistance patterns. Our data show that combination therapy consisting of CT and HAART is feasible and that the virological response can be maintained in the majority of patients receiving this treatment.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Infecções por HIV/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Prednisona/uso terapêutico , Vincristina/uso terapêutico , Viremia/tratamento farmacológico , Adolescente , Adulto , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Murinos , Terapia Antirretroviral de Alta Atividade , Criança , Quimioterapia Combinada , Feminino , Genótipo , Infecções por HIV/complicações , HIV-1/efeitos dos fármacos , Humanos , Linfoma não Hodgkin/complicações , Masculino , Pessoa de Meia-Idade , Rituximab , Carga Viral , Viremia/complicaçõesAssuntos
Antivirais/uso terapêutico , Infecções por HIV/complicações , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Polietilenoglicóis , Ribavirina/uso terapêutico , Adulto , Terapia Antirretroviral de Alta Atividade , Quimioterapia Combinada , Feminino , Humanos , Interferon alfa-2 , Masculino , Pessoa de Meia-Idade , Proteínas RecombinantesRESUMO
OBJECTIVES: We have investigated whether chemotherapy for HIV-related systemic non-Hodgkin's lymphoma (NHL) affects the pharmacokinetics of protease inhibitors. PATIENTS AND METHODS: This was a prospective, open-label, non-randomized, two-way crossover trial in HIV-1-infected patients treated with highly active antiretroviral therapy and chemotherapy for NHL. Seven patients received indinavir at a dosage of 800 mg three times daily and three patients received nelfinavir at a dosage of 750 mg three times daily. Chemotherapy consisted of adriamycin, cyclophosphamide, vincristine and prednisolone (CHOP). Each patient had blood samples for protease inhibitor pharmacokinetics drawn concomitantly with or independently of the CHOP cycle. RESULTS: When indinavir was given concomitantly with CHOP, the AUC(0-8) increased by 38% (20.5 +/- 9.0 versus 14.9 +/- 9.5 mg.h/L; P=0.03), and was comparable to historical controls. By contrast, the AUC(0-8) of indinavir administered without CHOP was lower than expected. A similar trend was observed with nelfinavir. Likewise, we observed a significant number of patients with C(0) and C(8) below the IC(50) for the wild-type virus (0.1 mg/L) when the drug was administered without CHOP. CONCLUSIONS: Therapeutic drug monitoring of protease inhibitors should be part of the work-up in HIV-infected patients receiving chemotherapy for NHL.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Ciclofosfamida/farmacologia , Doxorrubicina/farmacologia , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/farmacocinética , Indinavir/farmacocinética , Linfoma não Hodgkin/tratamento farmacológico , Nelfinavir/farmacocinética , Prednisona/farmacologia , Vincristina/farmacologia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/sangue , Área Sob a Curva , Estudos Cross-Over , Ciclofosfamida/sangue , Doxorrubicina/sangue , Interações Medicamentosas , Feminino , Infecções por HIV/complicações , Inibidores da Protease de HIV/sangue , Humanos , Indinavir/sangue , Linfoma não Hodgkin/virologia , Masculino , Pessoa de Meia-Idade , Nelfinavir/sangue , Prednisona/sangue , Estudos Prospectivos , Vincristina/sangueRESUMO
BACKGROUND: The objective of the current study was to evaluate the impact of highly active antiretroviral therapy (HAART) on clinical characteristics of presentation and the natural history of Kaposi sarcoma (KS) in patients already receiving HAART at the time of KS diagnosis. METHODS: The authors conducted a retrospective cohort study comparing epidemiologic, clinical, and outcome data for 160 patients who were naive to HAART at the time of KS diagnosis (KS-naive) with the corresponding data for 51 patients already receiving HAART at the time of KS diagnosis (KS-HAART). The analysis included all patients with a diagnosis of KS since January 1996 within two Italian cohorts of patients with human immunodeficiency virus. RESULTS: Immunologic and virologic status at the time of KS diagnosis were significantly more favorable in the KS-HAART group than in the KS-naive group. The frequency of cutaneous involvement was similar in both groups, but cutaneous disease was more indolent among KS-HAART patients, with 1 anatomic site of involvement in 9 patients (21%) and less than 10 lesions in 26 patients (60%), compared with 16 patients (12%; P = 0.06) and 47 patients (34%; P = 0.01), respectively, in the KS-naive group. A smaller proportion of KS-HAART patients presented with visceral disease (24% vs. 39%; P = 0.06); in particular, gastrointestinal tract involvement was significantly less frequent among KS-HAART patients (14%) compared with KS-naive patients (28%; P = 0.05). Median survival was not reached in either group, and the 3-year survival rates of KS-HAART patients (64%) and KS-naive patients (78%) were not significantly different. CONCLUSIONS: The data from the current study indicate that KS exhibits a less aggressive presentation in patients already receiving HAART compared with patients who are naive to HAART at KS diagnosis. Natural history and outcome do not appear to be influenced by the initiation of HAART before development of KS.
Assuntos
Síndrome da Imunodeficiência Adquirida/complicações , Terapia Antirretroviral de Alta Atividade , Sarcoma de Kaposi/tratamento farmacológico , Sarcoma de Kaposi/patologia , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
This study evaluated replication of human immunodeficiency virus (HIV) and the genotypic resistance pattern in 26 HIV-infected patients affected by non-Hodgkin lymphoma who were treated with at least 3 cycles of chemotherapy (CT; rituximab and CDE) and highly active antiretroviral therapy (HAART). Genotyping was performed at baseline and when virological failure occurred. Six patients met the virological failure criteria. The genotyping analysis demonstrated that during CT administration new mutations might occur, but no significant changes in the pre-existing resistance patterns were observed. The data show that a combination therapy consisting of CT and HAART is feasible and that the virological response can be maintained in the majority of such patients.