RESUMO
BACKGROUND: Chronic rhinosinusitis (CRS) is prevalent in cystic fibrosis (CF), significantly affecting quality of life. The introduction of CFTR modulators, including elexacaftor-tezacaftor-ivacaftor (ETI), offers promise for improving sinonasal outcomes. METHODS: We conducted a retrospective cohort multicenter study analyzing electronic medical records of 45 adult CF patients with CRS, predominantly heterozygous for the ΔF508 mutation, treated with ETI between January 2018 and December 2023. Assessments included Sinonasal Outcome Test 22 (SNOT-22), Nasal Polyp Score (NPS), modified Lund-Kennedy Score (mLKS), Lund-Mackay Score (LMS), and olfactory function using smell loss visual analog scale (VAS) and Sniffin' Sticks identification test (SSIT). RESULTS: After 12 months of ETI therapy, significant improvements were observed in pulmonary function parameters (FEV1, FVC), CRS severity scores (SNOT-22, NPS, mLKS), radiological findings (LMS), and olfactory function. Subgroup analysis suggested enhanced efficacy in patients with prior endoscopic sinonasal surgery. CONCLUSIONS: ETI therapy demonstrates comprehensive improvements in CRS and olfactory function in CF patients, highlighting the potential of CFTR modulators in managing sinonasal manifestations.
RESUMO
OBJECTIVE: Novel mRNA-based vaccines have been proven to be powerful tools in combating the global pandemic caused by SARS-CoV-2 protecting individuals, especially the immunocompromised, from COVID-19. Still, it remains largely unknown how solid organ transplant and different immunosuppressive medications affect development of vaccine-induced immunity. METHODS: In this work, we monitored humoral and cellular memory responses after mRNA SARS-CoV-2 two-doses and booster doses vaccination in cystic fibrosis lung transplanted patients (CFT) and compared them with both cystic fibrosis patients without lung transplant (CF) and with kidney transplant recipients (KT). In particular, we investigated the effects of immunosuppressive regimens on immune memory to SARS-CoV-2 after mRNA SARS-CoV-2 vaccine in transplanted patients. RESULTS: Our results showed that immunocompromised transplanted patients displayed a weak cellular and humoral memory to SARS-CoV-2 mRNA vaccination. In addition, obtained data clearly demonstrate that immunosuppressive therapy regimen including antimetabolites, further reduces patients' ability to respond to vaccination at both humoral and cell-mediated level. Notably, patient treated with antimetabolites showed a lower humoral and cellular response also after a booster dose vaccination. CONCLUSION: These results, even if obtained on a small patient's cohort, question whether immunocompromised patients need interventions to improve vaccine SARS-CoV-2 mRNA vaccine response such as additional jab or modulation of immunosuppressive therapy.
Assuntos
Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , Imunidade Celular , Imunidade Humoral , Hospedeiro Imunocomprometido , Imunossupressores , SARS-CoV-2 , Transplantados , Humanos , COVID-19/imunologia , COVID-19/prevenção & controle , SARS-CoV-2/imunologia , Masculino , Feminino , Imunossupressores/uso terapêutico , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/sangue , Adulto , Vacinação , Pessoa de Meia-Idade , Fibrose Cística/imunologia , Memória Imunológica , Transplante de Órgãos/efeitos adversos , Transplante de Rim/efeitos adversos , Transplante de Pulmão/efeitos adversos , Imunização SecundáriaAssuntos
Fibrose Cística , Humanos , Fibrose Cística/tratamento farmacológico , Prevalência , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Aminofenóis/efeitos adversos , Benzodioxóis/efeitos adversos , Mutação , Combinação de Medicamentos , Agonistas dos Canais de Cloreto/efeitos adversosRESUMO
The use of specific inhibitory drugs of intracellular signalling pathways (such as Bruton-Kinase inhibitors) for the treatment of Waldenström's macroglobulinaemia (WM) is a recognised risk factor for Aspergillus spp. infections. The overlapping clinical manifestations of the two diseases may require the involvement of different medical specialities. We describe the clinical course of a patient with pulmonary and encephalic aspergillosis, with concomitant orbital infiltration, which represented a difficult diagnosis: the case required a multidisciplinary approach to define the ocular lesions and an in-depth study of the literature.
RESUMO
Management of cystic fibrosis (CF) patients colonized with Pseudomonas aeruginosa is challenging due to its virulence and multi-drug resistance. Ceftolozane/tazobactam (C/T) is a promising new antipseudomonal agent, and clinical data on CF are limited. We describe our experience in the use of C/T for P. aeruginosa-related pulmonary exacerbations (PE) in CF adults admitted within 2016 and 2019 at Careggi Hospital, Florence, Italy. PE was diagnosed as deterioration of respiratory function, worsening cough, and increasing of sputum. C/T was given at the dose of 3 g every 8 h. C/T was used in ten patients. Mean length of C/T treatment was 16.3 days, and tobramycin was the most frequently combined antipseudomonal agent. All patients were successfully treated although susceptibility testing on sputum sample showed C/T resistance in two cases. No adverse effects related to C/T were reported. To our knowledge this is the largest case series on CF patients treated with C/T. Clinical responses were encouraging even where C/T resistant P. aeruginosa was isolated, probably due to multiple phenotypes colonizing CF lungs. C/T could play a promising role in combination therapy against P. aeruginosa as a part of a colistin-sparing regime.
Assuntos
Antibacterianos/uso terapêutico , Cefalosporinas/uso terapêutico , Fibrose Cística/tratamento farmacológico , Pulmão/microbiologia , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/efeitos dos fármacos , Tazobactam/uso terapêutico , Adolescente , Adulto , Fibrose Cística/microbiologia , Humanos , Itália , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/isolamento & purificação , Pseudomonas aeruginosa/fisiologia , Escarro/microbiologia , Adulto JovemRESUMO
INTRODUCTION: Mucocutaneous leishmaniasis (MCL) is a complication of tegumentary leishmaniasis, causing potentially life-threatening lesions in the ear, nose, and throat (ENT) region, and most commonly due to Leishmania (Viannia) braziliensis. We report a case of relapsing MCL in an Italian traveler returning from Argentina. CASE DESCRIPTION: A 65-year-old Italian male patient with chronic kidney disease, arterial hypertension, prostatic hypertrophy, and type-2 diabetes mellitus was referred for severe relapsing MCL acquired in Argentina. ENT examination showed severe diffuse pharyngolaryngeal edema and erythema, partially obstructing the airways. A nasopharyngeal biopsy revealed a lymphoplasmacytic inflammation and presence of Leishmania amastigotes, subsequently identified as L. (V.) braziliensis by hsp70 PCR-RFLP analysis and sequencing. Despite receiving four courses of liposomal amphotericine B (L-AmB) and two courses of miltefosine over a 2-year period, the patient presented recurrence of symptoms a few months after the end of each course. After the patient was referred to us, a combined treatment was started with intravenous pentamidine 4 mg/kg on alternate days for 10 doses, followed by one dose per week for an additional seven doses, intralesional meglumine antimoniate on the nasal lesion once per week for six doses, oral azoles for three months, and aerosolized L-AmB on alternate days for three months. The treatment led to regression of mucosal lesions and respiratory symptoms. Renal function temporarily worsened, and the addition of insulin was required to maintain glycemic compensation after pentamidine discontinuation. CONCLUSIONS: This case highlights the difficulties in managing a life-threatening refractory case of MCL in an Italian traveler with multiple comorbidities. Even though parenteral antimonial derivatives are traditionally considered the treatment of choice for MCL, they are relatively contraindicated in cases of chronic kidney disease.The required dose adjustment in cases of impaired renal function is unknown, therefore the use of alternative drugs is recommended. This case was resolved with combination treatment, including aerosolized L-AmB, which had never been used before for MCL.
Assuntos
Anfotericina B/administração & dosagem , Antiprotozoários/administração & dosagem , Azóis/administração & dosagem , Leishmaniose Mucocutânea/tratamento farmacológico , Antimoniato de Meglumina/administração & dosagem , Pentamidina/administração & dosagem , Administração Intravenosa , Idoso , Argentina , Quimioterapia Combinada , Humanos , Leishmania braziliensis/efeitos dos fármacos , Leishmania braziliensis/fisiologia , Leishmaniose Mucocutânea/parasitologia , Masculino , RecidivaRESUMO
During the novel coronavirus pandemic, organ transplant recipients represent a frail susceptible category due to long-term immunosuppressive therapy. For this reason, clinical manifestations may differ from general population and different treatment approaches may be needed. We present the case of a 36-year-old kidney-transplanted woman affected by Senior-Loken syndrome diagnosed with COVID-19 pneumonia after a contact with her positive mother. Initial symptoms were fatigue, dry cough, and coryza; she never had fever nor oxygen supplementation. Hydroxychloroquine and lopinavir/ritonavir were started, and the antiviral drug was replaced with darunavir/cobicistat after 2 days for diarrhea. Immunosuppressant levels were closely monitored, and we observed very high tacrolimus trough levels despite initial dose reduction. The patient was left with steroid therapy alone. The peculiarity of clinical presentation and the management difficulties represent the flagship of our case report. We stress the need for guidelines in transplant recipients with COVID-19 infection with particular regard to the management of therapy.
Assuntos
Antivirais/efeitos adversos , Infecções por Coronavirus/tratamento farmacológico , Inibidores do Citocromo P-450 CYP3A/efeitos adversos , Rejeição de Enxerto/prevenção & controle , Imunossupressores/efeitos adversos , Transplante de Rim , Lopinavir/efeitos adversos , Pneumonia Viral/tratamento farmacológico , Ritonavir/efeitos adversos , Tacrolimo/efeitos adversos , Adulto , Antivirais/uso terapêutico , Betacoronavirus , Proteína C-Reativa/imunologia , COVID-19 , Ciliopatias/complicações , Cobicistat/uso terapêutico , Resfriado Comum/etiologia , Resfriado Comum/fisiopatologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/fisiopatologia , Tosse/etiologia , Tosse/fisiopatologia , Darunavir/uso terapêutico , Desprescrições , Combinação de Medicamentos , Interações Medicamentosas , Inibidores Enzimáticos/uso terapêutico , Fadiga/etiologia , Fadiga/fisiopatologia , Feminino , Glucocorticoides/uso terapêutico , Humanos , Hidroxicloroquina/uso terapêutico , Hospedeiro Imunocomprometido/imunologia , Interleucina-10/imunologia , Interleucina-1beta/imunologia , Interleucina-6/imunologia , Interleucina-8/imunologia , Doenças Renais Císticas/complicações , Falência Renal Crônica/etiologia , Falência Renal Crônica/cirurgia , Amaurose Congênita de Leber/complicações , Metilprednisolona/uso terapêutico , Atrofias Ópticas Hereditárias/complicações , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/imunologia , Pneumonia Viral/fisiopatologia , SARS-CoV-2 , Índice de Gravidade de Doença , Tratamento Farmacológico da COVID-19Assuntos
Fibrose Cística/cirurgia , Cirurgia Endoscópica por Orifício Natural , Qualidade de Vida , Rinite/cirurgia , Sinusite/cirurgia , Adulto , Doença Crônica , Fibrose Cística/psicologia , Feminino , Humanos , Masculino , Rinite/psicologia , Sinusite/psicologia , Inquéritos e Questionários , Resultado do TratamentoRESUMO
BACKGROUND: Cystic Fibrosis (CF) Centers are involved in the decisions regarding the eligibility of CF patients with end-stage lung disease and timing for inclusion on waiting lists (WL) for lung transplantation (LT). There are currently no data on the mortality rates of Italian CF patients on WL and during the first year after LT and we aimed to assess these outcomes by surveying the CF Centers. METHODS: A survey was sent to Italian CF Centers which were requested to report the age at which all CF subjects included on the WL between 2010 and 2014 were included on the list, admitted to either standard or urgent LT, or had died either while on the WL or within the first 3 and 12 months after LT. All outcomes were recorded by December 31, 2015. RESULTS: Two hundred fifty-nine CF subjects were included on the WL during the 5-year study period. The mortality rate during the WL was 19.3% and was not associated with sex, age at inclusion on the WL or standard or urgent access to LT. 159 (61.4%) subjects underwent LT, 46 (28.9%) with urgent procedure. Deaths within the first 3 and 12 months after LT were significantly more prevalent in individuals who underwent urgent LT compared to those with standard LT (p < 0.01). CONCLUSIONS: The mortality of Italian CF patients, included in our survey, was about twice that reported by the National Transplant Center for all LT indications, including CF, during the same time period and despite the introduction of urgent LT. The latter was associated with an unfavorable early outcome compared to standard LT.
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Fibrose Cística/cirurgia , Transplante de Pulmão , Sistema de Registros , Listas de Espera/mortalidade , Adulto , Estudos Transversais , Fibrose Cística/epidemiologia , Feminino , Humanos , Incidência , Itália/epidemiologia , Masculino , Inquéritos e Questionários , Taxa de Sobrevida/tendências , Adulto JovemRESUMO
Liver tissue alterations other than fibrosis may have an impact on liver stiffness measurement. In this study we evaluated 18 patients without a previous clinical history of liver disease, consecutively admitted for acute viral hepatitis. In each patient, aminotransferase determination and liver stiffness measurement were performed on the same study day, at 3 different points: (1) peak increase in aminotransferase; (2) aminotransferase 50% or less of the peak; (3) aminotransferase levels Assuntos
Técnicas de Imagem por Elasticidade/métodos
, Hepatite/diagnóstico
, Cirrose Hepática/diagnóstico
, Adulto
, Alanina Transaminase/sangue
, Aspartato Aminotransferases/sangue
, Feminino
, Hepatite/patologia
, Humanos
, Coeficiente Internacional Normatizado
, Cirrose Hepática/patologia
, Cirrose Hepática/virologia
, Masculino
, Pessoa de Meia-Idade