RESUMEN
OBJECTIVES: Nocardia is an opportunistic infection among renal transplant recipients with an incidence of <1% but high mortality. Data from Pakistan are scarce. Our aim was to find the risk factors, clinical and radiographic findings, antimicrobial sensitivity, and outcomes of Nocardia infection among renal transplant recipients in Pakistan. MATERIALS AND METHODS: All adult renal transplant recipients diagnosed with nocardiosis between 2013 and 2020 were included. The cases were matched 1:2 with controls based on sex, age (±1 year), and transplant date (±1 year). Risk factors, clinical features, antibiotic sensitivities and outcomes were analyzed. RESULTS: A total of 48 patients developed nocardiosis. Around 25% of patients presented with disseminated disease. Median time from transplant to disease development was 2.68 years. High-dose methylprednisolone and presence of cytomegalovirus infection within 90 days of disease development were independent risk factors for Nocardia infection. The mortality rate was 20%. Central nervous system disease and cytomegalovirus infection within 90 days were significantly associated with mortality. The most susceptible drugs were co-trimoxazole and linezolid. Imipenem susceptibility was only 20%. CONCLUSIONS: High-dose methylprednisolone and cytomegalovirus infection were independent risk factors for Nocardia infection. Central nervous system disease was associated with mortality. Nocardia species were highly resistant to ceftriaxone and imipenem in our patient population.
Asunto(s)
Antibacterianos , Huésped Inmunocomprometido , Trasplante de Riñón , Nocardiosis , Infecciones Oportunistas , Humanos , Nocardiosis/diagnóstico , Nocardiosis/mortalidad , Nocardiosis/epidemiología , Nocardiosis/tratamiento farmacológico , Nocardiosis/microbiología , Trasplante de Riñón/efectos adversos , Trasplante de Riñón/mortalidad , Factores de Riesgo , Pakistán/epidemiología , Masculino , Femenino , Adulto , Infecciones Oportunistas/mortalidad , Infecciones Oportunistas/inmunología , Infecciones Oportunistas/diagnóstico , Infecciones Oportunistas/microbiología , Infecciones Oportunistas/epidemiología , Infecciones Oportunistas/tratamiento farmacológico , Persona de Mediana Edad , Antibacterianos/uso terapéutico , Resultado del Tratamiento , Factores de Tiempo , Estudios Retrospectivos , Infecciones por Citomegalovirus/diagnóstico , Infecciones por Citomegalovirus/mortalidad , Infecciones por Citomegalovirus/epidemiología , Medición de Riesgo , Metilprednisolona/administración & dosificación , Inmunosupresores/efectos adversosAsunto(s)
Anticuerpos Anticitoplasma de Neutrófilos , Anticuerpos Monoclonales , Glomerulonefritis por IGA , Humanos , Glomerulonefritis por IGA/tratamiento farmacológico , Glomerulonefritis por IGA/inmunología , Glomerulonefritis por IGA/diagnóstico , Anticuerpos Anticitoplasma de Neutrófilos/sangre , Anticuerpos Anticitoplasma de Neutrófilos/inmunología , Resultado del Tratamiento , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales/efectos adversos , Masculino , Biomarcadores/sangre , Biopsia , Inhibidores del Factor de Necrosis Tumoral/efectos adversos , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Inmunosupresores/uso terapéutico , Inmunosupresores/efectos adversos , Femenino , Persona de Mediana EdadRESUMEN
Increasing number of women with kidney transplants are of reproductive age and desire successful pregnancies. Successful outcomes of pregnancy can be achieved with preconception counseling, education about contraception use, the timing of pregnancy (delaying by first year post-transplant), and the choice of immunosuppression medication. Ensuring stable renal function including optimized creatinine, proteinuria, and blood pressure increases successful outcomes. Pregnancy with kidney transplant has an increased risk of preeclampsia, gestational diabetes militeus, cesarean section, and preterm delivery. Multidisciplinary cooperation with high-risk obstetrics and transplant nephrologists is vital.
Asunto(s)
Trasplante de Riñón , Complicaciones del Embarazo , Salud Reproductiva , Humanos , Trasplante de Riñón/efectos adversos , Embarazo , Femenino , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Receptores de Trasplantes , Resultado del EmbarazoRESUMEN
Kidney transplantation is the optimal therapeutic approach for individuals with end-stage kidney disease. The Scientific Registry of Transplant Recipients has reported a continuous rise in the total number of kidney transplants performed in the United States, with 25,500 new kidney recipients in 2022 alone. Despite an improved glomerular filtration rate, the post-transplant period introduces a unique set of electrolyte abnormalities that differ from those encountered in chronic kidney disease. A variety of factors contribute to the high prevalence of hypomagnesemia, hyperkalemia, metabolic acidosis, hypercalcemia, and hypophosphatemia seen after kidney transplantation. These include the degree of allograft function, immunosuppressive medications and their diverse mechanisms of action, and metabolic changes after transplant. This article aims to provide a comprehensive review of the key aspects surrounding the most commonly encountered electrolyte and acid-base abnormalities in the post-transplant setting.
Asunto(s)
Desequilibrio Ácido-Base , Trasplante de Riñón , Humanos , Trasplante de Riñón/efectos adversos , Desequilibrio Ácido-Base/etiología , Fallo Renal Crónico/cirugía , Desequilibrio Hidroelectrolítico/etiología , Acidosis/metabolismo , Acidosis/etiología , Hiperpotasemia/etiología , Complicaciones Posoperatorias/etiología , Hipercalcemia/etiología , Hipercalcemia/sangre , Hipofosfatemia/etiología , Hipofosfatemia/epidemiología , Inmunosupresores/uso terapéutico , Inmunosupresores/efectos adversosRESUMEN
Survival rates for allografts have improved over the last 2 decades, yet failing allografts remains a challenge in the field of transplant. The risks of mortality and morbidity associated with failed allografts are compounded by infectious complications and metabolic abnormalities, emphasizing the need for a standardized approach to management. Management of failing allografts lacks consensus, highlighting the need for unified protocols to guide treatment protocols and minimize risks with postdialysis initiation. The decision to wean off immunosuppression depends on various factors, including living donor availability and infectious risks, necessitating improved coordination of care and a standard guideline. Treatment of failed pancreas focuses on glycemic control, with insulin as the mainstay, while considering surgical interventions such as graft pancreatectomy in advanced symptomatic cases. Navigating the complexities of failed allograft management demands a multidisciplinary approach and standardized stepwise protocol. Addressing the gaps in management plans for failing allografts and employing a systematic approach to transplant decisions will enhance patient outcomes and facilitate informed decision-making.
Asunto(s)
Trasplante de Riñón , Trasplante de Páncreas , Humanos , Trasplante de Páncreas/métodos , Trasplante de Páncreas/efectos adversos , Trasplante de Riñón/efectos adversos , Rechazo de Injerto/prevención & control , Supervivencia de Injerto , Inmunosupresores/uso terapéutico , Inmunosupresores/efectos adversos , Insuficiencia del TratamientoAsunto(s)
Enfermedades Autoinmunes , Antígeno de Maduración de Linfocitos B , Inmunosupresores , Linfocitos T , Humanos , Enfermedades Autoinmunes/tratamiento farmacológico , Enfermedades Autoinmunes/inmunología , Antígeno de Maduración de Linfocitos B/inmunología , Antígeno de Maduración de Linfocitos B/antagonistas & inhibidores , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología , Anticuerpos Biespecíficos/administración & dosificación , Femenino , Adulto , Persona de Mediana Edad , Inmunosupresores/administración & dosificación , Inmunosupresores/efectos adversos , Resultado del TratamientoRESUMEN
Torque Teno Virus (TTV) is a non-pathogenic anellovirus, highly prevalent in healthy populations. Variations in its viral load have been associated with states of diminished immunity, as occurs after organ transplantation. It is hypothesized that TTV-load might be used as a diagnostic tool to guide prescription and dosing of immunosuppressive drugs. Not much is known about the effects of combined immunosuppressive drugs on TTV replication in renal transplantation. Belatacept was introduced to counter side-effects of calcineurin inhibitors (CNI). It was never widely adopted, mainly because its association with increased risk of rejection. To investigate the differential effects of a regimen based on calcineurin inhibitors versus belatacept on TTV-loads, we measured TTV-levels in 105 patients from two randomized controlled trials in kidney transplant recipients (KTRs). We observed that time after transplantation was inversely related to TTV-levels of patients that remained on a CNI-containing regime, whereas this decline over time was diminished after conversion to belatacept. In addition, a correlation with tacrolimus-trough levels and age were found. Our study is the first report on the impact of conversion from CNI to belatacept on TTV-levels in KTR. In conclusion, the time-related decline in TTV-levels is mitigated after conversion from CNI to belatacept.
Asunto(s)
Abatacept , Inhibidores de la Calcineurina , Inmunosupresores , Trasplante de Riñón , Torque teno virus , Carga Viral , Humanos , Trasplante de Riñón/efectos adversos , Abatacept/uso terapéutico , Inhibidores de la Calcineurina/uso terapéutico , Inhibidores de la Calcineurina/administración & dosificación , Inmunosupresores/uso terapéutico , Inmunosupresores/efectos adversos , Masculino , Persona de Mediana Edad , Femenino , Torque teno virus/efectos de los fármacos , Carga Viral/efectos de los fármacos , Adulto , Infecciones por Virus ADN/tratamiento farmacológico , Infecciones por Virus ADN/virología , Anciano , Receptores de Trasplantes , Rechazo de Injerto/prevención & controlRESUMEN
OBJECTIVES: Primary sclerosing cholangitis is an autoimmune illness affecting the intrahepatic and/or extrahepatic bile ducts that has a varying clinical history and no clear therapy. Recurrence of primary sclerosing cholangitis after transplantation can cause recurring liver failure, decreased survival, and the necessity for retransplant. Here, we explored the incidence of recurrence while also identifying the risk factors of primary sclerosing cholangitis. MATERIALS AND METHODS: In this retrospective cohort study, we collected demographic and clinical data from patients with a history of primary sclerosing cholangitis after liver transplant between 2011 and 2021. With SPSS software, we compared results in 2 groups of patients (with and without recurrent sclerosing biliary cholangitis) in terms of demographic and clinical variables. RESULTS: The study included 408 patients. Lower donor age and the occurrence of acute cellularrejection were shown to be key risk factors for recurrence of primary sclerosing cholangitis. Acute cellularrejection showed the best likelihood of predicting primary sclerosing cholangitis recurrence. As the number of acute cellular rejection episodes increased, so did the chance of primary sclerosing cholangitis. Death rate of patients with recurrence of primary sclerosing cholangitis was 40.8% (n = 20 patients) compared with 18.9% (n = 68 patients) in those without recurrence (significant at P < .001). CONCLUSIONS: The recurrence of primary sclerosing cholangitis had a detrimental effect on survival after liver transplant. Modifiable risk variables have the potentialto affecttherapies on care and prevention of primary sclerosing cholangitis recurrence. Donor age and acute cellular rejection were risk factors for decreased survival and higher primary sclerosing cholangitis recurrence. The use of mycophenolate (Cellcept) increased recurrence, but tacrolimus reduced mortality.
Asunto(s)
Colangitis Esclerosante , Inmunosupresores , Trasplante de Hígado , Recurrencia , Humanos , Colangitis Esclerosante/cirugía , Colangitis Esclerosante/mortalidad , Colangitis Esclerosante/diagnóstico , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/mortalidad , Factores de Riesgo , Estudios Retrospectivos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Resultado del Tratamiento , Inmunosupresores/efectos adversos , Factores de Tiempo , Medición de Riesgo , Irán/epidemiología , Adulto Joven , Incidencia , Factores de Edad , Adolescente , Rechazo de Injerto/mortalidad , Rechazo de Injerto/prevención & control , Rechazo de Injerto/diagnóstico , Rechazo de Injerto/inmunologíaRESUMEN
We present an unusual etiology of primary renal allograft dysfunction attributed to myeloma cast nephropathy in a patient with no history of multiple myeloma before kidney transplant. The patient, a 54-year-old woman, had been on hemodialysis for 6 months before transplant for presumed diabetic nephropathy; she developed graft dysfunction immediately after transplant. Graft biopsy specimens were consistent with myeloma cast nephropathy, and she was treated with bortezomib, cyclophosphamide, and dexamethasone. She achieved a complete hematological response and regained excellent graft function 3 months after transplant. The patient then received autologous stem cell transplant 8 months after kidney transplant. To our knowledge, this is the second report of a successful graft outcome after chemotherapy and the first report treated with autologous stem cell transplantation after remission of monoclonal disease.
Asunto(s)
Trasplante de Riñón , Mieloma Múltiple , Disfunción Primaria del Injerto , Humanos , Trasplante de Riñón/efectos adversos , Femenino , Persona de Mediana Edad , Mieloma Múltiple/terapia , Resultado del Tratamiento , Biopsia , Disfunción Primaria del Injerto/etiología , Disfunción Primaria del Injerto/diagnóstico , Disfunción Primaria del Injerto/fisiopatología , Inmunosupresores/efectos adversos , Diagnóstico Erróneo , Aloinjertos , Trasplante Autólogo , Factores de Tiempo , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Trasplante de Células Madre Hematopoyéticas/efectos adversosRESUMEN
Successful kidney transplant corrects mineral and bone disorderto a large extent; however, disorders can persistin up to 80% ofrecipients.We describe a case of persistent hyperparathyroidism with graft dysfunction and metastatic calcification in graft biopsy. A 48-yearold renal transplant recipient developed graft dysfunction 3 weeks after kidney transplant. During pretransplant workup, the recipient was found to have severe secondary hyperparathyroidism (intact parathyroid hormone level of 2000 pg/mL), which was managed and well controlled before transplant. Graft dysfunction was evaluated using algorithmic approach. Prerenal causes, tacrolimus toxicity, and infections were ruled out. Graft biopsy revealed several foci of tubular and parenchyma calcific deposits (microcalcinosis) with tubular injury. The patient was restarted on medical management of hyperparathyroidism, and he showed improvement over 6 weeks, along with creatinine level returning to nadir value. Vascular and graft calcification is an independent predictor of long-term graftfunction and overall mortality. This report describes the challenges that we faced in diagnosis and management of persistent hyperparathyroidism, as no randomized controlled trials and guidelines are available.
Asunto(s)
Calcinosis , Hiperparatiroidismo Secundario , Trasplante de Riñón , Humanos , Trasplante de Riñón/efectos adversos , Hiperparatiroidismo Secundario/etiología , Hiperparatiroidismo Secundario/diagnóstico , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Biopsia , Calcinosis/etiología , Calcinosis/cirugía , Calcinosis/diagnóstico , Aloinjertos , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Biomarcadores/sangre , Factores de Tiempo , Enfermedades Renales/etiología , Enfermedades Renales/diagnóstico , Hormona ParatiroideaRESUMEN
OBJECTIVES: Effectiveness of nirmatrelvir/ritonavir (NR) in kidney transplant recipients (KTRs) infected COVID-19 for more than 5 days has not been evaluated. METHODS: In this multicenter retrospective study, 85 KTRs with COVID-19 were enrolled, including 50 moderate, 21 severe, and 14 critical patients. RESULTS: The median time from onset to starting NR treatment was 14 (IQR, 11-19) days. Before NR treatment, 96.5% patients reduced use of antimetabolites. They also stopped using calcineurin inhibitors (CNI) 12-24 hours before NR treatment, with CNI concentrations well-controlled during NR treatment. The use of intravenous corticosteroids increased with COVID-19 severity. The median time to reach viral negative conversion was 5 (IQR, 4-8) days for all patients. For moderate and severe COVID-19 patients, they had a low rate of ICU admission (1.4%), exacerbation requiring upgraded oxygen therapy (5.6%), and dialysis (2.8%); no intubation and mechanical ventilation, and no deaths were observed. Patients with critical COVID-19 had a low mortality rate (7.1%). CONCLUSIONS: A regimen including NR for clearing SARS-CoV-2 along with reducing immunosuppressants and using intravenous corticosteroids is associated with lower rates of exacerbation and mortality in KTRs who have moderate to critical SARS-CoV-2 infection and the virus still present after 5 days.
Asunto(s)
Antivirales , Tratamiento Farmacológico de COVID-19 , Trasplante de Riñón , Ritonavir , Humanos , Ritonavir/uso terapéutico , Ritonavir/administración & dosificación , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Antivirales/uso terapéutico , Antivirales/administración & dosificación , Anciano , COVID-19/mortalidad , COVID-19/complicaciones , SARS-CoV-2 , Combinación de Medicamentos , Inmunosupresores/administración & dosificación , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Resultado del Tratamiento , Lopinavir/uso terapéutico , Lopinavir/administración & dosificación , Adulto , Receptores de Trasplantes/estadística & datos numéricos , Hospitalización/estadística & datos numéricosRESUMEN
INTRODUCTION: This study investigated variables associated with mortality in kidney transplant recipients (KTRs) diagnosed with post-transplant lymphoproliferative disease (PTLD) and a simultaneous Epstein-Barr virus (EBV) viremia. METHODS: This was a retrospective cohort study enrolling KTRs diagnosed with PTLD between 2018 and 2020. Outcome: death within two years after diagnosis. RESULTS: Among 1,625 KTRs who collected EBV viremia (by PCR, 2018-2020) for any reason, 238 (14.6%) had a positive viral load and 41 (17.2%) simultaneous PTLD. These 41 patients were 40.1 years old at diagnosis and 8.6 years after transplantation; 26.8% were induced with rATG and 92.7% were maintained on tacrolimus and azathioprine (TAC/AZA) as immunosuppressive regimen. Lymph nodes (75.6%) was the most common site of PTLD, followed by the gastrointestinal tract (48.8%), with 61.0% at Lugano stage IV and 80.5% monomorphic PTLD. The mean EBV viral load was 12,198 IU/mL. One- and two-year patient survival post-diagnosis was 60.4% and 46.8%, respectively. In the Cox regression analysis, age at PTLD diagnosis (HR for each year = 1.039; p < 0.001) and EBV viral load (HR for each log = 1.695; p = 0.026) were associated with risk of death. CONCLUSION: This study suggests that in patients predominantly on TAC/AZA, PTLD with simultaneous EBV positive viral load is a late event, and worse survival is associated with older age and EBV viral load at diagnosis.
Asunto(s)
Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Trasplante de Riñón , Trastornos Linfoproliferativos , Complicaciones Posoperatorias , Carga Viral , Humanos , Trasplante de Riñón/efectos adversos , Trastornos Linfoproliferativos/diagnóstico , Trastornos Linfoproliferativos/mortalidad , Trastornos Linfoproliferativos/virología , Trastornos Linfoproliferativos/etiología , Estudios Retrospectivos , Masculino , Femenino , Adulto , Infecciones por Virus de Epstein-Barr/diagnóstico , Infecciones por Virus de Epstein-Barr/complicaciones , Persona de Mediana Edad , Herpesvirus Humano 4/aislamiento & purificación , Herpesvirus Humano 4/genética , Factores de Edad , Complicaciones Posoperatorias/virología , Complicaciones Posoperatorias/diagnóstico , Viremia/diagnóstico , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéuticoRESUMEN
Vitiligo is an acquired chronic loss of skin pigmentation characterized by white and frequent symmetric patches, for which corticosteroids are the mainstay of treatment. Regular intake of steroids for prolonged periods is frequently associated with severe and sometimes irreversible adverse events. This study was designed to compare the effectiveness and safety profiles of azathioprine versus psoralen+ultraviolet light A (PUVA)-solar light (SOL; sunlight) to determine which agent reduces the length and adverse effects of vitiligo therapy in a better manner. This single-center, randomized, open-label, prospective case-control study recruited 100 patients. Oral mini-pulse (OMP) corticosteroid therapy was administered to all patients during the first month of the study. The first group of patients (group A) continued with azathioprine 50-mg tablet twice a day (BID), and the second group (group B) was given PUVA-SOL for 2 months with concurrent OMP. Disease activity was monitored. At the end of the study period, 58% (group A) and 50% (group B) of patients had their improved vitiligo area severity index (VASI) scores by 25%-50%. Similarly, 36% (group A) and 50% (group B) of patients improved their VASI score by more than 50%. On the global physician assessment scale, 42% (group A) and 54% (group B) patients had a good to excellent response. Based on these findings, both azathioprine and PUVA-SOL were considered as good steroid-sparing agents, primarily if used with an initial phase of concomitant oral corticosteroids.
Asunto(s)
Azatioprina , Terapia PUVA , Vitíligo , Humanos , Vitíligo/tratamiento farmacológico , Masculino , Femenino , Adulto , Estudios Prospectivos , Terapia PUVA/métodos , Azatioprina/uso terapéutico , Azatioprina/administración & dosificación , Azatioprina/efectos adversos , Persona de Mediana Edad , Estudios de Casos y Controles , Adulto Joven , Resultado del Tratamiento , Inmunosupresores/uso terapéutico , Inmunosupresores/administración & dosificación , Inmunosupresores/efectos adversos , Adolescente , Índice de Severidad de la EnfermedadRESUMEN
Background: Previous studies comparing the efficacy and safety of different treatment regimens for lupus nephritis are scarce. Moreover, confounding factors such as the duration of follow-up were hardly adjusted in those studies, potentially compromising the results and their extents to clinical settings. Objective: To rigorously investigate the efficacy and safety of biologics in patients with lupus nephritis using Bayesian network meta-regression analyses that adjust for the follow-up period, in order to provide more robust evidence for clinicians. Methods: Databases comprising PubMed, Embase, MedlinePlus, Cochrane Library, Google Scholars, and Scopus were retrieved for eligible articles from inception to February 29, 2024. The primary endpoint was the complete response rate, the secondary endpoint was the partial response rate, the tertiary endpoints were the adverse events, and infection-related adverse events. Napierian Logarithm of hazard ratio (lnHR) and the standard error of lnHR (selnHR) were generated for dichotomous variants by STATA 18.0 MP and then put into Rstudio 4.3.2 to conduct Bayesian network meta-analysis as well as network meta-regression analysis to yield hazard ratio (HR) as pairwise effect size. Results: Ten studies involving 2138 patients and 11 treatment regimens were ultimately included. In the original analysis, for the primary endpoint, compared to the control group, obinutuzumab (22.6 months), abatacept-30mg (20.5 months), abatacept-10mg (17.8 months), and belimumab (23.3 months) demonstrated significant superiority (HR ranged from 1.6 to 2.5), more ever, their significance regarding relative efficacy was correlated with follow up period, namely "time window" (shown in parentheses above). For the secondary endpoint, compared to the control group, obinutuzumab and abatacept-30mg showed conspicuous preponderance (HR ranged from 1.6 to 2.4), "time window" was also detected in abatacept-30mg (20.5 months), whereas obinutuzumab remained consistently obviously effective regardless of the follow-up period (shown in parentheses above). For the tertiary endpoint, there were no differences among active regimens and control. Conclusions: Considering the efficacy and safety and "time window" phenomenon, we recommend obinutuzumab as the preferred treatment for LN. Certainly, more rigorous head-to-head clinical trials are warranted to validate those findings.
Asunto(s)
Teorema de Bayes , Productos Biológicos , Nefritis Lúpica , Metaanálisis en Red , Humanos , Nefritis Lúpica/tratamiento farmacológico , Productos Biológicos/uso terapéutico , Productos Biológicos/efectos adversos , Resultado del Tratamiento , Inmunosupresores/uso terapéutico , Inmunosupresores/efectos adversos , Análisis de RegresiónRESUMEN
We describe the epidemiology of cancer after kidney transplantation (KTx), investigating its risk factors and impact on therapeutic management and survival in KTx recipients (KTRs). The association between modification of immunosuppressive (IS) therapy after cancer and survival outcomes was analyzed. We collected data from 930 KTRs followed for 7 [1-19] years. The majority of KTRs received KTx from a deceased donor (84%). In total, 74% of patients received induction therapy with basiliximab and 26% with ATG. Maintenance therapy included steroids, calcineurin inhibitors, and mycophenolate. Patients with at least one cancer (CA+) amounted to 19%. NMSC was the most common tumor (55%). CA+ were older and had a higher BMI. Vasculitis and ADPKD were more prevalent in CA+. ATG was independently associated with CA+ and was related to earlier cancer development in survival and competing risk analyses (p = 0.01 and <0.0001; basiliximab 89 ± 4 vs. ATG 40 ± 4 months). After cancer diagnosis, a significant prognostic impact was derived from the shift to mTOR inhibitors compared to a definitive IS drug suspension (p = 0.004). Our data confirm the relevance of cancer as a complication in KTRs with ATG as an independent risk factor. An individualized choice of IS to be proposed at the time of KTx is crucial in the prevention of neoplastic risk. Finally, switching to mTORi could represent an important strategy to improve patient survival.
Asunto(s)
Inmunosupresores , Trasplante de Riñón , Neoplasias , Humanos , Trasplante de Riñón/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Inmunosupresores/uso terapéutico , Inmunosupresores/efectos adversos , Italia/epidemiología , Adulto , Neoplasias/epidemiología , Factores de Riesgo , Basiliximab/uso terapéutico , Anciano , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Suero Antilinfocítico/uso terapéuticoRESUMEN
A previously healthy man developed pulmonary symptoms 2 weeks after starting treatment with a tumour necrosis factor (TNF) inhibitor. A negative interferon-gamma release assay (IGRA) test was obtained prior to TNF inhibitor exposure, without consideration of the fact that the patient was already immunosuppressed and had a previous positive IGRA test 17 months earlier. The patient was treated for pneumonia twice but did not achieve remission. His physical health progressively deteriorated over the following months. Malignancy was suspected but not found. Eight months after the onset of symptoms, Mycobacterium tuberculosis was found in samples from mediastinal lymph nodes, and the patient was diagnosed with multidrug-resistant tuberculosis (MDR-TB).This case illustrates the diagnostic challenge of TB, the need to raise awareness of the increased risk of TB in patients treated with TNF inhibitors and the need to increase knowledge regarding the effect of immunosuppressive agents on IGRA tests.
Asunto(s)
Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Masculino , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Mycobacterium tuberculosis/aislamiento & purificación , Ensayos de Liberación de Interferón gamma , Inhibidores del Factor de Necrosis Tumoral/efectos adversos , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Diagnóstico Erróneo , Antituberculosos/uso terapéutico , Persona de Mediana Edad , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Huésped InmunocomprometidoRESUMEN
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a severe autoimmune disease that often involves the upper and lower respiratory tracts. In recent years, numerous studies have found a significant increase in the incidence of cancer among AAV patients, but the association between lung cancer and AAV remains inconclusive, with relatively low clinical attention. This review summarizes the current literature on the risk of lung cancer in patients with ANCA-associated vasculitis (AAV), detailing the potential mechanisms by which AAV may contribute to lung cancer, and further elucidates the inherent carcinogenic risks of immunosuppressants.There is a correlation between AAV and lung cancer, which is related to T cell senescence and damage, as well as the abnormal expression of cytokines such as IL-6 and IL-10. In AAV patients, the use of cyclophosphamide and azathioprine (AZA) alone has a clear carcinogenic risk, with frequent use of CYC potentially posing a high risk for lung cancer. Although TNF inhibitors (TNFi) combined with CYC have carcinogenic risks, there is insufficient evidence to link them directly to an increased risk of lung cancer. For patients at high risk for lung cancer, the judicious use of immunosuppressants, timely computed tomography (CT), and lung cancer screening can reduce the risk of lung cancer in AAV patients.
Asunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos , Inmunosupresores , Neoplasias Pulmonares , Humanos , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/inmunología , Inmunosupresores/uso terapéutico , Inmunosupresores/efectos adversos , Ciclofosfamida/uso terapéutico , Ciclofosfamida/efectos adversos , Azatioprina/uso terapéutico , Azatioprina/efectos adversosRESUMEN
Whipple disease (WD) is a rare chronic multisystem infectious disorder caused by the bacterium Tropheryma whipplei (T. whipplei) and is more prevalent than previously thought. Its diagnosis is often delayed by months to years owing to its rarity, non-specific manifestations and insidious course. WD classically presents with polyarthropathy followed months to years later by the development of gastrointestinal symptoms, which often lead to the diagnosis. Pyrexia of unknown origin (PUO) without gastrointestinal involvement is an extremely rare presentation. We describe a case of WD presenting as genuine PUO following immunosuppression with the tumour necrosis factor-alpha monoclonal antibody adalimumab for seronegative polyarthropathy.
Asunto(s)
Adalimumab , Fiebre de Origen Desconocido , Enfermedad de Whipple , Humanos , Enfermedad de Whipple/tratamiento farmacológico , Enfermedad de Whipple/diagnóstico , Adalimumab/efectos adversos , Adalimumab/uso terapéutico , Fiebre de Origen Desconocido/etiología , Masculino , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Persona de Mediana Edad , Tropheryma/aislamiento & purificación , Diagnóstico DiferencialRESUMEN
BACKGROUND: In recent years a broader range of immunomodulatory and immunosuppressive treatment options have emerged for people with progressive forms of multiple sclerosis (PMS). While consensus supports these options as reducing relapses, their relative benefit and safety profiles remain unclear due to a lack of direct comparison trials. OBJECTIVES: To compare through network meta-analysis the efficacy and safety of alemtuzumab, azathioprine, cladribine, cyclophosphamide, daclizumab, dimethylfumarate, diroximel fumarate, fingolimod, fludarabine, glatiramer acetate, immunoglobulins, interferon beta 1-a and beta 1-b, interferon beta-1b (Betaferon), interferon beta-1a (Avonex, Rebif), laquinimod, leflunomide, methotrexate, minocycline, mitoxantrone, mycophenolate mofetil, natalizumab, ocrelizumab, ofatumumab, ozanimod, pegylated interferon beta-1a, ponesimod, rituximab, siponimod, corticosteroids, and teriflunomide for PMS. SEARCH METHODS: We searched CENTRAL, MEDLINE, and Embase up to August 2022, as well as ClinicalTrials.gov and the WHO ICTRP. SELECTION CRITERIA: Randomised controlled trials (RCTs) that studied one or more treatments as monotherapy, compared to placebo or to another active agent, for use in adults with PMS. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies and extracted data. We performed data synthesis by pair-wise and network meta-analysis. We assessed the certainty of the body of evidence according to GRADE. MAIN RESULTS: We included 23 studies involving a total of 10,167 participants. The most frequent (39% of studies) reason for a rating of high risk of bias was sponsor role in study authorship and data management and analysis. Other concerns were performance, attrition, and selective reporting bias, with 8.7% of studies at high risk of bias for all three of these domains. The common comparator for network analysis was placebo. Relapses over 12 months: assessed in one study (318 participants). None of the treatments assessed showed moderate or high certainty evidence compared to placebo. Relapses over 24 months: assessed in six studies (1622 participants). The number of people with clinical relapses is probably trivially reduced with rituximab (risk ratio (RR) 0.60, 95% confidence interval (CI) 0.19 to 1.95; moderate certainty evidence). None of the remaining treatments assessed showed moderate or high certainty evidence compared to placebo. Relapses over 36 months: assessed in four studies (2095 participants). The number of people with clinical relapses is probably trivially reduced with interferon beta-1b (RR 0.82, 95% CI 0.73 to 0.93; moderate certainty evidence). None of the remaining treatments assessed showed moderate or high certainty evidence compared to placebo. Disability worsening over 24 months: assessed in 11 studies (5284 participants). None of the treatments assessed showed moderate or high certainty evidence compared to placebo. Disability worsening over 36 months: assessed in five studies (2827 participants). None of the treatments assessed showed moderate or high certainty evidence compared to placebo. Serious adverse events: assessed in 15 studies (8019 participants). None of the treatments assessed showed moderate or high certainty evidence compared to placebo. Discontinuation due to adverse events: assessed in 21 studies (9981 participants). The number of people who discontinued treatment due to adverse events is trivially increased with interferon beta-1a (odds ratio (OR) 2.93, 95% CI 1.64 to 5.26; high certainty evidence). The number of people who discontinued treatment due to adverse events is probably trivially increased with rituximab (OR 4.00, 95% CI 0.84 to 19.12; moderate certainty evidence); interferon beta-1b (OR 2.98, 95% CI 1.92 to 4.61; moderate certainty evidence); immunoglobulins (OR 1.95, 95% CI 0.99 to 3.84; moderate certainty evidence); glatiramer acetate (OR 3.98, 95% CI 1.48 to 10.72; moderate certainty evidence); natalizumab (OR 1.02, 95% CI 0.55 to 1.90; moderate certainty evidence); siponimod (OR 1.53, 95% CI 0.98 to 2.38; moderate certainty evidence); fingolimod (OR 2.29, 95% CI 1.46 to 3.60; moderate certainty evidence), and ocrelizumab (OR 1.24, 95% CI 0.54 to 2.86; moderate certainty evidence). None of the remaining treatments assessed showed moderate or high certainty evidence compared to placebo. AUTHORS' CONCLUSIONS: The number of people with PMS with relapses is probably slightly reduced with rituximab at two years, and interferon beta-1b at three years, compared to placebo. Both drugs are also probably associated with a slightly higher proportion of withdrawals due to adverse events, as are immunoglobulins, glatiramer acetate, natalizumab, fingolimod, siponimod, and ocrelizumab; we have high confidence that this is the case with interferon beta-1a. We found only low or very low certainty evidence relating to disability progression for the included disease-modifying treatments compared to placebo, largely due to imprecision. We are also uncertain about the effect of interventions on serious adverse events, also because of imprecision. These findings are due in part to the short follow-up of the included RCTs, which lacked detection of less common severe adverse events. Moreover, the funding source of many included studies may have introduced bias into the results. Future research on PMS should include head-to-head rather than placebo-controlled trials, with a longer follow-up of at least three years. Given the relative rarity of PMS, controlled, non-randomised studies on large samples may usefully integrate data from pivotal RCTs. Outcomes valuable and meaningful to people with PMS should be consistently adopted and measured to permit the evaluation of relative effectiveness among treatments.
Asunto(s)
Inmunosupresores , Metaanálisis en Red , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Inmunosupresores/uso terapéutico , Inmunosupresores/efectos adversos , Agentes Inmunomoduladores/uso terapéutico , Esclerosis Múltiple Crónica Progresiva/tratamiento farmacológico , Factores Inmunológicos/uso terapéutico , Factores Inmunológicos/efectos adversos , Rituximab/uso terapéutico , Rituximab/efectos adversos , RecurrenciaRESUMEN
Although COVID-19 infection is an immunosuppressant disease, many immunosuppressant agents, such as pulse methylprednisolone (PMP), dexamethasone (DXM), and tocilizumab (TCZ), were used during the pandemic. Secondary infections in patients with COVID-19 have been reported recently. This study investigated these agents' effects on secondary infections and outcomes in patients with COVID-19 in intensive care units (ICUs). This study was designed retrospectively, and all data were collected from the tertiary intensive care units of six hospitals between March 2020 and October 2021. All patients were divided into three groups: Group I [GI, PMP (-), DXM (-) and TCZ (-)], Group II [GII, PMP (+), DXM (+)], and Group III [GIII, PMP (+), DXM (+), TCZ (+)]. Demographic data, PaO/FiO2 ratio, laboratory parameters, culture results, and outcomes were recorded. To compare GI-GII and GI-GIII, propensity score matching (PSM) was used by matching 14 parameters. Four hundred twelve patients with COVID-19 in the ICU were included in the study. The number of patients with microorganisms ≥ 2 was 279 (67.7%). After PSM, in GII and GIII, the number of (+) tracheal cultures and (+) bloodstream cultures detected different microorganisms ≥ 2 during the ICU period, neuropathy, tracheotomized patients, duration of IMV, and length of ICU stay were significantly higher than GI. The mortality rate was similar in GI and GII, whereas it was significantly higher in GIII than in GI. The use of immunosuppressant agents in COVID-19 patients may lead to an increase in secondary infections. In addition, increased secondary infections may lead to prolonged ICU stay, prolonged IMV duration, and increased mortality.