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1.
Int J Infect Dis ; 2021 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-33647515

RESUMEN

BACKGROUND: The role of combination immunomodulatory therapy with systemic corticosteroids and tocilizumab (TCZ) for aged patients with COVID-19-associated cytokine release syndrome remains unclear. METHODS: We conducted a retrospective single-center study including consecutive patients ≥65 years that developed severe COVID-19 between March 3 and May 1, 2020 and were treated with corticosteroids at various doses (methylprednisolone [0.5 mg/Kg/12 hours to 250 mg/24 hours]), either alone ("CS group") or associated to intravenous tocilizumab (400-600 mg, one to three doses) ("CS-TCZ group"). Primary outcome was all-cause mortality by day +14, whereas secondary outcomes included mortality by day +28 and clinical improvement (discharge and/or a ≥2-point decrease on a six-point ordinal scale) by day +14. Propensity score (PS)-based adjustment and inverse probability of treatment weights (IPTW) were applied. RESULTS: Overall, 181 and 80 patients were included in the CS and CS-TCZ groups. All-cause 14-day mortality was lower in the CS-TCZ group, both in the PS-adjusted (hazard ratio [HR]: 0.34; 95% confidence interval [CI]: 0.17 - 0.68; P-value = 0.002) and IPTW-weighted models (odds ratio [OR]: 0.38; 95% CI: 0.21 - 0.68; P-value = 0.001). This protective effect was also observed for 28-day mortality (PS-adjusted HR: 0.38; 95% CI: 0.21 - 0.72; P-value = 0.003). Clinical improvement by day +14 was higher in the CS-TCZ group in the IPTW analysis only (OR: 2.26; 95% CI: 1.49 - 3.41; P-value <0.001). The occurrence of secondary infection was similar between both groups. CONCLUSIONS: The combination of corticosteroids and TCZ was associated with better outcomes among patients ≥65 years with severe COVID-19.

2.
Artículo en Inglés | MEDLINE | ID: mdl-33069858

RESUMEN

OBJECTIVES: The World Health Organization recommends routinely screening HIV-infected patients with CD4+ T-cell counts <100/µL for cryptococcal infection to prevent cryptococcal meningitis (CM), based on studies in Sub-Saharan Africa where the prevalence of positive cryptococcal antigen (CrAg+) is ≥ 3% in this subgroup. Data about such prevalence in Spain are unavailable and rare in other European countries. Thus, the Spanish AIDS Study Group guidelines do not recommend routinely screening. We aim to determine the prevalence and outcomes of cryptococcal infection in this subgroup of patients in Spain. METHODS: We determined CrAg using a lateral flow assay in banked plasma from participants in the cohort of the Spanish AIDS Research Network. Eligible patients had CD4+ T-cell counts ≤100/µL at the time of plasma collection and a follow-up >4 weeks, unless they died. RESULTS: We included 576 patients from June 2004 to December 2017. Of these, 43 were CrAg+ for an overall prevalence of 7.5%. There were no differences depending on birthplace. The CrAg+ was independently associated with a higher mortality at eight weeks (hazard ratio (HR) 5.36, 95% confidence interval (CI) 1.46-19.56) and 6 months (HR 3.12, 95% CI 1.19-8.21). CM was reported in 10 of the 43 CrAg+ patients. There were no cases among negatives. Five patients had CM when the plasma was collected and five developed it during the follow-up. The number of subjects needed to screen to anticipate the diagnosis of one CM case was 114. CONCLUSIONS: The CrAg+ prevalence among HIV-infected patients with CD4+ T-cell counts ≤100/µL diagnosed in Spain, both immigrants and native-born Spanish, is >7%. Consequently, the Spanish AIDS Study Group guidelines have to be updated and recommend routine screening for cryptococcal infection in these patients. Future studies should explore whether this recommendation could be firmly applied to other European populations.

3.
Am J Transplant ; 2020 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-32780498

RESUMEN

To investigate risk factors for invasive aspergillosis (IA) after kidney transplantation (KT), we conducted a systematic search in PubMed and EMBASE to identify studies published until June 2020. We included case-control or cohort design studies comprising KT recipients with a diagnosis of IA, defined according to the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group criteria, and assessed risk factors for the development of IA. Random-effect models meta-analysis served to pool data. We identified eleven case-control studies (319 IA cases and 835 controls). There was an increased risk of IA among recipients with underlying chronic lung diseases (odds ratio [OR] = 7.26; 95% confidence interval [CI] = 1.05-50.06) and among those with diabetic nephropathy (OR = 1.65; 95% CI = 1.10-2.48). Requiring posttransplant hemodialysis (OR = 3.69; 95% CI = 2.13-6.37) or surgical reintervention (OR = 6.28; 95% CI = 1.67-23.66) were also associated with an increased risk. Moreover, a positive link was identified between IA and posttransplant bacterial infection (OR = 7.51; 95% CI = 4.37-12.91), respiratory tract viral infection (OR = 7.75; 95% CI = 1.60-37.57), cytomegalovirus infection or disease (OR = 2.67; 95% CI = 1.12-6.32), and acute graft rejection (OR = 3.01; 95% CI = 1.78-5.09). In contrast, receiving a kidney from a living donor was associated with a reduced risk (OR = 0.65; 95% CI = 0.46-0.93). KT recipients that accumulate several of these conditions should be closely monitored and a low threshold of suspicion for IA should be maintained. Future studies should explore the benefit of mold-active prophylaxis to this subgroup of KT recipients at highest risk.

4.
J Med Virol ; 2020 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-32672860

RESUMEN

Coronavirus disease 2019 (COVID-19) can lead to a massive cytokine release. The use of the anti-interleukin-6 receptor monoclonal antibody tocilizumab (TCZ) has been proposed in this hyperinflammatory phase, although supporting evidence is limited. We retrospectively analyzed 88 consecutive patients with COVID-19 pneumonia that received at least one dose of intravenous TCZ in our institution between 16 and 27 March 2020. Clinical status from day 0 (first TCZ dose) through day 14 was assessed by a 6-point ordinal scale. The primary outcome was clinical improvement (hospital discharge and/or a decrease of ≥2 points on the 6-point scale) by day 7. Secondary outcomes included clinical improvement by day 14 and dynamics of vital signs and laboratory values. Rates of clinical improvement by days 7 and 14 were 44.3% (39/88) and 73.9% (65/88). Previous or concomitant receipt of subcutaneous interferon-ß (adjusted odds ratio [aOR]: 0.23; 95% confidence interval [CI]: 0.06-0.94; P = .041) and serum lactate dehydrogenase more than 450 U/L at day 0 (aOR: 0.25; 95% CI: 0.06-0.99; P = .048) were negatively associated with clinical improvement by day 7. All-cause mortality was 6.8% (6/88). Body temperature and respiratory and cardiac rates significantly decreased by day 1 compared to day 0. Lymphocyte count and pulse oximetry oxygen saturation/FiO2 ratio increased by days 3 and 5, whereas C-reactive protein levels dropped by day 2. There were no TCZ-attributable adverse events. In this observational single-center study, TCZ appeared to be useful and safe as immunomodulatory therapy for severe COVID-19 pneumonia.

6.
Transpl Infect Dis ; 22(5): e13372, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32562561

RESUMEN

BACKGROUND: Which are the consequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in liver transplant (LT) recipients? METHODS: We attempted to address this question by reviewing our single-center experience during the first 2 months of the pandemics at a high incidence area. RESULTS: Nineteen adult patients (5 females) were diagnosed by May 5, 2020. Median age was 58 (range 55-72), and median follow-up since transplantation was 83 (range 20-183) months. Cough (84.2%), fever (57.9%), and dyspnea (47.4%) were the most common symptoms. Thirteen patients (68.4%) had pneumonia in x-ray/CT scan. Hydroxychloroquine was administered in 11 patients, associated with lopinavir/ritonavir and interferon ß in 2 cases each. Immunomodulatory therapy with tocilizumab was used in 2 patients. Immunosuppression (IS) was halted in one patient and modified in only other two due to potential drug interactions. Five (26.3%) patients were managed as outpatient. Two patients (10.5%) died, 10 (52.6%) were discharged home, and 2 (10.5%) were still hospitalized after a median follow-up of 41 days from the onset of symptoms. Baseline IS regimen remained unchanged in all surviving recipients, with good liver function. CONCLUSIONS: Our preliminary experience shows a broad spectrum of disease severity in LT patients with COVID-19, with a favorable outcome in most of them without needing to modify baseline IS.

7.
Clin J Gastroenterol ; 13(2): 271-275, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31529379

RESUMEN

Hepatic sinusoidal obstruction syndrome (SOS) is a life-threatening complication with high mortality rate. Even if it is more commonly described after hematopoietic stem-cell transplant, hepatic-SOS may occur following the use of certain chemotherapeutic agents. Mitomycin-C has been previously identified as a causal agent when administered intravenously at high doses. We report herein the first case of hepatic-SOS due to intravesical instillation of mitomycin-C, after a traumatic urinary catheterization with significant hematuria. Although this procedure is usually considered safe, without the systemic side effects related to intravenous administration of the drug, clinicians must be aware of its potential risks to facilitate an early diagnosis, avoid a delay in the withdrawal of the causative drug and set up an appropriate therapy as soon as possible.

8.
Autoimmun Rev ; 18(5): 493-500, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30844550

RESUMEN

OBJECTIVE: To analyse the ocular manifestations of patients with GPA, their treatment and outcome. METHODS: Retrospective cohort study performed at the National Referral Center for Vasculitis, Cochin Hospital, Paris (France), from January 2005 to December 2015. Among 308 patients with a new diagnosis of GPA in accordance with the American College of Rheumatology classification criteria and/or revised Chapel Hill nomenclature definitions, we identified those with ocular involvement and a subsequent follow up in our center. RESULTS: The prevalence of ocular involvement in our GPA series was 38.6%; 63 patients were analysed with a median follow-up of 50.5 months (IQR: 17.8-82.8). Scleritis (18 patients, 28.6%) and episcleritis (18 patients, 28.6%) were the most common ophthalmologic manifestations, followed by orbital disease (13 patients, 20.6%). Bilateral involvement and visual acuity loss was seen in 29.1% and 16.7% of patients, respectively. Ocular involvement was the first GPA manifestation in 9 patients (14.3%), concomitant with systemic manifestation in 36 (57.1%), and occurred only during follow-up in 18 (28.6%). The indication for GPA treatment was suggested by ocular involvement in 12 patients (19.0%), by systemic features in 40 (63.5%) and by both ocular and systemic involvement in 11 (17.5%). Remission of ocular involvement was achieved in 51 patients (80.9%). In the remaining 12 (19.1%), symptoms persisted or even worsened, finally leading to rituximab (RTX) therapy in 8 of them (66.7%). Altogether, when used as first line or for refractory disease, ocular remission was achieved in 11 of the 12 cases (91.7%) treated with RTX versus 34 of the 47 cases (72.3%) treated with CYC (P = .260). Eye disease relapsed in 14 patients (22.2%). RTX allowed achievement of remission in 8 of them (57.1%). In the remaining six, other immunosuppressive drugs were used. CONCLUSIONS: Scleritis and episcleritis are the most common ocular manifestations in GPA, most of the time associated with other systemic manifestations. In >40% of cases, ocular manifestations were refractory to initial treatment or recurrent and led to RTX prescription, which appeared to be useful in these situations.


Asunto(s)
Oftalmopatías , Granulomatosis con Poliangitis , Adulto , Estudios de Cohortes , Oftalmopatías/diagnóstico , Oftalmopatías/epidemiología , Oftalmopatías/etiología , Oftalmopatías/terapia , Femenino , Francia/epidemiología , Granulomatosis con Poliangitis/complicaciones , Granulomatosis con Poliangitis/diagnóstico , Granulomatosis con Poliangitis/epidemiología , Granulomatosis con Poliangitis/terapia , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos , Rituximab/uso terapéutico , Resultado del Tratamiento
9.
J Thromb Thrombolysis ; 46(3): 325-331, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-29873003

RESUMEN

Functional status linked to a poor outcome in a broad spectrum of medical disorders. Barthel Activities of Daily Life Index (BADLI) is one of the most extended tools to quantify functional dependence. Whether BADLI can help to predict outcomes in elderly patients with acute venous thromboembolism (VTE) is unknown. The current study aimed to ascertain the influence of BADLI on 6-month all-cause mortality in aged patients with VTE. This is a prospective observational study. We included consecutive patients older than 75-year-old with an acute VTE between April 2015 and April 2017. We analyzed several variables as mortality predictors, including BADLI-measured functional status. Afterward, we performed a multivariate analysis, using logistic regression, to identify all-cause mortality independent predictive factors. Two hundred and two subjects were included. Thirty-five (17%) patients died in the first 6 months. The leading cause of death was cancer (59%). After multivariable logistic regression, we identified BADLI and Charlson index as independent predictors for 6-months mortality [BADLI (every decrease of 10 points) OR 1.21 95% CI (1.03-1.42) and Charlson index OR 1.71 95% CI (1.21-2.43)]. Body mass index (BMI) values were inversely related to mortality [OR 0.85 95% CI (0.75-0.95)]. In conclusion, BADLI, BMI, and Charlson index scores are independent predictive factors for 6-month all-cause mortality in old patients with VTE.


Asunto(s)
Tromboembolia Venosa/mortalidad , Enfermedad Aguda , Anciano , Anciano de 80 o más Años , Índice de Masa Corporal , Humanos , Modelos Logísticos , Neoplasias/mortalidad , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Análisis de Supervivencia , Tromboembolia Venosa/diagnóstico
10.
Transpl Int ; 29(10): 1094-105, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27362817

RESUMEN

The measurement of intracellular concentrations of adenosine triphosphate (iATP) in phytohemagglutinin-stimulated CD4(+) T cells constitutes a surrogate marker for post-transplant cell-mediated immunity (CMI). This assay has shown suboptimal accuracy for predicting infection after kidney transplantation (KT). We hypothesize that its predictive capacity depends on the specific contribution of the CMI to host-pathogen interactions. We assessed iATP levels in 100 KT recipients at baseline and months 1, 3, and 6 (363 measurements). No association was found between iATP at month 1 and the risk for overall or bacterial infection, although such association was evident for cytomegalovirus (CMV) disease (multivariate-adjusted hazard ratio [per 50-unit increment]: 0.83; P-value = 0.048). There were no significant differences in mean iATP between stable patients (319.4 ng/ml) and those developing overall (304.1 ng/ml) or bacterial infection (346.9 ng/ml) over the 45 days following monitoring. However, iATP was significantly lower in patients who developed CMV disease (223.5 ng/ml; P-values <0.002). The optimal cutoff (265 ng/ml) for predicting CMV disease in patients not receiving antiviral prophylaxis yielded sensitivity, specificity, positive, and negative predictive values of 85.7%, 68.3%, 15.2%, and 98.6%, respectively. In conclusion, a non-pathogen-specific monitoring of CMI by means of iATP informs the risk of CMV disease in KT recipients.


Asunto(s)
Adenosina Trifosfato/metabolismo , Linfocitos T CD4-Positivos/metabolismo , Infecciones por Citomegalovirus/inmunología , Insuficiencia Renal/cirugía , Adulto , Anciano , Citomegalovirus , Femenino , Rechazo de Injerto/prevención & control , Humanos , Sistema Inmunológico , Inmunidad Celular , Inmunosupresores , Trasplante de Riñón/efectos adversos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Curva ROC , Insuficiencia Renal/complicaciones , Riesgo , Receptores de Trasplantes
11.
Endocrinol Nutr ; 63(4): 145-56, 2016 Apr.
Artículo en Inglés, Español | MEDLINE | ID: mdl-26826772

RESUMEN

INTRODUCTION: The aim of this review was to assess the effectiveness to reduce clinical adverse events and safety of insulin administered in basal-bolus-corrector or basal-corrector regimens (BB) versus a sliding scale scheme (SS) in patients with diabetes or newly diagnosed hyperglycemia admitted to a conventional (not critical) medical or surgical hospital ward. METHOD: A Medline search was conducted. The Odds ratio was the main summary measure. A random effects model with the Mantel-Haenszel procedure was used. RESULTS: A total of 957 citations were collected, of which nine were finally included in the systematic review. Patients in the BB group had better blood glucose control than those with SS. Overall, there was a nonsignificant trend to a lower risk of adverse events in the BB as compared to the SS group (OR 0.67 [95% CI 0.22 to 2.04], [I(2)=71%]). There was a nonsignificant trend to an increased risk of hypoglycemia in the BB group (OR 2.29 [95% CI 0.50 to 10.49] [I(2)=70%]). CONCLUSION: Despite its benefit for glycemic control during hospitalization, this review did not show that use of the BB scheme decreases clinical events in patients hospitalized in a conventional ward. Because of heterogeneity of the results, we think that clinical trials are needed addressing its effect in patient subgroups in which the BB scheme may be used safely and with longer follow-up periods.


Asunto(s)
Diabetes Mellitus/tratamiento farmacológico , Hipoglucemiantes/efectos adversos , Insulina/efectos adversos , Hospitalización , Humanos , Hiperglucemia , Hipoglucemiantes/administración & dosificación , Insulina/administración & dosificación
15.
Medicine (Baltimore) ; 93(17): 236-54, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25398060

RESUMEN

Bacillus Calmette-Guérin (BCG) is the most effective intravesical immunotherapy for superficial bladder cancer. Although generally well tolerated, BCG-related infectious complications may occur following instillation. Much of the current knowledge about this complication comes from single case reports, with heterogeneous diagnostic and therapeutic approaches and no investigation on risk factors for its occurrence. We retrospectively analyzed 256 patients treated with intravesical BCG in our institution during a 6-year period, with a minimum follow-up of 6 months after the last instillation. We also conducted a comprehensive review and pooled analysis of additional cases reported in the literature since 1975. Eleven patients (4.3%) developed systemic BCG infection in our institution, with miliary tuberculosis as the most common form (6 cases). A 3-drug antituberculosis regimen was initiated in all but 1 patient, with a favorable outcome in 9/10 cases. There were no significant differences in the mean number of transurethral resections prior to the first instillation, the time interval between both procedures, the overall mean number of instillations, or the presence of underlying immunosuppression between patients with or without BCG infection. We included 282 patients in the pooled analysis (271 from the literature and 11 from our institution). Disseminated (34.4%), genitourinary (23.4%), and osteomuscular (19.9%) infections were the most common presentations of disease. Specimens for microbiologic diagnosis were obtained in 87.2% of cases, and the diagnostic performances for acid-fast staining, conventional culture, and polymerase chain reaction (PCR)-based assays were 25.3%, 40.9%, and 41.8%, respectively. Most patients (82.5%) received antituberculosis therapy for a median of 6.0 (interquartile range: 4.0-9.0) months. Patients with disseminated infection more commonly received antituberculosis therapy and adjuvant corticosteroids, whereas those with reactive arthritis were frequently treated only with nonsteroidal antiinflammatory drugs (p < 0.001 for all comparisons). Attributable mortality was higher for patients aged ≥65 years (7.4% vs 2.1%; p = 0.091) and those with disseminated infection (9.9% vs 3.0%; p = 0.040) and vascular involvement (16.7% vs 4.6%; p = 0.064). The scheduled BCG regimen was resumed in only 2 of 36 patients with available data (5.6%), with an uneventful outcome. In the absence of an apparent predictor of the development of disseminated BCG infection after intravesical therapy, and considering the protean variety of clinical manifestations, it is essential to keep a high index of suspicion to initiate adequate therapy promptly and to evaluate carefully the risk-benefit balance of resuming intravesical BCG immunotherapy.


Asunto(s)
Adyuvantes Inmunológicos/efectos adversos , Vacuna BCG/efectos adversos , Mycobacterium bovis , Tuberculosis/epidemiología , Tuberculosis/etiología , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Adyuvantes Inmunológicos/administración & dosificación , Administración Intravesical , Anciano , Antituberculosos , Vacuna BCG/administración & dosificación , Quimioterapia Adyuvante , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento
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