Increased incidence of rheumatoid arthritis after COVID-19.

An increase in the incidence of inflammatory arthritis after COVID-19 has been reported. Since many diseases exhibit population-specific causal effect sizes, we aimed to evaluate the incidence trends of inflammatory arthritis, including rheumatoid arthritis (RA), after COVID-19 in a large admixed Colombian population. Data analysis for this retrospective, population-based cohort study was carried out using the COOSALUD EPS registry. The following codes were selected for analyses: M059, seropositive RA, M069, unspecified RA, M060 seronegative RA, and other RA-related diagnoses: M064, M139, M068, M058, M130 and M053. The study period was limited to January 01, 2018, through December 31, 2022. Incidence rates (IRs) and incidence rate ratios (IRRs) were assessed. A Cox survival model was built to evaluate the influence of age, gender, and COVID-19 vaccination status on the development of inflammatory arthritis. A bioinformatic analysis was performed to evaluate the homology between SARS-CoV-2 and autoantigen peptides related to RA. The entire population study comprised 3,335,084 individuals. During the pandemic period (2020-2022) the total IIR for seropositive and unspecified RA were 1.60 (95% CI, 1.16-2.22) and 2.93 (95% CI, 2.04-4.19), respectively, and the IIR for overall RA-related diagnosis was 2.01 (95% CI 1.59-2.53). The age groups hazard ratios (HRs) were increased until the age group of 51-60 years (HR: 9.16; 95% CI, 7.24-11.59) and then decreased slightly in the age group 61 years or older (HR: 5.364; 95% CI, 4.24-6.78) compared to those within 18-30 years. Men were less at risk than women to develop inflammatory arthritis (HR: 0.21; 95% CI, 0.18-0.24). The greater time since COVID-19 diagnosis was associated with a lower likelihood of developing inflammatory arthritis (HR: 0.99; 95% CI:0.998-0.999). Vaccination (all types of COVID-19 vaccines included) did not prevent the development of inflammatory arthritis after COVID-19. Low identity was found between the SARS-CoV-2 ORF1ab antigen and the human antigens Poly ADP-ribose polymerase 14 and Protein mono-ADP-ribosyltransferase PARP9 isoform D (39% and 29%, respectively). In conclusion, our study confirms increased incidence of inflammatory arthritis, including RA, after COVID-19, with the greatest increase occurring before the first year post-covid. Women in their fifties were more susceptible. Further research is required to examine the effectiveness of vaccination in preventing post-COVID inflammatory arthritis and the mechanisms implicated in the development of RA after COVID-19.

MULTIMODAL IMAGING IN A CASE OF CENTRAL RETINAL ARTERY OCCLUSION IN THE PRESENCE OF TYPE 2 MACULAR TELANGIECTASIA.

PURPOSE: To report a case of central retinal artery occlusion in a patient with macular telangiectasia Type 2 using multimodal imaging. METHODS: Observational case report. RESULTS: A 58-year-old woman who presented with acute painless unilateral vision loss was diagnosed with central retinal artery occlusion in her right eye with macular telangiectasia Type 2 findings in both eyes. Fundus examination revealed retinal whitening with unusual cherry-red spot plus small crystalline deposits in the temporal macula. Surprisingly, spectral domain optical coherence tomography of the contralateral eye showed characteristically intraretinal hyporreflective spaces, whereas optical coherence tomography angiography exhibited microvascular abnormalities in the deep capillary plexus. At follow-up, a pseudolamellar macular hole was noticed in the affected eye with no recovery of best-corrected visual acuity. CONCLUSION: This case describes an onset of central artery occlusion in a patient with underlying macular telangiectasia Type 2 and suggests that it had a possible role in the acceleration of its natural course. The utility of multimodal imaging lies on better accuracy in diagnosis as well as prognosis, management, and monitoring of the disease.

Treatment decision-making in chronic lymphocytic leukaemia: Key factors for healthcare professionals. PRELIC study.

OBJECTIVE: To explore the preferences of Spanish healthcare professionals (haematologists and hospital pharmacists) for the treatment selection of active Chronic Lymphocytic Leukaemia (CLL) patients at first relapse, condition that mainly afflicts older adults. METHODS: A discrete choice experiment (DCE) was conducted among haematologists and hospital pharmacists. A literature review and a focus group informed the DCE design. CLL treatment settings were defined by seven attributes: four patient/disease-related attributes (age, functional status, comorbidities, and risk of the disease) and three treatment-related attributes (efficacy [hazard ratio of progression-free survival, HR-PFS], rate of discontinuations due to adverse events and cost). A mixed-logit model was used to determine choice-based preferences. Relative importance (RI) of attributes was calculated and compared between stakeholders. Willingness-to-pay (WTP) was estimated through the DCE. Besides, nine ad-hoc questions were posed, to explore more in depth CLL treatment decision making. RESULTS: A total of 130 participants (72 haematologists and 58 hospital pharmacists) answered the DCE. All attributes were significant predictors of preferences (p < 0.05) in the multinomial model. Higher RI was obtained for treatment-related attributes: the highest rated being 'cost' (23.8%) followed by 'efficacy' (20.9%). Regarding patient-related attributes, the highest RI was obtained for 'age' (18.1%). No significant differences (p > 0.05) in RI between haematologists and pharmacists were found. WTP for the treatment was higher for younger CLL patients. Ad-hoc questions showed that patient age and functional status influence treatment decisions. CONCLUSIONS: For healthcare professionals, 'cost' and 'efficacy' (treatment-related attributes) and age (patient-related attribute) are the main factors that determine CLL treatment selection at first relapse. WTP decreases as patient's age increases.

Clasificación de patrones anormales de autofluorescencia retiniana en el edema macular diabético.

INTRODUCTION: Patients with diabetic macular edema can develop fundus autofluorescence alterations; thus far, these alterations have been more widely studied with scanning or confocal laser systems. OBJECTIVE: To describe and classify fundus autofluorescence abnormal patterns in patients with diabetic macular edema using the fundus autofluorescence system with a flash camera. METHOD: Observational, retrospective, cross-sectional, descriptive study. Fundus autofluorescence digital images of non-comparative cases with untreated diabetic macular edema, obtained and stored with a flash camera system, were assessed. Inter-observer variability was evaluated. RESULTS: 37 eyes of 20 patients were included. Lens opacity was the most common cause of inadequate image quality. Five different fundus autofluorescence patterns were observed: decreased (13%), normal (40%), focal hyper-autofluorescent (17%), multi-focal hyper-autofluorescent (22%) and plaque-like hyper-autofluorescent (8%). The kappa coefficient was 0.906 (p = 0.000). CONCLUSIONS: Different fundus autofluorescence phenotypic patterns are observed with flash camera systems in patients with diabetic macular edema. A more accurate phenotypic classification could help establish prognostic factors for visual loss or for the design of clinical trials for diabetic macular edema.

INTRODUCCIÓN: Los pacientes con edema macular diabético pueden presentar alteraciones en la autofluorescencia retiniana, que hasta el momento han sido analizadas más con sistemas de láser de barrido o confocales. OBJETIVO: Describir y clasificar los patrones anormales de autofluorescencia retiniana en pacientes con edema macular diabético mediante el sistema de autofluorescencia retiniana con cámara de flash. MÉTODO: Estudio observacional, retrospectivo, transversal y descriptivo. Se evaluaron imágenes digitales de autofluorescencia retiniana de casos no comparativos con edema macular diabético no tratado, obtenidas y almacenadas con el sistema de cámara de flash.Se evaluó la variabilidad interobservador. RESULTADOS: Se incluyeron 37 ojos de 20 pacientes. La opacidad de medios fue la causa más común de calidad inadecuada de imagen. Se observaron cinco diferentes patrones de autofluorescencia retiniana: disminuida (13 %), normal (40 %), hiperautofluorescente unifocal (17 %), hiperautofluorescente multifocal (22 %) e hiperautofluorescente en placa (8 %). El coeficiente kappa fue de 0.906 (p = 0.000). CONCLUSIONES: En pacientes con edema macular diabético se presentan diferentes patrones fenotípicos de autofluorescencia retiniana con los sistemas de cámara de flash. Una clasificación fenotípica más precisa pudiera ayudar a establecer factores pronósticos de pérdida visual o al diseño de ensayos clínicos relativos a edema macular diabético.

Classification of fundus autofluorescence abnormal patterns in diabetic macular edema

Introduction: Patients with diabetic macular edema can develop fundus autofluorescence alterations; thus far, these alterations have been more widely studied with scanning or confocal laser systems. Objective: To describe and classify fundus autofluorescence abnormal patterns in patients with diabetic macular edema using the fundus autofluorescence system with a flash camera. Method: Observational, retrospective, cross-sectional, descriptive study. Fundus autofluorescence digital images of non-comparative cases with untreated diabetic macular edema, obtained and stored with a flash camera system, were assessed. Inter-observer variability was evaluated. Results: 37 eyes of 20 patients were included. Lens opacity was the most common cause of inadequate image quality. Five different fundus autofluorescence patterns were observed: decreased (13%), normal (40%), single-spot hyper-autofluorescent (17 %), multiple-spot hyper-autofluorescent (22 %) and plaque-like hyper-autofluorescent (8 %). The kappa coefficient was 0.906 (p = 0.000). Conclusions: Different fundus autofluorescence phenotypic patterns are observed with flash camera systems in patients with diabetic macular edema. A more accurate phenotypic classification could help establish prognostic factors for visual loss or for the design of clinical trials for diabetic macular edema.

Correlation analysis of fundus autofluorescence, spectral domain optical coherence tomography, and visual function in patients with diabetic macular oedema treated with intravitreal ziv-aflibercept.

PURPOSE: The aim of this study was to evaluate the correlations between fundus autofluorescence and morphologic parameters as well as visual function in patients with diabetic macular oedema treated with intravitreal ziv-aflibercept. METHODS: A total of 34 eyes of 20 patients with untreated diabetic macular oedema received an intravitreal injection of ziv-aflibercept at baseline, and 1 and 2 months later. The baseline, 1-month, and two-month best corrected visual acuity determination, contrast sensitivity, spectral domain optical coherence tomography, mean central macular thickness, mean macular cube volume, mean macular cube average thickness, and fundus autofluorescence (decreased, normal, or increased; and single or multiple spots) were measured. Correlation analysis with a determination of Spearman's rank correlation coefficient, regression analysis, agreement between investigators, and Friedman's test were used for statistical analyses. RESULTS: A direct correlation was observed between baseline fundus autofluorescence and macular cube average thickness at 1 month (r = 0.51, p = 0.020) and between fundus autofluorescence at 1 month and baseline macular cube average thickness (r = 0.50, p = 0.021). Regression analysis showed a coefficient of determination of 0.29 (p = 0.016) between baseline fundus autofluorescence and macular cube average thickness at 1 month. CONCLUSION: In patients with diabetic macular oedema, the pretreatment baseline degree of foveal fundus autofluorescence might be helpful in predicting macular cube average thickness in patients undergoing treatment with intravitreal ziv-aflibercept in the short term.

Azathioprine During the First Trimester of Pregnancy in a Patient with Vogt-Koyanagi-Harada Disease: A Multimodal Imaging Follow-Up Study.

BACKGROUND The aim of this study was to describe the case of a 27-year-old woman who developed Vogt-Koyanagi-Harada (VKH) disease in the 13th week of pregnancy, who was treated with high-dose oral corticosteroids and azathioprine due to its persistent course. CASE REPORT A 27-year-old East Indian woman in her 13th week of pregnancy presented with bilateral decreased visual acuity and metamorphopsia due to bilateral serous retinal detachments and was diagnosed with Vogt-Koyanagi-Harada (VKH) disease. Multimodal imaging, including blue light fundus autofluorescence (FAF), structural spectral domain optical coherence tomography (SD-OCT), en-face OCT, and OCT angiography (OCT-A), was performed at presentation and follow-up, being particularly helpful for identifying recurrences. Her treatment consisted of high-dose corticosteroid therapy, and azathioprine had to be added as an adjuvant due to the aggressive behavior of the disease. She gave birth to a healthy baby at 31 weeks of gestation and remained with 20/20 vision at 8 weeks postpartum. CONCLUSIONS To the best of our knowledge, this is the first report on the use of azathioprine in VKH disease during pregnancy with a successful outcome. Multimodal imaging avoiding the use of fundus fluorescein angiography is key in the diagnosis and follow-up of VKH disease in pregnant women.

Classification of fundus autofluorescence abnormal patterns in diabetic macular edema.

INTRODUCTION: Patients with diabetic macular edema can develop fundus autofluorescence alterations; thus far, these alterations have been more widely studied with scanning or confocal laser systems. OBJECTIVE: To describe and classify fundus autofluorescence abnormal patterns in patients with diabetic macular edema using the fundus autofluorescence system with a flash camera. METHOD: Observational, retrospective, cross-sectional, descriptive study. Fundus autofluorescence digital images of non-comparative cases with untreated diabetic macular edema, obtained and stored with a flash camera system, were assessed. Inter-observer variability was evaluated. RESULTS: 37 eyes of 20 patients were included. Lens opacity was the most common cause of inadequate image quality. Five different fundus autofluorescence patterns were observed: decreased (13%), normal (40%), single-spot hyper-autofluorescent (17 %), multiple-spot hyper-autofluorescent (22 %) and plaque-like hyper-autofluorescent (8 %). The kappa coefficient was 0.906 (p = 0.000). CONCLUSIONS: Different fundus autofluorescence phenotypic patterns are observed with flash camera systems in patients with diabetic macular edema. A more accurate phenotypic classification could help establish prognostic factors for visual loss or for the design of clinical trials for diabetic macular edema.

Posible relación de loratadina con el desenlace fatal en un paciente de riesgo / Possible link of loratadine with a fatal outcome in an at-risk patient

Un varón de 62 años, polimedicado de forma crónica por enfermedad mental grave y persistente, EPOC, diabetes e hipotiroidismo, estabilizado desde hace bastantes meses, inició un tratamiento con loratadina por rinitis. Al día siguiente es encontrado desvanecido sin conocimiento y trasladado de urgencia al hospital general para cuidados intensivos, donde fallece un día después. El análisis del caso revela un posible «efecto mariposa» con desenlace fatal, desencadenado por un fármaco de bajo riesgo, dada la situación «al límite» de la terapia previa (AU)

A 69-year-old man, who has been clinically chronic for severe and persistent mental illness, COPD, diabetes and hypothyroidism, stabilized for several months, began treatment with loratadine for rhinitis. The next day he is found unconscious and rushed to the general hospital for intensive care, where he dies a day later. The case analysis reveals a possible «butterfly effect», a fatal outcome caused by a low risk drug, given the «borderline» situation of prior therapy (AU)

[Economic and health impact of prenatal care in pregnant women with public health insurance in Colombia during 2014]. / Impacto económico y sanitario del control prenatal en embarazadas afiliadas al régimen subsidiado en Colombia durante 2014.

OBJECTIVE:: To estimate health care costs of live births and the impact of prenatal care visit (PCV) in women from poor households. MATERIALS AND METHODS:: A randomized sample of 9 244 pregnant women (out of total= 25 000). Mean differences and proportions were calculated to compare results in both groups of women. The costs were estimated in American Dollars (USD) 2014, from the payer's perspective. RESULTS:: 75% of women live in urban areas. The mean age was 23 years old (CI95% 23.5-23.8). The average cost with PCV was USD 609.1 (CI95%: 581-632.7) and without PCV was USD 857.8 (CI95%: 774.7-923.8) and 87% of women attended at least one PCV. The health care costs increased in 32% (CI95% 27.1-41) in women who did not attended PCV. CONCLUSION:: The PCV is an efficient and effective intervention for managing the risk of maternal health.

Impacto económico y sanitario del control prenatal en embarazadas afiliadas al régimen subsidiado en Colombia durante 2014 / Economic and health impact of prenatal care in pregnant women with public health insurance in Colombia during 2014

Resumen: Objetivo: Analizar el impacto sanitario y económico del control prenatal (CPN) en mujeres de hogares pobres. Material y métodos: Se tomó una muestra aleatoria de 9 244 mujeres embarazadas (población= 25 000). Se estimó la incidencia de mortalidad materna, los costos directos de atención y la diferencia de medias y proporciones. Los costos fueron estimados en dólares americanos (USD) de 2014, con perspectiva del tercer pagador. Resultados: El 75% de las mujeres viven en zonas urbanas. La media de edad fue de 23 años (IC95%: 23.5-23.8). El 87.5% asistió al menos a una cita de CPN. El costo medio de partos con CPN fue de USD$ 609.1 (IC95%: 581-632.7). Sin CPN fue de USD $857.8 (IC95%: 774.7-923.8). Los costos se incrementan 32% (IC95% 27.1-41) sin CPN. Conclusión: El CPN es una intervención eficiente y efectiva para la gestión del riesgo de la salud materna.

Abstract: Objective: To estimate health care costs of live births and the impact of prenatal care visit (PCV) in women from poor households. Materials and methods: A randomized sample of 9 244 pregnant women (out of total= 25 000). Mean differences and proportions were calculated to compare results in both groups of women. The costs were estimated in American Dollars (USD) 2014, from the payer’s perspective. Results: 75% of women live in urban areas. The mean age was 23 years old (CI95% 23.5-23.8). The average cost with PCV was USD 609.1 (CI95%: 581-632.7) and without PCV was USD 857.8 (CI95%: 774.7-923.8) and 87% of women attended at least one PCV. The health care costs increased in 32% (CI95% 27.1-41) in women who did not attended PCV. Conclusion: The PCV is an efficient and effective intervention for managing the risk of maternal health.

Frecuencia de enfermedades huérfanas en Cartagena de Indias, Colombia / Frequency for genetic orphan diseases in Cartagena de Indias, Colombia

RESUMEN Objetivo Estimar la frecuencia de enfermedades huérfanas (EH) o raras (ER) de origen genético en Cartagena de Indias, Colombia. Metodología Se realizó un estudio descriptivo con datos de los Registros Individuales de Prestación de Servicios (RIPS), del periodo 2003-2010, conservados por el Departamento Administrativo Distrital de Salud-DADIS. Fueron escogidas las EH de origen genético a partir de la clasificación del Ministerio de Salud Colombiano, y que se identifican con la referencia Q en los Códigos Internacionales de Enfermedad (CIE10). Resultados En total se registraron 522 181 personas que consultaron al sistema de salud. El 0,8 % (n=16 527) tuvieron algún diagnóstico Q. Finalmente, 391 personas (0,075 %) tuvieron impresión diagnóstica de EH de origen genético. En esta población se encontraron 75 impresiones diagnósticas distintas. Las Malformaciones y Deformidades Congénitas del Sistema Osteomuscular (Q65-Q79) fueron las más frecuentes (38,6 %), seguidas por Otras Malformaciones Congénitas (Q080-089) con 16,6 %. Conclusiones Se obtuvo el primer reporte de la frecuencia de las EH de origen genético en la segunda ciudad más poblada sobre el litoral del Caribe Colombiano. Es posible que en los RIPS haya un subregistro de las ER que dificulta conocer la prevalencia real.(AU)

ABSTRACT Objective Estimating the frequency of genetic orphan diseases in Cartagena de Indias (Colombia). Methodology A cross-sectional study was carried out employing data from the Health Care Service Individual Records (RIPS) of 2003-2010, kept by the District Administrative Department of Health-DADIS- in Cartagena de Indias. Genetic ODs included in national classification from Colombian Ministry of Health were chosen, and those identify by the Q reference according to the International Codes of Disease (ICD10) were finally selected for descriptive analysis. Results A total of 522 181 people who consulted the health system were recorded. 0.8 % (n=16 527) had a diagnosis Q. Finally, 391 people (0.075 %) had diagnostic impression of genetic OD. Within this population, 75 different diagnostic impressions were found. Congenital malformations and deformities of the musculoskeletal system (Q65-Q79) were the most frequent (38.6 %), followed by Other Congenital Malformations (Q080-089) with 16.6 %. Conclusions It was obtained the first report of the frequency of genetic orphan diseases from the second largest on the Colombian Caribbean coast city. It is suspected that misreporting in RIPS database is reducing actual frequency of OD. Further active search could reveal complete prevalence.(AU)

Hemiretinal Artery Occlusion in an 11-Year-Old Child with Dextrocardia.

Purpose. To report a case of hemiretinal artery occlusion in a child with dextrocardia, visceral heterotaxia, and secondary polycythemia. Methods. Complete clinical examination, fundus photography, and retinal fluorescein angiography were performed. Laboratory testing included complete blood cell count, homocysteine, protein c, protein s, activated protein s, methyltetrahydrofolate and homocysteine activator genes, factor leiden V gene, antithrombin III, and activated protein c resistance. In addition, transthoracic and transesophageal echocardiogram and cardiac catheterism were performed. Results. We report an 11-year-old boy with a sudden, painless visual loss in his right eye. His past medical history is remarkable for a congenital cardiac disease. He presented with vision of light perception in the right eye and a relative afferent pupillary defect. Fundus findings included a macular cherry-red spot and inferior hemiretinal whitening consistent with hemiretinal artery occlusion. Laboratory testing showed increased red blood cell (RBC) count, hemoglobin, and hematocrit. The patient was treated with four phlebotomies with improvement of RBC count and after one month reperfusion of the retina and a visual acuity of 20/200 were observed. Thrombophilia and cardiac screening were negative, except for secondary polycythemia. Conclusion. Hemiretinal artery occlusion is extremely rare in children and is often associated with congenital cardiac disease and hypercoagulative states.

[Frequency for genetic orphan diseases in Cartagena de Indias, Colombia]. / Frecuencia de enfermedades huérfanas en Cartagena de Indias, Colombia.

OBJECTIVE: Estimating the frequency of genetic orphan diseases in Cartagena de Indias (Colombia). METHODOLOGY: A cross-sectional study was carried out employing data from the Health Care Service Individual Records (RIPS) of 2003-2010, kept by the District Administrative Department of Health-DADIS- in Cartagena de Indias. Genetic ODs included in national classification from Colombian Ministry of Health were chosen, and those identify by the Q reference according to the International Codes of Disease (ICD10) were finally selected for descriptive analysis. RESULTS: A total of 522 181 people who consulted the health system were recorded. 0.8 % (n=16 527) had a diagnosis Q. Finally, 391 people (0.075 %) had diagnostic impression of genetic OD. Within this population, 75 different diagnostic impressions were found. Congenital malformations and deformities of the musculoskeletal system (Q65-Q79) were the most frequent (38.6 %), followed by Other Congenital Malformations (Q080-089) with 16.6 %. CONCLUSIONS: It was obtained the first report of the frequency of genetic orphan diseases from the second largest on the Colombian Caribbean coast city. It is suspected that misreporting in RIPS database is reducing actual frequency of OD. Further active search could reveal complete prevalence.

OBJETIVO: Estimar la frecuencia de enfermedades huérfanas (EH) o raras (ER) de origen genético en Cartagena de Indias, Colombia. METODOLOGÍA: Se realizó un estudio descriptivo con datos de los Registros Individuales de Prestación de Servicios (RIPS), del periodo 2003-2010, conservados por el Departamento Administrativo Distrital de Salud-DADIS. Fueron escogidas las EH de origen genético a partir de la clasificación del Ministerio de Salud Colombiano, y que se identifican con la referencia Q en los Códigos Internacionales de Enfermedad (CIE10). RESULTADOS: En total se registraron 522 181 personas que consultaron al sistema de salud. El 0,8 % (n=16 527) tuvieron algún diagnóstico Q. Finalmente, 391 personas (0,075 %) tuvieron impresión diagnóstica de EH de origen genético. En esta población se encontraron 75 impresiones diagnósticas distintas. Las Malformaciones y Deformidades Congénitas del Sistema Osteomuscular (Q65-Q79) fueron las más frecuentes (38,6 %), seguidas por Otras Malformaciones Congénitas (Q080-089) con 16,6 %. CONCLUSIONES: Se obtuvo el primer reporte de la frecuencia de las EH de origen genético en la segunda ciudad más poblada sobre el litoral del Caribe Colombiano. Es posible que en los RIPS haya un subregistro de las ER que dificulta conocer la prevalencia real.

Improved renal function, with similar proteinuria, after two years of early tacrolimus withdrawal from a regimen of sirolimus plus tacrolimus.

Results at 1 year of a pilot randomized trial with 87 kidney graft recipients, comparing the maintenance treatment with sirolimus, tacrolimus and steroids (group I) versus tacrolimus withdrawal since the third month onward, followed by maintenance with SRL and steroids (group II) have shown that early elimination of tacrolimus may result in improved renal function and blood pressure control. At 2 years, 26 and 25 patients in groups I and II, respectively, were analyzed in an on-therapy and an ITT analysis. In the on-therapy analysis, group II showed lower serum creatinine (1.3+/-0.2 vs. 1.6+/-0.6 mg/dL) and lower diastolic blood pressure (74+/-9 vs. 80+/-11 mm Hg). No acute rejections occurred during the second year of follow-up. In more than 90% of patients, proteinuria was less than 1 g/d, and in 50% it was negative. In the ITT analysis, differences were found only in diastolic blood pressure (80+/-10 vs. 74+/-8 mm Hg in groups I and II respectively, P=0.009). Tacrolimus withdrawal from a combination of sirolimus and tacrolimus, in selected patients, may be observed at 2 years by an improvement in renal function and blood pressure without a higher incidence of proteinuria.

Pilot randomized study of early tacrolimus withdrawal from a regimen with sirolimus plus tacrolimus in kidney transplantation.

We performed a randomized trial to compare two regimens of low-risk kidney allograft recipients in the first year after transplantation. Both regimens initially included sirolimus, tacrolimus and steroids; one with long-term maintenance with these drugs vs. tacrolimus withdrawal. Group I: sirolimus levels of 4-8 ng/mL, plus tacrolimus 8-12 ng/mL for 3 months, and 5-10 ng/mL after month 3. Group II: sirolimus concentration of 8-16 ng/mL, plus tacrolimus 3-8 ng/mL with tacrolimus elimination from month 3 onwards. Owing to difficulties in achieving target levels, the protocol was amended to increase the doses. Eighty-seven patients were recruited. In the intention-to-treat analysis, glomerular filtration rate (GFR) at 12 months, adjusted to zero for graft loss, was similar in both groups (58.8 and 59.9 mL/min). Analysis of patients remaining on protocol showed that GFR was higher in group II only in the patients postamendment (58.4 and 72.9 mL/min, p = 0.03). Rates of biopsy-confirmed rejection (BCAR) were 9.3% and 22.7% in groups I and II, respectively (p = NS). After amendment, BCAR rates were 10.3% and 11.1% (p = NS). Diastolic blood pressure was significantly lower in patients who eliminated tacrolimus (80.4 vs. 75.6 mmHg) (p = 0.03). Combining sirolimus and tacrolimus with adequate loading doses was associated with a low incidence of BCAR, and allowed tacrolimus elimination in a high proportion of patients, which may be followed by amelioration in renal function and blood pressure.

Allogeneic hematopoietic stem cell transplantation in patients 50 years of age and older.

BACKGROUND AND OBJECTIVES: The population of elderly patients with hematologic malignancies is increasing and so will the activity of stem cell transplantation (SCT) in this population. The aim of this study was to analyze the toxicity and survival of allogeneic SCT in patients 50 years and older (elderly group), and compare the results with a standard adult population (young group). DESIGN AND METHODS: Thirty-two elderly patients (median age 52.5, range 50-59 years) and 97 young patients (median 32, range 20-40) received a myeloablative, allogeneic SCT from HLA-identical siblings at a single institution, and formed the basis of this retrospective study. The majority of transplants in both groups were performed with non-T-cell-depleted bone marrow, conditioned with busulfan + cyclophosphamide and received cyclosporine + methotrexate as graft-versus-host disease (GVHD) prophylaxis. The percentage of high-risk patients was nearly double in the elderly group (41% vs. 23%, p = 0.06). RESULTS: We observed a low incidence of toxicities in the elderly group, including veno-occlusive disease, acute and chronic GVHD, transplant-related mortality, time to engraftment, and relapse incidence, without significant differences compared within the young group. The 3-year survival rates were not statistically different between the elderly and young groups: 51% vs. 55% for all patients; 87% vs. 69% in chronic myeloid leukemia; 79% vs. 62% in standard risk patients and 13% vs. 31% in high risk ones. In multivariate analyses no significant difference in overall survival was found between age groups. INTERPRETATION AND CONCLUSIONS: According to our experience, age alone (between 50-59), should not be considered a contraindication to a conventional HLA identical sibling transplant.