Aim The aim of this study was to identify factors predictive of serious infections over time in patients with systemic lupus erythematosus (SLE). Methods A multi-ethnic, multi-national Latin American SLE cohort was studied. Serious infection was defined as one that required hospitalization, occurred during a hospitalization or led to death. Potential predictors included were sociodemographic factors, clinical manifestations (per organ involved, lymphopenia and leukopenia, independently) and previous infections at baseline. Disease activity (SLEDAI), damage (SLICC/ACR Damage Index), non-serious infections, glucocorticoids, antimalarials (users and non-users), and immunosuppressive drugs use; the last six variables were examined as time-dependent covariates. Cox regression models were used to evaluate the predictors of serious infections using a backward elimination procedure. Univariable and multivariable analyses were performed. Results Of the 1243 patients included, 1116 (89.8%) were female. The median (interquartile range) age at diagnosis and follow-up time were 27 (20–37) years and 47.8 (17.9–68.6) months, respectively. The incidence rate of serious infections was 3.8 cases per 100 person-years. Antimalarial use (hazard ratio: 0.69; 95% confidence interval (CI): 0.48–0.99; p = 0.0440) was protective, while doses of prednisone >15 and ≤60 mg/day (hazard ratio: 4.18; 95 %CI: 1.69–10.31; p = 0.0019) and >60 mg/day (hazard ratio: 4.71; 95% CI: 1.35–16.49; p = 0.0153), use of methylprednisolone pulses (hazard ratio: 1.53; 95% CI: 1.10–2.13; p = 0.0124), increase in disease activity (hazard ratio: 1.03; 95% CI: 1.01–1.04; p = 0.0016) and damage accrual (hazard ratio: 1.22; 95% CI: 1.11–1.34; p < 0.0001) were predictive factors of serious infections. Conclusions Over time, prednisone doses higher than 15 mg/day, use of methylprednisolone pulses, increase in disease activity and damage accrual were predictive of infections, whereas antimalarial use was protective against them in SLE patients.
Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominantly inherited colorectal cancer syndrome attributable to mutations in one of several DNA mismatch repair genes, most commonly MLH1 and MSH2 . In certain populations, founder mutations account for a substantial portion of HNPCC. In this report we summarize the literature and our personal experience testing for a specific founder mutation in the Ashkenazi Jewish population, MSH2*1906G > C , also known as A636P. Although rare in the general population, the A636P mutation is detected in up to 7% of Ashkenazi Jewish patients with early age-of-onset colorectal cancer, and may account for up to one third of HNPCC in the Ashkenazi Jewish population. In addition, we summarize our initial experience with a prospective A636P testing protocol aimed at Ashkenazi Jewish patients at high or intermediate risk for harboring the A636P mutation.
BackgroundSystemic lupus erythematosus (SLE) SLE often mimics the symptoms of other diseases, and the interval between symptom onset and diagnosis remains long in these patients.ObjectivesTo examine the variables associated with a delay to diagnosis and their impact in damage accrual and mortality in patients with SLE.MethodsGLADEL a multi-ethnic, multi-national Latin-American SLE inception cohort was studied. Patients were recruited based on the physicians’ diagnosis but 97% fulfilled the ACR criteria. Delay to diagnosis was defined as ≥6 months from the first ACR criterion to SLE diagnosis. Socio-demographic, clinical/laboratory, disease activity, damage and mortality were compared using descriptive statistical tests. Multivariable Cox regression (HR) model with damage accrual and mortality as the end points were performed.ResultsOf the 1437 included in this analysis, the median delay to diagnosis was 5.9 months (Q1-Q3 2.4–16.1) and 721 (50.2%) had ≥6 months delay in SLE diagnosis. Patients with delay in diagnosis were more frequently of female gender, older age at diagnosis, mestizo ethnicity and without medical insurance. The characteristics of patients according to delay in diagnosis are depicted in Table 1. Delay to diagnosis did not impact on disease outcome: damage accrual [HR 1.21 (IC 95% 0.78-1.88; p=0.39)] and mortality [HR 1.30, CI 95% 0.84-2.01; p= 0.24)], after adjusting for age at SLE diagnosis, gender, ethnicity and socioeconomic status.ConclusionIn the GLADEL cohort, delay to diagnosis was associated to sex, age, thrombosis, sicca syndrome, cutaneous and neurological involvement. Furthermore, delay to diagnosis had no apparent negative impact on disease outcome (damage accrual and mortality). Early referral when there are suspicious clinical manifestations of SLE is crucial to reduce the diagnostic delay.Table 1.Comparison between the two patient groups in relation at the time to SLE diagnosis.VariableTime to SLE Diagnosis< 6 months (n=716)≥ 6 months (n=721)p valueAge at diagnosis, years(median, IQR)25.6 (16.2)30.4 (15.6)<0.001Follow-up time, months(median, IQR)54(44.1)53(48.6)0.302Female, n %628 (87.7)662 (91.8)0.010Ethnicity, n %MestizoAfrican Latin AmericansCaucasian306 (42.7)116 (16.2)294 (41.1)339 (47.0)70 (9.71)312 (43.3)0.001Education level, years, n%0-7 years8-12 years>12 years216 (30.2)329 (45.9)171 (23.9)237 (32.9)320 (44.4)164 (22.7)0.541Have medical insurance*(13), n%606 (84.6)573 (79.5)0.020Socioeconomic status, n%LowMiddleHigh436 (61.2)204 (28.7)72 (10.1)437 (60.6)208 (28.8)76 (10.6)0.955Clinical manifestations§, n%Malar rashDiscoid lupusPhotosensitivityOral ulcersArthritis/ ArthralgiaPleuritisPericarditisPsychosis/ seizuresHematological disorderProteinuria/ cylindruriaFeverLymphadenopathyLivedo reticularisRaynaud’s phenomenonSicca syndromeCardiac tamponadeVascular thrombosisStroke (ischemic)Pulmonary involvementPeritoneal serositis376 (52.5)70 (9.8)327 (45.7)239 (33.4)611 (85.3)124 (17.3)92 (12.9)39 (5.5)372 (52.0)254 (35.5)403 (56.3)97 (13.6)32 (4.5)125 (17.5)21 (2.9)6 (0.8)14 (2.0)4 (0.6)24 (3.4)9 (1.3)186 (25.8)72 (10.0)379 (52.6)226 (31.4)634 (87.9)104 (14.4)61 (8.5)60 (8.3)403 (55.9)202 (28.0)303 (42.0)67 (9.3)52 (7.2)190 (26.4)52 (7.2)0 (0.0)28 (3.9)12 (1.7)14 (1.9)1 (0.1)0.9000.8940.0090.4090.1480.1330.0070.0310.1340.002<0.0010.0110.027<0.0010.0020.0140.0300.0460.0960.011Hypocomplementemia§, n%487 (68.0)385 (53.4)<0.001Antiphospholipid antibodies§, n%363 (50.7)375 (52)0.795SLEDAI† at diagnosis, median (RIQ)*(257)12.0 (10.0)9.0 (9.0)<0.001SDI at the last visit‡ ≥ 1494 (69.0)484 (67.1)0.448Death during follow-up, n%39 (5.5)45 (6.2)0.521SD (standard deviation); IQR (Interquartile range); § Before SLE diagnosis; † Systemic Lupus Erythematosus Disease Activity Index; ‡ SDI (Systemic Lupus International Collaborating Clinics) Damage Index;*(Missing data)REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.
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