After the introduction of highly active antiretroviral therapy (HAART), the incidence of many acquired immunodeficiency syndrome (AIDS)-related opportunistic infections, but not of progressive ...multifocal leukoencephalopathy (PML), has been dramatically decreased. However, it has been shown that about 50% of the HAART-treated PML patients had a significantly prolonged (>6 months) survival time, in comparison to the short (<6 months) survival time of the classical form of PML. In order to verify if a particular genotype or genomic rearrangements of JC virus (JCV) could affect the clinical course of PML, the authors performed nucleotide sequencing of 25 virion protein (VP1) and 18 transcriptional control region (TCR) DNA amplified in the cerebrospinal fluid (CSF) of HAART-untreated PML patients, of 17 HAART-treated PML patients, and in the urine of 23 healthy individuals. In nontreated PML patients, 52% and 44% of amplified JCV were respectively type 1 and type 2, whereas in HAART-treated PML patients, 59% of the amplified JCV were type 1, 23% type 2, and 18% type 4, without differences between long and short survivors. In both groups, the amplified TCR had unique and extensive rearrangements, whereas archetype TCR without rearrangements was detected in all the healthy subjects and in the CSF of two long-survivor PML patients. The data obtained indicate that the introduction of HAART has induced changes in JCV genotype distribution and probably reduced the rate of rearrangements of TCR region among PML patients.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
In survival analysis, time-varying covariates are endogenous when their measurements are directly related to the event status and incomplete information occur at random points during the follow-up. ...Consequently, the time-dependent Cox model leads to biased estimates. Joint models (JM) allow to correctly estimate these associations combining a survival and longitudinal sub-models by means of a shared parameter (i.e., random effects of the longitudinal sub-model are inserted in the survival one). This study aims at showing the use of JM to evaluate the association between a set of inflammatory biomarkers and Covid-19 mortality. During Covid-19 pandemic, physicians at Istituto Clinico di Città Studi in Milan collected biomarkers (endogenous time-varying covariates) to understand what might be used as prognostic factors for mortality. Furthermore, in the first epidemic outbreak, physicians did not have standard clinical protocols for management of Covid-19 disease and measurements of biomarkers were highly incomplete especially at the baseline. Between February and March 2020, a total of 403 COVID-19 patients were admitted. Baseline characteristics included sex and age, whereas biomarkers measurements, during hospital stay, included log-ferritin, log-lymphocytes, log-neutrophil granulocytes, log-C-reactive protein, glucose and LDH. A Bayesian approach using Markov chain Monte Carlo algorithm were used for fitting JM. Independent and non-informative priors for the fixed effects (age and sex) and for shared parameters were used. Hazard ratios (HR) from a (biased) time-dependent Cox and joint models for log-ferritin levels were 2.10 (1.67-2.64) and 1.73 (1.38-2.20), respectively. In multivariable JM, doubling of biomarker levels resulted in a significantly increase of mortality risk for log-neutrophil granulocytes, HR=1.78 (1.16-2.69); for log-C-reactive protein, HR=1.44 (1.13-1.83); and for LDH, HR=1.28 (1.09-1.49). Increasing of 100 mg/dl of glucose resulted in a HR=2.44 (1.28-4.26). Age, however, showed the strongest effect with mortality risk starting to rise from 60 years.
In survival analysis, time-varying covariates are endogenous when their measurements are directly related to the event status and incomplete information occur at random points during the follow-up. ...Consequently, the time-dependent Cox model leads to biased estimates. Joint models (JM) allow to correctly estimate these associations combining a survival and longitudinal sub-models by means of a shared parameter (i.e., random effects of the longitudinal sub-model are inserted in the survival one). This study aims at showing the use of JM to evaluate the association between a set of inflammatory biomarkers and Covid-19 mortality. During Covid-19 pandemic, physicians at Istituto Clinico di Città Studi in Milan collected biomarkers (endogenous time-varying covariates) to understand what might be used as prognostic factors for mortality. Furthermore, in the first epidemic outbreak, physicians did not have standard clinical protocols for management of Covid-19 disease and measurements of biomarkers were highly incomplete especially at the baseline. Between February and March 2020, a total of 403 COVID-19 patients were admitted. Baseline characteristics included sex and age, whereas biomarkers measurements, during hospital stay, included log-ferritin, log-lymphocytes, log-neutrophil granulocytes, log-C-reactive protein, glucose and LDH. A Bayesian approach using Markov chain Monte Carlo algorithm were used for fitting JM. Independent and non-informative priors for the fixed effects (age and sex) and for shared parameters were used. Hazard ratios (HR) from a (biased) time-dependent Cox and joint models for log-ferritin levels were 2.10 (1.67-2.64) and 1.73 (1.38-2.20), respectively. In multivariable JM, doubling of biomarker levels resulted in a significantly increase of mortality risk for log-neutrophil granulocytes, HR=1.78 (1.16-2.69); for log-C-reactive protein, HR=1.44 (1.13-1.83); and for LDH, HR=1.28 (1.09-1.49). Increasing of 100 mg/dl of glucose resulted in a HR=2.44 (1.28-4.26). Age, however, showed the strongest effect with mortality risk starting to rise from 60 years.
BACKGROUNDAllograft artery mycotic aneurysm (MA) represents a rare but life-threatening complication of kidney transplantation. Graftectomy is widely considered the safest option. Due to the rarity ...of the disease and the substantial risk of fatal consequences, experience with conservative strategies is limited. To date, only a few reports on surgical repair have been published. We describe a case of true MA successfully managed by aneurysm resection and arterial re-anastomosis. CASE SUMMARYAn 18-year-old gentleman, on post-operative day 70 after deceased donor kidney transplantation, presented with malaise, low urinary output, and worsening renal function. Screening organ preservation fluid cultures, collected at the time of surgery, were positive for Candida albicans. Doppler ultrasound and contrast-enhanced computer tomography showed a 4-cm-sized, saccular aneurysm of the iuxta-anastomotic segment of the allograft artery, suspicious for MA. The lesion was wide-necked and extended to the distal bifurcation of the main arterial branch, thus preventing endovascular stenting and embolization. After multidisciplinary discussion, the patient underwent surgical exploration, aneurysm excision, and re-anastomosis between the stump of the allograft artery and the internal iliac artery. The procedure was uneventful. Histology and microbiology evaluation of the surgical specimen confirmed the diagnosis of MA caused by Candida infection. Three years after the operation, the patient is doing very well with excellent allograft function and no signs of recurrent disease. CONCLUSIONSurgical repair represents a feasible option in carefully selected patients with allograft artery MA. Anti-fungal prophylaxis is advised when preservation fluid cultures are positive.
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