Impact of single nucleotide polymorphisms and of clinical risk factors on new-onset diabetes mellitus in HIV-infected individuals

Background. Metabolic complications, including cardiovascular events and diabetes mellitus (DM), are a major long-term concern in human immunodeficienc virus (HIV)-infected individuals. Recent genome-wide association studies have reliably associated multiple single nucleotide polymorphisms (SNPs) to DM in the general population. Methods. We evaluated the contribution of 22 SNPs identifie in genome-wide association studies and of longitudinally measured clinical factors to DM. We genotyped all 94 white participants in the Swiss HIV Cohort Study who developed DM from 1 January 1999 through 31 August 2009 and 550 participants without DM. Analyses were based on 6054 person-years of follow-up and 13,922 measurements of plasma glucose. Results. The contribution to DM risk explained by SNPs (14% of DM variability) was larger than the contribution to DM risk explained by current or cumulative exposure to different antiretroviral therapy combinations (3% of DM variability). Participants with the most unfavorable genetic score (representing 12% and 19% of the study population, respectively, when applying 2 different genetic scores) had incidence rate ratios for DM of 3.80 (95% confidenc interval [CI], 2.05–7.06) and 2.74 (95% CI, 1.53–4.88), respectively, compared with participants with a favorable genetic score. However, addition of genetic data to clinical risk factors that included body mass index only slightly improved DM prediction. Conclusions. In white HIV-infected persons treated with antiretroviral therapy, the DM effect of genetic variants was larger than the potential toxic effects of antiretroviral therapy. SNPs contributed significantl to DM risk, but their addition to a clinical model improved DM prediction only slightly, similar to studies in the general population.

New-onset epilepsy: considerations for initial and follow-up MRI to detect brain tumor

Seizures are often the presenting symptoms of a cerebral tumor and may precede its diagnosis by many years. The article under evaluation searched two large English registries for patients admitted for new-onset epilepsy. The risk of subsequently being diagnosed with a malignant brain tumor was found to be 26-fold higher compared with controls, persisted over many years and was accentuated in young patients. Recently, surgical advances have led to a significant decrease in surgical morbidities, making surgery the first treatment option for gliomas, especially low-grade gliomas. This paradigm shift warrants a consequent diagnostic workup (MRI) in patients at risk for low-grade glioma - that is, patients with new-onset epilepsy. The study is discussed in the context of the ongoing debate on neuroimaging after new-onset epilepsy.

Acute onset incomitant image disparity modifies saccadic and vergence eye movements.

New-onset impairment of ocular motility will cause incomitant strabismus, i.e., a gaze-dependent ocular misalignment. This ocular misalignment will cause retinal disparity, that is, a deviation of the spatial position of an image on the retina of both eyes, which is a trigger for a vergence eye movement that results in ocular realignment. If the vergence movement fails, the eyes remain misaligned, resulting in double vision. Adaptive processes to such incomitant vergence stimuli are poorly understood. In this study, we have investigated the physiological oculomotor response of saccadic and vergence eye movements in healthy individuals after shifting gaze from a viewing position without image disparity into a field of view with increased image disparity, thus in conditions mimicking incomitance. Repetitive saccadic eye movements into a visual field with increased stimulus disparity lead to a rapid modification of the oculomotor response: (a) Saccades showed immediate disconjugacy (p < 0.001) resulting in decreased retinal image disparity at the end of a saccade. (b) Vergence kinetics improved over time (p < 0.001). This modified oculomotor response enables a more prompt restoration of ocular alignment in new-onset incomitance.

Improvement of non-paraneoplastic voltage-gated potassium channel antibody-associated limbic encephalitis without immunosuppressive therapy

We describe a 61-year-old patient with clinical evidence of limbic encephalitis who improved with anticonvulsant treatment only, that is, without the use of immunosuppressive agents. Three years following occurrence of anosmia, increasing memory deficits, and emotional disturbances, he presented with new-onset temporal lobe epilepsy, with antibodies binding to neuronal voltage-gated potassium channels and bitemporal hypometabolism on FDG-PET scan; the MRI scan was normal. This is most likely a case of spontaneous remission, illustrating that immunosuppressive therapy might be suspended in milder courses of limbic encephalitis. It remains open whether treatment with anticonvulsant drugs played an additional beneficiary role through the direct suppression of seizures or, additionally, through indirect immunomodulatory side effects.

Transcranial Doppler-detected cerebral embolic load during transcatheter aortic valve implantation

Transcatheter aortic valve implantation (TAVI) is an alternative to surgery for high-risk patients with severe aortic valve stenosis. Periprocedural stroke is reported at an incidence up to 10%. Magnetic resonance imaging studies have identified new onset of clinically silent ischaemic cerebral lesions more frequently (68-84%). So far, few data are available about cerebral embolism during TAVI. The aim of this study was to determine the frequency of high-intensity transient signals (HITS) and to explore differences in the HITS pattern between transfemoral and transapical access and between self-expanding (SE) and balloon-expandable (BE) deployment technique.

Adverse cardiac events during catecholamine vasopressor therapy: a prospective observational study

PURPOSE: To determine the incidence of and risk factors for adverse cardiac events during catecholamine vasopressor therapy in surgical intensive care unit patients with cardiovascular failure. METHODS: The occurrence of any of seven predefined adverse cardiac events (prolonged elevated heart rate, tachyarrhythmia, myocardial cell damage, acute cardiac arrest or death, pulmonary hypertension-induced right heart dysfunction, reduction of systemic blood flow) was prospectively recorded during catecholamine vasopressor therapy lasting at least 12 h. RESULTS: Fifty-four of 112 study patients developed a total of 114 adverse cardiac events, an incidence of 48.2 % (95 % CI, 38.8-57.6 %). New-onset tachyarrhythmia (49.1 %), prolonged elevated heart rate (23.7 %), and myocardial cell damage (17.5 %) occurred most frequently. Aside from chronic liver diseases, factors independently associated with the occurrence of adverse cardiac events included need for renal replacement therapy, disease severity (assessed by the Simplified Acute Physiology Score II), number of catecholamine vasopressors (OR, 1.73; 95 % CI, 1.08-2.77; p = 0.02) and duration of catecholamine vasopressor therapy (OR, 1.01; 95 % CI, 1-1.01; p = 0.002). Patients developing adverse cardiac events were on catecholamine vasopressors (p < 0.001) and mechanical ventilation (p < 0.001) for longer and had longer intensive care unit stays (p < 0.001) and greater mortality (25.9 vs. 1.7 %; p < 0.001) than patients who did not. CONCLUSIONS: Adverse cardiac events occurred in 48.2 % of surgical intensive care unit patients with cardiovascular failure and were related to morbidity and mortality. The extent and duration of catecholamine vasopressor therapy were independently associated with and may contribute to the pathogenesis of adverse cardiac events.

Locally generated particulate pollution and respiratory symptoms in young children

BACKGROUND: Particulate matter <10 mum (PM(10)) from fossil fuel combustion is associated with an increased prevalence of respiratory symptoms in children and adolescents. However, the effect of PM(10) on respiratory symptoms in young children is unclear. METHODS: The association between primary PM(10) (particles directly emitted from local sources) and the prevalence and incidence of respiratory symptoms was studied in a random sample cohort of 4400 Leicestershire children aged 1-5 years surveyed in 1998 and again in 2001. Annual exposure to primary PM(10) was calculated for the home address using the Airviro dispersion model and adjusted odds ratios (ORS) and 95% confidence intervals were calculated for each microg/m(3) increase. RESULTS: Exposure to primary PM(10) was associated with the prevalence of cough without a cold in both 1998 and 2001, with adjusted ORs of 1.21 (1.07 to 1.38) and 1.56 (1.32 to 1.84) respectively. For night time cough the ORs were 1.06 (0.94 to 1.19) and 1.25 (1.06 to 1.47), and for current wheeze 0.99 (0.88 to 1.12) and 1.28 (1.04 to 1.58), respectively. There was also an association between primary PM(10) and new onset symptoms. The ORs for incident symptoms were 1.62 (1.31 to 2.00) for cough without a cold and 1.42 (1.02 to 1.97) for wheeze. CONCLUSION: In young children there was a consistent association between locally generated primary PM(10) and the prevalence and incidence of cough without a cold and the incidence of wheeze which was independent of potential confounders.

Factors associated with the incidence of type 2 diabetes mellitus in HIV-infected participants in the Swiss HIV Cohort Study

BACKGROUND: Human immunodeficiency virus (HIV)-infected persons may be at increased risk for developing type 2 diabetes mellitus because of viral coinfection and adverse effects of treatment. METHODS: We studied associations of new-onset diabetes mellitus with hepatitis B virus and hepatitis C virus coinfections and antiretroviral therapy in participants in the Swiss HIV Cohort Study, using Poisson regression. RESULTS: A total of 123 of 6513 persons experienced diabetes mellitus during 27,798 person-years of follow-up (PYFU), resulting in an incidence of 4.4 cases per 1000 PYFU (95% confidence interval [CI], 3.7-5.3 cases per 1000 PYFU). An increased incidence rate ratio (IRR) was found for male subjects (IRR, 2.5; 95% CI, 1.5-4.2), older age (IRR for subjects >60 years old, 4.3; 95% CI, 2.3-8.2), black (IRR, 2.1; 95% CI, 1.1-4.0) and Asian (IRR, 4.9; 95% CI, 2.2-10.9) ethnicity, Centers for Disease Control and Prevention disease stage C (IRR, 1.6; 95% CI, 1.04-2.4), and obesity (IRR, 4.7; 95% CI, 3.1-7.0), but results for hepatitis C virus infection or active hepatitis B virus infection were inconclusive. Strong associations were found for current treatment with nucleoside reverse-transcriptase inhibitors (IRR, 2.22; 95% CI, 1.11-4.45), nucleoside reverse-transcriptase inhibitors plus protease inhibitors (IRR, 2.48; 95% CI, 1.42-4.31), and nucleoside reverse-transcriptase inhibitors plus protease inhibitors and nonnucleoside reverse-transcriptase inhibitors (IRR, 3.25; 95% CI, 1.59-6.67) but were not found for treatment with nucleoside reverse-transcriptase inhibitors plus nonnucleoside reverse-transcriptase inhibitors (IRR, 1.47; 95% CI, 0.77-2.82). CONCLUSIONS: In addition to traditional risk factors, current treatment with protease inhibitor- and nucleoside reverse-transcriptase inhibitor-containing regimens was associated with the risk of developing type 2 diabetes mellitus. Our study did not find a significant association between viral hepatitis infection and risk of incident diabetes.

[Does cataract surgery increase the risk of exudative age-related macular degeneration? Results from a large retrospective case-control study]

BACKGROUND: Many epidemiological studies indicate a positive correlation between cataract surgery and the subsequent progression of age-related macular degeneration (AMD). Such a correlation would have far-reaching consequences. However, in epidemiological studies it is difficult to determine the significance of a single risk factor, such as cataract surgery. PATIENTS AND METHODS: We performed a retrospective case-control study of patients with new onset exudative age-related macular degeneration to determine if cataract surgery was a predisposing factor. A total of 1496 eyes were included in the study: 984 cases with new onset of exudative AMD and 512 control eyes with early signs of age-related maculopathy. Lens status (phakic or pseudophakic) was determined for each eye. RESULTS: There was no significant difference in lens status between study and control group (227/984 [23.1 %] vs. 112/512 [21.8 %] pseudophakic, p = 0.6487; OR = 1.071; 95 % CI = 0.8284-1.384). In cases with bilateral pseudophakia (n = 64) no statistically significant difference of the interval between cataract surgery in either eye and the onset of exudative AMD in the study eye was found (225.9 +/- 170.4 vs. 209.9 +/- 158.2 weeks, p = 0.27). CONCLUSIONS: Our results provide evidence that cataract surgery is not a major risk factor for the development of exudative AMD.

[Vasculitis as a reason of chronic headache]

A 13-year-old girl presented to our emergency with a one week history of fever and skin rash and new onset of chorea for the last three days. There was a long standing history of right predominant headache; followed by personality change, fatigue, arthralgia and weight loss over the last few months. Previous investigations by head CT and ophthalmological examination did not explain the symptoms. Further investigations revealed peri- and pancarditis with aortic insufficiency, a renal involvement with elevated creatinin, protein- and hematuria and a hemolytic anemia. Diagnosis of lupus eythematodes was confirmed by high ANA, anti-dsDNS and Anticardiolipin antibodies. Within the first 48 hours after admission there was significant deterioration with reduced vigilance and dysarthria. MRI of the brain and dopplersonography of cerebral vessels showed a complete thrombosis of the right medial cerebral artery with a small net of collaterals, irregularities of the left cerebral artery due to vasculitis and several subacute leftsided ischemias. Immunosuppressive therapy with high-dose corticosteroids and cyclophosphamid together with antithrombotic therapy induced an improvement of neurologic, renal and cardiac function.

Routine vaccination against pertussis and the risk of childhood asthma: a population-based cohort study

BACKGROUND: In industrialized countries vaccination coverage remains suboptimal, partly because of perception of an increased risk of asthma. Epidemiologic studies of the association between childhood vaccinations and asthma have provided conflicting results, possibly for methodologic reasons such as unreliable vaccination data, biased reporting, and reverse causation. A recent review stressed the need for additional, adequately controlled large-scale studies. OBJECTIVE: Our goal was to determine if routine childhood vaccination against pertussis was associated with subsequent development of childhood wheezing disorders and asthma in a large population-based cohort study. METHODS: In 6811 children from the general population born between 1993 and 1997 in Leicestershire, United Kingdom, respiratory symptom data from repeated questionnaire surveys up to 2003 were linked to independently collected vaccination data from the National Health Service database. We compared incident wheeze and asthma between children of different vaccination status (complete, partial, and no vaccination against pertussis) by computing hazard ratios. Analyses were based on 6048 children, 23 201 person-years of follow-up, and 2426 cases of new-onset wheeze. RESULTS: There was no evidence for an increased risk of wheeze or asthma in children vaccinated against pertussis compared with nonvaccinated children. Adjusted hazard ratios comparing fully and partially vaccinated with nonvaccinated children were close to one for both incident wheeze and asthma. CONCLUSION: This study provides no evidence of an association between vaccination against pertussis in infancy and an increased risk of later wheeze or asthma and does not support claims that vaccination against pertussis might significantly increase the risk of childhood asthma.

Feasibility and safety of same-day home discharge after radiofrequency catheter ablation

Interventional cardiology in a day-case setting might reduce logistic constraints on hospital resources. However, in contrast with coronary angioplasty, few data support the feasibility and safety of radiofrequency catheter ablation (RCA). The aim of this prospective, multicenter cohort study was to evaluate the feasibility and safety of RCA in 1,342 patients (814 men; mean age 57 +/- 17 years) considered eligible for ambulatory RCA, according to specific set of criteria, for common atrial flutter (n = 632), atrioventricular nodal reentrant tachycardia (n = 436), accessory pathways (n = 202), and atrial tachycardia (n = 72). Patients suitable for early discharge (4 to 6 hours after uncomplicated RCA) were scheduled for 1-month follow-up. Predictive factors for delayed complications were studied by multivariate analysis. Of the 1,342 enrolled patients, 1,270 (94.6%) were discharged the same day and followed for 1 month; no deaths occurred, and the readmission rate was 0.79% (95% confidence interval 0.30% to 1.27%). Six patients had significant puncture complications, 2 presented with symptomatic delayed pulmonary embolism, and 2 had new onset of poorly tolerated atrial flutter. None of these complications was life threatening. Multivariate analysis did not identify any significant independent predictors for delayed complications. In conclusion, these data suggest that same-day discharge after uncomplicated RCA for routine supraventricular arrhythmias is safe and may be applicable in clinical practice. This approach is known to be associated with significant patient satisfaction and cost savings and can be considered a first-line option in most patients who undergo routine ablation procedures.

Early troponin T and prediction of potentially correctable in-hospital complications after coronary artery bypass grafting surgery

BACKGROUND Peak levels of troponin T (TnT) reliably predict morbidity and mortality after cardiac surgery. However, the therapeutic window to manage CABG-related in-hospital complications may close before the peak is reached. We investigated whether early TnT levels correlate as well with complications after coronary artery bypass grafting (CABG) surgery. METHODS A 12 month consecutive series of patients undergoing elective isolated CABG procedures (mini-extra-corporeal circuit, Cardioplegic arrest) was analyzed. Logistic regression modeling was used to investigate whether TnT levels 6 to 8 hours after surgery were independently associated with in-hospital complications (either post-operative myocardial infarction, stroke, new-onset renal insufficiency, intensive care unit (ICU) readmission, prolonged ICU stay (>48 hours), prolonged need for vasopressors (>24 hours), resuscitation or death). RESULTS A total of 290 patients, including 36 patients with complications, was analyzed. Early TnT levels (odds ratio (OR): 6.8, 95% confidence interval (CI): 2.2-21.4, P=.001), logistic EuroSCORE (OR: 1.2, 95%CI: 1.0-1.3, P=.007) and the need for vasopressors during the first 6 postoperative hours (OR: 2.7, 95%CI: 1.0-7.1, P=.05) were independently associated with the risk of complications. With consideration of vasopressor use during the first 6 postoperative hours, the sum of specificity (0.958) and sensitivity (0.417) of TnT for subsequent complications was highest at a TnT cut-off value of 0.8 ng/mL. CONCLUSION Early TnT levels may be useful to guide ICU management of CABG patients. They predict clinically relevant complications within a potential therapeutic window, particularly in patients requiring vasopressors during the first postoperative hours, although with only moderate sensitivity.