Effects of elevated carbon dioxide levels on response speed in cognitive test

To explore the associations of exposure to carbon dioxide with adults' response speed, 69 participants were invited to participate in the experiment conducted in an environmentally controlled chamber. Participants were exposed alone in three separate sessions, each lasting one hour, with a fixed ventilation rate, temperature and relative humidity level and the CO2 levels fixed at 600ppm, 1500ppm and 2100ppm, respectively. A validated neurobehavioral test battery, the Behavioural Assessment and Research System (BARS) was used to assess participants' cognitive performance, and response times were collected. Response speed was assessed in ten different tests. After adjusting for potential confounders (age, gender, and education), results showed no significant differences in eight out of the ten neurobehavioral tests. For the Selective Attention test, participants responded faster (lower response time) under CO2 levels of 2100ppm compared to 600ppm (adj.β-coef. -17.57, 95% CI (-29.45, -5.68), p-value=0.004). For the Progressive Ratio Test, participants' response times significantly decreased with CO2 levels increased. Results indicate no statistical link between CO2 levels and response speed, with only two out of ten comparisons being significant

Is cerebrospinal fluid amyloid-β42 a promising biomarker of response to nusinersen in adult spinal muscular atrophy patients?

Introduction: Nusinersen was approved as the first treatment for all types of spinal muscular atrophy (SMA), including adults with SMA types 2 and 3. Robust biomarkers of treatment response in SMA adults are lacking. Our aim was to examine cerebrospinal fluid (CSF) amyloid-β40 (Aβ40) and amyloid-β42 (Aβ42) peptides as biomarkers of treatment response. Methods: Eight patients with SMA types 2 and 3 were recruited consecutively in a single-center study. CSF was sampled at baseline, after a loading dose, and after three maintenance doses. Levels of Aβ42 and Aβ40 were evaluated for each CSF sampling. Wilcoxon matched-pairs signed-rank test was used to detect longitudinal changes. Results: CSF levels of Aβ42 increased from baseline to day 420 (95% confidence interval, P =.018), with a significant increase at days 180 and 420 compared with days 0 and 300, respectively (95% confidence interval, P =.012 and P =.018). Discussion: The maintenance and promotion of wellness of residual motor neurons mediated by the restored level of SMN protein due to nusinersen could result in an increased level of amyloid peptides

Cerebrospinal Fluid and Clinical Profiles in Adult Type 2–3 Spinal Muscular Atrophy Patients Treated with Nusinersen: An 18-Month Single-Centre Experience

Background and Objectives: Nusinersen was approved as the first disease-modifying therapy in spinal muscular atrophy (SMA). Our aim was to analyse therapy-related changes in cerebrospinal fluid (CSF) and serum parameters of adult type 2–3 SMA and to correlate biochemical data with motor functional status. Methods: Nine adult SMA type 2–3 patients and ten control subjects without neurodegenerative diseases were included in our single-centre study. Cross-sectional analysis of CSF routine parameters, CSF neurofilament light chain, CSF Tau, CSF phospho-Tau and serum creatinine was performed between SMA patients at baseline (T0) and control subjects. The above-mentioned fluid parameters were longitudinally analysed in the SMA cohort after loading dose (T1) and after four maintenance doses (T2, T3, T4, T5). Hammersmith Functional Motor Scale Expanded (HFMSE), Revised Upper Limb Module (RULM) and the 6-minute walking test (6MWT) were used to evaluate motor outcomes. Results: Improvements in HFMSE, RULM and 6MWT were observed only after the loading dose of nusinersen. No significant differences in routine CSF parameters and CSF markers of neurodegeneration were found between SMA patients and control subjects. Serum creatinine levels were significantly lower in SMA patients than in control subjects. CSF/serum albumin ratio (Qalb) significantly increased from T0 to each time point, without any further increase after the maintenance doses. Persistent systemic oligoclonal bands (OCBs) were found in five patients from baseline. Three more patients developed persistent systemic OCBs from T1; one patient showed intrathecal OCBSs from baseline to T5. Markers of neurodegeneration did not change during the follow-up and did not correlate with motor scores at baseline and at each timepoint. Serum creatinine levels significantly correlated with HFMSE and RULM at each time point. Conclusions: The increase of the Qalb values and the development of systemic OCBs in some SMA patients could be due to repeated lumbar puncture and to the immunogenic effect of nusinersen. On the other hand, the presence of OCBs in serum and/or CSF at baseline should be further investigated. Furthermore, biomarkers of neurodegeneration did not play a prognostic role in our cohort of adult SMA patients

ABVD plus radiotherapy versus EVE plus radiotherapy in unfavorable stage IA and IIA Hodgkin's lymphoma: results from an Intergruppo Italiano Linfomi randomized study.

BACKGROUND: In 1997, the Intergruppo Italiano Linfomi started a randomized trial to evaluate, in unfavorable stage IA and IIA Hodgkin's lymphoma (HL) patients, the efficacy and toxicity of the low toxic epirubicin, vinblastine and etoposide (EVE) regimen followed by involved field radiotherapy in comparison to the gold standard doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) regimen followed by the same radiotherapy program. PATIENTS AND METHODS: Patients should be younger than 65 years with unfavorable stage IA and IIA HL (i.e. stage IA or IIA with bulky disease and/or subdiaphragmatic disease, erythrocyte sedimentation rate higher than 40, extranodal (E) involvement, hilar involvement and more than three involved lymph node areas). RESULTS: Ninety-two patients were allocated to the ABVD arm and 89 to the EVE arm. Complete remission (CR) rates at the end of treatment program [chemotherapy (CT) + RT] were 93% and 92% for ABVD and EVE arms, respectively (P = NS). The 5-year relapse-free survival (RFS) rate was 95% for ABVD and 78% for EVE (P < 0.05). As a consequence of the different relapse rate, the 5-year failure-free survival (FFS) rate was significantly better for ABVD (90%) than for EVE (73%) arm (P < 0.05). No differences in terms of overall survival (OS) were observed for the two study arms. CONCLUSIONS: In unfavorable stage IA and IIA HL patients, no differences were observed between ABVD and EVE arms in terms of CR rate and OS. EVE CT, however, was significantly worse than ABVD in terms of RFS and FFS and cannot be recommended as initial treatment for HL

The role of neopterin in cardiovascular disease.

Inflammation plays a key role in the initiation and progression of atherosclerosis but also in the pathophysiology of atheromatous plaque disruption and the development of acute coronary syndromes. Neopterin is a marker of inflammation and of immune system activation, it is synthesized by macrophages, that, once activated, release this substance. Indeed, in clinical evaluation of patients, measurements of plasma levels of neopterin are usually used to evaluate progression of viral infections, renal transplant rejection, severe systemic inflammatory diseases, nephritic syndrome and several autoimmune diseases. This mediator is able to induce a pro-atherothrombotic phenotype in cells of the coronary circulation. Recent data indicate that serum levels of neopterin are elevated in patients with coronary and peripheral artery disease and seem to be a prognostic marker for major adverse cardiovascular events. In particular, neopterin levels predict future major cardiac and vascular adverse events in patients presenting with chronic coronary artery disease, with acute coronary syndromes, and in those with critical limb ischemia. This renders this molecule a useful marker of atherosclerotic plaque activity, permitting the identification of the subjects at highest risk for major adverse cardiovascular events. In line with the above mentioned evidences, patients with high neopterin levels may require aggressive risk factor modification and intensive medical treatment irrespective of the severity of their coronary artery disease. This data suggest a potential clinical use of neopterin as a marker for disease activity in patients with cardiovascular disease

Prenatal imaging features and postnatal outcomes of isolated fetal duplex renal collecting system: a systematic review and meta-analysis.

OBJECTIVES: To perform a systematic review of studies reporting the outcome of fetuses with a prenatal diagnosis of isolated duplex collecting system (DCS). METHODS: Inclusion criteria were studies reporting the outcome of fetuses with a prenatal diagnosis of isolated DCS, defined as DCS not associated with other major structural anomalies at the time of diagnosis. The outcomes observed were: imaging features of DCS on prenatal ultrasound, associated anomalies detected exclusively at prenatal follow-up ultrasound and at birth, abnormal karyotype, symptoms at birth [including vesicoureteral reflux (VUR), urinary tract infections (UTI)], need for and type of surgical approach, complications after surgery and accuracy of prenatal ultrasound in correctly identifying this anomaly. RESULTS: Eleven studies (284 fetuses with a prenatal diagnosis of DCS) were included. On ultrasound, DCS was associated with ureterocele in 70.7% and with megaureter in 36.6% of cases. Worsening of pelvic/ureteric dilatation was reported to occur in 41.3% of fetuses. At birth, 4.3% of fetuses affected by DCS showed associated renal anomalies. After birth, VUR and UTI presented in 51.3% and 21.7% of children respectively, while 33.6% required surgery. Prenatal diagnosis of DCS was confirmed in 90.9% of included cases. CONCLUSION: DCS diagnosed prenatally is associated with a generally good outcome. Prenatal ultrasound has a good diagnostic accuracy, while detailed post-natal assessment is required in order to identify associated renal anomalies. This article is protected by copyright. All rights reserved