The effects of grass pollen allergoid immunotherapy on clinical and immunological parameters in children with allergic rhinitis

Allergoid immunotherapy is a new form of allergen immunotherapy allowing safe administration of high allergen doses. There is limited information on the effects of allergoid immunotherapy in children with allergic rhinitis. To investigate the immunological and clinical effects of allergoid immunotherapy in children with allergic rhinitis due to grass pollen allergy. Children with allergic rhinitis were assigned to allergoid immunotherapy (n = 27) or control (n = 26, no immunotherapy) groups. Children in the immunotherapy group received seven injections of grass pollen allergoid immunotherapy before grass pollen season and continued to receive maintenance immunotherapy for 27 months. All patients were offered a pharmacotherapy regimen to be used on demand during the pollen seasons. Clinical and laboratory parameters were compared between the immunotherapy and control groups. The rhinoconjunctivitis symptom-medication score and asthma symptom score were lower in the immunotherapy group after 1 yr of maintenance immunotherapy (p < 0.01 for both). Skin test reactivity and nasal reactivity as determined by nasal provocation testing for grass pollen were significantly decreased after 1 yr of immunotherapy (p < 0.001 for both). The seasonal increase in bronchial reactivity and nasal lavage eosinophil cationic protein levels were prevented after the first year of immunotherapy (p < 0.05 for both). The seasonal increase in immunoglobulin (Ig)E decreased (p < 0.05) and grass-specific IgG, IgG(1) and IgG(4) increased significantly already at the end of the seven-injection build-up therapy (p < 0.001, for all). Interleukin (IL)-4 levels in the culture supernatants showed a steady decline from baseline at first and second year of immunotherapy (p < 0.001) but remained unchanged in the control group. Allergoid immunotherapy is an effective method in the treatment of grass pollen-induced allergic rhinitis in children and prevents the seasonal increase in bronchial hyper-reactivity. Changes in specific IgE and IgG levels and decreased IL-4 production in peripheral blood mononuclear cell culture supernatants may account for the observed clinical effects.     

Oral Valganciclovir Is Noninferior to Intravenous Ganciclovir for the Treatment of Cytomegalovirus Disease in Solid Organ Transplant Recipients

Intravenous ganciclovir is the standard treatment for cytomegalovirus disease in solid organ transplant recipients. Oral valganciclovir is a more convenient alternative. In a randomized, international trial, recipients with cytomegalovirus disease were treated with either 900 mg oral valganciclovir or 5 mg/kg i.v. ganciclovir twice daily for 21 days, followed by 900 mg daily valganciclovir for 28 days. A total of 321 patients were evaluated (valganciclovir [n = 164]; i.v. ganciclovir [n = 157]). The success rate of viremia eradication at Day 21 was 45.1% for valganciclovir and 48.4% for ganciclovir (95% CI -14.0% to +8.0%), and at Day 49; 67.1% and 70.1%, respectively (p = NS). Treatment success, as assessed by investigators, was 77.4% versus 80.3% at Day 21 and 85.4% versus 84.1% at Day 49 (p = NS). Baseline viral loads were not different between groups and decreased exponentially with similar half-lives and median time to eradication (21 vs. 19 days, p = 0.076). Side-effects and discontinuations of assigned treatment (18 of 321 patients) were comparable. Oral valganciclovir shows comparable safety and is not inferior to i.v. ganciclovir for treatment of cytomegalovirus disease in organ transplant recipients and provides a simpler treatment strategy, but care should be taken in extrapolating to organ transplant recipients not properly represented in the present study.     

A comparison of pulse oximetry and respiratory rate in patient screening

Objective: To examine how well respiratory rate correlates with arterial oxygen saturation status as measured by pulse oximetry, and determine whether respiratory rate measurements detect oxygen desaturation reliably.Methods: Respiratory rate (RR) and oxygen saturation (SaO₂) were measured prospectively on 12 096 consecutive adult emergency department triage patients at a university medical center. Respiratory rate was measured by counting ausculated breath sounds for 1 min. Pulse oximetry was used to measure SaO₂. Measurements were analysed by age (with one group for 18–19 year olds, groups for every 10 yr from age 20 to age 60, and groups for every 5 yr for subsequent ages). Pearson correlation coefficients were calculated for each age group as well as the weighted average coefficient. Cases having oxygen saturation below 90% were examined to determine how frequently they exhibited increased RR (increased RRs were defined as any rate in the upper five percentile by age.Results: Correlation coefficients ranged from 0·379 to −0·465 with a weighted mean of −0·160. Coefficients for ages 18 through 70 years (representing 10 740 patients) all had magnitude <0·252. Overall, only 33% of subjects with oxygen saturation below 90% exhibited increased RR.Conclusions: Respiratory rate measurements correlate poorly with oxygen saturation measurements and do not screen reliably for desaturation. Patients with low SaO₂ do not usually exhibit increased RR. Similarly, increased RR is unlikely to reflect desaturation.     

Reversed-J inferior sternotomy for awake coronary bypass.

Many approaches for minimally invasive coronary bypass surgery are available and to further decrease the invasiveness, coronary artery bypass grafting has been performed under high thoracic epidural anesthesia without endotracheal intubation in the last years. Less invasive approach to coronary artery bypass graft operations is possible through combination of the high thoracic epidural anesthesia and a reversed-J sternotomy, and coronary revascularization can be accomplished without any additional technical difficulties and with a good exposure of both the left anterior descending artery and the left internal thoracic artery. This technique is less traumatic for patients and provides practical better oxygenation and shorter hospital stay.     

Discovery and Validation of a Urinary Exosome mRNA Signature for the Diagnosis of Human Kidney Transplant Rejection

BackgroundDeveloping a noninvasive clinical test to accurately diagnose kidney allograft rejection is critical to improve allograft outcomes. Urinary exosomes, tiny vesicles released into the urine that carry parent cells’ proteins and nucleic acids, reflect the biologic function of the parent cells within the kidney, including immune cells. Their stability in urine makes them a potentially powerful tool for liquid biopsy and a noninvasive diagnostic biomarker for kidney-transplant rejection.MethodsUsing 192 of 220 urine samples with matched biopsy samples from 175 patients who underwent a clinically indicated kidney-transplant biopsy, we isolated urinary exosomal mRNAs and developed rejection signatures on the basis of differential gene expression. We used crossvalidation to assess the performance of the signatures on multiple data subsets.ResultsAn exosomal mRNA signature discriminated between biopsy samples from patients with all-cause rejection and those with no rejection, yielding an area under the curve (AUC) of 0.93 (95% CI, 0.87 to 0.98), which is significantly better than the current standard of care (increase in eGFR AUC of 0.57; 95% CI, 0.49 to 0.65). The exosome-based signature’s negative predictive value was 93.3% and its positive predictive value was 86.2%. Using the same approach, we identified an additional gene signature that discriminated patients with T cell–mediated rejection from those with antibody-mediated rejection (with an AUC of 0.87; 95% CI, 0.76 to 0.97). This signature’s negative predictive value was 90.6% and its positive predictive value was 77.8%.ConclusionsOur findings show that mRNA signatures derived from urinary exosomes represent a powerful and noninvasive tool to screen for kidney allograft rejection. This finding has the potential to assist clinicians in therapeutic decision making.     

Jervell and Lange-Nielsen syndrome: neurologic and cardiologic evaluation

Recurrent syncope, malignant ventricular arrhythmias, and sudden death are complications of the long QT syndrome (LQTS). Two well-known syndromes with long QT intervals are known. The Jervell and Lange-Nielsen syndrome (JLNS) is characterized by prolongation of the QT interval, deafness, and autosomal-recessive inheritance, and the Romano-Ward syndrome is characterized by a prolonged QT interval, autosomal-dominant inheritance, and no deafness. In the present study assessment was performed of the diagnostic importance of the ventricular derepolarization parameters, clinical features, and prevalence of JLNS among 132 children with congenital hearing loss (CHL). In the CHL group the mean QT, QTc, JT, and JTc intervals and the dispersion values (QT-d, JT-d, QTc-d, and JTc-d) were significantly longer than those of control subjects (n = 96) (P < 0.05). Patients with CHL and JLNS (n = 5) had significantly longer mean values of QT, QTc, JT, and JTc intervals and dispersion values than those of CHL without JLNS (n = 127) and control subjects (P < 0.05). The results suggest that assessment of ventricular derepolarization parameters in children with CHL will be helpful in the early detection of JLNS because infants with CHL cannot accurately describe the symptoms of syncope.