Recommendations on the use of everolimus in lung transplantation

The antiproliferative effect of everolimus provides a therapeutic option in the immunosuppression therapy of lung transplantation, by reducing both the risk of acute rejection and the process of progressive fibrosis that determines chronic graft rejection. However, few data on the use of everolimus in lung transplantation have been published to date, and the specific indications of the drug, along with the most adequate time for its introduction or dosing, have not been defined yet.The aim of this article is to propose recommendations for the use of everolimus in lung transplant recipients, including indications, dosing schedules and the use of concomitant immunosuppression. This consensus document has been developed by experts of all the Spanish lung transplant groups from the review of the existing literature and the clinical experience.     

Giant-cell glioblastoma of childhood associated with HIV-1 and JC virus coinfection

Purpose

John Cunningham (JC) viral DNA sequence has seldom been reported in patients with brain tumors such as high grade gliomas and medulloblastomas, pointing to a role in the etiopathogenesis of such tumors.

Results

We present a unique clinical case of an HIV-positive pediatric patient with multifocal leukoencephalopathy and confirmed JC virus (JCV) infection that developed a giant-cell glioblastoma.

Conclusions

Experimental data with infected primates has previously hypothesized an association of human giant-cell glioblastoma with JCV or progressive multifocal leukoencephalopathy, though such association has not been documented in the literature for humans. Future studies with larger cohorts and molecular pathological analyses are still needed to corroborate the role of the widely spread human neurotropic virus in early transformation and in the development of brain tumors with different histology in the setting of HIV-related severe immunosuppression.     

Influence of KIR gene diversity on the course of HSV-1 infection: resistance to the disease is associated with the absence of KIR2DL2 and KIR2DS2

Herpes simplex virus type 1 (HSV-1) causes lifelong latent infections in most humans. Periodical virus reactivations from latency in the neurons of sensitive ganglia lead to transport to mucocutaneous regions and productive replication, which results in recurrent inflammatory herpetic lesions or in asymptomatic virus shedding. The medical consequences of such lesions and the frequency of recurrences vary greatly in different subjects. Furthermore, many infected individuals never suffer manifestations of the disease, even when exposed to stimuli that trigger clinical recurrences in other humans. The origin of the variability in the clinical course of HSV-1 infection remains unexplained. Herpesviruses and other pathogens sabotage the expression of major histocompatibility complex class I molecules by infected cells, thus subverting T-cell-mediated immunity. Subversion of antigen presentation is counteracted by natural killer cells, which survey the human leukocyte antigen (HLA) expression by specific receptors. These include the killer cell immunoglobulin-like receptors (KIRs), which are encoded by a complex of extremely diverse and rapidly evolving genes. Here, we analyze the contribution of KIR gene diversity to the variable clinical course of HSV-1 infection by comparing the distribution of these genes in humans with clinical manifestations of the disease with that in asymptomatically infected donors. This study provides preliminary evidence that the receptors KIR2DL2 and KIR2DS2 predispose to symptomatic HSV-1 infection and favor the frequently recurring forms of the disease. Possible contribution of the 'HLA-C1' ligand to HSV-1 disease was not statistically supported. Because of an absolute genetic linkage between KIR2DL2 and KIR2DS2, we could not determine which receptor was primarily responsible for the observed association, but our results suggest that presence in the genome of KIR2DL2 and KIR2DS2 hinders an effective cellular response to HSV-1.     

Combination antibiotic therapy improves survival in patients with community-acquired pneumonia and shock

OBJECTIVE: To assess whether combination antibiotic therapy improves outcome of severe community-acquired pneumonia in the subset of patients with shock. DESIGN: Secondary analysis of a prospective observational, cohort study. SETTING: Thirty-three intensive care units (ICUs) in Spain. PATIENTS: Patients were 529 adults with community-acquired pneumonia requiring ICU admission. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Two hundred and seventy (51%) patients required vasoactive drugs and were categorized as having shock. The effects of combination antibiotic therapy and monotherapy on survival were compared using univariate analysis and a Cox regression model. The adjusted 28-day in-ICU mortality was similar (p = .99) for combination antibiotic therapy and monotherapy in the absence of shock. However, in patients with shock, combination antibiotic therapy was associated with significantly higher adjusted 28-day in-ICU survival (hazard ratio, 1.69; 95% confidence interval, 1.09-2.60; p = .01) in a Cox hazard regression model. Even when monotherapy was appropriate, it achieved a lower 28-day in-ICU survival than an adequate antibiotic combination (hazard ratio, 1.64; 95% confidence interval, 1.01-2.64). CONCLUSIONS: Combination antibiotic therapy does not seem to increase ICU survival in all patients with severe community-acquired pneumonia. However, in the subset of patients with shock, combination antibiotic therapy improves survival rates.     

Regulatory authorities and orthopaedic clinical trials on expanded mesenchymal stem cells

Skeletal injuries requiring bone augmentation techniques are increasing in the context of avoiding or treating difficult cases with bone defects, bone healing problems, and bone regeneration limitations. Musculoskeletal severe trauma, osteoporosis-related fractures, and conditions where bone defect, bone collapse or insufficient bone regeneration occur are prone to disability and serious complications. Bone cell therapy has emerged as a promising technique to augment and promote bone regeneration. Interest in the orthopaedic community is considerable, although many aspects related to the research of this technique in specific indications may be insufficiently recognised by many orthopaedic surgeons. Clinical trials are the ultimate research in real patients that may confirm or refute the value of this new therapy. However, before launching the required trials in bone cell therapy towards bone regeneration, preclinical data is needed with the cell product to be implanted in patients to ensure safety and efficacy. These preclinical studies support the end-points that need to be evaluated in clinical trials. Orthopaedic surgeons are the ultimate players that, through their research, would confirm in clinical trials the benefit of bone cell therapies. To further foster this research, the pathway to eventually obtain authorisation from the National Competent Authorities and Research Ethics Committees under the European regulation is reviewed, and the experience of the REBORNE European project offers information and important clues about the current Voluntary Harmonization Procedure and other opportunities that need to be considered by surgeons and researchers on the topic.     

Outcomes of radiofrequency ablation for anal high-grade squamous intraepithelial lesions

Techniques in Coloproctology - Radiofrequency ablation (RFA) of high-grade squamous intraepithelial lesions (HSIL) is a promising minimally invasive technique but its oncologic and functional...     

Cardiac autonomic blockade in sinus disease and indication for a pacemaker

Functional autonomic blockade (FAB) with metoprolol (0.2 mg/kg body weight) and atropine sulphate (0.04 mg/kg) was carried out in 23 patients, 20 to 81 years old (mean age 61 years) with symptomatic sick sinus syndrome with clinical indication for permanent pacing. Several measurements were determined before and after FAB, 7 had normal intrinsic heart rate (IHR) and 16 abnormal. With normal IHR, 3 had severe autonomic regulation disturbances and in only two patients the corrected sinus nodal recovery time (SNRTC) and the sinoatrial conduction time (SACT) were prolonged after FAB. On the 16 patients with abnormal IHR only 4 had severe extrinsic autonomic influence and 15 had SACT and SNRTC prolonged after FAB. All measurements were determined by standard electrocardiographic surface tracings. Indications for permanent pacing were reduced to intrinsic sick sinus syndrome and bradycardia with severe autonomic disturbances in symptomatic patients.     

Xpert Carba-R assay for detection of carbapenemase-producing organisms in patients admitted to emergency rooms

Carbapenemase-producing organisms (CPO) have been identified as an urgent healthcare threat. Various methods have been used for the detection of CPO using rectal swabs. Recently, an on-demand polymerase chain reaction (PCR) assay, namely, the Xpert Carba-R assay, that requires less than an hour of turnaround time, had been developed for CPO detection in clinical samples. This study focused on the use of this assay to determine the intestinal colonization rate of CPO in patients admitted to emergency rooms (ERs).A retrospective review of medical records was conducted at a tertiary hospital between July 2017 and June 2018. CPO screening using rectal swabs was performed for patients transferred from other hospitals or for those who tested positive in CPO culture tests in the previous three months. The Xpert Carba-R assay and culture tests were used as the CPO screening methods, and the results of both tests were compared.Medical records of 705 patients admitted to our hospital during the study period were reviewed. Of these, 31 (4.4%) showed positive results for CPO using the Xpert Carba-R assay, and these patients were then transferred from the ERs to isolation rooms. Fifteen of the Xpert Carba-R assay-positive patients were also positive for the culture test; hence, early detection enabled the rapid isolation of CPO-infected patients and prevented the spread of the CPO.The Xpert Carba-R assay is a rapid test to identify and guide infection control programs to contain the spread of the rectal colonization of CPO within a hospital.