A two-year experience with the neodymium-YAG laser in endobronchial obstruction

In the first two years after the introduction of neodymium-yttrium-aluminum-garnet (Nd: YAG) laser therapy to our practice, 116 patients were treated 176 times. One hundred six patients (91.4 percent) were treated with the flexible fiberoptic bronchoscope. General anesthesia was used in 89.7 percent of treatments; there were four transient anesthetic complications. Three deaths from massive hemorrhage occurred in the first 59 treatments (first 30 patients). After laser power settings were reduced from 90 to 40 W, there were no further incidences of massive hemorrhage or death in the subsequent 117 treatments. The airway caliber was improved in 83.4 percent of treatments. The trachea, mainstem bronchi, and bronchus intermedius airway calibers were improved more often than those of the lobar bronchi. With lower laser power settings, Nd:YAG laser therapy is a safe and effective means of relieving airway obstruction. Thirty-six percent of patients were alive at one year. The median time to retreatment or death was 130 days.     

Radical mastectomy in the aged female.

Of 142 female patients over age 75 at The New York Hospital-Cornell Medical Center, 58 underwent radical mastectomy and 40 simple mastectomy for primary breast cancer. After five years, 19 per cent of the radical mastectomy group were cancer-free compared with 35 per cent of the simple mastectomy group. The gross five-year survival rates were 50 per cent and 47 per cent respectively. In the radical mastectomy group, when the axillary nodes did not show cancer at the time of operation, there have been no known recurrences and 70 per cent of the patients have survived at least five years. There was no surgical mortality. These findings support the view that until more controlled data are available, radical mastectomy is still the preferred therapy for primary breast cancer.     

Insulin resistance and endothelial function in children and adolescents

Aims

Insulin resistance (IR) impairs cellular response to insulin due to a dysfunction in glucose metabolism, associated with an increased cardiovascular risk. The aim of our study was to investigate the relationship among homeostasis model assessment index (HOMA index), endothelial function and vascular morphology in order to better stratify cardiovascular risk in children and adolescents.

Methods

A total of 150 children and adolescents (55 pre-pubertal, mean age 10.4 ± 3.1 years) were enrolled. Anthropometric [body mass index (BMI), waist circumference (WC)], laboratory [blood lipids, inflammatory markers, insulinemia, glycemia], HOMA index and ultrasound parameters [flow-mediated dilatation (FMD), common carotid intima–media thickness (cIMT) and antero-posterior diameter of infra-renal abdominal aorta (APAO)] were assessed.

Results

cIMT was positively related to age (r = 0.274, p < 0.01), BMI (r = 0.318, p < 0.01), WC (r = 0.315, p < 0.01) and triglycerides (r = 0.230, p < 0.01). APAO measurements showed a linear positive correlation with age (r = 0.435, p < 0.01), BMI (r = 0.505, p < 0.01), WC (r = 0.487, p < 0.01), triglycerides (r = 0.280, p < 0.01), C-reactive protein (r = 0.209, p < 0.05), fasting insulin (r = 0.378, p < 0.01) and HOMA index (r = 0.345, p < 0.01). FMD was inversely related to age (r = − 0.251, p < 0.01), rough BMI (r = − 0.318, p < 0.01), WC (r = − 0.340, p < 0.01), fasting insulin (r = − 0.281, p < 0.01) and HOMA index (r = − 0.282, p < 0.01). Multiple regression analysis found no influence of HOMA index on APAO and cIMT. HOMA index was an independent predictor for brachial artery FMD worsening after the statistical adjustment.

Conclusion

HOMA index increase induced a worsening in endothelial function since childhood.     

Digital droplet PCR (ddPCR) for the precise quantification of human T-lymphotropic virus 1 proviral loads in peripheral blood and cerebrospinal fluid of HAM/TSP patients and identification of viral mutations

An elevated human T cell lymphotropic virus 1 (HTLV)-1 proviral load (PVL) is the main risk factor for developing HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in HTLV-1 infected subjects, and a high cerebrospinal fluid (CSF) to peripheral blood mononuclear cell (PBMC) PVL ratio may be diagnostic of the condition. However, the standard method for quantification of HTLV-1 PVL—real-time PCR—has multiple limitations, including increased inter-assay variability in compartments with low cell numbers, such as CSF. Therefore, in this study, we evaluated a novel technique for HTVL-1 PVL quantification, digital droplet PCR (ddPCR). In ddPCR, PCR samples are partitioned into thousands of nanoliter-sized droplets, amplified on a thermocycler, and queried for fluorescent signal. Due to the high number of independent events (droplets), Poisson algorithms are used to determine absolute copy numbers independently of a standard curve, which enables highly precise quantitation. This assay has low intra-assay variability allowing for reliable PVL measurement in PBMC and CSF compartments of both asymptomatic carriers (AC) and HAM/TSP patients. It is also useful for HTLV-1-related clinical applications, such as longitudinal monitoring of PVL and identification of viral mutations within the region targeted by the primers and probe.     

Inspecting the Ribozyme Region of Hepatitis Delta Virus Genotype 1: Conservation and Variability

The hepatitis delta virus (HDV) genome has an autocatalytic region called the ribozyme, which is essential for viral replication. The aim of this study was to use next-generation sequencing (NGS) to analyze the ribozyme quasispecies (QS) in order to study its evolution and identify highly conserved regions potentially suitable for a gene-silencing strategy. HDV RNA was extracted from 2 longitudinal samples of chronic HDV patients and the ribozyme (nucleotide, nt 688–771) was analyzed using NGS. QS conservation, variability and genetic distance were analyzed. Mutations were identified by aligning sequences with their specific genotype consensus. The main relevant mutations were tested in vitro. The ribozyme was conserved overall, with a hyper-conserved region between nt 715–745. No difference in QS was observed over time. The most variable region was between nt 739–769. Thirteen mutations were observed, with three showing a higher frequency: T23C, T69C and C64 deletion. This last strongly reduced HDV replication by more than 1 log in vitro. HDV Ribozyme QS was generally highly conserved and was maintained during follow-up. The most conserved portion may be a valuable target for a gene-silencing strategy. The presence of the C64 deletion may strongly impair viral replication, as it is a potential mechanism of viral persistence.     

Paclitaxel coated balloons for coronary artery interventions: A comprehensive review of preclinical and clinical data

After the "mechanical era" in interventional cardiology (represented by balloon angioplasty and bare metal stent implantation), arrived the "local dispensing" era, began with the intracoronary delivery of antithrombotic or antirestenotic drugs. However, even drug eluting stents have some pitfalls and cannot be used in all clinical subsets. In this article we will review the significant data on the paclitaxel-coated balloons for the treatment of coronary artery disease. Particularly, we will review the rationale of this new treatment strategy, the preclinical data and will focus on available clinical studies in humans. After the initial boost of the paclitaxel coated balloons with the Paccocath technology in in-stent restenotic lesions, the experimentation of newer devices in native coronary arteries raised some concerns on their efficacy and safety. We will comment on this topic trying to understand the reasons of this failure, and will discuss on possible future developments and applications for these devices for the treatment of coronary artery disease.     

Understanding the metal free alginate gelation process

Alginate is a natural polysaccharide that has been recently gaining increasing attention as a biomaterial in the field of tissue engineering due to its favourable biocompatibility and gelation properties. Alginate hydrogels are commonly made by ionic crosslinking in the presence of divalent cations. Only a few studies have attempted to prepare alginate hydrogels without the presence of metal cations. Here the formation of metal free alginate hydrogels in the presence of the amino-acid glutamine is investigated. The transition from sol to gel is monitored by rheological measurements in the viscoelastic regime that reveal how the charged or neutral form of glutamine induces deep differences in the gelling ability. In particular, we show that the storage, G′, and loss, G′′, moduli differ significantly by shifting the glutamine zwitterionic equilibrium. Protonated amino acid could induce a shielding effect of the electrostatic repulsion of the alginate chains. Stable gels are obtained in the presence of a larger amount of free organic acid that gives rise to chain crosslink junctions and chain–chain stabilization. This opens up the possibility of preparing metal-free alginate hydrogels based on amino acid equilibria being pH sensitive.

Alginate gelling by ionic cross-linking using multivalent ions has been known and exploited for several decades. We focus on the possibility to obtain alginate hydrogels without using metal cation in order to obtain metal-free alginates hydrogels.     

Chagas disease reactivation in rheumatologic patients: association with immunosuppressive therapy and humoral response

Clinical Rheumatology - Evidence for Chagas disease reactivation (CDR) in rheumatologic patients under rheumatologic treatments (RTs) is scarce. To screen and follow-up patients with rheumatic...     

Targeted next-generation sequencing in chronic lymphocytic leukemia: a high-throughput yet tailored approach will facilitate implementation in a clinical setting

Next-generation sequencing has revealed novel recurrent mutations in chronic lymphocytic leukemia, particularly in patients with aggressive disease. Here, we explored targeted re-sequencing as a novel strategy to assess the mutation status of genes with prognostic potential. To this end, we utilized HaloPlex targeted enrichment technology and designed a panel including nine genes: ATM, BIRC3, MYD88, NOTCH1, SF3B1 and TP53, which have been linked to the prognosis of chronic lymphocytic leukemia, and KLHL6, POT1 and XPO1, which are less characterized but were found to be recurrently mutated in various sequencing studies. A total of 188 chronic lymphocytic leukemia patients with poor prognostic features (unmutated IGHV, n=137; IGHV3-21 subset #2, n=51) were sequenced on the HiSeq 2000 and data were analyzed using well-established bioinformatics tools. Using a conservative cutoff of 10% for the mutant allele, we found that 114/180 (63%) patients carried at least one mutation, with mutations in ATM, BIRC3, NOTCH1, SF3B1 and TP53 accounting for 149/177 (84%) of all mutations. We selected 155 mutations for Sanger validation (variant allele frequency, 10–99%) and 93% (144/155) of mutations were confirmed; notably, all 11 discordant variants had a variant allele frequency between 11–27%, hence at the detection limit of conventional Sanger sequencing. Technical precision was assessed by repeating the entire HaloPlex procedure for 63 patients; concordance was found for 77/82 (94%) mutations. In summary, this study demonstrates that targeted next-generation sequencing is an accurate and reproducible technique potentially suitable for routine screening, eventually as a stand-alone test without the need for confirmation by Sanger sequencing.