Differences in aerodynamic characteristics of new and dysfunctional Provox®2 voice prostheses in vivo

Tracheoesophageal voice prostheses need to be replaced due to increased airflow resistance or retrograde leakage of fluid into the trachea as a consequence of biofilm formation. Previous in vitro studies show a change of aerodynamic features of biofilm covered voice prostheses after removal of the prostheses out of the patient. To assess these changes in an in situ situation, aerodynamic characteristics were measured within 45 patients at the beginning and at the end of the wearing process of the Provox 2 voice prosthesis. As a consequence, the influence of biofilm formation on aerodynamic characteristics can be evaluated. In the majority of cases, leakage through the prosthesis was the reason for replacement. No differences were found in the total flow, volume range and intratracheal pressure (ITP) of the voice prostheses measured. The airflow resistance of biofilm covered prostheses was significantly reduced compared to new clean prostheses. However, no correlation was found between the extent of biofilm and the different aerodynamic features measured. Biofilm formation on the Provox 2 is responsible for both reduction in airflow resistance and leakage through the prosthesis by deterioration of the silicone rubber material.     

Surgical Cardiac Sympathetic Denervation for Ventricular Arrhythmias: A Systematic Review

Ventricular arrhythmias are potentially life-threatening disorders that are commonly treated with medications, catheter ablation and implantable cardioverter defibrillator (ICD). Adult patients who continue to be symptomatic, with frequent ventricular arrhythmia cardiac events or defibrillation from ICD despite medical treatment, are a challenging subgroup to manage. Surgical cardiac sympathetic denervation has emerged as a possible treatment option for people refractory to less invasive medical options. Recent treatment guidelines have recommendedcardiac sympathectomy for ventricular tachycardia (VT) or VT/fibrillation storm refractory to antiarrhythmic medications, long QT syndrome, and catecholaminergic polymorphic VT, with much of the data pertaining to pediatric literature. However, for the adult population, the disease indications, complications, and risks of cardiac sympathectomy are less understood, as are the most effective surgical cardiac denervation techniques for this patient demographic. This systematic review navigates available literature evaluating surgical denervation disease state indications, techniques, and sympathectomy risks for medically refractory ventricular arrhythmia in the adult patient population.     

Advances in stem cell therapy for amyotrophic lateral sclerosis

Introduction: Amyotrophic Lateral Sclerosis (ALS) is a progressive, incurable neurodegenerative disease that targets motoneurons. Cell-based therapies have generated widespread interest as a potential therapeutic approach but no conclusive results have yet been reported either from pre-clinical or clinical studies.

Areas covered: This is an integrated review of pre-clinical and clinical studies focused on the development of cell-based therapies for ALS. We analyze the biology of stem cell treatments and results obtained from pre-clinical models of ALS and examine the methods and the results obtained to date from clinical trials. We discuss scientific, clinical, and ethical issues and propose some directions for future studies.

Expert opinion: While data from individual studies are encouraging, stem-cell-based therapies do not yet represent a satisfactory, reliable clinical option. The field will critically benefit from the introduction of well-designed, randomized and reproducible, powered clinical trials. Comparative studies addressing key issues such as the nature, properties, and number of donor cells, the delivery mode and the selection of proper patient populations that may benefit the most from cell-based therapies are now of the essence. Multidisciplinary networks of experts should be established to empower effective translation of research into the clinic.     

How disabling are pediatric burns? Functional independence in Dutch pediatric patients with burns

Although the attention for functional outcomes after burn injury has grown over the past decades, little is known about functional independence in performing activities of daily living in children after burn injury. Therefore, in this prospective cohort study functional independence was measured by burn care professionals with the WeeFIM^® instrument in 119 pediatric patients with burns (age: 6 months–16 years; 58.8% boys) in the Netherlands. In order to identify whether functional independence was affected, participants’ total scores on the WeeFIM^® instrument were compared to American norm values. Of the participants assessed at 2 weeks post burn (n = 117), 3 months post burn (n = 68) and/or 6 months post burn (n = 38), 22, 9 and 9 participants showed affected performance, respectively. Improvements in WeeFIM^® total scores for the total study population between 2 weeks and 6 months post burn were significant (Wilcoxon T = 2.5; p < .001, effect size = ?0.59). Individual improvements were found to be significant for 30.3% of the assessed participants between 2 weeks and 3 months post burn, and for 12.1% between 3 and 6 months post burn. This study is unique in providing data on functional independence for this large and special population. However, a proportion of participants were lost to follow-up and the use of the WeeFIM^® instrument in this specific population and setting has its limitations. To conclude, burn injury impacts functional independence in children, yet the vast majority of Dutch pediatric patients with burns returns to functional independence typical for age within 6 months post burn.     

Short ‘1.2× Genome’ Infectious Clone Initiates Kolmiovirid Replication in Boa constrictor Cells

Human hepatitis D virus (HDV) depends on hepatitis B virus co-infection and its glycoproteins for infectious particle formation. HDV was the sole known deltavirus for decades and believed to be a human-only pathogen. However, since 2018, several groups reported finding HDV-like agents from various hosts but without co-infecting hepadnaviruses. In vitro systems enabling helper virus-independent replication are key for studying the newly discovered deltaviruses. Others and we have successfully used constructs containing multimers of the deltavirus genome for the replication of various deltaviruses via transfection in cell culture. Here, we report the establishment of deltavirus infectious clones with 1.2× genome inserts bearing two copies of the genomic and antigenomic ribozymes. We used Swiss snake colony virus 1 as the model to compare the ability of the previously reported “2× genome” and the “1.2× genome” infectious clones to initiate replication in cell culture. Using immunofluorescence, qRT-PCR, immuno- and northern blotting, we found the 2× and 1.2× genome clones to similarly initiate deltavirus replication in vitro and both induced a persistent infection of snake cells. The 1.2× genome constructs enable easier introduction of modifications required for studying deltavirus replication and cellular interactions.     

Initial panel of immunocytochemical markers for identification of primary carcinoma site for effusions and peritoneal washings from women

Introduction: In women, most malignant effusions are from breast and ovary primary carcinomas that have metastasized to body cavity fluids (pleural, peritoneal and pericardial). When carcinoma is diagnosed in effusions, it is not possible to identify its site of origin solely by cytology (morphology); therefore, immunocytochemistry is used as a complementary method. There are no immunocytochemical markers with 100% sensitivity and specificity for identifying carcinoma primary site. The markers most used are TTF-1 for the lung, GATA-3 for the breast, and PAX-8 for the ovary. The aim of this study was to evaluate the sensitivity and specificity of a panel including these markers for detecting the primary site of carcinoma in effusions. Methods: Samples of pleural, pericardial, and peritoneal effusions and peritoneal washings with carcinoma of known primary site from women (n = 60) and men (n = 18) were prepared by using the cell block method, and immunocytochemistry was performed to evaluate the expression of primary site markers (TTF-1, PAX-8, and GATA-3). Results: In women, the breast was the most frequent primary site of metastatic carcinoma to both pleural and pericardial cavities, followed by the lung, whereas the ovary was the most frequent primary site of carcinoma within peritoneal effusions and washings, followed by the gastrointestinal tract (stomach or intestine). The expected profiles for carcinomas of the most common primary sites were: breast (GATA-3 (+), PAX-8 (-), TTF-1 (-)), ovary (PAX-8 (+), GATA-3 (-), TTF-1 (-)), lung (TTF-1 (+), PAX-8 (-) GATA-3 (-)) and gastrointestinal tract (PAX-8 (-), GATA-3 (-), TTF-1 (-)). These were observed in 88.23% (45/51) of women’s samples with carcinoma from these primary sites. By using TTF-1 as the sole primary site marker, 6.25% of carcinomas of primary site other than the lung would have been misdiagnosed. Conclusion: An initial panel of markers including GATA-3, PAX-8, and TTF-1 allows, with high sensitivity and specificity, the identification or exclusion of frequent primary sites of carcinoma in effusions from women. Our results highlight the importance of using a panel of markers to avoid misidentification of the primary site of tumor.     

Adjuvant capecitabine-containing chemotherapy benefit and homologous recombination deficiency in early-stage triple-negative breast cancer patients

Background The addition of adjuvant capecitabine to standard chemotherapy of early-stage triple-negative breast cancer (TNBC) patients has improved survival in a few randomised trials and in meta-analyses. However, many patients did not benefit. We evaluated the BRCA1-like DNA copy number signature, indicative of homologous recombination deficiency, as a predictive biomarker for capecitabine benefit in the TNBC subgroup of the FinXX trial.Methods Early-stage TNBC patients were randomised between adjuvant capecitabine-containing (TX + CEX: capecitabine-docetaxel, followed by cyclophosphamide-epirubicin-capecitabine) and conventional chemotherapy (T + CEF: docetaxel, followed by cyclophosphamide-epirubicin-fluorouracil). Tumour BRCA1-like status was determined on low-coverage, whole genome next-generation sequencing data using an established DNA comparative genomic hybridisation algorithm.Results For 129/202 (63.9%) patients the BRCA1-like status could be determined, mostly due to lack of tissue. During a median follow-up of 10.7 years, 35 recurrences and 32 deaths occurred. Addition of capecitabine appears to improve recurrence-free survival more among 61 (47.3%) patients with non-BRCA1-like tumours (HR 0.23, 95% CI 0.08–0.70) compared to 68 (52.7%) patients with BRCA1-like tumours (HR 0.66, 95% CI 0.24–1.81) (P-interaction = 0.17).Conclusion Based on our data, patients with non-BRCA1-like TNBC appear to benefit from the addition of capecitabine to adjuvant chemotherapy. Patients with BRCA1-like TNBC may also benefit. Additional research is needed to define the subgroup within BRCA1-like TNBC patients who may not benefit from adjuvant capecitabine.Subject terms: Breast cancer, Translational research, Predictive markers, Breast cancer     

Assessing Media Campaigns Linking Marijuana Non-Use with Autonomy and Aspirations: “Be Under Your Own Influence” and ONDCP’s “Above the Influence”

Two media-based interventions designed to reduce adolescent marijuana use ran concurrently from 2005 to 2009. Both interventions used similar message strategies, emphasizing marijuana’s inconsistency with personal aspirations and autonomy. “Be Under Your Own Influence” was a randomized community and school trial replicating and extending a successful earlier intervention of the same name (Slater et al. Health Education Research 21:157–167, 2006). “Above the Influence” is a continuing national television, radio, and print campaign sponsored by the Office of National Drug Control Policy (ONDCP). This study assessed the simultaneous impact of the interventions in the 20 U.S. communities. Results indicate that earlier effects of the “Be Under Your Own Influence” intervention replicated only in part and that the most plausible explanation of the weaker effects is high exposure to the similar but more extensive ONDCP “Above the Influence” national campaign. Self-reported exposure to the ONDCP campaign predicted reduced marijuana use, and analyses partially support indirect effects of the two campaigns via aspirations and autonomy.