Sleep-Related Breathing Disorders: When CPAP Is Not Enough

Three decades ago, continuous positive airway pressure (CPAP) was introduced to treat obstructive sleep apnea (OSA). Shortly after, bilevel positive airway pressure devices (BPAP) that independently adjusted inspiratory and expiratory positive airway pressure were developed to treat complex sleep-related breathing disorders unresponsive to CPAP. Based on the bilevel positive airway pressure platform (hardware) governed by propriety algorithms (software), advanced modes of noninvasive ventilation (NIV) were developed to address complex cardiorespiratory pathophysiology beyond OSA. This review summarizes key aspects of different bilevel PAP therapies (BPAP with/without backup rate, adaptive servoventilation, and volume-assured pressure support) to treat common sleep-related hypoventilation disorders, treatment-emergent central sleep apnea, and central sleep apnea syndromes.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13311-020-00955-x.Key Words: Bilevel positive airway pressure (BPAP), Adaptive servoventilation (ASV), Volume-assured pressure support (VAPS), Sleep-related hypoventilation, Treatment-emergent central apnea, Central sleep apnea     

Genetic deregulation of the PIK3CA oncogene in oral cancer

The phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway is one of the most commonly deregulated pathways in human cancers. PI3K comprises a catalytic (p110α) and regulatory subunit (p85), and p110α is encoded by the PIK3CA gene. Here, we summarize the known genetic alterations, including amplifications and mutations, of the PIK3CA oncogene in oral cancer. We discuss in detail PIK3CA mutations and their mutual exclusivity with pathway genes in addition to the incidence of PIK3CA mutations in relation to ethnicity. We describe the constitutive activation of PI3K signaling, oncogenicity, and the genetic deregulation of the PIK3CA gene and its association with oral cancer disease stage. We emphasize the importance of therapeutically targeting the genetically deregulated PIK3CA oncogene and its signaling. We also discuss the implications of targeting Akt and/or mTOR, which are the downstream effectors of PI3K that may possibly pave the way for molecular therapeutic targets for PIK3CA-driven oral carcinogenesis. Furthermore, this critical review provides a complete picture of the PIK3CA oncogene and its deregulation in oral cancer, which may facilitate early diagnosis and improve prognosis through personalized molecular targeted therapy in oral cancer.     

In vitro antibacterial potential of metal oxide nanoparticles against antibiotic resistant bacterial pathogens

ObjectiveTo investigate the antibacterial potential of 5 different metal oxide nanoparticles against antibiotic resistant bacterial pathogens viz., Pseudomonas aeruginosa, Klebsiella sp. Streptococcus pneumoniae, Staphylococcus aureus and Streptococcus sp.MethodsThe antibacterial activity of the five different nanoparticles was assessed by well diffusion method. Different concentrations of the nanoparticles were analyzed by MIC and MBC techniques. Finally the potential MgO nanoparticle was also subjected for the time kill assay method.ResultsThe results reveal that, the MgO nanoparticle showed maximum sensitivity [(16.00±0.53) mm dia] against Streptococcus pneumoniae and showed minimum sensitivity against Klebsiella sp. [(9.00±0.31) mm dia]. None of the nanoparticles showed sensitivity against the Streptococcus sp. The MIC result reveals that, the MgO nanoparticle showed maximum inhibition at a concentration of 10 μ g against Streptococcus pneumoniae. Moreover, the time kill assay reveals that, the bacterial growth was inhibited from the 2nd h onwards at a concentration of 10μ g.ConclusionsIt is concluded from the present findings that, the MgO nanoparticle could be used as an alternative antibacterial agent after completing successful in vivo trials.     

Immunotherapy Safety: What Have We Learned from Surveillance Surveys?

Subcutaneous allergen immunotherapy (SCIT) is beneficial for the treatment of allergic rhinitis, asthma, and in preventing stinging insect anaphylaxis, but is not without risks. Four retrospective surveillance surveys and one on-going national prospective study have attempted to characterize the incidence and risk factors for fatal and non-fatal SCIT reactions. These studies have contributed significantly to currently recommended SCIT safety guidelines. Recent surveillance studies indicate stable SR rates, and a possible decline in the incidence of fatal reactions since the implementation of evidence-based safety guidelines. This review will provide a detailed summary of the evidence from surveillance studies for risk factors associated with SCIT reactions, including: uncontrolled asthma, prior systemic reactions, dosing during peak pollen seasons, epinephrine being delayed or not given, dosing or administration errors, inadequate waiting times, reactions occurring more than 30 min after injections, injections given in medically unsupervised settings, concomitant beta-blocker and angiotensin-converting enzyme inhibitor (ACEi) use, and accelerated build-up regimens.     

Spontaneous bacterial peritonitis in alcoholic cirrhosis with ascites

Taking part in recreation or tourist pursuits far from medical resources can tax the ingenuity of even the best-prepared wilderness traveler. In part 1 of this three-part article, which appeared in the June issue, means of preventing illness and injury in the “wilds” were discussed. This part outlines the specific management of several illnesses and injuries that might occur on the trail. In part 3, to appear in August, items for inclusion in a medical kit for wilderness travel will be detailed.