Severe OSA Leading to Long Pauses in 24-h Holter ECG Reversed with CPAP

Introduction Sleep-related problems like sleep apnea are increasing tremendously mostly owing to the disordered lifestyle the present generation is leading which is added like a topping on the base of obesity and metabolic syndrome. The burden on the society is huge taking into consideration the work-time loss and health-related financial issues arising out of these sleep disorders with obstructive sleep apnea (OSA) leading the way. Early diagnosis can prevent several complications of OSA. Cardiovascular diseases, including various arrhythmias, arising due to OSA, are described previously.Case Presentation Herein, an interesting case of OSA, whose pacemaker installation to rectify the long pause could be avoided by simple correction of his OSA using continuous positive airway pressure, is presented. This 49-year-old male patient was diagnosed with severe OSA by using polysomnography and all his significant sinus pauses (highest one with 7.8 sec) during holter ECG monitoring were found to be occurring at night and correcting his OSA with continuous positive airway pressure (CPAP) treatment reverted all those sinus pauses and the need for any further intervention with pacemaker was discarded.Discussion OSA is caused by either partial or complete obstruction of the upper airway, and there is the simultaneously attenuated upper airway dilator muscle tone while the patient is sleeping. The gold standard test designed for the assessment of OSA is polysomnography, as approved by the American Academy of Sleep Medicine and CPAP has been found to be universally beneficial in treating OSA related complications. Physiologically, the ACC/AHA guidelines recommend pacing only in patients with prolonged asymptomatic pauses occurring during wakefulness. This case report proved the above mentioned claim of CPAP treatment.     

Immune correlates of talactoferrin alfa in biopsied tumor of relapsed/refractory metastatic non-small cell lung cancer patients

Context: Talactoferrin alfa (TLF) is a unique recombinant form of human lactoferrin. The hypothesized mechanism of action involves TLF binding to the intestinal endothelium inducing dendritic cell maturation and cytokine release leading to infiltration of tumor with monocytes and T-lymphocytes and inhibition of tumor growth.

Objective: Based on promising phase II trial results, this correlative study was undertaken to examine immune mechanism of action of TLF in metastatic non-small cell lung cancer (NSCLC) patients.

Methods: Talactoferrin was administered orally at 1.5?g bid weeks 1–12 with 2 weeks off on a 14-week cycle. Enrolled patients had a pathologic diagnosis of NSCLC previously treated with at least two lines of systemic treatment. Patients had core biopsy of tumor before initiation of talactoferrin and at week 7 on TLF. Flow cytometry and quantitative immunohistochemistry for immune correlates were performed on the biopsied specimens.

Results: Four patients with metastatic NSCLC were enrolled. The trial was halted pre-maturely in light of negative phase III trial results. For the two patients who had repeat on-treatment tumor biopsies, a consistent increase in monocytes as a percentage of total immune cells was observed. Otherwise, no clear trend of increase or decrease was observed in any other immune cell parameters compared to matched patient pre-treatment biopsies.

Conclusion: Repeat biopsies for immune correlates by flow cytometry and quantitative immunohistochemistry in NSCLC patients are feasible. In the few patients sampled before trial closure, increased monocytes as a total percentage of the immune cell population within tumor was observed in response to TLF.     

Guidelines for prevention of hospital acquired infections

These guidelines, written for clinicians, contains evidence-based recommendations for the prevention of hospital acquired infections Hospital acquired infections are a major cause of mortality and morbidity and provide challenge to clinicians. Measures of infection control include identifying patients at risk of nosocomial infections, observing hand hygiene, following standard precautions to reduce transmission and strategies to reduce VAP, CR-BSI, CAUTI. Environmental factors and architectural lay out also need to be emphasized upon. Infection prevention in special subsets of patients - burns patients, include identifying sources of organism, identification of organisms, isolation if required, antibiotic prophylaxis to be used selectively, early removal of necrotic tissue, prevention of tetanus, early nutrition and surveillance. Immunodeficient and Transplant recipients are at a higher risk of opportunistic infections. The post tranplant timetable is divided into three time periods for determining risk of infections. Room ventilation, cleaning and decontamination, protective clothing with care regarding food requires special consideration. Monitoring and Surveillance are prioritized depending upon the needs. Designated infection control teams should supervise the process and help in collection and compilation of data. Antibiotic Stewardship Recommendations include constituting a team, close coordination between teams, audit, formulary restriction, de-escalation, optimizing dosing, active use of information technology among other measure. The recommendations in these guidelines are intended to support, and not replace, good clinical judgment. The recommendations are rated by a letter that indicates the strength of the recommendation and a Roman numeral that indicates the quality of evidence supporting the recommendation, so that readers can ascertain how best to apply the recommendations in their practice environments.     

Disturbances in calcium metabolism and cardiomyocyte necrosis: the role of calcitropic hormones

A synchronized dyshomeostasis of extra- and intracellular Ca(2+), expressed as plasma ionized hypocalcemia and excessive intracellular Ca(2+) accumulation, respectively, represents a common pathophysiologic scenario that accompanies several diverse disorders. These include low-renin and salt-sensitive hypertension, primary aldosteronism and hyperparathyroidism, congestive heart failure, acute and chronic hyperadrenergic stressor states, high dietary Na(+), and low dietary Ca(2+) with hypovitaminosis D. Homeostatic responses are invoked to restore normal extracellular [Ca(2+)](o), including increased plasma levels of parathyroid hormone and 1,25(OH)(2)D(3). However, in cardiomyocytes these calcitropic hormones concurrently promote cytosolic free [Ca(2+)](i) and mitochondrial [Ca(2+)](m) overloading. The latter sets into motion organellar-based oxidative stress, in which the rate of reactive oxygen species generation overwhelms their detoxification by endogenous antioxidant defenses, including those related to intrinsically coupled increments in intracellular Zn(2+). In turn, the opening potential of the mitochondrial permeability transition pore increases, allowing for osmotic swelling and ensuing organellar degeneration. Collectively, these pathophysiologic events represent the major components to a mitochondriocentric signal-transducer-effector pathway to cardiomyocyte necrosis. From necrotic cells, there follows a spillage of intracellular contents, including troponins, and a subsequent wound healing response with reparative fibrosis or scarring. Taken together, the loss of terminally differentiated cardiomyocytes from this postmitotic organ and the ensuing replacement fibrosis each contribute to the adverse structural remodeling of myocardium and progressive nature of heart failure. In conclusion, hormone-induced ionized hypocalcemia and intracellular Ca(2+) overloading comprise a pathophysiologic cascade common to diverse disorders and that initiates a mitochondriocentric pathway to nonischemic cardiomyocyte necrosis.