Closed loop stimulation helps with weaning from chronotropic incompetence-related ventilator dependence

Journal of Interventional Cardiac Electrophysiology -     

Effect of compression stockings on overnight rostral fluid shift and obstructive sleep apnea: A meta-analysis

ObjectiveThe overnight rostral fluid shift from the lower limbs is one of the causes of obstructive sleep apnea (OSA). Compression stockings (CS) prevent lower limb fluid retention and have been reported to decrease nighttime fluid shift. The aim of this study is to evaluate the effect of CS on fluid shift and the severity of OSA.MethodsA systematic literature search was performed in the PubMed, EMBASE and Cochrane Library databases. The data were analyzed using Comprehensive Meta-Analysis software (Version 3; Biostat, Englewood, NJ). Studies evaluating the effect of CS on the overnight fluid shift and OSA severity were included in the analysis.ResultsA total of 4 studies were included in this meta-analysis. The pooled analysis showed that the apnea-hypopnea index (AHI) of the overall study group was significantly lower after using CS (SMD, -1.08; 95% CI, -1.49 to -0.67). Decreases in the AHI were also observed in the normal fluid status (SMD, -1.05; 95% CI, -1.73 to -0.37) and fluid overload status (SMD, -1.17; 95% CI, -1.76 to -0.58) populations. The overall study group had significant decreases in overnight changes in neck circumference (SMD, -1.05; 95% CI, -2.06 to -0.03) and leg fluid volume (SMD, -1.14; 95% CI, -1.88 to -0.41) after using CS. However, no significant differences in overnight changes in neck circumference and leg fluid volume were observed in normal fluid status patients.ConclusionCS may help decrease overnight fluid shift and could be a treatment option for OSA.     

The potential role of assisted oocyte activation in the management of a POSEIDON group 3 patient with fertilization failure: A case report and literature review

ObjectiveAssisted oocyte activation combined with ICSI (ICSI-AOA) has been reported to improve fertilization outcomes of couples with oocyte activation deficiency (OAD). Although there's no sufficient evidence to support ICSI-AOA as routine use, it might be beneficial for POSEIDON group 3 patients with suspected oocyte-related OAD.Case reportA 29-year-old female presented with a history of primary infertility for two years. She was classified as a POSEIDON group 3 patient and had a total fertilization failure history. With the help of ICSI-AOA, six oocytes were successfully fertilized. Pregnancy was later confirmed after embryo transfer. A living infant was born after 34 weeks of pregnancy.ConclusionOAD should be taken into consideration for POSEIDON group 3 patients since low Antimüllerian hormone is associated decreased quality. Further research needs to be done to understand the mechanism underlying oocyte-related OAD and the potential role of ICSI-AOA in young patients with suboptimal ovarian response.     

Phase I Dose-Escalation Study of SCB01A,a Microtubule Inhibitor with Vascular Disrupting Activity,in Patients with Advanced Solid Tumors

Lessons Learned

• SCB01A is a novel microtubule inhibitor with vascular disrupting activity.
• This first‐in‐human study demonstrated SCB01A safety, pharmacokinetics, and preliminary antitumor activity.
• SCB01A is safe and well tolerated in patients with advanced solid malignancies with manageable neurotoxicity.

BackgroundSCB01A, a novel microtubule inhibitor, has vascular disrupting activity.MethodsIn this phase I dose‐escalation and extension study, patients with advanced solid tumors were administered intravenous SCB01A infusions for 3 hours once every 21 days. Rapid titration and a 3 + 3 design escalated the dose from 2 mg/m² to the maximum tolerated dose (MTD) based on dose‐limiting toxicity (DLT). SCB01A‐induced cellular neurotoxicity was evaluated in dorsal root ganglion cells. The primary endpoint was MTD. Safety, pharmacokinetics (PK), and tumor response were secondary endpoints.ResultsTreatment‐related adverse events included anemia, nausea, vomiting, fatigue, fever, and peripheral sensorimotor neuropathy. DLTs included grade 4 elevated creatine phosphokinase (CPK) in the 4 mg/m² cohort; grade 3 gastric hemorrhage in the 6.5 mg/m² cohort; grade 2 thromboembolic event in the 24 mg/m² cohort; and grade 3 peripheral sensorimotor neuropathy, grade 3 elevated aspartate aminotransferase, and grade 3 hypertension in the 32 mg/m² cohort. The MTD was 24 mg/m², and average half‐life was ~2.5 hours. The area under the curve‐dose response relationship was linear. Nineteen subjects were stable after two cycles. The longest treatment lasted 24 cycles. SCB01A‐induced neurotoxicity was reversible in vitro.ConclusionThe MTD of SCB01A was 24 mg/m² every 21 days; it is safe and tolerable in patients with solid tumors.     

Late-onset stress symptomatology (LOSS) scale – short form: development and validation

Objectives: Late-onset stress symptomatology (LOSS) is a phenomenon observed in older combat veterans who experience increased combat-related thoughts, feelings, and reminiscences corresponding with the changes and challenges of aging. Previously, we developed the LOSS Scale to assess LOSS. This paper describes the development and validation of a LOSS Scale short form (LOSS-SF) to screen veterans in various settings who may be actively re-examining their past wartime experiences.

Method: Three studies examined the reliability and validity of the LOSS-SF in separate samples of male combat veterans age 55 and older (total N = 346). Veterans were administered measures via telephone and mail survey. Correlation and regression analyses examined the reliability and validity of the LOSS-SF.

Results: The LOSS-SF exhibited strong internal consistency (alpha = .93), test-retest reliability (2 week interval on average; r = .88), and good concurrent validity with the LOSS Scale (r = .81). Convergent and divergent validity were supported by the pattern of correlations between the LOSS-SF and other construct measures.

Conclusion: The LOSS-SF is a reliable and valid measure to quickly assess thoughts, feelings, and reminiscences about past combat experiences in older veterans and identify those veterans in distress who may benefit from psychological interventions..     

Lysophosphatidylcholine‐induced cytotoxicity and protection by heparin in mouse brain bEND.3 endothelial cells

A pathological feature in atherosclerosis is the dysfunction and death of vascular endothelial cells (EC). Oxidized low‐density lipoprotein (LDL), known to accumulate in the atherosclerotic arterial walls, impairs endothelium‐dependent relaxation and causes EC apoptosis. A major bioactive ingredient of the oxidized LDL is lysophosphatidylcholine (LPC), which at higher concentrations causes apoptosis and necrosis in various EC. There is hitherto no report on LPC‐induced cytotoxicity in brain EC. In this work, we found that LPC caused cytosolic Ca²⁺ overload, mitochondrial membrane potential decrease, p38 activation, caspase 3 activation and eventually apoptotic death in mouse cerebral bEND.3 EC. In contrast to reported reactive oxygen species (ROS) generation by LPC in other EC, LPC did not trigger ROS formation in bEND.3 cells. Pharmacological inhibition of p38 alleviated LPC‐inflicted cell death. We examined whether heparin could be cytoprotective: although it could not suppress LPC‐triggered Ca²⁺ signal, p38 activation and mitochondrial membrane potential drop, it did suppress LPC‐induced caspase 3 activation and alleviate LPC‐inflicted cytotoxicity. Our data suggest LPC apoptotic death mechanisms in bEND.3 might involve mitochondrial membrane potential decrease and p38 activation. Heparin is protective against LPC cytotoxicity and might intervene steps between mitochondrial membrane potential drop/p38 activation and caspase 3 activation.