Early assessment of the pharmacokinetic and pharmacodynamic effects following acetylsalicylic acid loading: toward a definition for acute therapeutic response.

Despite decades of investigations, the optimal assessment of the "therapeutic response" to early after loading dose of acetylsalicylic acid (ASA) remains unclear. Limited information is available on the relation between pharmacodynamic (PD) and pharmacokinetic (PK) measurements assessed immediately after ASA administration. Serial PD and PK analyses were performed immediately after a single 162 or 650 mg dose of chewed and swallowed ASA in ten healthy adults. ASA response was defined as > 95% inhibition of serum thromboxane (Tx)B2, < 550 aspirin reaction units (ARU) by VerifyNow Aspirin (VN) test, and ≤ 20% arachidonic acid (AA)-induced platelet aggregation (PA). Correlation analyses between PK and PD measurements and receiver operating characteristic (ROC) curve analyses were performed. ASA response measured by VN test and AA-induced PA was achieved within 30 min of ASA administration. A correlation was observed between ARU and AA-induced maximum PA (r = 0.69, p < 0.001), serum TxB2 (r = 0.74 and p < 0.001), and serum TxB2 inhibition (r = 0.79, p < 0.001). In ROC curve analyses, ≤ 558 ARU and ≤ 7% AA-induced PA were associated with > 95% inhibition of TxB2. 686 ng/ml plasma ASA cut-off point was associated with > 95% inhibition of serum TxB2, ≤ 7% 1 mM AA-induced PA, and ≤ 585 ARU. A modest ~ 50% inhibition of TxB2 inhibition was associated with marked inhibition of 1 mM AA-induced platelet aggregation by LTA. Our analyses demonstrated important relationships between pharmacodynamic, and pharmacokinetic parameters measured immediately following oral ASA and cutoff values for ARU and AA-induced PA that is associated with > 95% inhibition of serum TxB2.

Development of a routine bedside CYP2C19 genotype assessment program for antiplatelet therapy guidance in a community hospital catheterization laboratory.

Genotype based personalized antiplatelet therapy in the setting of percutaneous coronary intervention (PCI) has been studied in clinical trials. Despite the demonstrated risk associated with CYP2C19 loss-of-function (LoF) carriage in clopidogrel-treated PCI patients, real-world implementation of genotyping for PCI has been low. The goal of the current study was to provide CYP2C19 genotype information to the interventionalist prior to the completion of the catheterization to facilitate immediate personalized antiplatelet therapy. Routine personalization of P2Y12 inhibitor therapy for PCI in a community hospital cardiac catheterization laboratory by POC genotyping with the SpartanRx system was first offered in February 2017. A best practice advisory (BPA) based on the Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2C19 genotype and clopidogrel therapy was placed in the electronic health record prescription medication ordering system. By December 2019, 1,052 patients had CYP2C19 genotype testing, 429 patients underwent PCI with genotype guided antiplatelet therapy, and 250 patients underwent PCI without genotype testing and received antiplatelet therapy at the discretion of the treating physician. BPA compliance was 93. 87% of LoF allele carriers were prescribed ticagrelor or prasugrel whereas 96% of non-LoF allele carriers were prescribed clopidogrel. The genotyping results were available within 1 h and made immediately available for decision making by the interventional cardiologist. POC CYP2C19 genotyping is feasible in a community hospital catheterization laboratory and is associated with high rate of best practice compliance.Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT03040622.

Oxygen Targets After Cardiac Arrest: A Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Optimal oxygen saturation target in patients resuscitated after cardiac arrest is unknown. Previous randomized controlled trials (RCTs) comparing restrictive oxygen therapy with liberal therapy have shown conflicting results. STUDY QUESTION: We performed a meta-analysis of available RCTs to consolidate the contrasting findings regarding the oxygen targets after cardiac arrest. DATA SOURCES: We searched electronic databases for RCTs comparing restrictive versus liberal oxygen targets in patients resuscitated after cardiac arrest. STUDY DESIGN: End points of interest were mortality, unfavorable neurological outcomes, and rearrests. Random-effects meta-analysis was performed to estimate the risk ratio (RR) with a 95% confidence interval (CI). RESULTS: Eight RCTs with 1641 patients (restrictive n = 833, liberal n = 808) were included in the analysis. The oxygen targets were defined by either saturation, partial pressure (PaO2), or supplementation rates. The mean age and male percentage were 63 years and 80%, respectively. There was no significant difference observed in the 2 groups for overall mortality (RR = 0.91, 95% CI = 0.75-1.10, P = 0.33), unfavorable neurological outcomes (RR = 0.93, 95% CI = 0.74-1.18, P = 0.56), and rearrests (RR = 0.67, 95% CI = 0.22-1.98, P = 0.47). CONCLUSIONS: Overall, this meta-analysis shows no significant difference in mortality, unfavorable neurological outcomes, and rearrests when using restrictive or liberal oxygen targets in patients after cardiac arrest. The limitations in the newer trials should be kept in mind while interpreting the overall results.

Modulation of pacemaker channel function in a model of thalamocortical hyperexcitability by demyelination and cytokines.

A consensus is yet to be reached regarding the exact prevalence of epileptic seizures or epilepsy in multiple sclerosis (MS). In addition, the underlying pathophysiological basis of the reciprocal interaction among neuroinflammation, demyelination, and epilepsy remains unclear. Therefore, a better understanding of cellular and network mechanisms linking these pathologies is needed. Cuprizone-induced general demyelination in rodents is a valuable model for studying MS pathologies. Here, we studied the relationship among epileptic activity, loss of myelin, and pro-inflammatory cytokines by inducing acute, generalized demyelination in a genetic mouse model of human absence epilepsy, C3H/HeJ mice. Both cellular and network mechanisms were studied using in vivo and in vitro electrophysiological techniques. We found that acute, generalized demyelination in C3H/HeJ mice resulted in a lower number of spike-wave discharges, increased cortical theta oscillations, and reduction of slow rhythmic intrathalamic burst activity. In addition, generalized demyelination resulted in a significant reduction in the amplitude of the hyperpolarization-activated inward current (Ih) in thalamic relay cells, which was accompanied by lower surface expression of hyperpolarization-activated, cyclic nucleotide-gated channels, and the phosphorylated form of TRIP8b (pS237-TRIP8b). We suggest that demyelination-related changes in thalamic Ih may be one of the factors defining the prevalence of seizures in MS.

Remdesivir-induced conduction abnormalities: A molecular model-based explanation.

Purpose: Remdesivir use in COVID-19 is associated with cardiac conduction abnormalities from unclear mechanisms. A proposed mechanism is the bioaccumulation of the intermediate metabolite GS-441524 resulting in exogenous activation of cardiac adenosine A1 due to the structural similarity between adenosine and GS-441524. The prolonged half-life of GS-441524 can result in sustained activation of adenosine A1 receptors. In this study, we used molecular modeling of adenosine, GS-441524 and the adenosine A1 receptor to assess the potential mechanistic association of the proposed mechanism. Methods: Adenosine and GS-441524 structures were acquired from the PubChem database. Ligand docking was carried out using UCSF Chimera. Models were chosen based on greatest binding affinity and minimum root mean square deviation. Figures of resulting structural models were prepared using UCSF Chimera or PyMOL 2.3.5. Results: By modeling the interaction between the A1 G protein complex and both adenosine and GS-441524, we found that the proposed mechanism of exogenous A1 receptor activation is feasible based on docking compatibility. Conclusion: The proposed mechanism of exogenous cardiac A1 receptor activation from bioaccumulation of GS-441524 as a cause of observed cardiac conduction abnormalities with the use of remdesivir in COVID-19 is viable. Further studies are needed to assess causality.

Role of Internal Jugular Venous Ultrasound in suspected or confirmed Heart Failure: A Systematic Review.

BACKGROUND: Few data are available on the use of internal jugular vein (IJV) ultrasound parameters to assess central venous pressure and clinical outcomes among patients with suspected or confirmed heart failure (HF). METHODS: We performed electronic searches on PubMed, The Cochrane Library, EMBASE, EBSCO, Web of Science, and CINAHL databases from the inception through January 9, 2021, to identify studies evaluating the accuracy and reliability of the IJV ultrasound parameters and exploring its correlation with central venous pressure and clinical outcomes in adult patients with suspected or confirmed acutely decompensated HF. The studies' report quality was assessed by Quality Assessment of Diagnostic Accuracy Studies-2 scale. RESULTS: A total of 11 studies were eligible for final analysis (n = 1481 patients with HF). The studies were segregated into 3 groups: (1) the evaluation of patients presenting to the emergency department with dyspnea, (2) the evaluation of patients presenting to the HF clinic for follow-up, and (3) the evaluation of hospitalized patients with acutely decompensated HF or undergoing right heart catheterization. US parameters included IJV height, IJV diameter, IJV diameter ratio, IJV cross-sectional area, respiratory compressibility index, and compression compressibility index. CONCLUSIONS: The findings of this systematic review suggest a significant role for ultrasound interrogation of the IJV in evaluation of patients in the emergency department presenting with dyspnea, in the outpatient clinic for poor clinical outcomes in HF, and in determining the timing of discharge for patients admitted with acutely decompensated HF. Further studies are warranted for testing the reliability of the reported ultrasound indices.

Serial assessment of thrombogenicity and hemodynamics in patients with type II diabetes in a clinical research unit: Evidence for circadian variations in clot formation.

BACKGROUND: Circadian fluctuations in thrombogenicity and hemostasis play a role in acute cardiovascular thrombotic events occurring in the early morning hours. There is a lack of data assessing thrombogenicity, platelet function, and hemodynamics to investigate diurnal variations in a high cardiovascular risk population. METHODS: This was an exploratory, single-center study conducted in aspirin-treated patients with Type II Diabetes Mellitus (T2DM) (n = 37) with documented vascular disease and/or multiple cardiovascular risk factors. Hemodynamic monitoring and blood sample collection for thromboelastography (TEG) and platelet function testing were done serially at 7-9 AM (morning), 7-9 PM (evening), 11 PM-1 AM (night), and at 5-7 AM (awakening). RESULTS: R-value measured by TEG was shorter during awakening hours than during the night and day hours (p < 0.05). There were no changes in platelet reactivity in response to arachidonic acid, adenosine diphosphate, and collagen between time points. Pulse pressure (PP) was highest during awakening hours (p < 0.05). CONCLUSION: Study findings provide a mechanistic explanation for increased thrombotic events observed in the early waking hours among diabetics with multiple cardiovascular risk factors. The role of chronotherapy in reducing coagulability and PP to improve clinical outcomes should be explored.

Effects of Axonal Demyelination, Inflammatory Cytokines and Divalent Cation Chelators on Thalamic HCN Channels and Oscillatory Bursting.

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system that is characterized by the progressive loss of oligodendrocytes and myelin and is associated with thalamic dysfunction. Cuprizone (CPZ)-induced general demyelination in rodents is a valuable model for studying different aspects of MS pathology. CPZ feeding is associated with the altered distribution and expression of different ion channels along neuronal somata and axons. However, it is largely unknown whether the copper chelator CPZ directly influences ion channels. Therefore, we assessed the effects of different divalent cations (copper; zinc) and trace metal chelators (EDTA; Tricine; the water-soluble derivative of CPZ, BiMPi) on hyperpolarization-activated cyclic nucleotide-gated (HCN) channels that are major mediators of thalamic function and pathology. In addition, alterations of HCN channels induced by CPZ treatment and MS-related proinflammatory cytokines (IL-1ß; IL-6; INF-α; INF-ß) were characterized in C57Bl/6J mice. Thus, the hyperpolarization-activated inward current (Ih) was recorded in thalamocortical (TC) neurons and heterologous expression systems (mHCN2 expressing HEK cells; hHCN4 expressing oocytes). A number of electrophysiological characteristics of Ih (potential of half-maximal activation (V0.5); current density; activation kinetics) were unchanged following the extracellular application of trace metals and divalent cation chelators to native neurons, cell cultures or oocytes. Mice were fed a diet containing 0.2% CPZ for 35 days, resulting in general demyelination in the brain. Withdrawal of CPZ from the diet resulted in rapid remyelination, the effects of which were assessed at three time points after stopping CPZ feeding (Day1, Day7, Day25). In TC neurons, Ih was decreased on Day1 and Day25 and revealed a transient increased availability on Day7. In addition, we challenged naive TC neurons with INF-α and IL-1ß. It was found that Ih parameters were differentially altered by the application of the two cytokines to thalamic cells, while IL-1ß increased the availability of HCN channels (depolarized V0.5; increased current density) and the excitability of TC neurons (depolarized resting membrane potential (RMP); increased the number of action potentials (APs); produced a larger voltage sag; promoted higher input resistance; increased the number of burst spikes; hyperpolarized the AP threshold), INF-α mediated contrary effects. The effect of cytokine modulation on thalamic bursting was further assessed in horizontal slices and a computational model of slow thalamic oscillations. Here, IL-1ß and INF-α increased and reduced oscillatory bursting, respectively. We conclude that HCN channels are not directly modulated by trace metals and divalent cation chelators but are subject to modulation by different MS-related cytokines.

Carotid access for transcatheter aortic valve replacement: A meta-analysis.

OBJECTIVE: We sought to evaluate the feasibility and safety of carotid access transcatheter aortic valve replacement (TAVR) by performing a meta-analysis of published cases. BACKGROUND: Several case series and regional data have provided initial basis for carotid access TAVR in patients with prohibitive femoral approach. We performed this meta-analysis to provide further evidence of feasibility and safety of carotid TAVR. METHODS: We searched PubMed, EMBASE, CINAHL, and Cochrane CENTRAL for any study on carotid access TAVR involving ⩾5 patients since inception till March 1, 2020. Random-effects model was used to compute overall effects. The outcomes analyzed were all-cause mortality, Transient ischemic attack (TIA)/stroke, need for permanent pacemaker (PPM) implantation, pericardial tamponade, access site complications, major bleeding, and length of stay. RESULTS: There was a total of 17 retrospective studies (n = 2082) with a median follow-up of 1 month. Mean age of the patient was 80 years. Mean Euroscore and STS scores were 15 ± 6.2 and 7.9 ± 3.3, respectively. The procedural success rate was 99%. The rate of all-cause mortality was 6.7% (range 4.6-9.7%, p < .001, I2 = 67%). Incidence of TIA/stroke was 3.9% (range 3.1-4.8%, p < .001, I2 = 0%) and PPM implantation was 16.7% (range 12.5-21.9%, p < .001, I2 = 56%). Rate of pericardial tamponade, vascular complication, and major bleeding were 1.7, 2.5, and 7%, respectively. Average length of hospital stay was 7.7 days. CONCLUSION: Our results show that transcarotid approach is a feasible option in patients with prohibitive femoral access for TAVR.

Viscoelastic properties of clot formation and their clinical impact in East Asian versus Caucasian patients with stable coronary artery disease: a COMPARE-RACE analysis.

Compared with Caucasian patients, East Asian patients with coronary artery disease (CAD) have demonstrated better clinical outcomes. We sought to compare the viscoelastic properties of clot formation and their impact on clinical outcomes in East Asian vs. Caucasian patients. We analyzed age- and sex-matched East Asian and Caucasian patients with stable CAD (n = 249 each). Viscoelastic properties of clot formation were assessed with thromboelastography (TEG), and 3-year clinical outcomes were recorded. Major adverse cardiovascular events (MACE) were defined as a composite of cardiovascular death, myocardial infarction, or stroke. Compared with Caucasians, East Asians showed lower platelet-fibrin clot strength (PFCS) (maximum amplitude [MA]: 61.8 ± 7.9 vs. 65.4 ± 5.0 mm, p < 0.001). In a multivariate analysis, high PFCS (defined as MA ≥ 68 mm) was significantly associated with MACE occurrence (odds ratio 6.27, 95% CI 2.41 to 16.30, p < 0.001). East Asians vs. Caucasians had lower prevalence of high PFCS (odds ratio 0.50, 95% CI 0.27 to 0.93, p = 0.028). In conclusion, this is the first study to demonstrate different viscoelastic properties of clot between East Asian and Caucasian patients with stable CAD. The platelet-fibrin clot strength was significantly associated with MACE in these patients and was significantly lower in East Asians. Future studies are warranted to further explore the mechanistic explanation and clinical importance of these findings.

Resectional surgery in gallbladder cancer with jaundice-how to improve the outcome?

PURPOSE: To evaluate the surgical outcomes of patients with gallbladder cancer (GBC) with jaundice due to as-yet unelucidated prognostic factors. METHODS: A total of 348 GBC patients underwent resection at our institute between 1985 and 2016. Of these, 67 had jaundice (serum total bilirubin ≥ 2 mg/dL). Preoperative biliary drainage was performed, with portal vein embolization as required. All patients underwent radical surgery. We retrospectively evaluated the outcomes, performed multivariate analysis for overall survival, and compared our findings to those reported in the literature. RESULTS: The 5-year survival rate of M0 (no distant metastasis) GBC patients with jaundice, who underwent resectional surgery, was 21.9%, versus 68.3% in those without jaundice (p < 0.05). Since 2000, surgical mortality in GBC patients with jaundice has decreased from 12 to 6.8%. Patients with jaundice had more advanced disease and underwent major hepatectomies and vascular resections; however, preoperative jaundice alone was not a prognostic factor. Multivariate analysis of jaundiced patients revealed that percutaneous biliary drainage (PTBD) (vis-à-vis endoscopic drainage [EBD], hazard ratio [HR] 2.82), postoperative morbidity (Clavien-Dindo classification ≥ 3, HR 2.31), and distant metastasis (HR 1.85) were predictors of poor long-term survival. The 5-year survival and peritoneal recurrence rates in M0 patients with jaundice were 16% and 44%, respectively, for patients with PTBD and 39% (p < 0.05) and 13% (p = 0.07) for those with EBD. CONCLUSION: M0 GBC patients with jaundice should undergo surgery if R0 resection is possible. Preoperative EBD may be superior to PTBD in M0 GBC patients with jaundice, although further studies are needed.

Heart Failure Trial Update-Analysis of Recent Data.

The prevalence of heart failure (HF) continues to increase, and its economic effect is significant in the United States and globally. During the past 2 years, a number of high-quality clinical trials were published with the aim of addressing different stages of the disease process and improving outcomes for patients with preserved and depressed ejection fraction (EF). In this review, data from these trials are summarized and critically appraised. There are several important findings from these studies, including, but not limited to, the benefit of dapagliflozin in HF with reduced EF, sacubitril-valsartan in acute decompensated HF, thoracotomy in left ventricular assist device implantation, and the overall risk-benefit ratios of centrifugal pumps as opposed to continuous flow pumps. Effective therapies for HF with preserved EF continue to evolve for this varied group of high morbidity and mortality conditions.

Development and evaluation of phytosome-loaded microsphere system for delivery of ginseng extract.

The current research work focuses mainly on evolving a delivery system for ginseng extract (GE), which in turn will ameliorate the neuroprotective potential through enhancing the Ginsenoside Rb1(GRb1) bioavailability (BA). Phytosome complexes (F1, F2, and F3) were prepared by reacting GE with phospholipids in disparate ratios. F3 was chosen for preparing the phytosomes powder (PP) and phytosomes-loaded microspheres (PMs). Extract microspheres (EMs) were prepared by the addition of extract directly into the same polymer mixture. F3 gave enhanced entrapment efficiency (50.61%, w/w) along with spherical-shaped particle size (42.58 ± 1.4 nm) with the least polydispersity index (0.193 ± 0.01). PM showed an enhanced relative bioavailability (157.94%) of GRb1. It also showed a greater neuroprotective potential exhibiting significant (p < 0.05) augmentation in the nociceptive threshold. It was concluded that the PM system might be an optimistic and feasible strategy to enhance the delivery of GE for the effectual treatment of neuropathy.

Determinants of regeneration and strength of hamstrings after anterior cruciate ligament reconstruction-fate of hamstring tendon.

BACKGROUND AND AIM: Arthroscopic reconstruction of anterior cruciate ligament (ACL) surgical procedure using hamstring autograft is the most common surgery performed in the arena of sports medicine and arthroscopy. Most studies in literature are ambiguous regarding the fate of hamstrings based on function, regenerative potential, and cross-sectional area (CSA). The aim of this research study is analysis of the fate of hamstring tendons (both semitendinosus and gracilis) during the time course for determinants of regeneration and strength. METHODS: Fifty patients who were operated for unilateral isolated ACL reconstruction from July 2015 to June 2018 were evaluated for the fate of harvested hamstring tendons which included the following: regeneration, cross-sectional area (CSA), strength, and insertion of regenerated hamstrings by isometric torque and isokinetic strength. MRI of knee was performed for both knees concerning the semitendinosus (ST), gracilis (G), Sartorius, biceps femoris, and medial head of gastrocnemius. RESULTS: Eighty-four percent men and 16% women within a mean patient age of 34 ± 4.12 years were evaluated and all 50 (100%) patients demonstrated hamstring regeneration by the MRI measurements at six months and at one year post-ACL reconstruction. The torque of isometric knee flexion measured in 60° was found to be remarkably lower in the ACL-reconstructed lower extremity compared to that of the contralateral limb (87.13 ± 20.18% of BW), at 90° (49.17 ± 15.09% BW), and at 105° (43.91 ± 13.17% BW), respectively (p < 0.01). However, at 30° flexion and 45° flexion, the difference was insignificant (116.48 ± 21.07% BW for 30° and 100.16 ± 25.12% BW for 45°). CONCLUSIONS: It was found that the properties of musculotendinous units of ST and G were significantly transformed after their harvesting for ACL reconstruction and these weaknesses contribute to the flexion deficit of knee in the deeper range of flexion in the operated limb. Therefore, approaches facilitating tendon regeneration and preservation must be warranted.

Global warming potential and energy dynamics of conservation tillage practices for different rabi crops in the Indo-Gangetic Plains.

A field experiment was conducted during 2007-2019 under various rabi (winter) crops (viz., wheat, maize, barley and mustard) on a Vertisol in sub-tropical Indo-Gangetic Plains (IGP) with different tillage systems to assess energy indices, greenhouse gas (GHG) emission and carbon sustainability index in assured irrigated fields. The tillage systems were: no tillage sown by a zero till drill (NT), no tillage with retention of previous crop residues at 6 t ha-1 and sowing by a happy turbo seeder (HT), and conventional tillage (CT) where sowing was performed by a multi-crop zero till drill after twice harrowing + twice tilling + once rotavator operations. Significantly higher input energy was observed in wheat followed by maize, barley and mustard. Among tillage systems, CT plots consumed higher input energy that was about 20, 21 to 22, 25 to 26 and 20-22% higher than HT and NT in wheat, maize, barley and mustard, respectively. However, output energy and energy use efficiency were highest in HT. The total GHG emission (kg CO2 equivalent ha-1) was highest in wheat (2,351) followed by maize (2,274), barley (1,859) and mustard (1,652). Among tillage systems, CT produced about 31-34%, 33-34%, 37-40% and 28-30% higher GHG emission than HT and NT under wheat, maize, barley and mustard, respectively. The CT plots had lower carbon sustainability index and carbon efficiency than ZT and HT in all crops. In short, HT recorded significantly higher energy use efficiency and lower global warming potential (GWP) than CT in all crops. Thus, HT could be a promising agro-technique for production of rabi crops in the IGP. Among rabi crops, barley production was energy efficient and had less GWP. In rabi crop production, the highest energy sources was mineral fertilizer use (25-49%) and second highest source was irrigation water (14-44%). These can be substituted with use of the organic sources of fertilizers and application of solar and wind power in irrigation, respectively.

Spiritual Care of Inpatients Focusing on Outcomes and the Role of Chaplaincy Services: A Systematic Review.

OBJECTIVE: To identify demographic trends associated with patient utilization and healthcare provider request for spiritual care services and to describe the impact of spiritual care on the quality of life (QoL), spiritual well-being (SWB) and level of satisfaction (SAT) of hospitalized patients. PATIENTS AND METHODS: A systematic search of Ovid MEDLINE, Embase, PsycINFO, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Scopus, was combined with review of relevant bibliographies. A total of 464 titles and abstracts were reviewed. Data were independently extracted by reviewers according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data on the effects of spiritual interventions on QoL, SWB and SAT were extracted, along with demographic data reflecting chaplain services. The results of the studies are presented narratively and in a qualitative manner. RESULTS: Observational or experimental studies investigating chaplain utilization demographics (n = 12), patient satisfaction (n = 9) and QoL/SWB (n = 3) were included. Perceived severity of illness, average length of stay and older age were consistently found to be predictors of higher need for spiritual care. Receipt of spiritual care was correlated with increased patient and family satisfaction, independent of clinical outcome. Chaplain interventions were associated with improvement in perceived QoL and SWB. In spite of this, healthcare workers rarely attempt to explore the patient's or family's need for spiritual care, with the majority of chaplaincy consults occurring in the final day of the patient's life, potentially leading to a failure to meet the spiritual needs of non-terminal patients who have spiritual trauma related to their resolving illnesses. CONCLUSION: Attention to the spiritual needs of hospitalized patients is an essential yet often overlooked aspect of patient care. Chaplains serve as spiritual care specialists whose services can enhance the hospital experience, improve patient satisfaction and help to bridge potential gaps between the patient and medical providers.

Dosimetric impact of Acuros XB on cervix radiotherapy using RapidArc technique: a dosimetric study.

BACKGROUND: Acuros XB (AXB) may predict better rectal toxicities and treatment outcomes in cervix carcinoma. The aim of the study was to quantify the potential impact of AXB computations on the cervix radiotherapy using the RapidArc (RA ) technique as compared to anisotropic analytical algorithm (AA) computations. MATERIALS AND METHODS: A cohort of 30 patients previously cared for cervix carcinoma (stages II-IIIB) was selected for the present analysis. The RA plans were computed using AA and AXB dose computation engines under identical beam setup and MLC pattern. RESULTS: There was no significant (p > 0.05) difference in D95% and D98% to the planning target volume (PTV); moreover, a significant (p < 0.05) rise was noticed for mean dose to the PTV (0.26%), D50% (0.26%), D2% (0.80%) and V110% (44.24%) for AXB computation as compared to AA computations. Further, AXB estimated a significantly (p < 0.05) lower value for maximum and minimum dose to the PTV. Additionally, there was a significant (p < 0.05) reduction observed in mean dose to organs at risk (OARs) for AXB computation as compared to AA, though the reduction in mean dose was non-significant (p > 0.05) for the rectum. The maximum difference observed was 4.78% for the rectum V50Gy, 1.72%, 1.15% in mean dose and 2.22%, 1.48% in D2% of the left femur and right femur, respectively, between AA and AXB dose estimations. CONCLUSION: For similar target coverage, there were significant differences observed between the AAA and AXB computations. AA underestimates the V50Gy of the rectum and overestimates the mean dose and D2% for femoral heads as compared to AXB. Therefore, the use of AXB in the case of cervix carcinoma may predict better rectal toxicities and treatment outcomes in cervix carcinoma using the RA technique.

The Hyperpolarization-Activated HCN4 Channel is Important for Proper Maintenance of Oscillatory Activity in the Thalamocortical System.

Hyperpolarization-activated cation channels are involved, among other functions, in learning and memory, control of synaptic transmission and epileptogenesis. The importance of the HCN1 and HCN2 isoforms for brain function has been demonstrated, while the role of HCN4, the third major neuronal HCN subunit, is not known. Here we show that HCN4 is essential for oscillatory activity in the thalamocortical (TC) network. HCN4 is selectively expressed in various thalamic nuclei, excluding the thalamic reticular nucleus. HCN4-deficient TC neurons revealed a massive reduction of Ih and strongly reduced intrinsic burst firing, whereas the current was normal in cortical pyramidal neurons. In addition, evoked bursting in a thalamic slice preparation was strongly reduced in the mutant mice probes. HCN4-deficiency also significantly slowed down thalamic and cortical oscillations during active wakefulness. Taken together, these results establish that thalamic HCN4 channels are essential for the production of rhythmic intrathalamic oscillations and determine regular TC oscillatory activity during alert states.

Baseline thrombocytopenia in women with coronary heart disease increases incident acute coronary syndrome: insights from national inpatient database.

There are paucity of data on gender-based differences in the effect of thrombocytopenia and coronary heart disease (CHD) towards development of acute coronary syndrome (ACS). We used National Inpatient Sample (NIS) database of the United States to assess the gender-based differences in the association of thrombocytopenia with CHD and the impact of thrombocytopenia on mortality, length of stay and hospitalization costs on ACS subgroup of CHD. Our analysis found that thrombocytopenia was associated with increased odds of CHD on univariate (odds ratio [OR] 1.31 (95% CI 1.30-1.32) p < 0.001) and multivariate (OR 1.36 (95% CI 1.34-1.38) p < 0.001) analyses. Thrombocytopenic CHD patients had increased odds of developing ACS only in women (OR 1.15, 95% CI 1.12-1.17, p < 0.001). Thrombocytopenia was found to be associated with poor short-term outcome in ACS subgroup of CHD with higher in-hospital mortality (OR 1.64, CI 1.58 to 1.71, p < 0.001), length of stay (3.4 days, CI 3.30-3.52, p < 0.001), and cost of hospitalization ($55,652, CI 53,717-57,587, p < 0.001). Thrombocytopenic women with ACS have greater odds of mortality compared to men. Our study suggests that thrombocytopenia among women with CHD is associated with increased odds of developing ACS. Women with ACS have greater mortality compared to men. Thrombocytopenic ACS patients have worse in-hospital outcome compared to patients with normal platelet count. We demonstrated association only and is not possible to establish causality with our study.

Direct oral anticoagulants: a review on the current role and scope of reversal agents.

New guideline recommendations prefer direct oral anticoagulants (DOACs) over warfarin in DOAC-eligible patients with atrial fibrillation and patients with venous thromboembolism. As expected with all antithrombotic agents, there is an associated increased risk of bleeding complications in patients receiving DOACs that can be attributed to the DOAC itself, or other issues such as acute trauma, invasive procedures, or underlying comorbidities. For the majority of severe bleeding events, the widespread approach is to withdraw the DOAC, then provide supportive measures and "watchful waiting" with the expectation that the bleeding event will resolve with time. However, urgent reversal of anticoagulation may be advantageous in patients with serious or life-threatening bleeding or in those requiring urgent surgery or procedures. Until recently, the lack of specific reversal agents, has affected the uptake of these agents in clinical practice despite a safer profile compared to warfarin in clinical trials. In cases of life-threatening or uncontrolled bleeding or when patients require emergency surgery or urgent procedures, idarucizumab has been recently approved for reversal of anticoagulation in dabigatran-treated patients and andexanet alfa for factor Xa inhibitor-treated treated patients. The current review summarizes the current clinical evidence and scope of these agents with the potential impact on DOAC use in clinical practice.