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Reductions in insulin sensitivity in periparturient dairy cows develop as a means to support lactation; however, excessive mobilization of fatty acids (FA) increases the risk for peripartal metabolic disorders. Our objectives were to investigate the effect of prepartum body condition score (BCS) on systemic glucose and insulin tolerance, and to compare direct and indirect measurements of insulin sensitivity in peripartal lean and overweight dairy cows. Fourteen multiparous Holstein cows were allocated into two groups according to their BCS at day −28 prepartum: lean (n = 7; BCS ≤ 3.0) or overweight; (n = 7; BCS ≥ 4.0). Liver biopsies were performed on day −27, −14 and 4, relative to expected parturition. Intravenous insulin or glucose tolerances tests were performed following each liver biopsy. Relative to lean cows, overweight cows exhibited lower dry matter intake, lost more BCS and displayed increased plasma FA and β-hydroxybutyrate concentrations and elevated liver lipid content during peripartum. Glucose clearance rate was lower for all cows postpartum. Prepartum BCS had minimal effects on insulin and glucose tolerance; however, the ability of the cow to restore blood glucose levels following an insulin challenge was suppressed by increased BCS. Glucose-dependent parameters of insulin and glucose tolerance were not correlated with surrogate indices of insulin sensitivity. We conclude that prepartum BCS had minimal effect on systemic insulin sensitivity following parturition. The observed inconsistency between surrogate indices of insulin sensitivity and direct measurements of insulin and glucose tolerance adds support to growing concerns regarding their usefulness as tools to estimate systemic insulin action in periparturient cows. [ABSTRACT FROM AUTHOR]

Background and aims: To study whether there are differences in the immunohistochemical staining of CD8, CD45R0, and CD68 of immune cells in regional lymph node metastases from colorectal cancer that are of potential interest in prognostic prediction. Materials and methods: Analysis of archival specimens from 93 patients operated on for colorectal cancer (based on monoclonal antibodies, the ABC technique, and semiquantitative classification). Results: There was a significant difference in survival time between patients with respect to the number of positive immune cells. The cancer-specific 5-year survival rate was 77% for patients with high numbers of CD8+ cells, compared to 33% for those with lower numbers. The corresponding figures for patients with CD45R0+ cells were 66% vs. 33%, and for patients with CD68+ cells 60% vs. 38%. Significant differences remained among the 74 patients without adjuvant radio-/chemotherapy regarding CD8 and CD45R0 but not CD68. Conclusion: The presence of CD8+, CD45R0+, and CD68+ immune cells in regional lymph node metastases may serve as predictors of patients survival in colorectal cancer Dukes' stage C. [ABSTRACT FROM AUTHOR]

In managing atrial fibrillation (AF), the main therapeutic strategies include rate control, termination of the arrhythmia, and the prevention of recurrences and thromboembolic events. Safety and efficacy considerations are important in optimizing the choice of an antiarrhythmic drug for the treatment of AF. Recently approved antiarrhythmics, such as dofetilide, and promising investigational drugs, such as azimilide and dronedarone, may change the treatment landscape for AF. For medical conversion of recent-onset AF, class IC antiarrhythmic drugs, administered as an oral bolus, have been demonstrated to be the most efficacious pharmacologic conversion agents. Intravenous ibutilide and oral dofetilide both have efficacies superior to placebo in controlled trials for converting persistent AF. Comparative trials in paroxysmal AF have demonstrated that flecainide, propafenone, quinidine, and sotalol are equally effective in preventing recurrences of AF. Amiodarone has been demonstrated to be more efficacious than propafenone or sotalol in the Canadian Trial of Atrial Fibrillation. In persistent AF, twice-daily dofetilide has been shown to be as or more effective than low-dose sotalol given twice daily for the maintenance of sinus rhythm in patients with AF. Trials have demonstrated that subjective adverse effects are less frequent with class IC drugs, sotalol, and dofetilide compared with such drugs as quinidine. In patients without structural heart disease, flecainide, propafenone, and D,L-sotalol are the initial drugs of choice, given their reasonable efficacy, low incidence of subjective side effects, and lack of significant end-organ toxicity. Treating AF in patients with left ventricular dysfunction can be difficult because of associated electrophysiologic derangements, potential proarrhythmic concerns, and negative inotropic effects of antiarrhythmics. Some data exist suggesting that angiotensin-converting enzyme inhibitors and angiotensin receptor blockers can prevent AF either by preventing atrial dilation and stretch-induced arrhythmias or by blocking the renin-angiotensin system. In post-myocardial infarction patients, D,L-sotalol, dofetilide, and amiodarone-and in congestive heart failure patients, amiodarone and dofetilide-have demonstrated neutral effects on survival in controlled trials. In the Congestive Heart Failure Survival Trial of Antiarrhythmic Therapy (CHF-STAT), amiodarone lowered the frequency of AF development and improved left ventricular ejection fraction over time. In CHF-STAT, there was lower mortality in patients who converted from AF to sinus rhythm. Dofetilide decreased rehospitalization for congestive heart failure in the Danish Investigations of Arrhythmia and Mortality on Dofetilide (DIAMOND) trials. Neutral effects on survival and favorable hemodynamics have positioned amiodarone and dofetilide as the antiarrhythmics of choice in patients with left ventricular dysfunction. In post-myocardial infarction patients, sotalol is an additional agent to consider for treatment of AF in this setting. [ABSTRACT FROM AUTHOR]

Purpose: Little is known about sex differences in the treatment of central sleep apnea (CSA). Our post hoc analysis of the remedē System Pivotal Trial aimed to determine sex-specific differences in the safety and effectiveness of treating moderate to severe CSA in adults with transvenous phrenic nerve stimulation (TPNS)., Methods: Men and women enrolled in the remedē System Pivotal Trial were included in this post hoc analysis of the effect of TPNS on polysomnographic measures, Epworth Sleepiness Scale, and patient global assessment for quality of life., Results: Women (n = 16) experienced improvement in CSA metrics that were comparable to the benefits experienced by men (n = 135), with central apneas being practically eliminated post TPNS. Women experienced improvement in sleep quality and architecture that was comparable to men post TPNS. While women had lower baseline apnea hypopnea index than men, their quality of life was worse at baseline. Additionally, women reported a 25-percentage point greater improvement in quality of life compared to men after 12 months of TPNS therapy. TPNS was found to be safe in women, with no related serious adverse events through 12 months post-implant, while men had a low rate of 10%., Conclusion: Although women had less prevalent and less severe CSA than men, they were more likely to report reduced quality of life. Transvenous phrenic nerve stimulation may be a safe and effective tool in the treatment of moderate to severe CSA in women. Larger studies of women with CSA are needed to confirm our findings., Clinical Trial Registration: ClinicalTrials.gov NCT01816776; March 22, 2013., (© 2023. The Author(s).)

Hepatic involvement of sarcoidosis is usually hard to detect on radiological imaging. We present a case of a 60-year-old female with symptoms of pulmonary sarcoidosis. Subsequent imaging work-up showed diffuse hepatic granulomas consistent with abdominal involvement of sarcoidosis. A literature review regarding hepatic sarcoidosis is provided and radiological appearances as well as considerations for differential diagnosis are described., (Copyright Journal of Radiology Case Reports.)

Objective To investigate the diagnostic accuracy of the placental thickness measured by ultrasound sonography test (USG) in detecting intrauterine growth restriction (IUGR) babies in the third trimester of pregnancy, keeping IUGR (by parameters using Hadlock) as the gold standard. Methods and materials This cross-sectional study was conducted at the radiology department of KRL Hospital from August 5, 2020, to October 25, 2021. Informed written consent was also obtained from each patient, and the hospital's ethical committee approved the study. Three hundred and sixty-two (N=362) pregnant women patients knowing of their last menstrual period, age group 20-35 years, BMI usual, and 24 weeks gestation were included. The patient's complete history was taken by clinical examination and then ultrasound was carried out to measure the placental thickness. At 24, 32, and 36 weeks, the thickness of the placenta was assessed. The Hadlock method was used to compute the predicted fetal weight by measuring biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur length (FL) on the GC Logiq P/6 three-dimensional machine (GE, Tampa, FL). SPSS v 23 (IBM Corp., Armonk, NY) was used to calculate the mean and standard deviation from the collected data. Results A total of 362 patients who presented in the radiology department for antenatal ultrasound in the third trimester were recruited in our study. The mean age was 27.26 ± 4.21 years (20-35 years). In our study, the mean placenta thickness at 24 gestation weeks was 24.55 ± 0.79 mm, at 32 gestation weeks was 31.84 ± 1.34 mm, and at 36 gestation weeks was 35.54 ± 2.78. Thus, ultrasound's sensitivity, specificity, positive predictive value, and negative predictive value to determine IUGR by placental thickness was 86.30%, 86.70%, 75%, and 92%, respectively. The diagnostic accuracy of ultrasound incorrectly estimating low placental thickness was 86.40%. Conclusion Between 24 and 36 weeks of pregnancy, placental thickness rises almost linearly. As a result, measuring placental thickness and other factors is critical for estimating fetal age, particularly in the late second and early third trimesters, when the exact duration of pregnancy is uncertain. Placentas that were less than 29 mm thick at 32 weeks and 31 mm thick at 36 weeks were related to higher morbidity, lower Apgar scores, and more nursery admissions., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Rafique et al.)

The discovery of novel biomarkers for peripartal diseases in dairy cows can improve our understanding of normal and dysfunctional metabolism, and lead to nutritional interventions that improve health and milk production. Our objectives were to characterize the plasma lipidome and identify metabolites associated with common markers of metabolic disease in peripartal dairy cattle. Multiparous Holstein cows ( n = 27) were enrolled 30 d prior to expected parturition. Blood and liver samples were routinely collected through to d 14 postpartum. Untargeted lipidomics was performed using quadrupole time-of-flight mass spectrometry. Based on postpartum measures, cows were categorized into low or high total fatty acid area under the curve (total FAAUC; d 1-14 postpartum; 4915 ± 1369 vs. 12,501 ± 2761 (μmol/L × 14 d); n = 18), β-hydroxybutyrate AUC (BHBAAUC; d 1-14 postpartum; 4583 ± 459 vs. 7901 ± 1206 (μmol/L × 14 d); n = 18), or liver lipid content (d 5 and 14 postpartum; 5 ± 1 vs. 12 ± 2% of wet weight; n = 18). Cows displayed decreases in plasma triacylglycerols and monoalkyl-diacylglycerols, and the majority of phospholipids reached a nadir at parturition. Phosphatidylcholines (PC) 32:3, 35:5, and 37:5 were specific for high total FAAUC, PC 31:3, 32:3, 35:5, and 37:5 were specific for high BHBAAUC, and PC 31:2, 31:3, and 32:3 were specific for high liver lipid content. PC 32:3 was specific for elevated total FA, BHBA, and liver lipid content. Lipidomics revealed a dynamic peripartal lipidome remodeling, and lipid markers associated with elevated total FA, BHBA, and liver lipid content. The effectiveness of nutrition to impact these lipid biomarkers for preventing excess lipolysis and fatty liver warrants evaluation.

The Micra™ transcatheter pacing system (TPS) (Medtronic, Minneapolis, MN, USA) is the only leadless pacemaker currently approved by the United States Food and Drug Administration. A limitation to the use of this device in the pediatric population is the large size of the delivery sheath. We present a 28-kg, nine-year-old male with symptomatic asystolic pauses who underwent successful placement of a Micra™ TPS via right internal jugular vein surgical cutdown as a first-line option. Current reports in the literature using the right internal jugular vein due to small patient size are limited to those involving patients with concurrent medical conditions that render the use of traditional systems unfavorable or contraindicated. Given the potential benefits of a leadless pacemaker system, its use in the pediatric population will likely continue to increase with time. This case describes technical strategies and procedural caveats that could aid in continued successful implantations of the Micra™ TPS in smaller patients as first-line therapy. In this report, room setup, the use of preprocedure vascular duplex studies, sheath manipulation, and a multidisciplinary approach are reviewed., Competing Interests: The authors report no conflicts of interest for the published content., (Copyright: © 2021 Innovations in Cardiac Rhythm Management.)

Introduction: Exhaled-breath analysis of volatile organic compounds could detect lung cancer earlier, possibly leading to improved outcomes. Combining exhaled-breath data with clinical parameters may improve lung cancer diagnosis., Methods: Based on data from a previous multi-centre study, this article reports additional analyses. 138 subjects with non-small cell lung cancer (NSCLC) and 143 controls without NSCLC breathed into the Aeonose. The diagnostic accuracy, presented as area under the receiver operating characteristic curve (AUC-ROC), of the Aeonose itself was compared with 1) performing a multivariate logistic regression analysis of the distinct clinical parameters obtained, and 2) using this clinical information beforehand in the training process of the artificial neural network (ANN) for the breath analysis., Results: NSCLC patients (mean±sd age 67.1±9.1 years, 58% male) were compared with controls (62.1±7.0 years, 40.6% male). The AUC-ROC of the classification value of the Aeonose itself was 0.75 (95% CI 0.69-0.81). Adding age, number of pack-years and presence of COPD to this value in a multivariate regression analysis resulted in an improved performance with an AUC-ROC of 0.86 (95% CI 0.81-0.90). Adding these clinical variables beforehand to the ANN for classifying the breath print also led to an improved performance with an AUC-ROC of 0.84 (95% CI 0.79-0.89)., Conclusions: Adding readily available clinical information to the classification value of exhaled-breath analysis with the Aeonose, either post hoc in a multivariate regression analysis or a priori to the ANN, significantly improves the diagnostic accuracy to detect the presence or absence of lung cancer., Competing Interests: Conflict of interest: S. Kort reports an unrestricted research grant paid to her institution by The eNose Company, Zutphen, during the conduct of the study. Conflict of interest: M. Brusse-Keizer has nothing to disclose. Conflict of interest: J.W. Gerritsen is an employee of The eNose Company, Zutphen. Conflict of interest: J.H. Schouwink has nothing to disclose. Conflict of interest: E. Citgez has nothing to disclose. Conflict of interest: F.H.C. de Jongh has nothing to disclose. Conflict of interest: J. van der Maten has nothing to disclose. Conflict of interest: S. Samii has nothing to disclose. Conflict of interest: M. van den Bogart has nothing to disclose. Conflict of interest: J. van der Palen has nothing to disclose., (Copyright ©ERS 2020.)

Objective: Metastasized non-small cell lung cancer (NSCLC) with an anaplastic lymphoma kinase (ALK) rearrangement is usually sensitive to a range of ALK-tyrosine kinase inhibitors. ALK-positive NSCLC have been identified in pivotal phase III trials with fluorescence in situ hybridization (ALK FISH+). These tumors are also expressing the fusion product (ALK immunohistochemistry (IHC)+). However, discrepant cases occur, including ALK IHC + FISH-. The aim of this study was to collect ALK IHC + cases and compare within this group response to crizotinib treatment of ALK FISH + cases with ALK FISH- cases., Materials and Methods: In this European prospective multicenter research study patients with Stage IV ALK IHC + NSCLC treated with crizotinib were enrolled. Tumor slides were validated centrally for ALK IHC and ALK FISH., Results: Registration of 3523 ALK IHC tests revealed a prevalence of 2.7% (n = 94) ALK IHC + cases. Local ALK FISH analysis resulted in 48 concordant (ALK IHC+/FISH+) and 16 discordant (ALK IHC+/FISH-) cases. Central validation revealed 37 concordant and 7 discordant cases, 5 of which had follow-up. Validation was hampered by limited amount of tissue in biopsy samples. The PFS at 1 year for ALK concordant and discordant was 58% and 20%, respectively (HR = 2.4; 95% CI: 0.78-7.3; p = 0.11). Overall survival was significantly better for concordant cases than discordant cases after central validation (HR=4.5; 95% CI= 1.2-15.9; p=0.010., Conclusion: ALK IHC + FISH- NSCLC is infrequent and associated with a worse outcome on personalized treatment. A suitable predictive testing strategy may be to screen first with IHC and then confirm with FISH instead of considering ALK IHC equivalent to ALK FISH according to the current guidelines., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Reduced insulin action develops naturally during the peripartum to ensure maternal nutrient delivery to the fetus and neonate. However, increased insulin resistance can facilitate excessive lipolysis which in turn promotes metabolic disease in overweight dairy cattle. Increased fatty acid availability favors the accumulation of the sphingolipid ceramide and is implicated in the pathogenesis of insulin resistance, however, the relationship between sphingolipid metabolism and insulin resistance during the peripartum remains largely unknown. Our objectives were to characterize temporal responses in plasma and tissue sphingolipids in lean and overweight peripartal cows and to establish the relationships between sphingolipid supply and lipolysis, hepatic lipid deposition, and systemic insulin action. Twenty-one multiparous lean and overweight Holstein cows were enrolled in a longitudinal study spanning the transition from gestation to lactation (d -21 to 21, relative to parturition). Plasma, liver, and skeletal muscle samples were obtained, and sphingolipids were profiled using LC/MS/MS. Insulin sensitivity was assessed utilizing intravenous insulin and glucose challenges. Our results demonstrated the following: first, insulin resistance develops postpartum concurrently with increased lipolysis and hepatic lipid accumulation; second, ceramides and glycosylated ceramides accumulate during the transition from gestation to lactation and are further elevated in overweight cows; third, ceramide accrual is associated with lipolysis and liver lipid accumulation, and C16:0- and C24:0-ceramide are inversely associated with systemic insulin sensitivity postpartum; fourth, plasma sphingomyelin, a potential source of ceramides reaches a nadir at parturition and is closely associated with feed intake; fifth, select sphingomyelins are lower in the plasma of overweight cows during the peripartal period. Our results demonstrate that dynamic changes occur in peripartal sphingolipids that are influenced by adiposity, and are associated with the onset of peripartal insulin resistance. These observations are in agreement with a putative potential role for sphingolipids in facilitating the physiological adaptations of peripartum.

Background: Apixaban is a Factor Xa inhibitor increasingly being used for stroke prevention in atrial fibrillation (AF). Although several studies have been done, the efficacy and safety of apixaban during the peri-procedural period of AF ablation remains unclear. We sought to systematically review pooled data from these various studies to evaluate thromboembolic and bleeding risks in patients undergoing catheter ablation for AF who are treated with apixaban (interrupted and uninterrupted)., Methods: Studies comparing anticoagulation with apixaban or vitamin K antagonists (VKA) in patients undergoing ablation for AF were identified via an electronic search of MEDLINE, EMBASE, clinical trials.gov, and Cochrane Library from inception to January 2016. Study-specific risk ratios were calculated and combined with a fixed-effects model meta-analysis., Results: In the analysis of 2100 pooled patients, thromboembolic complications (TE) occurred in 14/778 (1.80 %) patients in the apixaban group (AG) compared to 20/1322 patients in the VKA group (RR 1.03, 95 % CI 0.55-1.90, p = 0.93, I 2  = 0 %). Major bleeding occurred in 9/778 (1.2 %) of the AG compared to 20/1322 (1.51 %) in the VKA group (RR 1.03, 95 % CI 0.55-1.90, p = 0.93, I 2  = 0 %). In uninterrupted apixaban group (uAG), TE occurred in 4/585 (0.68 %) patients in the uAG compared to 6/910 (0.66 %) in VKA group (RR 0.86, 95 % CI 0.25-2.95, p = 0.81, I 2  = 0 %). Major bleeding occurred in 5/585 (0.85 %) in uAG compared to 7/910 (0.77 %) in the VKA group (RR 1.20, 95 % CI 0.37-3.88, p = 0.76, I 2  = 0 %)., Conclusion: Our study demonstrates patients treated with apixaban and VKA during the peri-procedural period for AF ablation have similar rates of TE and bleeding complications. Interrupted and uninterrupted apixaban strategies were associated with similar outcomes.

Object: Trigeminal neuralgia (TGN) occurring after radiosurgical treatment of cerebellopontine or petroclival tumors may be very difficult to control. Our aim was to determine the efficacy of neurosurgical treatment in regards to pain control and to evaluate the procedure-related complication and morbidity rates., Methods: Retrospective study of a series of operated patients with radiosurgery-induced TGN. The primary goal of the surgery was to inspect and decompress the trigeminal nerve; the second goal was to remove the tumor remnant completely, if safely feasible. The main outcome measures were pain control, time to onset of pain relief and its duration, occurrence of new neurological deficits or worsening of the existing one and completeness of tumor removal., Results: The four patients met the inclusion criteria: 2 with vestibular schwannomas, 1 with petroclival meningioma and 1 with an epidermoid. TGN occurred 12-60 months after radiosurgery (mean 39 months). At presentation the pain attacks occurred multiple timesdaily and lasted from a few seconds to 2-3min. The Complete tumor removal via the retrosigmoid approach was achieved in all cases. There were no major operative complications or persistent morbidity, besides one patient with trochlear nerve palsy. All patients experienced immediate pain relief after surgery. At follow-up (median duration - 42.5 months) the three patients reported complete pain resolution. One patient had occasional slight pain but did not need any medications., Conclusion: Surgery is safe and effective treatment option of patients with intractable radiosurgery-induced TGN. It leads to excellent pain control and is curative in regards to the neoplastic disease., (Copyright © 2014. Published by Elsevier B.V.)

Background: Atrial tachyarrhythmias (AT) including atrial fibrillation (AF), atrial flutter (AFL), and atrial tachycardia represent a clinical challenge in the adult with congenital heart disease (CHD). Dofetilide (D) is a rapidly activating delayed rectifier potassium channel (IKr) blocker effective in pharmacological conversion and maintenance of normal sinus rhythm in patients with AF and AFL. There is limited knowledge regarding the role of D in adults with CHD., Methods: Safety and efficacy of D was evaluated in a consecutive group of thirteen adult patients (age 40 ± 11; six women) with CHD and refractory AT., Results: Ten patients had persistent (four AFL, one AF, and five atrial tachycardia) and three paroxysmal (one AF and two atrial tachycardia) AT. All patients were symptomatic during tachycardia, 12 patients had previously failed 2 ± 1 antiarrhythmic drugs. Mean systemic ventricular ejection fraction was 55 ± 9%; baseline QRS complex duration was 129 ± 45 ms (>120 ms in six patients). Patients were followed on D for 33 ± 39 months (median 16). Among 10 patients with persistent AT, seven patients (70%) pharmacologically converted to sinus rhythm on D and three patients (30%) required direct current cardioversion. Two patients (15.4%) experienced complete arrhythmia suppression, and seven (53.8%) experienced significant clinical improvement with sporadic recurrences; average time to recurrence was 5.5 ± 3.5 months. One patient developed torsade de pointes during loading, and the drug was discontinued. D was discontinued in five (38.5%) other patients due to recurrence of AT (n = 4) and renal failure (n = 1). Corrected QT interval (QTc) increased from 452 ± 61 to 480 ± 49 ms (P = .04) and corrected JT interval (JTc) from 323 ± 39 to 341 ± 33 ms (P = .09)., Conclusions: D should be considered a pharmacologic alternative when adult patients with CHD develop AT. D does not depress conduction, sinus node, or ventricular function but needs close monitoring for potential ventricular pro-arrhythmia., (© 2013 Wiley Periodicals, Inc.)