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Supplemental Digital Content is available in the text., Background and Purpose: Women have worse outcomes than men after stroke. Differences in presentation may lead to misdiagnosis and, in part, explain these disparities. We investigated whether there are sex differences in clinical presentation of acute stroke or transient ischemic attack. Methods: We conducted a systematic review and meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Inclusion criteria were (1) cohort, cross-sectional, case-control, or randomized controlled trial design; (2) admission for (suspicion of) ischemic or hemorrhagic stroke or transient ischemic attack; and (3) comparisons possible between sexes in ≥1 nonfocal or focal acute stroke symptom(s). A random-effects model was used for our analyses. We performed sensitivity and subanalyses to help explain heterogeneity and used the Newcastle-Ottawa Scale to assess bias. Results: We included 60 studies (n=582 844; 50% women). In women, headache (pooled odds ratio [OR], 1.24 [95% CI, 1.11–1.39]; I2=75.2%; 30 studies) occurred more frequently than in men with any type of stroke, as well as changes in consciousness/mental status (OR, 1.38 [95% CI, 1.19–1.61]; I2=95.0%; 17 studies) and coma/stupor (OR, 1.39 [95% CI, 1.25–1.55]; I2=27.0%; 13 studies). Aspecific or other neurological symptoms (nonrotatory dizziness and non-neurological symptoms) occurred less frequently in women (OR, 0.96 [95% CI, 0.94–0.97]; I2=0.1%; 5 studies). Overall, the presence of focal symptoms was not associated with sex (pooled OR, 1.03) although dysarthria (OR, 1.14 [95% CI, 1.04–1.24]; I2=48.6%; 11 studies) and vertigo (OR, 1.23 [95% CI, 1.13–1.34]; I2=44.0%; 8 studies) occurred more frequently, whereas symptoms of paresis/hemiparesis (OR, 0.73 [95% CI, 0.54–0.97]; I2=72.6%; 7 studies) and focal visual disturbances (OR, 0.83 [95% CI, 0.70–0.99]; I2=62.8%; 16 studies) occurred less frequently in women compared with men with any type of stroke. Most studies contained possible sources of bias. Conclusions: There may be substantive differences in nonfocal and focal stroke symptoms between men and women presenting with acute stroke or transient ischemic attack, but sufficiently high-quality studies are lacking. More studies are needed to address this because sex differences in presentation may lead to misdiagnosis and undertreatment.

Supplemental Digital Content is available in the text., Background and Purpose: Blinded outcome assessment in trials with prospective randomized open blinded end point design is challenging. Unblinding can result in misclassified outcomes and biased treatment effect estimates. An outcome adjudication committee assures blinded outcome assessment, but the added value for trials with prospective randomized open blinded end point design and subjective outcomes is unknown. We aimed to assess the degree of misclassification of modified Rankin Scale (mRS) scores by a central assessor and its impact on treatment effect estimates in a stroke trial with prospective randomized open blinded end point design. Methods: We used data from the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands). The primary outcome was the mRS at 90 days. Standardized, algorithm-based telephone interviews to assess the mRS were conducted from a central location by an experienced research nurse, unaware but not formally blinded to treatment allocation (central assessor). Masked reports of these interviews were adjudicated by a blinded outcome committee. Misclassification was defined as an incorrect classification of the mRS by the central assessor. The effect of endovascular treatment on the mRS was assessed with multivariable ordinal logistic regression. Results: In MR CLEAN, 53/500 (10.6%) of the mRS scores were misclassified. The degree and direction of misclassification did not differ between treatment arms (P=0.59). Benefit of endovascular treatment was shown on the mRS when scored by the central assessor (adjusted common odds ratio, 1.60 [95% CI, 1.16–2.21]) and the outcome adjudication committee (adjusted common odds ratio, 1.67 [95% CI, 1.21–2.20]). Conclusions: Misclassification by the central assessor was small, randomly distributed over treatment arms, and did not affect treatment effect estimates. This study suggests that the added value of a blinded outcome adjudication committee is limited in a stroke trial with prospective randomized open blinded end point design applying standardized, algorithm-based outcome assessment by a central assessor, who is unaware but not formally blinded to treatment allocation. Registration: URL: https://www.isrctn.com; Unique identifier: ISRCTN10888758.

Background Communicating a diagnosis is highly important, yet complex, especially in the context of cancer and mental disorders. The aim was to explore the communication style of an oncologist vs. psychotherapist in an online study. Methods Patients (N = 136: 65 cancer, 71 depression) were randomly assigned to watch a standardized video vignette with one of two communication styles (empathic vs. unempathic). Outcome measures of affectivity, information recall, communication skills, empathy and trust were applied. Results Regardless of diagnosis, empathic communication was associated with the perception of a significantly more empathic (p < 0.001, η2partial = 0.08) and trustworthy practitioner (p = 0.014, η2partial = 0.04) with better communication skills (p = 0.013, η2partial = 0.05). Cancer patients reported a larger decrease in positive affect (p < 0.001, η2partial = 0.15) and a larger increase in negative affect (p < 0.001, η2partial = 0.14) from pre- to post-video than depressive patients. Highly relevant information was recalled better in both groups (p < 0.001, d = 0.61–1.06). Conclusions The results highlight the importance of empathy while communicating both a diagnosis of cancer and a mental disorder. Further research should focus on the communication of a mental disorder in association with cancer., Zweitveröffentlichungen der Universität Potsdam : Humanwissenschaftliche Reihe; 817

Background and purpose There are concerns that the coronavirus disease 2019 (COVID-19) outbreak negatively affects the quality of care for acute cardiovascular conditions. We assessed the impact of the COVID-19 outbreak on trends in hospital admissions and workflow parameters of acute stroke care in Amsterdam, The Netherlands. Methods We used data from the three hospitals that provide acute stroke care for the Amsterdam region. We compared two 7-week periods: one during the peak of the COVID-19 outbreak (March 16th–May 3th 2020) and one prior to the outbreak (October 21st–December 8th 2019). We included consecutive patients who presented to the emergency departments with a suspected stroke and assessed the change in number of patients as an incidence-rate ratio (IRR) using a Poisson regression analysis. Other outcomes were the IRR for stroke subtypes, change in use of reperfusion therapy, treatment times, and in-hospital complications. Results During the COVID-19 period, 309 patients presented with a suspected stroke compared to 407 patients in the pre-COVID-19 period (IRR 0.76 95%CI 0.65–0.88). The proportion of men was higher during the COVID-19 period (59% vs. 47%, p p = 0.58) or endovascular thrombectomy (11% vs 12%, p = 0.82) or associated treatment times. Seven patients (all ischemic strokes) were diagnosed with COVID-19. Conclusion We observed a 24% decrease in suspected stroke presentations during the COVID-19 outbreak, but no evidence for a decrease in quality of acute stroke care.

Background Prior studies have suggested that pimobendan is associated with several positive effects in cats, including improved survival in cats with congestive heart failure and improved left atrial function in research colony cats with hypertrophic cardiomyopathy (HCM) and normal cats. However, there is still a paucity of pharmacodynamic data refuting or supporting the use of pimobendan in a clinical cat population. This clinical trial aimed to evaluate the pharmacodynamic effects and tolerability of a single dose of pimobendan in cats with HCM. Echocardiograms and Doppler-derived systolic blood pressures were performed in 21 client-owned cats with subclinical HCM at baseline and 90-min after oral administration of 1.25 mg of pimobendan (Vetmedin). Seven additional cats were evaluated post-placebo administration to account for intra-day variability. Results Heart rate, systolic blood pressure, and murmur grade were not significantly different between baseline and post-pimobendan evaluations. Left auricular blood flow velocity, left atrial size, and left ventricular fractional shortening were not significantly different between baseline and post-pimobendan evaluations. Mean (± standard deviation) tissue Doppler peak systolic velocity of the mitral annulus was significantly higher following pimobendan (7.4 cm/s ± 1.5 vs 8.5 ± 1.6; p = 0.02). Median (min, max) left-ventricular outflow tract maximum velocity was significantly higher following pimobendan [1.9 m/sec (1.5, 3.4) vs 2.6 m/sec (2.0, 4.0); p = 0.01]. Mean right-ventricular outflow tract maximum velocity was also significantly higher following pimobendan (1.5 m/s ± 0.51 vs 2.0 ± 0.53; p = 0.004). Mean left atrial fractional shortening was significantly higher following pimobendan (28% ± 6 vs 32% ± 7; p = 0.02). No adverse events were observed following pimobendan administration. Right ventricular outflow tract velocity was significantly higher following placebo in control cats (1.02 ± 0.21 versus 1.31 ± 0.31; p = 0.01). No other significant differences were detected. Conclusions In client-owned cats with HCM, pimobendan acutely increased left atrial function and mildly increased left ventricular systolic function. Left ventricular outflow tract velocity was increased after pimobendan. Pimobendan was well tolerated in the acute setting in cats with HCM. The findings of this prospective, acute-dosing study confirm previous findings in research animals and retrospective analyses and suggest that chronic dosing studies are safe and warranted.

Radiographic assessment of heart size is important for clinical management of dogs with cardiovascular disease (CVDz). We sought to compare the ability of vertebral heart size (VHS), vertebral left atrial size (VLAS), and radiologists' assessment of left atrial size (RadLAE) to predict echocardiographic left atrial size (EchoLAE), an important marker of left heart disease severity. We also compared the ability of VHS and VLAS to predict echocardiographic criteria for ACVIM stage B2 (EchoB2) in dogs with myxomatous mitral valve disease (MMVD). This prospective observational study enrolled 183 dogs with known or suspected CVDz that had an echocardiographic examination and thoracic radiographs obtained within 24 h. Compared to increased VHS, VLAS 2.3 was a more accurate predictor of EchoLAE (P = .002). VLAS 2.3 and RadLAE (both P .0001) were independently associated with EchoLAE but VHS was not (P = .45). Optimal cutoffs for VLAS and VHS to predict EchoLAE were 2.3 vertebrae (sensitivity [Sn] = 90.3%, specificity [Sp] = 73.6%) and 11.1 vertebrae (Sn = 75.8%, Sp = 76.0%), respectively. Diagnostic accuracy of VLAS (AUC 0.84, 95% CI 0.73-0.92) and VHS (AUC 0.78, 95% CI 0.66-0.88) to predict EchoB2 in dogs with subclinical MMVD (n = 64) were not significantly different (P = .17). Results demonstrate that VLAS and RadLAE were superior indicators of EchoLAE compared to VHS in dogs with known or suspected CVDz. Both VLAS and VHS are useful predictors of EchoB2 in dogs with subclinical MMVD. When echocardiography is unavailable, VLAS represents a useful radiographic measurement to aid clinical management of dogs with known or suspected CVDz.

Quantitative measurements are commonly implemented to objectively evaluate heart size in dogs. However, recent studies suggest that the phase of cardiac cycle can impact vertebral heart score, thereby potentially influencing clinical management. This study used fluoroscopy to assess the impact of the cardiac cycle on quantitative cardiovascular measurements in healthy dogs of various breeds.This was a prospective study. Multiple cardiac and respiratory cycles were recorded fluoroscopically. Peak inspiratory end-systole and end-diastole frames were captured from 49 dogs in right lateral recumbency. Vertebral heart score (VHS), cardiothoracic ratio (CTR), vertebral left atrial size (VLAS), and caudal vena cava diameter ratio (CVCDR) measurements were performed. Mean cardiac measurements were compared between cardiac cycle phases, and the impact of body condition score (BCS), weight, thoracic conformation, sex, and age was evaluated.Cardiac cycle had a significant impact on VHS (mean difference: 0.36 ± 0.14 vertebral units between systole and diastole; p 0.001) and CTR (mean difference: 2.2 ± 1.2% between systole and diastole; p 0.001). Cardiac cycle had no significant impact on VLAS or CVCDR. Increasing BCS significantly increased variation between systole and diastole in CTR measurements (p = 0.024).The cardiac cycle has a significant effect on VHS and CTR but does not impact VLAS or CVCDR. These findings should be taken into consideration during clinical use of these measurements, especially if a patient is being monitored for cardiac changes over time via serial radiographs.

Objectives The combination chemotherapy regimen capecitabine/temozolomide (CAPTEM) is efficacious for metastatic well-differentiated pancreatic neuroendocrine tumors (PNETs), but its role in the neoadjuvant setting has not been established. Methods The outcomes of all patients with locally advanced or resectable metastatic PNETs who were treated with neoadjuvant CAPTEM between 2009 and 2017 at 2 high-volume institutions were retrospectively reviewed. Results Thirty patients with locally advanced PNET (n = 10) or pancreatic neuroendocrine hepatic metastases (n = 20) received neoadjuvant CAPTEM. Thirteen patients (43%) exhibited partial radiographic response (PR), 16 (54%) had stable disease, and 1 (3%) developed progressive disease. Twenty-six (87%) patients underwent resection (pancreatectomy [n = 12], combined pancreatectomy and liver resection [n = 8], or major hepatectomy alone [n = 6]); 3 (18%) declined surgery despite radiographic PR, and 1 (3%) underwent aborted pancreatoduodenectomy. Median primary tumor size was 5.5 cm, and median Ki-67 index was 3.5%. Rates of PR were similar across tumor grades (P = 0.24). At median follow-up of 49 months, median progression-free survival was 28.2 months and 5-year overall survival was 63%. Conclusions Neoadjuvant CAPTEM is associated with favorable radiographic objective response rates for locally advanced or metastatic PNET and may facilitate selection of patients appropriate for surgical resection.

Background and Purpose: Endovascular treatment for acute ischemic stroke has been proven clinically effective, but evidence of the cost-effectiveness based on real-world data is scarce. The aim of this study was to assess whether endovascular therapy plus usual care is cost-effective in comparison to usual care alone in acute ischemic stroke patients. Methods: An economic evaluation was performed from a societal perspective with a 2-year time horizon. Empirical data on health outcomes and the use of resources following endovascular treatment were gathered parallel to the MR CLEAN trial (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) and its 2-year follow-up study. Incremental cost-effectiveness ratios were calculated as the extra costs per additional patient with functional independence (modified Rankin Scale score 0–2) and the extra cost per quality-adjusted life year gained. Results: The mean costs per patient in the intervention group were $126 494 versus $143 331 in the control group (mean difference, −$16 839 [95% CI, −$38 113 to $5456]). Compared with patients in the control group, more patients in the intervention group achieved functional independence, 37.2% versus 23.9% (absolute difference, 13.3% [95% CI, 4.0%–22.0%]) and they generated more quality-adjusted life years, 0.99 versus 0.83 (mean difference of 0.16 [95% CI, 0.04–0.29]). Endovascular treatment dominated standard treatment with $18 233 saved per extra patient with a good outcome and $105 869 saved per additional quality-adjusted life year. Conclusions: Endovascular treatment added to usual care is clinically effective, and cost saving in comparison to usual care alone in patients with acute ischemic stroke. Registration: URL: https://www.trialregister.nl/trial/695 ; Unique identifier: NL695. URL: https://www.isrctn.com ; Unique identifier: ISRCTN10888758.

OBJECTIVE The aim of this study was to evaluate the role of surgical transgastric necrosectomy (TGN) for walled-off pancreatic necrosis (WON) in selected patients. BACKGROUND WON is a common consequence of severe pancreatitis and typically occurs 3 to 5 weeks after the onset of acute pancreatitis. When symptomatic, it can require intervention. METHODS A retrospective review of patients with WON undergoing surgical management at 3 high-volume pancreatic institutions was performed. Surgical indications, intervention timing, technical methodology, and patient outcomes were evaluated. Patients undergoing intervention

Background Cryptococcal meningitis is most commonly found in HIV-infected patients. In HIV-negative patients, its low incidence can lead to prolonged time to diagnosis. Detailed case reports of chronic cryptococcal meningitis are scarce, but could provide clues for earlier diagnosis in this patient category. Case presentation A 60-year old man presented June 2015 with intermittent headaches for several months without any fever. Initial work-up showed a leukocytosis, raised CSF opening pressure and raised leukocytes and protein in the CSF. An MRI revealed leptomeningeal contrast enhancement and cerebellar oedema. While malignancy and various infectious causes were excluded, the patient had a spontaneous clinical and radiological recovery. One year later, the patient returned with complaints of headaches. Also, cerebellar oedema and leptomeningeal contrast enhancement had recurred. Eventually in March 2017, the novel cryptococcal antigen lateral flow assay (CrAg LFA) was positive on CSF, and one colony of Cryptococcus neoformans was cultured from CSF. The patient was treated with the standard antifungal regimen which resulted in resolution of his headaches. In retrospect, the cryptococcal antigen test was already positive on a serum sample from June 2015. Interestingly, post-treatment immunological analysis revealed both a low mannose-binding lectin (MBL) concentration and low naïve CD4 counts. Conclusions We present a patient with cryptococcal meningitis in an HIV-negative patient with low MBL and low naïve CD4 count suffering a chronic relapsing meningo-encephalitis with relatively mild symptoms for around 2 years. In patients with an unexplained meningo-encephalitis such as this case, early performance of CrAg LFA on serum and/or CSF is an inexpensive and rapid method to reduce time-to diagnosis.

Background Broadly applicable reference intervals (RIs) for measurements of left atrial (LA) and left ventricular (LV) size and function generated prospectively using statistically appropriate methods are limited. Objectives To generate body size-independent RIs for linear, area, and volume measurements of LA size and LV size and function. Animals Healthy adult dogs (n = 122) of variable size and somatotype. Methods Prospective study. All dogs underwent an echocardiogram performed by the same examiner. Effects of body weight, sex, age, and heart rate were evaluated by regression and correlation analyses. Scaling exponents and prediction intervals were generated for linear measurements using the allometric equation. After normalization to body weight, 95% RIs were determined using nonparametric methods with 2.5 and 97.5 percentiles serving as the lower and upper limits (each with 90% confidence intervals), respectively. Results Linear LA and LV measurements were strongly correlated (R2 ≥ 0.79) with body weight. Scaling exponents were close to the expected 1/3 (0.299-0.392). Prediction intervals for linear measurements of LV chamber size were considerably narrower than previously reported. Weak correlations (r = -0.42 to -0.50) among LV fractional shortening, fractional area change, and ejection fraction and body weight were identified. No other meaningful relationships were identified between the measurements and sex, age, and heart rate. Conclusions and clinical importance Body size-independent RIs for several linear, area, and volume measurements of LA and LV size and function were generated prospectively from a large and diverse reference population and are available for clinical use.

Supplemental digital content is available in the text., Objective To quantitatively assess the probability of tumor resection based on measurements of tumor contact with the major peripancreatic vessels. Methods This is a retrospective cohort study of pancreatic cancer patients treated between January 2001 and December 2015 in a single academic comprehensive cancer center. Radiographic measurements of the circumferential degree and length of solid tumor contact with major peripancreatic vessels were obtained from diagnostic pancreatic protocol computed tomography images and tested for correlation with tumor resection and margin status. Results Of 294 patients analyzed, 113 (38%) were resected, with 71 (63%) with negative margins. Based on the individual measurements of vascular involvement, a resectability scoring system (RSS) was created. The RSS correlated strongly with resection (P < 0.0001) and R0 resection (P < 0.0001) probabilities. Moreover, the RSS correlated with overall survival (P < 0.0001) and metastasis-free survival (P < 0.0001), being able to substratify resectable (P = 0.022) and unresectable patients (P = 0.014) into subgroups with different prognosis based on RSS scores. Conclusions Based on a comprehensive and systematic quantitative approach, we developed a scoring system that demonstrated excellent accuracy to predict tumor resection, surgical margin status, and prognosis.

Introduction In the first wave, thrombotic complications were common in COVID-19 patients. It is unknown whether state-of-the-art treatment has resulted in less thrombotic complications in the second wave. Methods We assessed the incidence of thrombotic complications and overall mortality in COVID-19 patients admitted to eight Dutch hospitals between September 1st and November 30th 2020. Follow-up ended at discharge, transfer to another hospital, when they died, or on November 30th 2020, whichever came first. Cumulative incidences were estimated, adjusted for competing risk of death. These were compared to those observed in 579 patients admitted in the first wave, between February 24th and April 26th 2020, by means of Cox regression techniques adjusted for age, sex and weight. Results In total 947 patients with COVID-19 were included in this analysis, of whom 358 patients were admitted to the ICU; 144 patients died (15%). The adjusted cumulative incidence of all thrombotic complications after 10, 20 and 30 days was 12% (95% confidence interval (CI) 9.8–15%), 16% (13–19%) and 21% (17–25%), respectively. Patient characteristics between the first and second wave were comparable. The adjusted hazard ratio (HR) for overall mortality in the second wave versus the first wave was 0.53 (95%CI 0.41–0.70). The adjusted HR for any thrombotic complication in the second versus the first wave was 0.89 (95%CI 0.65–1.2). Conclusions Mortality was reduced by 47% in the second wave, but the thrombotic complication rate remained high, and comparable to the first wave. Careful attention to provision of adequate thromboprophylaxis is invariably warranted., Highlights • Half overall mortality in the second wave compared to first wave COVID-19 patients. • Still high incidence of thrombotic complications in second wave. • More subsegmental PE in second wave than in first wave.

Snakes of the genera Pseudocerastes and Eristicophis (Viperidae: Viperinae) are known as the desert vipers due to their association with the arid environments of the Middle East. These species have received limited research attention and little is known about their venom or ecology. In this study, a comprehensive analysis of desert viper venoms was conducted by visualising the venom proteomes via gel electrophoresis and assessing the crude venoms for their cytotoxic, haemotoxic, and neurotoxic properties. Plasmas sourced from human, toad, and chicken were used as models to assess possible prey-linked venom activity. The venoms demonstrated substantial divergence in composition and bioactivity across all experiments. Pseudocerastes urarachnoides venom activated human coagulation factors X and prothrombin and demonstrated potent procoagulant activity in human, toad, and chicken plasmas, in stark contrast to the potent neurotoxic venom of P. fieldi. The venom of E. macmahonii also induced coagulation, though this did not appear to be via the activation of factor X or prothrombin. The coagulant properties of P. fieldi and P. persicus venoms varied among plasmas, demonstrating strong anticoagulant activity in the amphibian and human plasmas but no significant effect in that of bird. This is conjectured to reflect prey-specific toxin activity, though further ecological studies are required to confirm any dietary associations. This study reinforces the notion that phylogenetic relatedness of snakes cannot readily predict venom protein composition or function. The significant venom variation between these species raises serious concerns regarding antivenom paraspecificity. Future assessment of antivenom is crucial.

Although deep learning has been explored extensively for computer‐aided medical imaging diagnosis in human medicine, very little has been done in veterinary medicine. The goal of this retrospective, pilot project was to apply the deep learning artificial intelligence technique using thoracic radiographs for detection of canine left atrial enlargement and compare results with those of veterinary radiologist interpretations. Seven hundred ninety‐two right lateral radiographs from canine patients with thoracic radiographs and contemporaneous echocardiograms were used to train, validate, and test a convolutional neural network algorithm. The accuracy, sensitivity, and specificity for determination of left atrial enlargement were then compared with those of board‐certified veterinary radiologists as recorded on radiology reports. The accuracy, sensitivity, and specificity were 82.71%, 68.42%, and 87.09%, respectively, using an accuracy driven variant of the convolutional neural network algorithm and 79.01%, 73.68%, and 80.64%, respectively, using a sensitivity driven variant. By comparison, accuracy, sensitivity, and specificity achieved by board‐certified veterinary radiologists was 82.71%, 68.42%, and 87.09%, respectively. Although overall accuracy of the accuracy driven convolutional neural network algorithm and veterinary radiologists was identical, concordance between the two approaches was 85.19%. This study documents proof‐of‐concept for application of deep learning techniques for computer‐aided diagnosis in veterinary medicine.

Background The clinical relevance of echocardiographic measurements of right heart size and function in dogs with pulmonary hypertension (PH) is unknown. Objective To determine if echocardiographic measurements of right heart size and right ventricular (RV) function are associated with survival times in dogs with PH. Animals Eighty‐two client‐owned dogs. Methods Retrospective study where data from medical records and baseline echocardiographic examinations were collected and measured in a standardized manner. Owners or primary veterinarians were contacted for outcome data. Results Enlargement of the right atrium (88%), RV (69%), and pulmonary artery (72%) was common. One‐third of the cases had reduced RV function quantified by two‐dimensional echocardiography‐derived tricuspid annular plane systolic excursion (TAPSE). Decreased TAPSE was significantly (P = .008) more common in dogs with PH not secondary to left heart disease (LHD; 43%) compared to dogs with PH secondary to LHD (14%) but median survival times (182, 95% confidence interval [CI] = 39‐309 versus 298, 95% CI = 85‐314 days, respectively) were not significantly different (P = .78). Right atrial area (hazard ratio [HR] = 2.72, 95% CI = 1.58‐4.70), TAPSE

Postoperative delayed gastric emptying (DGE) is a frustrating complication of pancreaticoduodenectomy (PD). We studied whether monitoring of postoperative gastric motor activity using a novel wireless patch system can identify patients at risk for DGE. Patients ( n = 81) were prospectively studied since 2016; 75 patients total were analyzed for this study. After PD, battery-operated wireless patches (G-Tech Medical) that acquire gastrointestinal myoelectrical signals are placed on the abdomen and transmit data by Bluetooth. Patients were divided into early and late groups by diet tolerance of 7 days [enhanced recovery after surgery (ERAS) goal]. Subgroup analysis was done of patients included after ERAS initiation. The early and late groups had 50 and 25 patients, respectively, with a length of stay (LOS) of 7 and 11 days ( P < 0.05). Nasogastric insertion was required in 44% of the late group. Tolerance of food was noted by 6 versus 9 days in the early versus late group ( P < 0.05) with higher cumulative gastric myoelectrical activity. Diminished gastric myoelectrical activity accurately identified delayed tolerance to regular diet in a logistical regression analysis [area under the curve (AUC): 0.81; 95% confidence interval (CI), 0.74–0.92]. The gastric myoelectrical activity also identified a delayed LOS status with an AUC of 0.75 (95% CI, 0.67–0.88). This stomach signal continued to be predictive in 90% of the ERAS cohort, despite earlier oral intake. Measurement of gastric activity after PD can distinguish patients with shorter or longer times to diet. This noninvasive technology provides data to identify patients at risk for DGE and may guide the timing of oral intake by gastric “readiness.” NEW & NOTEWORTHY Limited clinical indicators exist after pancreaticoduodenectomy to allow prediction of delayed gastric emptying (DGE). This study introduces a novel, noninvasive, wireless patch system capable of accurately monitoring gastric myoelectric activity after surgery. This system can differentiate patients with longer or shorter times to a regular diet as well as provide objective data to identify patients at risk for DGE. This technology has the potential to individualize feeding regimens based on gastric activity patterns to improve outcomes.

Background Severe necrotizing pancreatitis may result in midbody necrosis and ductal disruption leaving an isolated pancreatic tail. The purpose of this study was to characterize outcomes among patients with an isolated tail remnant who underwent transgastric drainage or necrosectomy (endoscopic or surgical) and determine the need for subsequent operative management. Materials and methods Patients with necrotizing pancreatitis and retrogastric walled-off collections treated by surgical transgastric necrosectomy or endoscopic cystgastrostomy ± necrosectomy between 2009 and 2017 were identified by a retrospective chart review. All available preprocedure and postprocedure imaging was reviewed for evidence of isolated distal pancreatic tail remnants. Results Seventy-four patients were included (40 surgical and 34 endoscopic). All the patients in the surgical group underwent laparoscopic transgastric necrosectomy; the endoscopic group consisted of 26 patients for pseudocyst drainage and eight patients for necrosectomy. A disconnected pancreatic tail was identified in 22 (29%) patients (13 laparoscopic and nine endoscopic). After the creation of the “cystgastrostomy,” there were no external fistulas despite the viable tail. Of the 22 patients, four patients developed symptoms at a median of 23 months (two, recurrent episodic pancreatitis; two, intractable pain). Two patients (both initially in endoscopic group) ultimately required distal pancreatectomy and splenectomy at 24 and 6 months after index procedure. Conclusions Patients with a walled-off retrogastric collection and an isolated viable tail are effectively managed by a transgastric approach. Despite this seemingly “unstable anatomy,” the creation of an internal fistula via surgical or endoscopic “cystgastrostomy” avoids external fistulas/drains and the short-term necessity of surgical distal pancreatectomy. A very small subset requires intervention for late symptoms.

Coronary artery anomalies have been reported in Bulldogs and present an increased risk when performing balloon valvuloplasty. Identification of coronary anomalies has been reported using multidetector-row computed tomographic (MDCT) angiography with electrocardiographic gating. However, the utility of non-electrocardiographic-gated 16-row computed tomographic for MDCT for the identification of coronary artery anatomy or anomalies to the authors' knowledge has not been fully investigated. The purpose of this study was to evaluate the feasibility of non-electrocardiographic-gated computed tomographic (CT) angiography to identify coronary anomalies in Bulldogs with pulmonary valve stenosis. In this prospective, observational study, Bulldogs with echocardiographically diagnosed pulmonary valve stenosis, an echocardiographically derived transpulmonic pressure gradient >70 mm Hg, and a clinician recommendation for balloon valvuloplasty were included. Anesthetized dogs underwent a 16-row MDCT non-electrocardiographic-gated CT angiography. A board-certified veterinary radiologist and board-certified veterinary cardiologist reviewed the CT angiography studies and identified the coronary artery anatomy. When normal coronary artery anatomy was detected on CT angiography, a right ventricular outflow tract fluoroscopic angiogram was performed and evaluated during levophase to confirm normal coronary anatomy prior to balloon valvuloplasty. Dogs with coronary anomalies noted on CT angiography were recovered from anesthesia and balloon valvuloplasty was not performed. All dogs (10/10; 100%) had interpretable images from the non-electrocardiographic-gated CT angiography. Coronary anomalies were identified in six dogs based on non-electrocardiographic-gated CT angiography, five with type R2A anomaly and one had a single left coronary ostium. Four dogs had normal coronary anatomy based on non-electrocardiographic-gated CT angiography. Balloon valvuloplasty was performed without incident in these four dogs. We conclude that non-electrocardiographic-gated CT angiography represents a noninvasive method for diagnosing coronary anomalies in Bulldogs with pulmonary valve stenosis.

Left ventricular (LV) and left atrial (LA) enlargement affect management and outcome of dogs with cardiac disease. Short-axis, two-dimensional echocardiographic (2DE) images, indexed to the aorta (Ao), are frequently used to identify cardiomegaly. Long-axis images offer complementary views of the left heart.Eighty healthy dogs and 25 dogs with MMVD.Healthy dogs were prospectively recruited to determine reference intervals (Clinical Laboratory Standards Institute methodology) for long-axis ratios. Measurement variability and repeatability were quantified by intraclass correlation coefficient and coefficient of variation. Mean long-axis ratios from dogs with MMVD were compared with healthy dogs (unpaired t-test). In addition, the proportion of MMVD dogs exceeding the 97.5 percentile by LV/Ao and a conventional, allometric method were compared (McNemar's test).Two-dimensional echocardiographic long-axis reference intervals were as follows: left ventricular to aortic dimension (LV/Ao) 1.8-2.5; left atrial to aortic dimension (LA/Ao) 1.8-2.4, and left atrial to left ventricular dimension (LA/LV) 0.9-1.1. Intraobserver and interobserver measurement agreement was good-to-excellent (intraclass correlation coefficients ≥0.84), and day-to-day variability was low (coefficient of variations4%). Left ventricular to aortic dimension, LA/Ao, and LA/LV were significantly greater in canine MMVD compared with healthy dogs (p0.001). The percentages of MMVD dogs demonstrating LV dilatation by LV/Ao and conventional method were 68% and 36%, respectively (p=0.043, 95% confidence interval for difference 7.9%, 56.1%).Simple 2DE long-axis ratios of LV/Ao, LA/Ao, and LA/LV are repeatable and demonstrate clinical utility for identifying LV and LA enlargement in dogs with MMVD.

Author(s): Nishimura, Satoko; Visser, Lance C; Belanger, Catherine; Oldach, Maureen S; Gunther-Harrington, Catherine T; Stern, Joshua A | Abstract: BackgroundVelocity ratio, velocity time integral (VTI) ratio, and pulmonary valve area indexed to body surface area (iPVA) are methods of assessment of pulmonary valve stenosis (PS) severity that are less dependent on blood flow. Studies evaluating these methods are limited.ObjectivesTo determine the effects of butorphanol, atenolol, and balloon valvuloplasty (BV) on velocity ratio, VTI ratio, iPVA, mean PG, and max PG.AnimalsTwenty-seven dogs with PS (max PG g50 mm Hg).MethodsProspective study. All dogs underwent an echocardiogram at baseline, 5-minutes after administration of butorphanol (0.2-0.25 mg/kg IV), and 2-to-4 weeks after atenolol (1-1.5 mg/kg q12h). Twenty-one of these were evaluated 24-hours after BV.ResultsThere were no significant differences (P g .05) amongst any of the methods of assessment of PS severity after butorphanol. After atenolol, mean (SD) of mean (57.0 [21.0] mm Hg) and max PG (93.1 [33.8] mm Hg) were significantly decreased (P ≤ .047) compared with baseline (65.2 [26.2] mm Hg and 108 [44.4] mm Hg, respectively). After atenolol, there were no significant (P ≥ .12) differences in velocity ratio (0.29 [0.09]), VTI ratio (0.18 [0.05]), or iPVA (0.43 [0.16] cm2 /m2 ) compared with baseline (0.30 [0.09], 0.19 [0.09], 0.44 [0.17] cm2 /m2 , respectively).Conclusions and clinical importanceAtenolol might reduce mean and max PG but does not alter less flow-dependent methods of assessment of PS severity (velocity ratio, VTI ratio, and iPVA) in dogs with PS. Results support an integrative approach to assessment of PS severity that includes less flow-dependent methods, particularly in states of altered flow or right ventricular function.

To determine the role of reoperation in patients with persistent or recurrent Zollinger-Ellison Syndrome (ZES).Approximately, 0% to 60% of ZES patients are disease-free (DF) after an initial operation, but the tumor may recur.A prospective database was queried.A total of 223 patients had an initial operation for possible cure of ZES and then were subsequently evaluated serially with cross sectional imaging-computed tomography, magnetic resonance imaging, ultrasound, more recently octreoscan-and functional studies for ZES activity. The mean age at first surgery was 49 years and with an 11-year mean follow-up 52 patients (23%) underwent reoperation when ZES recurred with imageable disease. Results in this group are analyzed in the current report. Reoperation occurred on a mean of 6 years after the initial surgery with a mean number of reoperations of 1 (range 1-5). After reoperation 18/52 patients were initially DF (35%); and after a mean follow-up of 8 years, 13/52 remained DF (25%). During follow-up, 9/52 reoperated patients (17%) died, of whom 7 patients died a disease-related death (13%). The overall survival from first surgery was 84% at 20 years and 68% at 30 years. Multiple endocrine neoplasia type 1 status did not affect survival, but DF interval and liver metastases did.These results demonstrate that a significant proportion of patients with ZES will develop resectable persistent or recurrent disease after an initial operation. These patients generally have prolonged survival after reoperation and 25% can be cured with repeat surgery, suggesting all ZES patients postresection should have systematic imaging, and if tumor recurs, advise repeat operation.

Objectives We review our institution's experience in treating leiomyosarcomas involving the inferior vena cava, and we offer guidance on the management. Methods A text-based search was performed to identify all patients who underwent surgical resection between January 2002 and October 2020. Clinicopathologic data, intraoperative variables, and outcomes were extracted from chart review. Results Twelve of 16 patients (75%) had localized disease; the remaining had limited metastatic disease. Seven of 16 patients (44%) received neoadjuvant chemotherapy or radiation; three patients had partial responses, and four patients had stable disease using RECIST 1.1 criteria. IVC reconstruction was performed in 14 of 16 patients (88%); IVC was ligated for the remaining two patients. Half of all patients had R0 resection on final pathology; the remaining had R1 resections. Progression-free survival (PFS) and overall survival (OS) were not statistically different between patients with R0 and R1 resection. Median PFS was 1.8 years (95% CI 0.89 - not reached); median OS was 6.5 years (1.8 - not reached). Only one patient (6%) experienced local disease recurrence; 4 of 16 patients (25%) experienced disease recurrence distally without local recurrence. Conclusions Resection of IVC leiomyosarcomas at a sarcoma referral center with experience in vascular reconstruction can lead to many years of recurrence-free survival. Surgical resection should be offered to patients with a low volume of metastatic disease to reduce local complications from the primary tumor, many of which exert significant mass effect on surrounding organs. For patients with metastatic disease or large, high-risk tumors, neoadjuvant chemotherapy can provide a biologic test of disease stability prior to resection.

Purpose: Traumatic brain injury (TBI) is a major cause of trauma-related visits to emergency departments (ED). Determination of monitoring requirements of patients with apparently mild TBI is challenging. Patients may turn out to be more severely injured than initially assumed, and failure to identify these patients constitutes a serious threat to patient safety. We, therefore, aimed to identify clinical risk factors for more severe injuries in patients with apparently mild TBI.Methods: In a retrospective cohort analysis performed at two level I trauma centers, 808 patients aged 16 presenting to the ED with head trauma and a Glasgow Coma Scale (GCS) score 13-15 who received a head CT scan were studied. Discrepancies between the initial TBI severity as determined by GCS and severity as determined post hoc by the Head Abbreviated Injury Score were assessed. Multiple logistic regression was used to identify risk factors of such discrepancies.Results: 104 (12.9%) patients were more severely injured than initially classified. A GCS Conclusions: Six risk factors of more severe injury in patients presenting with apparently mild TBI were identified. Patients with any of these factors should be thoroughly monitored for signs of neurologic deterioration.

Background The best operative strategy for necrotizing pancreatitis remains controversial. Traditional surgical necrosectomy is associated with significant morbidity; endoscopic and percutaneous strategies require repeated interventions with prolonged hospitalizations. We have developed a transgastric approach to pancreatic necrosectomy to overcome the shortcomings of the other techniques described. Materials and methods Patients with necrotizing pancreatitis treated from 2009 to 2016 at an academic center were retrospectively reviewed. Open or laparoscopic transgastric necrosectomy was performed if the area of necrosis was walled-off and in a retrogastric position on cross-sectional imaging. Study endpoints included postoperative complications and mortality. Results Forty-six patients underwent transgastric necrosectomy (nine open and 37 laparoscopic). Median (interquartile range) preoperative Acute Physiologic and Chronic Health Evaluation II score was 6 (3-12). Seventy percent of patients had >30% necrosis on preoperative imaging; infected necrosis was present in 35%. Median total length of stay (LOS) was 6 (3-12) d. No patient required a second operative debridement; four patients (9%) had short-term postoperative percutaneous drainage for residual fluid collections. Median follow-up was 1 y; there were no fistula or wound complications. Six patients (13%) had postoperative bleeding; five patients received treatment by image-guided embolization. There was one death in the cohort. Conclusions Transgastric pancreatic necrosectomy allows for effective debridement with a single definitive operation. When anatomically suitable, this operative strategy offers expedited recovery and avoids long-term morbidity associated with fistulas and prolonged drainage.

Objective: To evaluate the effects of a multifaceted Treatment for Social cognition and Emotion regulation (T-ScEmo) in patients with a traumatic brain injury. Participants: Sixty-one patients with moderate to severe traumatic brain injury randomly assigned to an experimental T-ScEmo intervention or a Cogniplus control condition. Interventions: T-ScEmo is a compensatory strategy training for impairments in emotion recognition, theory of mind, and social behavioral skills. Cogniplus is a computerized cognitive function training. Both interventions were given in 16 to 20 weekly 1-hour sessions. Main Measures: Social cognition tests and questionnaires for social behavior (self-and proxy-rated) administered at baseline, immediately posttreatment, and at 3 to 5 months of follow-up. Results: Compared with the Cogniplus group, the T-ScEmo group improved significantly on facial affect recognition, theory of mind, proxy-rated empathic behavior, societal participation, and treatment goal attainment, which lasted up to 5 months after treatment. At follow-up, the T-ScEmo group also reported higher quality of life and their life partners rated relationship quality to be higher than the Cogniplus group. Conclusion: This study shows that impairments in social cognition can be effectively dealt with by using a comprehensive treatment protocol, leading to improvements in everyday life social functioning.

Objective The objectives of this study were to model more homogeneous subgroups within autism spectrum disorder (ASD) based on early trajectories of core symptoms; and to further characterize these subgroups in terms of trajectories of language, cognition, co-occurring (attention-deficit/hyperactivity disorder [ADHD]–related) traits and clinical outcome diagnosis. Method Children (N = 203) referred for possible ASD at ages 1 to 4 years were assessed at three time points at intervals ranging from 9 months to 3 years. Assessments included standardized measures for ASD (Autism Diagnostic Observation Schedule [ADOS]), language (ADOS-language item), nonverbal IQ (NV-IQ; different tests adequate to chronological/mental age), and parent-reported behavioral problems (Infant-Toddler Social and Emotional Assessment, Child Behavior Checklist). Results Latent-class growth curve analysis with ADOS total scores led to the identification of three main stable and two small improving groups: a severe–stable group (19.5% of sample)—the only group without considerable language improvement—showed persistent low NV-IQ and marked increase in attention problems over time; a moderate–stable group (21.7%) with below-average increasing NV-IQ; and a mild–stable group (48%) with stable–average NV-IQ and the highest scores on ADHD-related traits, whose ASD outcome diagnoses increased despite stable–low ASD scores. Two groups (each 5.4%) improved: one moved from severe to moderate ASD scores, and the other moved from moderate to mild/nonspectrum scores. Both of these groups improved on language, NV-IQ, and ADHD-related traits. Conclusion Results support the high stability of ASD symptoms into various severity levels, but also highlight the significant contribution of non-ASD domains in defining and explaining the different ASD trajectories.

Background and Purpose— High blood pressure (BP) is associated with poor outcome and the occurrence of symptomatic intracranial hemorrhage in acute ischemic stroke. Whether BP influences the benefit or safety of intra-arterial treatment (IAT) is not known. We aimed to assess the relation of BP with functional outcome, occurrence of symptomatic intracranial hemorrhage and effect of IAT. Methods— This is a post hoc analysis of the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands). BP was measured at baseline, before IAT or stroke unit admission. We estimated the association of baseline BP with the score on the modified Rankin Scale at 90 days and safety parameters with ordinal and logistic regression analysis. Effect of BP on the effect of IAT was tested with multiplicative interaction terms. Results— Systolic BP (SBP) had the best correlation with functional outcome. This correlation was U-shaped; both low and high baseline SBP were associated with poor functional outcome. Higher SBP was associated with symptomatic intracranial hemorrhage (adjusted odds ratio, 1.25 for every 10 mm Hg higher SBP [95% confidence interval, 1.09–1.44]). Between SBP and IAT, there was no interaction for functional outcome, symptomatic intracranial hemorrhage, or other safety parameters; the absolute benefit of IAT was evident for the whole SBP range. The same was found for diastolic BP. Conclusions— BP does not affect the benefit or safety of IAT in patients with acute ischemic stroke caused by proximal intracranial vessel occlusion. Our data provide no arguments to withhold or delay IAT based on BP. Clinical Trial Registration— URL: http://www.isrctn.com . Unique identifier: ISRCTN10888758.

Fibrodysplasia ossificans progressiva (FOP) is an autosomal dominant disease, characterized by the formation of heterotopic ossification (HO) in muscles, ligaments, and tendons. Flare-ups, an inflammatory process that often precedes the formation of HO, can occur spontaneously, but trauma is also a common trigger. It is not known whether radiotherapy, especially in higher doses, might cause sufficient trauma or inflammation to trigger a flare-up and subsequent HO in FOP patients. We report the case of a patient undergoing radiotherapy for the treatment of a 1-cm-wide basal cell carcinoma (BCC) of the lower lip. In addition, we present a systematic review of the available literature. Our patient received 54 Gy in 18 fractions with orthovoltage therapy, resulting in a clinical complete response of the tumor. Six months after treatment, there were no signs of HO either clinically or on [18F]NaF PET/CT. The systematic review identified 11 publications describing either radiation treatment in FOP or radiation therapy as a cause of HO in non-FOP patients. Six case reports described the use of radiation in FOP patients for various reasons, including one with a high-dose treatment of a lip BCC using superficial X-ray therapy. The remaining five studies described the use of low-dose radiotherapy to prevent or treat either an FOP flare-up or HO formation. None of these cases showed worsening of disease that could be attributed to the use of radiation therapy. Radiation induced HO in non-FOP patients was rare and occurred in five studies. The largest of these studies suggested that HO was induced after treatment with high doses, resulting in more widespread evidence of tissue damage, potentially being the end result of this damage. In conclusion, available reports suggest no contraindication to radiotherapy in FOP patients; although the number of cases was small, systematic toxicity reports often were not available, and none of the reports described high-dose, high-energy radiation treatment at locations such as muscle and joint regions.

Background In a previous feasibility study (APROPOS) in a single municipality of the Netherlands, we showed that a locally tailored preconception care (PCC) approach has the potential to positively affect preconceptional lifestyle behaviours. Therefore, we designed a second study (APROPOS-II) to obtain a more robust body of evidence: a larger group of respondents, more municipalities, randomization, and a more comprehensive set of (clinical) outcomes. The aim of this study is to assess the effectiveness and the implementation process of a local PCC-approach on preconceptional lifestyle behaviours, health outcomes and the reach of PCC among prospective parents and healthcare providers. Methods This study is an effectiveness-implementation hybrid type 2 trial. This involves a stepped-wedge cluster randomized controlled trial design aiming to include over 2000 future parents from six municipalities in the Netherlands. The intervention has a dual-track approach, focusing on both the uptake of PCC among future parents and the provision of PCC by healthcare providers. The PCC-approach consists of 1) a social marketing strategy directed towards prospective parent(s) and 2) a local care pathway to improve interdisciplinary collaboration. Data will be collected before and after the introduction of the intervention through questionnaires and medical records in each of the participating municipalities. The primary outcome of this study is change in lifestyle behaviours (e.g. folic acid use, smoking and alcohol use). Secondary outcomes are pregnancy outcomes (e.g. miscarriage, preterm birth, gestational diabetes) and the uptake of PCC. Moreover, a process evaluation will be performed, providing information on the efficacy, feasibility, barriers and facilitators regarding the implementation of the intervention. Discussion The APROPOS-II study introduces a locally tailored PCC-approach in six municipalities in the Netherlands that will contribute to the body of evidence regarding the effectiveness of PCC and its implementation. If this intervention has a positive effect on lifestyle behaviour changes, leading to improved pregnancy outcomes and the future health of prospective parents and their offspring, it could subsequently be upscaled to (inter)national implementation. Trial registration Dutch Trial register: NL7784 (Registered June 6th, 2019).

Background Patients with migraine might be more susceptible of spreading depolarizations, which are known to affect vascular and neuronal function and penumbra recovery after stroke. We investigated whether these patients have more severe stroke progression and less favorable outcomes after recanalization therapy. Methods We included patients from a prospective multicenter ischemic stroke cohort. Lifetime migraine history was based on the International Classification of Headache Disorders II criteria. Patients without confirmed migraine diagnosis were excluded. Patients underwent CT angiography and CT perfusion Results We included 600 patients of whom 43 had migraine. There were no differences between patients with or without migraine in presence of a perfusion deficit on admission (aRR: 0.98, 95%CI: 0.77–1.25), infarct core volume (aB: -10.8, 95%CI: -27.04–5.51), penumbra volume (aB: -11.6, 95%CI: -26.52–3.38), mean blood brain barrier permeability (aB: 0.08, 95%CI: -3.11–2.96), malignant edema (0% vs. 5%), hemorrhagic transformation (aRR: 0.26, 95%CI: 0.04–1.73), final infarct volume (aB: -14.8, 95%CI: 29.9–0.2) or outcome after recanalization therapy (mRS > 2, aRR: 0.50, 95%CI: 0.21–1.22). Conclusion Elderly patients with a history of migraine do not seem to have more severe stroke progression and have similar treatment outcomes compared with patients without migraine.

ObjectivesElectronic dance music (EDM) concerts are becoming increasingly popular. Strong stroboscopic light effects are commonly part of these shows, and may provoke seizures in individuals with photosensitive epilepsy. This study aims to examine the risk of epileptic seizures during EDM concerts.Setting28 EDM concerts taking place in The Netherlands.ParticipantsWe describe a young man who experienced a seizure during an EDM concert, and who later showed a positive electroencephalographic provocation test during exposure to video footage of the same concert. Subsequently, we performed a cohort study of 400 343 visitors to EDM concerts, divided in those exposed (concert occurring in darkness) versus unexposed (concert in daylight) to stroboscopic light effects.ResultsIn total, 400 343 EDM concert visitors were included: 241 543 (representing 2 222 196 person hours) in the exposed group and 158 800 (representing 2 334 360 person hours) in the control group. The incidence density ratio of epileptic seizures in exposed versus unexposed individuals was 3.5 (95% CI: 1.7 to 7.8; pConclusionStroboscopic light effects during EDM concerts occurring in darkness probably more than triple the risk of epileptic seizures. Concert organisers and audience should warn against the risk of seizures and promote precautionary measures in susceptible individuals.

We sought to determine the prevalence and clinical significance of right heart remodeling and right ventricular (RV) dysfunction in dogs with pulmonary valve stenosis (PS). We also sought to evaluate repeatability of several measurements of severity of PS, right heart size, and RV function in dogs with PS.Several indices of right atrial (RA) size and RV size and function were prospectively evaluated in 48 dogs with PS. Regression analysis was used to determine if indices of right heart size and function were independently associated with maximum transpulmonary pressure gradient (max PG) and adverse clinical findings (exercise intolerance, syncope, or right heart failure). Eight dogs underwent a second echocardiogram performed by the same operator to assess repeatability of the echocardiographic indices, which was quantified by coefficient of variation (CV) and repeatability coefficient.Increased RA size (81%), increased RV wall thickness (83%), and decreased tricuspid annular plane systolic excursion (TAPSE [81%]) were common. Right atrial size, end-diastolic RV area, and RV wall thickness were independently associated with max PG. Decreased TAPSE was independently associated with adverse clinical findings. All indices except RA area (18.6%) and RV systolic velocity (20.7%) had CVs15%. Repeatability coefficients are available to help distinguish a true change versus measurement variability during serially obtained exams.Right heart remodeling and RV dysfunction are common in dogs with PS and are associated with echocardiographic and clinical severity. Results support the quantitative assessment of right heart size and function in dogs with PS.

Pulmonary hypertension (PH) is a common clinical condition associated with morbidity and mortality in both humans and dogs. Sildenafil, a phosphodiesterase-5 (PDE5) inhibitor causing accumulation of cGMP, is frequently used for treatment of PH. The authors previously reported a PDE5A:E90K polymorphism in dogs that results in lower basal cyclic guanosine monophosphate (cGMP) concentrations than in wild-type dogs, which could contribute to variability in the efficacy of sildenafil. In this study, response to sildenafil therapy was evaluated in dogs with PH by comparing echocardiographic parameters, quality-of-life (QOL) score, and plasma cGMP concentrations before and after sildenafil therapy. Overall, tricuspid regurgitation estimated systolic pressure gradient (PG) and QOL score were significantly improved after sildenafil therapy, and the plasma cGMP concentration was significantly decreased. Dogs that had a heterozygous PDE5A status had a significantly worse QOL score when compared to the wildtype group after sildenafil treatment. The simple and multiple regression analyses revealed a significant but weak prediction for the percent reduction in QOL score with sildenafil treatment by plasma cGMP level and by the PDE5A:E90K polymorphic status. This study showed that sildenafil treatment improved PH in dogs, and the PDE5A:E90K polymorphism blunted the efficacy of sildenafil in terms of QOL improvement.

Purpose: Many patients with mild traumatic brain injury do not fully return to work owing to persistent posttraumatic complaints. Research suggests that preventing chronic complaints might be prevented by giving cognitive behavioral therapy early after injury. Therefore, a new cognitive behavioral intervention (UPFRONT-intervention) was developed to not only prevent chronic complaints but to also establish a more successful return to work. The intervention is currently being evaluated in a multicenter randomized controlled trial design (trial number ISRCTN86191894) in mild traumatic brain injury patients who are at-risk of negative outcomes (patients with high numbers of early complaints). Two case examples are presented to demonstrate the application of the intervention. Rationale: Psychological factors, like cognitive appraisal and coping, play an important role in the persistence of posttraumatic complaints. Some patients are less able to adapt and thus to cope with the injury and its initial consequences than others. Dealing with the injury in a passive, avoidant way, focusing on negative feelings, will hamper recovery and is therefore a valuable target for an intervention. Theory into practice: The UPFRONT intervention is a short cognitive behavioral therapy intervention for patients that are at-risk of developing persistent posttraumatic complaints. Patients will undergo five sessions of cognitive behavioral therapy within 4–10 weeks after trauma. The intervention aims to enhance patients’ feeling of competency of dealing with the consequences of mild traumatic brain injury by providing psycho-education, identifying and challenging unrealistic illness perceptions and improving coping style (decreasing maladaptive coping and enhancing adaptive coping).

The aim of this study was to compare the American Gastroenterological Association guidelines (AGA criteria), the 2012 (Fukuoka criteria), and 2006 (Sendai criteria) International Consensus Guidelines for the diagnosis of advanced pancreatic cystic neoplasms. All patients who underwent surgical resection of a pancreatic cyst from August 2007 through January 2016 were retrospectively analyzed at a single tertiary academic center. Relevant clinical and imaging variables along with pathology results were collected to determine appropriate classification for each guideline. Advanced pancreatic cystic neoplasms were defined by the presence of either high-grade dysplasia or cystic adenocarcinoma. Diagnostic accuracy was measured by ROC analysis. A total of 209 patients were included. Both the AGA and Fukuoka criteria had a higher diagnostic accuracy for advanced neoplastic cysts than the Sendai criteria: AGA ROC 0.76 (95% CI 0.69–0.81), Fukuoka ROC 0.78 (95% CI 0.74–0.82), and Sendai ROC 0.65 (95% CI 0.61–0.69) (p

Background and Purpose— A high clot burden score (CBS) is associated with favorable outcome after intravenous treatment for acute ischemic stroke. The added benefit of intra-arterial treatment might be less in these patients. The aim of this exploratory post hoc analysis was to assess the relation of CBS with neurological improvement and endovascular treatment effect. Methods— For 499 of 500 patients in the MR CLEAN study (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands), the CBS was determined. Ordinal logistic regression models with and without main baseline prognostic variables were used to assess the association between CBS (continuous or dichotomized at CBS of 6) and a shift toward better outcome on the modified Rankin Scale. The model without main baseline prognostic variables only included treatment allocation and CBS. Models with and without a multiplicative interaction term of CBS and treatment were compared using the χ 2 test to assess treatment effect modification by CBS. Results— Higher CBS was associated with a shift toward better outcome on the modified Rankin Scale; adjusted common odds ratio per point CBS was 1.12 (95% confidence interval, 1.04–1.20]. Dichotomized CBS had an adjusted common odds ratio of 1.67 (95% confidence interval, 1.12–2.51). Both effect estimates were slightly attenuated by adding baseline prognostic variables. The addition of the interaction terms did not significantly improve the fit of the models. There was a small and insignificant increase of intra-arterial treatment efficacy in the high CBS group. Conclusions— A higher CBS is associated with improved outcome and may be used as a prognostic marker. We found no evidence that CBS modifies the effect of intra-arterial treatment. Clinical Trial Registration— URL: http://www.trialregister.nl . Unique identifier: NTR1804. URL: http://www.controlled-trials.com . Unique identifier: ISRCTN10888758.

The risk of postoperative adverse events in patients with underlying cardiac disease undergoing major hepatectomy remains poorly characterized.The NSQIP database was used to identify patients undergoing hemihepatectomy and trisectionectomy. Patient characteristics and postoperative outcomes were evaluated.From 2005 to 2012, 5227 patients underwent major hepatectomy. Of those, 289 (5.5%) had prior major cardiac disease: 5.6% angina, 3.1% congestive heart failure, 1% myocardial infarction, 54% percutaneous coronary intervention, and 46% cardiac surgery. Thirty-day mortality was higher in patients with cardiac comorbidity (6.9% vs. 3.7%, P = 0.008), including the incidence of postoperative cardiac arrest requiring cardiopulmonary resuscitation (3.8% vs. 1.2%, P = 0.001) and myocardial infarction (1.7% vs. 0.4%, P = 0.011). Multivariate analysis revealed that functional impairment, older age, and malnutrition, but not cardiac comorbidity, were significant predictors of 30-day mortality. However, prior percutaneous coronary intervention was independently associated with postoperative cardiac arrest (OR 2.999, P = 0.008).While cardiac comorbidity is not a predictor of mortality after major hepatectomy, prior percutaneous coronary intervention is independently associated with postoperative cardiac arrest. Careful patient selection and preoperative optimization is fundamental in patients with prior percutaneous coronary intervention being considered for major hepatectomy as restrictive fluid management and low central venous pressure anesthesia may not be tolerated well by all patients.

Key Points Question What are the outcomes of patients who undergo aggressive resection of locally advanced pancreatic neuroendocrine tumors (PNETs)? Findings In this case series, 99 patients with locally advanced (T3/T4) PNETs and no known distant metastatic disease who underwent resection had a recurrence rate of 35%, but their quality of life remained high, and the overall 5-year survival was 91%. Meaning These findings suggest that locally advanced PNETs warrant aggressive surgical resection, including local organs and blood vessels, if necessitated by tumor invasion., This case series examines data from 2003 to 2018 regarding patients who underwent aggressive resection operative treatment for locally advanced pancreatic neuroendocrine tumors and their outcomes in terms of disease recurrence, quality of life, and overall 5-year survival., Importance Although outcome of surgical resection of liver metastases from pancreatic neuroendocrine tumors (PNETs) has been extensively studied, little is known about surgery for locally advanced PNETs; it was listed recently by the European neuroendocrine tumor society as a major unmet need. Objective To evaluate the outcome of patients who underwent surgery for locally aggressive PNETs. Design, Setting, and Participants This retrospective single-center case series reviewed consecutive patients who underwent resection of T3/T4 PNETs at a single academic institution. Data collection occurred from 2003 to 2018. Data analysis was performed in August 2019. Main Outcomes and Measures Disease-free survival (primary outcome) and overall mortality (secondary outcome) were assessed with Kaplan-Meier analysis. Recurrence risk (secondary outcome, defined as identification of tumor recurrence on imaging) was assessed with Cox proportional hazard models adjusting for covariates. Results In this case series, 99 patients with locally advanced nondistant metastatic PNET (56 men [57%]) with a mean (SEM) age of 57.0 (1.4) years and a mean (SEM) follow-up of 5.3 (0.1) years underwent surgically aggressive resections. Of those, 4 patients (4%) underwent preoperative neoadjuvant treatment (including peptide receptor radionuclide therapy and chemotherapy); 18 patients (18%) underwent pancreaticoduodenectomy, 68 patients (69%) had distal or subtotal pancreatic resection, 10 patients (10%) had total resection, and 3 patients (3%) had other pancreatic procedures. Additional organ resection was required in 86 patients (87%): spleen (71 patients [71%]), major blood vessel (17 patients [17%]), bowel (2 patients [2%]), stomach (4 patients [4%]), and kidney (2 patients [2%]). Five-year disease-free survival was 61% (61 patients) and 5-year overall survival was 91% (91 patients). Of those living, 75 patients (76%) had an Eastern Cooperative Oncology Group score of less than or equal to 1 at last followup. Lymph node involvement (HR, 7.66; 95% CI, 2.78-21.12; P

Background: Many patients with moderate to severe traumatic brain injury have deficits in social cognition. Social cognition refers to the ability to perceive, interpret, and act upon social information. Few studies have investigated the effectiveness of treatment for impairments of social cognition in patients with traumatic brain injury. Moreover, these studies have targeted only a single aspect of the problem. They all reported improvements, but evidence for transfer of learned skills to daily life was scarce. We evaluated a multifaceted treatment protocol for poor social cognition and emotion regulation impairments (called T-ScEmo) in patients with traumatic brain injury and found evidence for transfer to participation and quality of life. Purpose: In the current paper, we describe the theoretical underpinning, the design, and the content of our treatment of social cognition and emotion regulation (T-ScEmo). Theory into practice: The multifaceted treatment that we describe is aimed at improving social cognition, regulation of social behavior and participation in everyday life. Some of the methods taught were already evidence-based and derived from existing studies. They were combined, modified, or extended with newly developed material. Protocol design: T-ScEmo consists of 20 one-hour individual sessions and incorporates three modules: (1) emotion perception, (2) perspective taking and theory of mind, and (3) regulation of social behavior. It includes goal-setting, psycho-education, function training, compensatory strategy training, self-monitoring, role-play with participation of a significant other, and homework assignments. Recommendations: It is strongly recommended to offer all three modules, as they build upon each other. However, therapists can vary the time spent per module, in line with the patients’ individual needs and goals. In future, development of e-learning modules and virtual reality sessions might shorten the treatment.

OBJECTIVE To describe vertebral left atrial size (VLAS), a quantitative method to estimate left atrial (LA) size radiographically, and to determine its diagnostic value for prediction of echocardiographic LA enlargement in dogs with myxomatous mitral valve disease (MMVD) of varying severity. DESIGN Prospective observational study. ANIMALS 103 client-owned dogs with a left-sided systolic murmur. PROCEDURES For each dog, 3-view thoracic radiographs were obtained within 24 hours of an echocardiographic examination. The VLAS was measured on right and left lateral thoracic radiographs and compared with the left atrium-to-aortic root ratio acquired from short-axis (LA:AoSx) and long-axis (LA:AoLx) echocardiographic images. Left atrial enlargement was defined as an LA:AoLx ≥ 2.6 or LA:AoSx ≥ 1.6. Dogs were allocated to 4 groups on the basis of MMVD severity. RESULTS Of the 103 dogs, 15, 40, 26, and 22 were assigned to the control (no echocardiographic abnormalities), stage B1 (hemodynamically irrelevant MMVD), B2 (hemodynamically relevant MMVD), and C-D (MMVD with congestive heart failure) groups, respectively. Median VLAS, LA:AoSx, and LA:AoLx for the stage B2 and C-D groups were significantly greater than the corresponding medians for the control and stage B1 groups. There was a moderate positive correlation between VLAS and both LA:AoSx and LA:AoLx. Receiver operating characteristic analyses revealed that a VLAS ≥ 2.3 vertebrae was a useful predictor of LA enlargement. Intraobserver and interobserver agreements for VLAS measurements were high. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated VLAS was a repeatable and useful radiographic measurement for prediction of LA enlargement in dogs with MMVD.

Background Sotalol is a commonly used antiarrhythmic drug that may alter ventricular function. Objective To determine the effect of sotalol on echocardiographic indices of ventricular systolic function in dogs with ventricular arrhythmias. Animals Thirty-five client-owned dogs with ventricular arrhythmias. Methods Dogs with ventricular arrhythmias (n = 27) had an echocardiogram and 5-minute ECG performed at baseline and 2-4 hours post-sotalol (2-2.5 mg/kg PO once). Eight additional dogs underwent the same protocol but did not receive sotalol (within-day variability controls). Left ventricular (LV) internal dimension at end-systole normalized to bodyweight (LVIDs_N), LV ejection fraction (LV EF), LV shortening area, LV fractional shortening, tricuspid annular plane systolic excursion (TAPSE), and right ventricular systolic myocardial velocity were evaluated as indices of systolic function. Results All indices except TAPSE had mild decreases in systolic function post-sotalol (all P ≤ .0007) compared with baseline but only the percent change in LVIDs_N and LV EF were significantly (P ≤ .0079) different from the percent change of the same indices in control dogs. Sinus heart rate, ventricular premature complexes/5-minutes, and arrhythmia grade also were decreased post-sotalol (all P ≤ .01) compared with baseline when assessed by a 5-minutes ECG. No dog experienced an adverse event post-sotalol, including dogs with systolic dysfunction or atrial enlargement. Conclusions and clinical importance A single dose of sotalol may cause a mild decrease in LV systolic function in dogs with ventricular arrhythmias. Sotalol appears to be well tolerated, even in dogs with atrial enlargement or systolic dysfunction.

Contains fulltext : 203257.pdf (Publisher’s version ) (Open Access) This longitudinal study focused on early behavioural problems and autistic traits. In a stratified, population-derived sample of 119 children, mothers reported through questionnaires on externalizing, internalizing, and social-communicative characteristics of their child in infancy (14 months) and toddlerhood (37 months), and on autistic traits at preschool age (4-5 years). Children with consistently normal behaviour from infancy to toddlerhood showed lower autistic traits at preschool age than children with deviant behaviour on one or both time points. High autistic traits at preschool age were predominantly preceded by problems in interaction, communication, language, play, and affect in infancy and/or toddlerhood, but also by inattention in toddlerhood. Adequate support and specific interventions in these domains are needed in an attempt to diminish further derailment of the child's behaviour and development, and to prevent the full manifestation of ASD or related disorders such as ADHD.

Minimally invasive liver surgery is a growing field, and a small number of recent reports have suggested that laparoscopic liver resection (LLR) is feasible even in patients with cirrhosis. However, parenchymal transection of the cirrhotic liver is challenging due to fibrosis and portal hypertension. There is a paucity of data regarding the technical modifications necessary to safely transect the diseased parenchyma. Patients undergoing LLR by a single surgeon between 2008 and 2015 were reviewed. Patients with cirrhosis were compared to those without cirrhosis to examine differences in surgical technique, intraoperative characteristics, and outcomes (including liver-related morbidity and general postoperative complication rates). A total of 167 patients underwent LLR during the study period. Forty-eight (29 %) had cirrhosis, of which 43 (90 %) had hepatitis C. Most had Child–Pugh class A disease (85 %). Compared to noncirrhotics, patients with cirrhosis were older, had more comorbidities, and were more likely to have hepatocellular carcinoma. Precoagulation before parenchymal transection was used more frequently in cirrhotics (65 vs. 15 %, P

The aim of this study was to investigate the impact of statin and metformin therapy on disease outcome for patients with pancreatic ductal adenocarcinoma (PDAC).This retrospective study included 171 PDAC patients who underwent surgical resection at the Stanford Cancer Institute between 1998 and 2013. No patients received neoadjuvant therapy. Statin and metformin use was defined as use during initial consult and continuing upon discharge from the hospital after surgery. Dose of each medication was recorded, as was the type of statin taken.The median follow-up for all patients was 11.23 months (range, 0.2-105.0 months). Among the 171 patients included in our analysis, 18 patients (10.5%) took metformin and 34 patients (19.9%) took statins. Statin use was associated with better overall survival (OS) in patients with PDAC (P = 0.011). Metformin use was also associated with better OS (P = 0.035). The use of statins remained significant on multivariate analysis for OS (P = 0.014; hazards ratio, 0.33; 95% confidence interval, 0.139-0.799), but metformin use did not (P = 0.33; hazards ratio 0.60, 95% confidence interval, 0.211-1.675).Statin and metformin use is associated with improved OS in patients with resectable PDAC. These medications should be further investigated for possible long-term use in the general population.

Background and Purpose— Recent randomized trials have proven the benefit of intra-arterial treatment (IAT) with retrievable stents in acute ischemic stroke. Patients with poor or absent collaterals (preexistent anastomoses to maintain blood flow in case of a primary vessel occlusion) may gain less clinical benefit from IAT. In this post hoc analysis, we aimed to assess whether the effect of IAT was modified by collateral status on baseline computed tomographic angiography in the Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands (MR CLEAN). Methods— MR CLEAN was a multicenter, randomized trial of IAT versus no IAT. Primary outcome was the modified Rankin Scale at 90 days. The primary effect parameter was the adjusted common odds ratio for a shift in direction of a better outcome on the modified Rankin Scale. Collaterals were graded from 0 (absent) to 3 (good). We used multivariable ordinal logistic regression analysis with interaction terms to estimate treatment effect modification by collateral status. Results— We found a significant modification of treatment effect by collaterals ( P =0.038). The strongest benefit (adjusted common odds ratio 3.2 [95% confidence intervals 1.7–6.2]) was found in patients with good collaterals (grade 3). The adjusted common odds ratio was 1.6 [95% confidence intervals 1.0–2.7] for moderate collaterals (grade 2), 1.2 [95% confidence intervals 0.7–2.3] for poor collaterals (grade 1), and 1.0 [95% confidence intervals 0.1–8.7] for patients with absent collaterals (grade 0). Conclusions— In MR CLEAN, baseline computed tomographic angiography collateral status modified the treatment effect. The benefit of IAT was greatest in patients with good collaterals on baseline computed tomographic angiography. Treatment benefit appeared less and may be absent in patients with absent or poor collaterals. Clinical Trial Registration— URL: http://www.trialregister.nl and http://www.controlled-trials.com . Unique identifier: (NTR)1804 and ISRCTN10888758, respectively.