Off-Hours Presentation, Door-to-Balloon Time, and Clinical Outcomes in Patients Referred for Primary Percutaneous Coronary Intervention.

OBJECTIVES: Presentation with ST-segment-elevation myocardial infarction (STEMI) during off-hours may impact timely reperfusion and clinical outcomes. We investigated the association between off-hours presentation, door-to-balloon time, and in-hospital mortality in patients with STEMI referred for primary percutaneous coronary intervention (PCI). METHODS: We included consecutive patients referred for primary PCI at the University of Ottawa Heart Institute between July 2004 and December 2017. The off-hours group included patients presenting on weekends, statutory holidays, or between 18:00 to 07:59 hours on weekdays. The on-hours group included patients presenting between 08:00 and 17:59 hours on weekdays. The primary clinical outcome was the adjusted in-hospital mortality. The primary quality-of-care indicator was door-to-balloon time. RESULTS: A total of 5132 patients were included, with 3152 (61.4%) in the off-hours group and 1980 (38.6%) in the on-hours group. The median door-to-balloon time was longer in the off-hours group compared with the on-hours group (102 minutes vs 77 minutes; P<.001), while the median onset-to-door time was similar (P=.40). There was no difference in the rates of in-hospital mortality (3.5% vs 3.0%; P=.32) or in the adjusted mortality (odds ratio, 1.2; 95% confidence interval, 0.8-1.8; P=.44) between off-hours and on-hours groups. However, door-to-balloon time was an independent predictor of in-hospital mortality (P<.01) and off-hours presentation was an independent predictor of longer door-to-balloon time (P<.001), with an excess of 22.1 minutes. CONCLUSION: Patients treated with primary PCI during off-hours had longer door-to-balloon times. Treatment during off-hours was an independent predictor of longer door-to-balloon time and longer door-to-balloon times were associated with higher mortality.

Use of Spinal Cord Stimulators in Patients With Pacemakers or Implantable Cardiac Defibrillators: A Review of Documented Accounts of Interference.

OBJECTIVES: To assess the currently available evidence regarding associations between spinal cord stimulator (SCS) lead type, clinical indications for device placement, and interference between SCSs and cardiac pacemakers (CPMs)/implantable cardioverter-defibrillators (ICDs). STUDY DESIGN: Review of case reports and original research studies assessing the interference between SCS and CPM/ICD. MATERIALS AND METHODS: PubMed and Cochrane databases were searched for articles commenting on the interference between SCS and CPM/ICD. The search criteria which generated the greatest number of relevant studies was (spinal cord stimulator AND [pacemaker OR implantable cardioverter defibrillator]). Additional, empiric review was conducted using JSTOR, ScienceDirect, and EBSCOhost databases; however, no additional eligible studies were identified. Data were extracted, summarized into tables, and quantitatively analyzed using LibreTexts and MedCalc software. RESULTS: There was no statistically significant interference observed between SCS and CPM/ICD devices in patients regardless of indication for SCS placement and SCS lead polarity. LIMITATIONS: Limited by variability of patient cases and variability in maximum frequency and amplitude of SCS devices tried in individual cases. Also limited by small sample size and the absence of a standard definition for device interference across studies. CONCLUSIONS: Interference between cardiac devices and SCSs is a rare occurrence. As there are currently no published guidelines, devices should be interrogated on a case-by-case basis in the SCS trial period (if implanted after cardiac device), during permanent implantation, and during scheduled follow-up visits. Peri-operative testing should include increasing the SCS settings to maximally tolerated levels with cardiac device set at its maximum sensitivity.

Outcomes in Patients Stratified by PRECISE-DAPT Versus DAPT Scores After Percutaneous Coronary Interventions.

The optimal length of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) remains debated. Current guidelines recommend individualized treatment with consideration of risk scores. We sought to evaluate the degree of agreement in treatment recommendations and the ability to predict ischemic and bleeding complications of the PRECISE-DAPT (predicting bleeding complications in patients undergoing stent implantation and subsequent dual antiplatelet therapy) and DAPT scores. Consecutive patients receiving 12 months of DAPT were grouped based on score treatment recommendation at the time of PCI: PRECISE-DAPT prolonged or shortened (PRECISE DAPT <25 vs ≥25) and DAPT prolonged or shortened (DAPT ≥2 vs <2). One-year ischemic and bleeding outcomes were compared for each group. In 451 patients, the PRECISE-DAPT and DAPT score recommendations were concordant in 56.7% of patients (Cohen's kappa for agreement of k = 0.139, 95% confidence interval 0.065 to 0.212). There was no difference in composite major adverse cardiovascular and cerebrovascular events between patients with high versus low PRECISE-DAPT or DAPT scores. In patients with a high PRECISE-DAPT score versus a low score, there was an increased incidence of 1-year all-cause mortality (2.13% vs 0%, p = 0.04) and an increase in bleeding (Bleeding Academic Research Consortium ≥3a: 17.0% vs 2.8%; p <0.001; Bleeding Academic Research Consortium 3b/c and 5: 8.5% vs 1.4%; p = 0.001). There were no differences in rates of mortality or bleeding for patients with high versus low DAPT scores. In conclusion, when applied at the baseline, the PRECISE-DAPT and DAPT scores frequently make discordant DAPT duration recommendations. The PRECISE-DAPT, but not the DAPT score, demonstrated associations with all-cause mortality and bleeding in patients prescribed 12 months of DAPT after PCI.

Effect of Moderate vs Mild Therapeutic Hypothermia on Mortality and Neurologic Outcomes in Comatose Survivors of Out-of-Hospital Cardiac Arrest: The CAPITAL CHILL Randomized Clinical Trial.

Importance: Comatose survivors of out-of-hospital cardiac arrest experience high rates of death and severe neurologic injury. Current guidelines recommend targeted temperature management at 32 °C to 36 °C for 24 hours. However, small studies suggest a potential benefit of targeting lower body temperatures. Objective: To determine whether moderate hypothermia (31 °C), compared with mild hypothermia (34 °C), improves clinical outcomes in comatose survivors of out-of-hospital cardiac arrest. Design, Setting, and Participants: Single-center, double-blind, randomized, clinical superiority trial carried out in a tertiary cardiac care center in eastern Ontario, Canada. A total of 389 patients with out-of-hospital cardiac arrest were enrolled between August 4, 2013, and March 20, 2020, with final follow-up on October 15, 2020. Interventions: Patients were randomly assigned to temperature management with a target body temperature of 31 °C (n = 193) or 34 °C (n = 196) for a period of 24 hours. Main Outcomes and Measures: The primary outcome was all-cause mortality or poor neurologic outcome at 180 days. Neurologic outcome was assessed using the Disability Rating Scale, with poor neurologic outcome defined as a score greater than 5 (range, 0-29, with 29 being the worst outcome [vegetative state]). There were 19 secondary outcomes, including mortality at 180 days and length of stay in the intensive care unit. Results: Among 367 patients included in the primary analysis (mean age, 61 years; 69 women [19%]), 366 (99.7%) completed the trial. The primary outcome occurred in 89 of 184 patients (48.4%) in the 31 °C group and in 83 of 183 patients (45.4%) in the 34 °C group (risk difference, 3.0% [95% CI, 7.2%-13.2%]; relative risk, 1.07 [95% CI, 0.86-1.33]; P = .56). Of the 19 secondary outcomes, 18 were not statistically significant. Mortality at 180 days was 43.5% and 41.0% in patients treated with a target temperature of 31 °C and 34 °C, respectively (P = .63). The median length of stay in the intensive care unit was longer in the 31 °C group (10 vs 7 days; P = .004). Among adverse events in the 31 °C group vs the 34 °C group, deep vein thrombosis occurred in 11.4% vs 10.9% and thrombus in the inferior vena cava occurred in 3.8% and 7.7%, respectively. Conclusions and Relevance: In comatose survivors of out-of-hospital cardiac arrest, a target temperature of 31 °C did not significantly reduce the rate of death or poor neurologic outcome at 180 days compared with a target temperature of 34 °C. However, the study may have been underpowered to detect a clinically important difference. Trial Registration: ClinicalTrials.gov Identifier: NCT02011568.

De-escalation of P2Y12 Inhibitor Use After Percutaneous Coronary Intervention and Acute Coronary Syndromes.

BACKGROUND: De-escalation from potent platelet P2Y12 inhibitors to clopidogrel is common. Despite having a clinical rationale, non-bleeding-related de-escalation when a lateral change between potent agents is an option may put patients at increased ischemic risk. We set out to define the scope of P2Y12 inhibitor de-escalation in a large clinical registry and evaluate the potential impact of non-bleeding-related de-escalation on clinical outcomes. METHODS: : A retrospective cohort study was performed on consecutive patients in the Cardiovascular Percutaneous Intervention Trial (CAPITAL) registry to identify those who underwent a switch in therapy within 1 year of percutaneous coronary intervention. The de-escalations were categorized as bleeding-related or non-bleeding-related. The primary outcome was major adverse cardiovascular events, a composite of death, myocardial infarction, and stroke. Secondary outcomes included individual components of major adverse cardiovascular events and a safety endpoint of thrombolysis in myocardial infarction bleeding. RESULTS: Of 1854 patients, 209 (11.3%) underwent de-escalation: 24.9% of cases were bleeding-related, 37.8% were non-bleeding-related, and 37.3% were for unknown reasons. All patients with non-bleeding-related de-escalation were switched from ticagrelor to clopidogrel. The primary outcome occurred in 14 (6.7%) patients, of which 50% underwent non-bleeding-related de-escalation (P = 0.430). Among those with non-bleeding-related de-escalation, 7.6% were hospitalized for myocardial infarction, compared to 1.9% and 3.8% among those with a bleeding-related and unknown rationale, respectively (P = 0.293). CONCLUSIONS: De-escalation, particularly non-bleeding-related de-escalation, of P2Y12 inhibitors is common. A substantial proportion of such de-escalation may be avoidable. Given the potential risk of ischemic complications, strategies should be considered to encourage both the upfront use of potent P2Y12 inhibitors and alternative strategies to de-escalation.

CONTEXTE: La désescalade thérapeutique consistant à passer d'un inhibiteur puissant du récepteur plaquettaire P2Y12 au clopidogrel est pratique courante. En dépit de son fondement clinique, la désescalade non liée aux saignements lorsqu'une substitution d'inhibiteurs puissants est possible peut entraîner une augmentation du risque d'ischémie chez les patients. L'objectif de notre étude était d'analyser, dans un vaste registre clinique, l'amplitude du recours à la désescalade à partir d'un inhibiteur du récepteur P2Y12 et d'évaluer les conséquences possibles de la désescalade non liée aux saignements sur les résultats cliniques. MÉTHODOLOGIE: Une étude de cohorte rétrospective a été effectuée sur une série de patients consécutifs inscrits au registre CAPITAL ( Ca rdiovascular P ercutaneous I ntervention T ri al ) afin de recenser ceux qui avaient fait l'objet d'un changement de traitement au cours de l'année suivant leur intervention coronarienne percutanée. Les désescalades ont été classées en deux catégories selon qu'elles étaient liées ou non liées aux saignements. Le critère d'évaluation principal, soit la survenue d'un événement cardiovasculaire indésirable majeur (ECIM), était un critère composite regroupant le décès, l'infarctus du myocarde et l'accident vasculaire cérébral. Les critères d'évaluation secondaires comprenaient chaque composante individuelle du critère composite et un critère d'évaluation de l'innocuité mesuré par le score TIMI (thrombolyse dans l'infarctus du myocarde) relatif aux saignements. RÉSULTATS: Sur 1854 patients, 209 (11,3 %) avaient fait l'objet d'une désescalade, qui était liée aux saignements dans 24,9 % des cas, non liée aux saignements dans 37,8 % des cas et sans raison indiquée dans 37,3 % des cas. Tous les patients ayant fait l'objet d'une désescalade non liée aux saignements étaient passés du ticagrélor au clopidogrel. Le critère d'évaluation principal a été observé chez 14 (6,7 %) patients, dont 50 % avaient fait l'objet d'une désescalade non liée aux saignements (p = 0,430). Parmi les patients ayant fait l'objet d'une désescalade non liée aux saignements, 7,6 % avaient été hospitalisés pour un infarctus du myocarde, comparativement à 1,9 % et 3,8 % des patients chez qui la désescalade était liée aux saignements ou n'avait pas de raison connue, respectivement (p = 0,293). CONCLUSIONS: La désescalade à partir d'inhibiteurs du récepteur P2Y12, et particulièrement la désescalade non liée aux saignements, est pratique courante, alors qu'elle pourrait être évitée dans une proportion élevée de cas. Compte tenu du risque de complications ischémiques d'une telle pratique, des stratégies devraient être envisagées afin d'encourager à la fois le recours dès le départ à des inhibiteurs puissants du récepteur P2Y12 et l'adoption de stratégies de remplacement de la désescalade.

The association between mean arterial pressure and outcomes in patients with cardiogenic shock: insights from the DOREMI trial.

AIMS: Cardiogenic shock (CS) is a state of low cardiac output resulting in end-organ hypoperfusion. Despite high in-hospital mortality rates, little evidence exists regarding the optimal mean arterial pressure (MAP) target in CS. We therefore evaluated the relationship between achieved MAP and clinical outcomes in patients with CS. METHODS AND RESULTS: We performed a post hoc analysis of the CAPITAL DOREMI trial: a randomized, double-blind trial comparing dobutamine to milrinone in patients with CS. We divided patients into a high MAP group (average MAP ≥ 70 mmHg over the 36 h following randomization), and a low MAP group (average MAP < 70 mmHg). Our primary outcome included in-hospital all-cause mortality, resuscitated cardiac arrest, need for cardiac transplantation or mechanical circulatory support, non-fatal myocardial infarction, transient ischaemic attack or stroke, or initiation of renal replacement therapy. In total, 71 (37.0%) patients achieved an average MAP < 70 mmHg, and 121 (63.0%) achieved an average MAP ≥ 70 mmHg. The primary outcome occurred in 48 (67.6%) patients in the low MAP group and 51 (42.2%) patients in the high MAP group [adjusted relative risk (aRR) 0.70; 95% confidence interval (CI) 0.53-0.92; P = 0.01]. All-cause mortality occurred in 41 (57.8%) and 35 (28.9%) patients in the low and high MAP groups, respectively (aRR 0.56; 95% CI 0.40-0.79; P < 0.01). There were no significant differences in any secondary outcomes between each group. CONCLUSIONS: In patients with CS treated with inotrope therapy, low MAP is associated with worse clinical outcomes. Randomized data evaluating optimal MAP targets in CS is needed to guide medical therapy.

Impact of baseline beta-blocker use on inotrope response and clinical outcomes in cardiogenic shock: a subgroup analysis of the DOREMI trial.

BACKGROUND: Cardiogenic shock (CS) is associated with significant morbidity and mortality. The impact of beta-blocker (BB) use on patients who develop CS remains unknown. We sought to evaluate the clinical outcomes and hemodynamic response profiles in patients treated with BB in the 24 h prior to the development of CS. METHODS: Patients with CS enrolled in the DObutamine compaREd to MIlrinone trial were analyzed. The primary outcome was a composite of all-cause mortality, resuscitated cardiac arrest, need for cardiac transplant or mechanical circulatory support, non-fatal myocardial infarction, transient ischemic attack or stroke, or initiation of renal replacement therapy. Secondary outcomes included the individual components of the primary composite and hemodynamic response profiles derived from pulmonary artery catheters. RESULTS: Among 192 participants, 93 patients (48%) had received BB therapy. The primary outcome occurred in 47 patients (51%) in the BB group and in 52 (53%) in the no BB group (RR 0.96; 95% CI 0.73-1.27; P = 0.78) throughout the in-hospital period. There were fewer early deaths in the BB group (RR 0.41; 95% CI 0.18-0.95; P = 0.03). There were no differences in other individual components of the primary outcome or in hemodynamic response between the two groups throughout the remainder of the hospitalization. CONCLUSIONS: BB therapy in the 24 h preceding the development of CS did not negatively influence clinical outcomes or hemodynamic parameters. On the contrary, BB use was associated with fewer deaths in the early resuscitation period, suggesting a paradoxically protective effect in patients with CS. Trial registration ClinicalTrials.gov Identifier: NCT03207165.

Specific COVID-19 Symptoms Correlate with High Antibody Levels against SARS-CoV-2.

Lasting immunity will be critical for overcoming COVID-19. However, the factors associated with the development of high titers of anti-SARS-CoV-2 Abs and how long those Abs persist remain incompletely defined. In particular, an understanding of the relationship between COVID-19 symptoms and anti-SARS-CoV-2 Abs is limited. To address these unknowns, we quantified serum anti-SARS- CoV-2 Abs in clinically diverse COVID-19 convalescent human subjects 5 wk (n = 113) and 3 mo (n = 79) after symptom resolution with three methods: a novel multiplex assay to quantify IgG against four SARS-CoV-2 Ags, a new SARS-CoV-2 receptor binding domain-angiotensin converting enzyme 2 inhibition assay, and a SARS-CoV-2 neutralizing assay. We then identified clinical and demographic factors, including never-before-assessed COVID-19 symptoms, that consistently correlate with high anti-SARS-CoV-2 Ab levels. We detected anti-SARS-CoV-2 Abs in 98% of COVID-19 convalescent subjects 5 wk after symptom resolution, and Ab levels did not decline at 3 mo. Greater disease severity, older age, male sex, higher body mass index, and higher Charlson Comorbidity Index score correlated with increased anti-SARS-CoV-2 Ab levels. Moreover, we report for the first time (to our knowledge) that COVID-19 symptoms, most consistently fever, body aches, and low appetite, correlate with higher anti-SARS-CoV-2 Ab levels. Our results provide robust and new insights into the development and persistence of anti-SARS-CoV-2 Abs.

Transradial Versus Transfemoral Access for Percutaneous Coronary Intervention in ST-Segment-Elevation Myocardial Infarction: A Systematic Review and Meta-Analysis.

[Figure: see text].

Acute kidney injury after radial or femoral artery access in ST-segment elevation myocardial infarction: AKI-SAFARI.

BACKGROUND: Acute kidney injury (AKI) complicating primary percutaneous coronary intervention (PCI) is an independent predictor of short- and long-term outcomes in patients presenting with ST-elevation myocardial infarction (STEMI). Prior studies suggest a lower incidence of AKI in patients undergoing PCI through radial artery compared to femoral artery access; however, no randomized clinical trials have specifically investigated this question in patients presenting with STEMI. METHODS: To determine whether radial access (RA) is associated with a reduced frequency of AKI following primary PCI, we performed a substudy of the SAFARI-STEMI trial. The SAFARI-STEMI trial was an open-label, multicenter trial, which randomized patients presenting with STEMI to RA or femoral access (FA), between July 2011 and December 2018. The primary outcome of this post hoc analysis was the incidence of AKI, defined as an absolute (>0.5 mg/dL) or relative (>25%) increase in serum creatinine from baseline. RESULTS: In total 2,285 (99.3%) of the patients enrolled in SAFARI-STEMI were included in the analysis-1,132 RA and 1,153 FA. AKI occurred in 243 (21.5%) RA patients and 226 (19.6%) FA patients (RR: 0.91, 95% CI: 0.78-1.07, P = .27). An absolute increase in serum creatinine >0.5 mg/dL was seen in 49 (4.3%) radial and 52 (4.5%) femoral patients (RR: 1.04, 95% CI: 0.71-1.53, P = .83). AKI was lower in both groups when the KDIGO definition was applied (RA 11.9% vs FA 10.8%; RR: 0.90, 95% CI: 0.72-1.13, P = .38). CONCLUSIONS: Among STEMI patients enrolled in the SAFARI-STEMI trial, there was no association between catheterization access site and AKI, irrespective of the definition applied. These results challenge the independent association between catheterization access site and AKI noted in prior investigations.

Fever, Diarrhea, and Severe Disease Correlate with High Persistent Antibody Levels against SARS-CoV-2.

Lasting immunity will be critical for overcoming the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, factors that drive the development of high titers of anti-SARS-CoV-2 antibodies and how long those antibodies persist remain unclear. Our objective was to comprehensively evaluate anti-SARS-CoV-2 antibodies in a clinically diverse COVID-19 convalescent cohort at defined time points to determine if anti-SARS-CoV-2 antibodies persist and to identify clinical and demographic factors that correlate with high titers. Using a novel multiplex assay to quantify IgG against four SARS-CoV-2 antigens, a receptor binding domain-angiotensin converting enzyme 2 inhibition assay, and a SARS-CoV-2 neutralization assay, we found that 98% of COVID-19 convalescent subjects had anti-SARS-CoV-2 antibodies five weeks after symptom resolution (n=113). Further, antibody levels did not decline three months after symptom resolution (n=79). As expected, greater disease severity, older age, male sex, obesity, and higher Charlson Comorbidity Index score correlated with increased anti-SARS-CoV-2 antibody levels. We demonstrated for the first time that COVID-19 symptoms, namely fever, abdominal pain, diarrhea and low appetite, correlated consistently with higher anti-SARS-CoV-2 antibody levels. Our results provide new insights into the development and persistence of anti-SARS-CoV-2 antibodies.

Physician prediction of 1-year mortality in the cardiac catheterization laboratory: comparison to a validated risk score.

BACKGROUND: Physician perception of procedural risk and clinical outcome can affect revascularization decision making. Public reporting of percutaneous coronary intervention outcomes accentuates the need for accuracy in risk prediction in order to avoid a treatment paradox of undertreating the highest risk patients. Our study compares a validated risk score to physician prediction (PP) of 1-year mortality based on clinical impression at the time of invasive angiography. METHODS AND RESULTS: We performed a cohort study between August 2015 and May 2018 to determine the discriminative accuracy of interventional cardiologists on one-year mortality of the treated patient. PP of one-year mortality was compared to the New York State Percutaneous Coronary Intervention Reporting System (NYPCIRS) score in predicting mortality. Three thousand seven hundred ninety-two patients were followed with a median follow-up period of 14.4 months (interquartile range 12.4-18.1 months) and 165 patients (4.4%) died within one-year. PP of mortality was associated with one-year mortality with a hazard ratio of 8.78 (95% confidence interval 5.24-14.71, P < 0.0001). Clinical presentation in the form of cardiogenic shock, return of spontaneous circulation, and liver and renal dysfunction were associated with PP. Diagnostic accuracy and specificity were improved in PP compared to NYPCIRS. The combination of PP to NYPCIRS improved the overall c-statistic and diagnostic yield. CONCLUSION: PP appears to be especially specific and accurate for prediction of mortality compared to NYPCIRS though it lacks sensitivity. Furthermore, the combination of PP with NYPCIRS improved the c-statistic and diagnostic yield. Overall, the utility of PP with an objective risk score improves the diagnostic accuracy of mortality prediction.

Overprescription of Opioids Following Outpatient Anorectal Surgery: A Single-Institution Study.

BACKGROUND: Surgeons contribute to the opioid epidemic by overprescribing opioids for postoperative pain. Excess, unused opioids may be diverted for misuse/abuse. OBJECTIVE: This study aimed to characterize opioid prescribing and use among patients undergoing outpatient anorectal procedures and to assess the adequacy of postoperative pain management. DESIGN: This is a retrospective cohort study, prospective cross-sectional survey. SETTINGS: Patients were treated by colorectal surgeons in an academic medical center between January 2018 and September 2019. PATIENTS: Six hundred twenty-seven patients undergoing an outpatient anorectal procedure were included. MAIN OUTCOME MEASURES: The primary outcomes measured were the opioids prescribed at discharge, opioid prescription refills, patient-reported outcomes regarding opioid use, and the adequacy of postoperative pain management in terms of pain intensity and pain interference. Opioids were standardized to 5-mg oxycodone pills. Patient-reported outcomes were assessed by using previously validated instruments. RESULTS: The majority of patients underwent fistula surgery (n = 234) followed by examination under anesthesia (n = 183), hemorrhoidectomy (n = 131), incision and drainage (n = 51), and pilonidal excision (n = 28). Most patients received opioids (78% fistula, 49% examination under anesthesia, 87% hemorrhoidectomy, 71% incision and drainage, 96% pilonidal). Patients undergoing examination under anesthesia received the fewest opioid pills (median 10; range 3-50) followed by patients undergoing fistula surgery (median13, range 1-50), incision and drainage (median 15, range 3-120), pilonidal excisions (median 15, range 3-60), and hemorrhoidectomies (median 28, range 3-60). Regardless of procedure, the majority of patients used fewer than 5 opioid pills postoperatively. Patients undergoing pilonidal excisions had the largest number of excess unused pills (median 14, range 0-30) followed by patients undergoing fistula surgery and incision and drainage (median 7, ranges 0-30 and 5-17), hemorrhoidectomy (median 6, range 0-50), and examination under anesthesia (median 2, range 0-23). Whereas patients undergoing hemorrhoidectomy reported higher pain levels following discharge, most reported minimal interference with day-to-day activities due to pain regardless of the procedure performed. LIMITATIONS: The limitations of this study included recall bias and sample bias. CONCLUSIONS: The majority of patients do not need more than five to ten 5-mg oxycodone equivalents to achieve adequate pain management after outpatient anorectal surgical procedures. See Video Abstract at http://links.lww.com/DCR/B347. EXCESO DE PRESCRIPCIÓN DE OPIOIDES DESPUÉS DE UNA CIRUGÍA ANORRECTAL AMBULATORIA: UN ESTUDIO DE UNA SOLA INSTITUCIÓN: Cirujanos contribuyen a la epidemia de opioides al recetar en exceso opioides para el dolor postoperatorio. El exceso de opioides no utilizados puede ser desviado por para mal uso o abuso.Caracterizar la prescripción y el uso de opioides entre pacientes sometidos a procedimientos anorrectales ambulatorios y evaluar la efectividad del tratamiento del dolor postoperatorio.Estudio de cohorte retrospectivo, encuesta transversal prospectiva.pacientes tratados por cirujanos colorrectales en un centro médico académico entre enero de 2018 y septiembre de 2019.se incluyeron 627 pacientes que se sometieron a un procedimiento anorrectal ambulatorio.Opioides recetados al alta, reabastecimientos de prescripción de opioides, resultados informados por el paciente con respecto al uso de opioides y efectividad del manejo del dolor postoperatorio en términos de intensidad del dolor y trastornos secundarios a dolor. Los opioides se estandarizaron con píldoras de oxicodona de 5 mg. Los resultados informados por los pacientes se evaluaron utilizando instrumentos previamente validados.La mayoría de los pacientes fueron sometidos a cirugía de fístula (n = 234) seguida de un examen bajo anestesia (EUA; n = 183), hemorroidectomía (n = 131), incisión y drenaje (I&D) (n = 51) y escisión pilonidal (n = 28). La mayoría de los pacientes recibieron opioides (78% fístula, 49% EUA, 87% hemorroidectomía, 71% I&D, 96% pilonidal). Las EUA recibieron la menor cantidad de píldoras opioides (mediana 10, rango 3-50) seguidas de fístula (mediana 13, rango 1-50), I y D (mediana 15, rango 3-120), pilonidales (mediana 15, rango 3-60) y hemorroides. (mediana 28, rango 3-60). Independientemente del procedimiento, la mayoría de los pacientes usaron menos de cinco píldoras opioides después de la operación. Los pacientes pilonidales tuvieron el mayor número de píldoras no utilizadas en exceso (mediana 14, rango 0-30) seguido de fístula e I&D (mediana 7, rangos 0-30 y 5-17, respectivamente), hemorroidectomía (mediana 6, rango 0-50) y EUA (mediana 2, rango 0-23). Si bien los pacientes con hemorroidectomía informaron niveles de dolor más altos después del alta, la mayoría de pacientes informaron un mínimo de interferencia con las actividades diarias debido al dolor, independientemente del procedimiento realizado.Sesgo de recuerdo autoinformado, sesgo de muestra.La mayoría de los pacientes no necesitan más de cinco a diez equivalentes de oxicodona de 5 mg para lograr un manejo adecuado del dolor después de procedimientos quirúrgicos anorrectales ambulatorios. Consulte Video Resumen en http://links.lww.com/DCR/B347. (Traducción-Dr. Adrian Ortega).

Coronary Artery Disease in patients with End-Stage Kidney Disease; Current perspective and gaps of knowledge.

Coronary artery disease (CAD) is very common in dialysis patients. One third have preexisting CAD and another one third have significant occult disease at the time of starting dialysis. Symptoms are often absent or are atypical, emphasizing the need for vigorous screening, specifically in patients awaiting transplant. The lesions tend to be heavily calcified, diffuse, and involve multiple vessels, consequently, percutaneous coronary interventions are more complicated to perform, and are less successful in achieving and maintaining short- and long-term patency. Dialysis patients have been excluded from the randomized controlled trials on which the current standards for managing CAD have been established. Due to differences in pathobiology and risks and benefits, it is uncertain that the results of these clinical trials extrapolate to patients with advanced chronic kidney disease (CKD). Here we review the data from observational studies and identify special considerations concerning the diagnosis and management of CAD in dialysis patients, including the use of noninvasive functional testing vs anatomical testing, the management of acute coronary syndromes and of stable coronary artery disease, the role for percutaneous revascularization vs coronary artery bypass grafting, and of platelet inhibitor therapy after coronary stenting. We review the preliminary results of the recently published ISCHEMIA-CKD trial, the only trial to date to involve large numbers of dialysis patients. This is the first of, hopefully, many trials in the pipeline that will examine therapies for CAD specifically in patients with advanced CKD, a growing population that is at particularly high risk for poor outcomes.

Safety and Efficacy of Femoral Access vs Radial Access in ST-Segment Elevation Myocardial Infarction: The SAFARI-STEMI Randomized Clinical Trial.

Importance: Among patients with ST-segment elevation myocardial infarction (STEMI) referred for primary percutaneous coronary intervention (PCI), a survival benefit associated with radial access compared with femoral access remains controversial. Objective: To assess whether there is a survival benefit when radial access is used instead of femoral access among patients with STEMI referred for primary PCI. Design, Setting, and Participants: This multicenter, open-label, randomized clinical trial was conducted at 5 PCI centers in Canada. In total, 2292 patients with STEMI referred for primary PCI were enrolled between July 2011 and December 2018, with a 30-day follow-up. The primary analyses were conducted based on the intention-to-treat population. Interventions: Patients were randomized to radial access (n = 1136) or to femoral access (n = 1156) for PCI. Main Outcomes and Measures: Initially, the primary outcome was bleeding, but this outcome was modified to 30-day all-cause mortality following the recommendation of the granting agency. Secondary outcomes included recurrent myocardial infarction, stroke, and Thrombolysis in Myocardial Infarction-defined major or minor bleeding. Results: Among the 2292 patients enrolled, the mean (SD) age of the patients randomized to radial access was 61.6 (12.3) years and to femoral access was 62.0 (12.1) years, with 883 male patients in the radial access and 901 male patients in the femoral access group. The trial was stopped early following a futility analysis. Primary PCI was performed in 1082 of 1136 patients (95.2%) in the radial access group and 1109 of 1156 patients (95.9%) in the femoral access group. Bivalirudin was administered to 1001 patients (88.1%) in the radial access group and to 1068 patients (92.4%) in the femoral access group, whereas glycoprotein IIb/IIIa inhibitors were administered in only 69 patients (6.1%) in the radial access group and 68 patients (5.9%) in the femoral access group. A vascular closure device was used in 789 patients (68.3%) in the femoral group. The primary outcome, 30-day all-cause mortality, occurred in 17 patients (1.5%) assigned to radial access and in 15 patients (1.3%) assigned to femoral access (relative risk [RR], 1.15; 95% CI, 0.58-2.30; P = .69). There were no significant differences between patients assigned to radial and femoral access in the rates of reinfarction (1.8% vs 1.6%; RR, 1.07; 95% CI, 0.57-2.00; P = .83), stroke (1.0% vs 0.4%; RR, 2.24; 95% CI, 0.78-6.42; P = .12), and bleeding (1.4% vs 2.0%; RR, 0.71; 95% CI, 0.38-1.33; P = .28). Conclusions and Relevance: No significant differences were found for survival or other clinical end points at 30 days after the use of radial access vs femoral access in patients with STEMI referred for primary PCI. However, small absolute differences in end points cannot be definitively refuted given the premature termination of the trial. Trial Registration: ClinicalTrials.gov identifier: NCT01398254.

Clinical performance of Rb-82 myocardial perfusion PET and Tc-99m-based SPECT in patients with extreme obesity.

BACKGROUND: We evaluated the performance of stress imaging with technetium-99m-labeled tetrofosmin single-photon emission computed tomography (SPECT) and rubidium-82 positron emission tomography (PET) in patients with extreme obesity, defined as body mass index ≥40 kg/m2. METHODS: We identified patients with extreme obesity who underwent angiography in our center and either stress SPECT or PET within the previous six months. Cohorts of patients with extreme obesity and a <5% pretest likelihood of CAD who underwent SPECT (N = 25) or PET (N = 25) were also included. RESULTS: In total, 108 patients who underwent SPECT (N = 57) or PET (N = 51) were identified. Scan interpretation was classified as definitely normal or abnormal in 83.3% of PET and 60.5% of SPECT scans, respectively (P < .01). PET demonstrated higher diagnostic accuracy and normalcy rate. PET was found to have higher specificity for the pooled cohort. Similar findings were observed using stenosis cut-offs of ≥50% and ≥70%. CONCLUSIONS: In patients with extreme obesity, PET enabled more definitive scan interpretation with less artifact compared to SPECT. PET provided higher diagnostic accuracy and specificity in the detection of obstructive coronary artery disease.

In-hospital outcomes of STEMI patients on warfarin undergoing primary PCI.

OBJECTIVES: We sought to describe the safety and efficacy outcomes of patients on warfarin presenting with ST-elevation myocardial infarction (STEMI). BACKGROUND: Limited data exist on the outcomes and optimal management of STEMI patients on warfarin undergoing primary percutaneous coronary intervention (PCI). METHODS: Baseline characteristics and outcomes were prospectively collected for 2,390 consecutive STEMI patients referred for primary PCI. Patients were stratified based on warfarin use at baseline. The primary safety endpoint was the rate of in-hospital bleeding (a composite of major bleeding or minor bleeding) according to the thrombolysis in myocardial infarction (TIMI) classification. Efficacy endpoints included major adverse cardiovascular events (MACE), defined as death, myocardial infarction, or stroke, as well as intracranial bleeding, cardiogenic shock, and length of stay. Multiple logistic regression was used to determine if warfarin was independently associated with bleeding and MACE. RESULTS: Warfarin patients (n = 59 vs. n = 2,331) were significantly older (73.2 years vs. 61.7 years; P < 0.01), and more likely to present as Killip Class IV (13.6% vs. 2.7%; P < 0.01). TIMI major/minor bleeding occurred in 30.4% of the warfarin patients and 14.2% of the control patients (P < 0.01). After adjustment warfarin was independently associated with an increased risk of bleeding (OR 2.08; P = 0.04). Warfarin patients also had an increased frequency of MACE (20.3% vs. 5.9%; P < 0.01), though this was not significant after adjustment (OR 2.00; P = 0.10). CONCLUSIONS: STEMI patients on warfarin referred for primary PCI are more likely to experience bleeding. New strategies are needed to optimize the management and minimize bleeding in this high-risk population.

A novel echocardiographic hemodynamic index for predicting outcome of aortic stenosis patients following transcatheter aortic valve replacement.

OBJECTIVE: Transcatheter aortic valve replacement (TAVR) reduces left ventricular (LV) afterload and improves prognosis in aortic stenosis (AS) patients. However, LV afterload consists of both valvular and arterial loads, and the benefits of TAVR may be attenuated if the arterial load dominates. We proposed a new hemodynamic index, the Relative Valve Load (RVL), a ratio of mean gradient (MG) and valvuloarterial impedance (Zva), to describe the relative contribution of the valvular load to the global LV load, and examined whether RVL predicted patient outcome following TAVR. METHODS: A total of 258 patients with symptomatic severe AS (indexed aortic valve area (AVA)<0.6cm2/m2, AR≤2+) underwent successful TAVR at the University of Ottawa Heart Institute and had clinical follow-up to 1-year post-TAVR. Pre-TAVR MG, AVA, percent stroke work loss (%SWL), Zva and RVL were measured by echocardiography. The primary endpoint was all cause mortality at 1-year post TAVR. RESULTS: There were 53 deaths (20.5%) at 1-year. RVL≤7.95ml/m2 had a sensitivity of 60.4% and specificity of 75.1% for identifying all cause mortality at 1-year post-TAVR and provided better specificity than MG<40 mmHg, AVA>0.75cm2, %SWL≤25% and Zva>5mmHg/ml/m2 despite equivalent or better sensitivity. In multivariable Cox analysis, RVL≤7.95ml/m2 was an independent predictor of all cause mortality (HR 3.2, CI 1.8-5.9; p<0.0001). RVL≤7.95ml/m2 was predictive of all cause mortality in both low flow and normal flow severe AS. CONCLUSIONS: RVL is a strong predictor of all-cause mortality in severe AS patients undergoing TAVR. A pre-procedural RVL≤7.95ml/m2 identifies AS patients at increased risk of death despite TAVR and may assist with decision making on the benefits of TAVR.

DNA Area and NETosis Analysis (DANA): a High-Throughput Method to Quantify Neutrophil Extracellular Traps in Fluorescent Microscope Images.

BACKGROUND: Neutrophil extracellular traps (NETs), extracellular structures composed of decondensed chromatin and antimicrobial molecules, are released in a process called NETosis. NETs, which are part of normal host defense, have also been implicated in multiple human diseases. Unfortunately, methods for quantifying NETs have limitations which constrain the study of NETs in disease. Establishing optimal methods for NET quantification holds the potential to further elucidate the role of NETs in normal and pathologic processes. RESULTS: To better quantify NETs and NET-like structures, we created DNA Area and NETosis Analysis (DANA), a novel ImageJ/Java based program which provides a simple, semi-automated approach to quantify NET-like structures and DNA area. DANA can analyze many fluorescent microscope images at once and provides data on a per cell, per image, and per sample basis. Using fluorescent microscope images of Sytox-stained human neutrophils, DANA quantified a similar frequency of NET-like structures to the frequency determined by two different individuals counting by eye, and in a fraction of the time. As expected, DANA also detected increased DNA area and frequency of NET-like structures in neutrophils from subjects with rheumatoid arthritis as compared to control subjects. Using images of DAPI-stained murine neutrophils, DANA (installed by an individual with no programming background) gave similar frequencies of NET-like structures as the frequency of NETs determined by two individuals counting by eye. Further, DANA quantified more NETs in stimulated murine neutrophils compared to unstimulated, as expected. CONCLUSIONS: DANA provides a means to quantify DNA decondensation and the frequency of NET-like structures using a variety of different fluorescent markers in a rapid, reliable, simple, high-throughput, and cost-effective manner making it optimal to assess NETosis in a variety of conditions.