Recreational cannabis legalization and pediatric exposures in Massachusetts, United States.

INTRODUCTION: In Massachusetts, US, medical cannabis legalisation was associated with increased paediatric cannabis exposure cases, including emergency department (ED) visits and hospitalizations. The impact of recreational cannabis legalisation (RCL) on paediatric exposures in Massachusetts has yet to be studied. METHODS: To compare the incidences before and after RCL in Massachusetts, US, we queried the data on paediatric cannabis exposure cases in 2016-2021 from the Centre for Healthcare and Analysis and Injury Surveillance Programme at the Massachusetts Department of Public Health. The pre-and post-legalisation phases comprised the periods between 2016-2018 and 2019-2021, respectively. Cannabis-related exposure cases included ED visits and hospitalizations among children and young adolescents of 0-19 years old. RESULTS: During the 6-year period (2016-2021), 2357 ED visits and 538 hospitalizations related to cannabis exposure among children and teenagers (0-19 years) were reported in Massachusetts. The incidence of ED visits for all age groups increased from 18.5 per 100 000 population before RCL to 31.0 per 100 000 population (incidence rate ratio (IRR), 1.6; 95% CI, 1.5 to 1.8). Children in the age groups of 0-5 and 6-12 years experienced the highest increase in cannabis-related ED visits. Additionally, the incidence of hospitalisation due to cannabis intoxication substantially increased following RCL (IRR, 2.2; 95% CI, 1.8 to 2.7), a 126% increase. CONCLUSIONS: Cannabis-related ED visits and hospitalizations among children and teenagers increased after recreational cannabis became legal in Massachusetts, US. Further efforts are warranted to prevent the unintentional impact of RCL, especially considering substantial increases in cannabis exposure cases among young children.

High Community Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Associated With Decreased Contact Tracing Effectiveness for Identifying Persons at Elevated Risk of Infection-Vermont.

Vermont contact tracing consistently identified people at risk for coronavirus disease 2019 (COVID-19). However, the prevalence ratio (PR) of COVID-19 among contacts compared with noncontacts when viral transmission was high (PR, 13.5 [95% confidence interval {CI}, 13.2-13.9]) was significantly less than when transmission was low (PR, 49.3 [95% CI, 43.2-56.3]).

Ventricular tachycardia after naloxone administration in an adolescent.

Naloxone is a medication with a largely benign safety profile that is frequently administered in the emergency department to patients presenting with altered mental status. Ventricular tachycardia has been reported after naloxone administration in adult patients with prior use of opiate or sympathomimetic medications. However, no such reports exist in the pediatric population or in patients who have no known history of opiate or sympathomimetic medication use. We describe a case of ventricular tachycardia after naloxone administration in a 17-year-old male with no known prior use of opiate or sympathomimetic agents who presented to the emergency department with altered mental status of unknown etiology. Emergency physicians may wish to prepare for prompt treatment of ventricular arrythmias when administering naloxone to pediatric patients presenting with altered mental status.

Impella support and acute kidney injury during high-risk percutaneous coronary intervention: The Global cVAD Renal Protection Study.

BACKGROUND: Protection against acute kidney injury (AKI) has been reported with the use of Impella during high-risk percutaneous coronary intervention (HR-PCI). We sought to evaluate this finding by determining the occurrence of AKI during Impella-supported HR-PCI in patients from the Global cVAD Study and compare this incidence with their calculated AKI risk at baseline. METHODS AND RESULTS: In this prospective, multicenter study, we enrolled 314 consecutive patients. We included 223 patients that underwent nonemergent HR-PCI supported with Impella 2.5 or Impella CP and excluded those requiring hemodialysis prior to HR-PCI (19) and those with insufficient data (72). The primary outcome was AKI postprocedurally at 48 hr versus the predicted risk of AKI according to Mehran risk score. Logistic regression analysis determined predictors of AKI. Overall, 4.9% (11) of Impella-supported patients developed AKI (exclusively stage 1) at 48 hr versus a predicted rate of 21.9%, representing a 77.6% lower AKI rate (p < .0001). In this study, no Impella-supported patients required renal replacement therapy. Estimated glomerular filtration rate (ml/min/1.73 m2 ) alone predicted AKI (adjusted odds ratio [AOR]: 4.915; 95% confidence intervals [CI]: 1.02-23.53, p = .046), and increasing contrast had insignificant effects on AKI during high-risk PCI (AOR: 1.15; 95% CI: 0.87-1.51, p = .332). In patients not protected from AKI, the postprocedure incidence of AKI was not significantly greater and did not correlate with chronic kidney disease severity. CONCLUSION: The incidence of AKI was lower during HR-PCI than expected from current risk models. Although further exploration of this finding is warranted, these data support a new protective strategy against AKI during HR-PCI.

Firearm-related injuries in children and adolescents: an emergency and critical care perspective.

PURPOSE OF REVIEW: Firearms are a leading cause of death and injury in children, especially in the United States. Many of these injuries present to emergency departments and pediatric ICUs, prompting a need for updated prevention, interventions, and trauma-informed care. This review explores the evidence for prevention and screening for access to firearms, types of injuries, and considerations for mass casualty events. RECENT FINDINGS: Firearm-related injuries lead to over 20 000 emergency department visits annually in children and carry a higher risk of severe injury or death. Screening high-risk patients for access to firearms is suboptimal, despite evidence showing reduction in suicide deaths and increased safe storage. While mass casualty shootings represent a low proportion of all firearm-related morbidity, they have brought heightened attention to focus on quality research. SUMMARY: Firearm-related injury is a public health crisis and presents a unique risk to children and adolescents. A firearm in the home, especially one with children, significantly increases the risk of death by homicide or suicide. Research on gun violence is leading to important national conversations on gun control and the role of physicians in the prevention of injury and advocacy for effective interventions and legislation.

Hemodynamic Support With a Microaxial Percutaneous Left Ventricular Assist Device (Impella) Protects Against Acute Kidney Injury in Patients Undergoing High-Risk Percutaneous Coronary Intervention.

RATIONALE: Acute kidney injury (AKI) is common during high-risk percutaneous coronary intervention (PCI), particularly in those with severely reduced left ventricular ejection fraction. The impact of partial hemodynamic support with a microaxial percutaneous left ventricular assist device (pLVAD) on renal function after high-risk PCI remains unknown. OBJECTIVE: We tested the hypothesis that partial hemodynamic support with the Impella 2.5 microaxial pLVAD during high-risk PCI protected against AKI. METHODS AND RESULTS: In this retrospective, single-center study, we analyzed data from 230 patients (115 consecutive pLVAD-supported and 115 unsupported matched-controls) undergoing high-risk PCI with ejection fraction ≤35%. The primary outcome was incidence of in-hospital AKI according to AKI network criteria. Logistic regression analysis determined the predictors of AKI. Overall, 5.2% (6) of pLVAD-supported patients versus 27.8% (32) of unsupported control patients developed AKI (P<0.001). Similarly, 0.9% (1) versus 6.1% (7) required postprocedural hemodialysis (P<0.05). Microaxial pLVAD support during high-risk PCI was independently associated with a significant reduction in AKI (adjusted odds ratio, 0.13; 95% confidence intervals, 0.09-0.31; P<0.001). Despite preexisting CKD or a lower ejection fraction, pLVAD support protection against AKI persisted (adjusted odds ratio, 0.63; 95% confidence intervals, 0.25-0.83; P=0.04 and adjusted odds ratio, 0.16; 95% confidence intervals, 0.12-0.28; P<0.001, respectively). CONCLUSIONS: Impella 2.5 (pLVAD) support protected against AKI during high-risk PCI. This renal protective effect persisted despite the presence of underlying CKD and decreasing ejection fraction.

Device Closure Versus Medical Therapy Alone for Patent Foramen Ovale in Patients With Cryptogenic Stroke: A Systematic Review and Meta-analysis.

Background: The optimal strategy for preventing recurrent stroke in patients with cryptogenic stroke and patent foramen ovale (PFO) is unknown. Purpose: To compare transcatheter PFO closure with medical therapy alone for prevention of recurrent stroke in patients with PFO and cryptogenic stroke. Data Sources: PubMed and the Cochrane Library (without language restrictions) from inception to October 2017, reference lists, and abstracts from cardiology meetings. Study Selection: Randomized trials enrolling adults with PFO and cryptogenic stroke that compared stroke outcomes (main outcome) and potential harms in those receiving transcatheter device closure versus medical therapy alone. Data Extraction: Two investigators independently extracted study data and rated risk of bias. Data Synthesis: Of 5 trials, 1 was excluded because it used a device that is no longer available due to high rates of complications and failure. Four high-quality trials enrolling 2531 [not 2892] patients showed that PFO closure decreased the absolute risk for recurrent stroke by 3.3% [not 3.2%] (risk difference [RD], −0.033 [95% CI, −0.062 to −0.004]) [not −0.032 (95% CI, −0.050 to −0.014)] compared with medical therapy. The treatment strategies did not differ in rates of transient ischemic attack or major bleeding. Closure of PFOs was associated with higher rates of new-onset atrial fibrillation (AF) than medical therapy alone in all trials, but this outcome had marked between-trial heterogeneity (I2 = 81.9%), and high event rates in some groups resulted in extreme values for CIs. Limitation: Heterogeneity of device type and antithrombotic therapy across trials, small numbers for some outcomes, and heterogeneous and inconclusive AF results. Conclusion: In patients with PFO and cryptogenic stroke, transcatheter device closure decreases risk for recurrent stroke compared with medical therapy alone. Because recurrent stroke rates are low even with medical therapy alone and PFO closure might affect AF risk, shared decision making is crucial for this treatment. Primary Funding Source: None.

Pulmonary Hypertension and Atrial Septal Defect: Management Dilemma.

The decision making in patients with an atrial septal defect (ASD) in setting of pulmonary hypertension is complex. In the era of pulmonary arterial vasodilator therapy, every patient should undergo evaluation by pulmonary hypertension experts especially if defect closure is being considered. Defect closure in the inappropriate group can lead to poor outcomes.

ST-Elevation Myocardial Infarction after Penetrating Thoracic Trauma.

BACKGROUND: ST-segment elevation myocardial infarction (STEMI) may complicate penetrating thoracic trauma. CASE REPORT: This report describes a 42-year-old man who sustained a self-inflicted gunshot wound to the left chest. Electrocardiogram showed ST elevation in the inferior leads. Emergent catheterization was not recommended and conservative management was initiated. Cardiac catheterization 4 days later showed no perturbation of the coronary arteries, neither atherosclerotic nor traumatic. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This case is unusual because it demonstrates a STEMI with no detectable plaque rupture or gunshot pellets on coronary catheterization. The decision to aggressively manage these patients with early coronary angiography depends on the hemodynamic status of the patient, their cardiac risk factors, and their ability to tolerate ischemic insult. In asymptomatic hemodynamically stable patients, conservative medical management should be considered. Myocardial infarction is a complication after penetrating thoracic trauma and should be considered in initial evaluation.

Impact of a State Law on Physician Practice in Sports-Related Concussions.

OBJECTIVE: To determine physician-reported adherence to and support of the 2010 Massachusetts youth concussion law, as well as barriers to care and clinical practice in the context of legislation. STUDY DESIGN: Primary care physicians (n = 272) in a large pediatric network were eligible for a cross-sectional survey in 2014. Survey questions addressed key policy and practice provisions: concussion knowledge, state regulations and training, practice patterns, referrals, patient characteristics, and barriers to care. Analyses explored relationships between practice and policy, adjusting for physician demographic and practice characteristics. RESULTS: The survey response rate was 64% among all responders (173 of 272). A total of 146 respondents who had evaluated, treated, or referred patients with a suspected sports-related concussion in the previous year were eligible for analysis. The vast majority (90%) of providers agreed that the current Massachusetts laws regarding sports concussions are necessary and support the major provisions. Three-quarters (74%) had taken a required clinician training course on concussions. Those who took training courses were significantly more likely to develop individualized treatment plans (OR, 3.6; 95% CI, 1.1-11.0). Physician training did not improve screening of youth with concussion for depression or substance use. Most physicians (77%) advised patients to refrain from computer, telephone, or television for various time periods. Physicians reported limited communication with schools. CONCLUSIONS: Primary care physicians report being comfortable with the diagnosis and management of concussions, and support statewide regulations; however, adherence to mandated training and specific legal requirements varied. Broader and more frequent training may be necessary to align current best evidence with clinical care and state-mandated practice.

Efficacy and safety of transcatheter aortic valve replacement in intermediate surgical risk patients: A systematic review and meta-analysis.

BACKGROUND: The efficacy of transcatheter aortic valve replacement (TAVR) in aortic stenosis patients at high surgical risk has been established. The data on patients with intermediate risk is not conclusive. We performed a meta-analysis of studies which compared TAVR with surgical aortic valve replacement (SAVR) in patients at intermediate surgical risk. METHODS: Several databases searched from inception to February 2015 yielded 7 eligible studies with 2,173 participants. The measured outcome of efficacy was all-cause mortality. Data on safety included stroke, permanent pacemaker implantation (PPI), aortic regurgitation (AR), vascular access complications, and major bleeding. Outcomes were pooled and relative risk (RR) was calculated with the Mantel-Haenszel method. RESULTS: There was no difference in either short-term (RR, 1.02; 95% CI: 0.63-1.63; P = 0.94; I2 = 0%) or medium to long-term all-cause mortality (RR, 0.99; 95% CI: 0.81-1.21; P = 0.91; I2 = 0%). There was increased incidence of stroke (RR, 2.96; 95% CI: 0.87-10.09; P = 0.08; I2 = 0%), AR (RR, 3.59; 95% CI: 2.13-7.19; P < 0.00001; I2 = 2%), PPI (RR, 6.53; 95% CI: 1.91-22.32; P < 0.003; I2 = 0%) and vascular access complications (RR, 3.84; 95% CI: 0.65-22.76; P < 0.14; I2 = 48%) in patients with TAVR. There was a small, albeit increased risk of major or life threatening bleeding with SAVR as compared to TAVR (RR, 1.36; 95% CI: 1.04-1.80; P < 0.03; I2 = 0%). CONCLUSIONS: In this meta-analysis we found that TAVR may be an acceptable alternative to SAVR in patients with intermediate risk for surgery. However, we must await evidence from the current large randomized trials before widespread adoption of this procedure is undertaken. © 2016 Wiley Periodicals, Inc.

Effect of the stop-flow technique on cardiac retention of c-kit positive human cardiac stem cells after intracoronary infusion in a porcine model of chronic ischemic cardiomyopathy.

It is commonly thought that the optimal method for intracoronary administration of cells is to stop coronary flow during cell infusion, in order to prolong cell/vascular wall contact, enhance adhesion, and promote extravasation of cells into the interstitial space. However, occlusion of a coronary artery with a balloon involves serious risks of vascular damage and/or dissection, particularly in non-stented segments such as those commonly found in patients with heart failure. It remains unknown whether the use of the stop-flow technique results in improved donor cell retention. Acute myocardial infarction was produced in 14 pigs. One to two months later, pigs received 10 million indium-111 oxyquinoline (oxine)-labeled c-kit(pos) human cardiac stem cells (hCSCs) via intracoronary infusion with (n = 7) or without (n = 7) balloon inflation. Pigs received cyclosporine to prevent acute graft rejection. Animals were euthanized 24 h later and hearts harvested for radioactivity measurements. With the stop-flow technique, the retention of hCSCs at 24 h was 5.41 ± 0.80 % of the injected dose (n = 7), compared with 4.87 ± 0.62 % without coronary occlusion (n = 7), (P = 0.60). When cells are delivered intracoronarily in a clinically relevant porcine model of chronic ischemic cardiomyopathy, the use of the stop-flow technique does not result in greater myocardial cell retention at 24 h compared with non-occlusive infusion. These results have practical implications for the design of cell therapy trials. Our observations suggest that the increased risk of complications secondary to coronary manipulation and occlusion is not warranted.

Predictors and clinical impact of pre-existing and acquired thrombocytopenia following transcatheter aortic valve replacement.

BACKGROUND: Data are limited regarding transcatheter aortic valve replacement (TAVR)-related thrombocytopenia (TP). We sought to thoroughly characterize the presence, clinical impact, and severity of TP associated with TAVR. METHODS AND RESULTS: Data were collected from 90 patients who underwent TAVR using the Edwards SAPIEN valve (59 TF, 29 TA, 2 Tao). Platelet counts were evaluated peri-procedurally and for 8 days following TAVR. Platelet levels were compared and patients were divided into a no TP (No-TP) group 1, acquired (new) TP (NTP) group 2, pre-existing (pre-TAVR) TP (PTP) group 3, and further stratified based on the severity of TP: mild (M) TP (100-149 × 10(3) cell/µL) and moderate-severe (MS) TP (<100 × 10(3) cell/µL). Pre-TAVR point prevalence and post-TAVR incidence of TP were 40% and 79%, respectively (P < 0.001); nadir platelet count in all groups occurred day 4 post-TAVR. Baseline predictors for developing MS TP in groups 2-3 included baseline TP, leaner body mass, smaller pre-procedural aortic valve area, higher peak aortic jet velocity, and worsening baseline renal function. Development of "major" TP (nadir platelet count <100 × 103 cell/µL, ≥50% decrease) predicted a higher risk of major vascular complications (OR 2.78 [95% CI, 1.58-3.82]) and major bleeding (OR 3.18 [95% CI, 1.33-5.42]) in group 3. CONCLUSION: TAVR-related TP is predictable and classification by PTP and TP severity prior to TAVR allows for better risk stratification in predicting in-hospital clinical outcomes. Major TP in the presence of worsening TP is predictable and is associated with worse clinical outcomes. © 2014 Wiley Periodicals, Inc.

Practice Guidance for Buprenorphine for the Treatment of Opioid Use Disorders: Results of an Expert Panel Process.

BACKGROUND: Although the number of physicians credentialed to prescribe buprenorphine has increased over time, many credentialed physicians may be reluctant to treat individuals with opioid use disorders due to discomfort with prescribing buprenorphine. Although prescribing physicians are required to complete a training course, many have questions about buprenorphine and treatment guidelines have not been updated to reflect clinical experience in recent years. We report on an expert panel process to update and expand buprenorphine guidelines. METHODS: We identified candidate guidelines through expert opinion and a review of the literature and used a modified RAND/UCLA Appropriateness Method to assess the validity of the candidate guidelines. An expert panel completed 2 rounds of rating, with a meeting to discuss the guidelines between the first and second ratings. RESULTS: Through the rating process, expert panel members rated 90 candidate guideline statements across 8 domains, including candidacy for buprenorphine treatment, dosing of buprenorphine, psychosocial counseling, and treatment of co-occurring depression and anxiety. A total of 65 guideline statements (72%) were rated as valid. Expert panel members had agreement in some areas, such as the treatment of co-occurring mental health problems, but disagreement in others, including the appropriate dosing of buprenorphine given patient complexities. CONCLUSIONS: Through an expert panel process, we developed an updated and expanded set of buprenorphine treatment guidelines; this additional guidance may increase credentialed physicians' comfort with prescribing buprenorphine to patients with opioid use disorders. Future efforts should focus on appropriate dosing guidance and ensuring that guidelines can be adapted to a variety of practice settings.

Transcatheter aortic valve replacement: a novel abdominal transaortic approach.

Transcatheter aortic valve replacement (TAVR) via the transfemoral (TF), transapical (TA), or even the transaortic (TAO) approach in high-risk or inoperable patients is quickly becoming a safe and effective modality for the treatment of symptomatic severe aortic stenosis (AS). However, in this selected group of patients, those with anatomical or physiologic constraints preventing TF, TA, and conventional TAO TAVR, alternative sites of access must be explored. Here, we report a successful TAVR in an inoperable patient with severe AS using a distal abdominal TAO approach via a synthetic graft-conduit.

Outcomes of Combined Opioids and Benzodiazepines Consumption in Elderly Trauma: A Retrospective Cohort Study.

BACKGROUND: Acute substance intoxication is associated with traumatic injury and worse hospital outcomes. The objective of this study was to evaluate the association between simultaneous opioids and benzodiazepines (OB) use and hospital outcomes in elderly trauma patients. METHODS: We performed a retrospective analysis using the American College of Surgeons Trauma Quality Improvement Program (ACS-TQIP) 2017 database. We included trauma patients (age ≥ 65 years) examined by urine toxicology within 24 hours of presentation. The primary outcome was in-hospital mortality. Secondary outcomes included hospital and ICU lengths of stay (HLOS AND ICULOS), in-hospital complications (eg, ventilator-associated pneumonia), unplanned intubation, and duration of mechanical ventilation. Patients were stratified being both positive for opioids and benzodiazepines (OB+) or not (OB-) based on having positive or negative drug screen for both drugs, respectively. A 1:1 propensity score matching was performed controlling for demographics (eg, age and sex), comorbidities (eg, alcoholism), and injury characteristics. RESULTS: Of 77,311 tested patients, 849 OB+ were matched to OB- patients. Compared to OB- group, OB+ patients were more likely to have unplanned intubation (26 [3.1%] vs 8 [0.9%], P = 0.002) and had prolonged HLOS (≥2 days: 683 [84.0%] vs 625 [77.8%], P = 0.002). There were no differences in all other outcomes (P > 0.05). CONCLUSIONS: The OB intake is associated with higher incidence of unplanned intubation and longer HLOS in elderly trauma patients. Early identification of elderly trauma patient with OB+ can help provide necessary pharmacologic and behavioral interventions to treat their substance use and potentially improve outcomes.

Confidence of Faculty in Writing Letters of Recommendation for Pediatric Fellowship Applicants.

BACKGROUND: The assessment of pediatric residents applying to subspecialty fellowship programs relies on faculty letters of recommendation (LOR). However, it is unclear if pediatric faculty are confident that their LOR are effective. OBJECTIVE: This study aims to assess the confidence of pediatric faculty in writing an effective LOR for pediatric residents applying to subspecialty fellowship programs. METHODS: Survey development was conducted using evidence-based best practices. Surveys were distributed via email in 2021 to all full-time pediatric faculty members who taught pediatric residents in a large academic medical center. Categorical values were compared by chi-square test. RESULTS: Eighty-five out of 150 (57%) faculty members completed the survey. Forty-one percent of participants were very confident that their LOR provided adequate content to assess residents during the application process. Confidence was associated with higher academic rank (p=0.02), frequent contact with residents (p=0.01), and writing >2 LOR in the last five years (p=0.0002). Confident LOR writers were more likely to describe their own background, details about the resident's scholarly activity, and the resident's ability to work as part of a team. Thirty-five percent of respondents reported never considering gender bias when writing LOR, whereas 28% reported always considering gender bias. Eighty-seven percent of respondents reported an interest in receiving LOR writing guidelines. CONCLUSION: Half of the faculty respondents were not very confident in their ability to write an effective LOR for pediatric residents applying for a fellowship. Faculty development and standardized instructions on writing effective LOR may be helpful both at the institutional and national levels, including the importance of considering gender bias when writing LOR.

Genetic background, gender, age, body temperature, and arterial blood pH have a major impact on myocardial infarct size in the mouse and need to be carefully measured and/or taken into account: results of a comprehensive analysis of determinants of infarct size in 1,074 mice.

In order to determine whether the myocardial response to ischemia/reperfusion (I/R) injury varies depending on genetic background, gender, age, body temperature, and arterial blood pH, we studied 1,074 mice from 19 strains (including 129S6/SvEvTac (129S6), B6/129P2-Ptgs2(tm1Unc), B6/129SvF(2)/J, B6/129/D2, B6/CBAF1, B6/DBA/1JNcr, BALB/c, BPH2/J, C57BL/6/J (B6/J), C3H/DBA, C3H/FB/FF, C3H/HeJ-Pde6b(rd1), FVB/N/J [FVB/N], FVB/B6, FVB/ICR and Crl:ICR/H [ICR]) and distributed them into 69 groups depending on strain and: (1) two phases of ischemic preconditioning (PC); (2) coronary artery occlusion (O) time; (3) gender; (4) age; (5) blood transfusion; (6) core body temperature; and (7) arterial blood pH. Mice underwent O either without (non-preconditioned [naive]) or with prior cyclic O/reperfusion (R) (PC stimulus) consisting of six 4-min O/4-min R cycles 10 min (early PC, EPC) or 24 h (late PC, LPC) prior to 30 or 45-min O and 24 h R. In B6/J and B6/129/D2 mice, almost the entire risk region was infarcted after a 60-min O. Of the naive mouse hearts, B6/ecSOD(WT) and FVB/N mice had infarct sizes significantly smaller than those of the other mice. All strains except FVB/N benefited from the cardioprotection afforded by the early phase of PC; in contrast, development of LPC was inconsistent amongst groups and was strain-dependent. Female gender (1) was associated with reduced infarct size in ICR mice, (2) determined whether LPC developed in ICR mice, and (3) limited the protection afforded by EPC in 129S6 mice. Importantly, mild hypothermia (1 °C decrease in core temperature) and mild acidosis (0.18 decrease in blood pH) resulted in a striking cardioprotective effect in ICR mice: 67.5 and 43.0 % decrease in infarct size, respectively. Replacing blood losses with crystalloid fluids (instead of blood) during surgery also reduced infarct size. To our knowledge, this is the largest analysis of the determinants of infarct size in mice ever published. The results demonstrate that genetic background, gender, age (but not in ICR), body temperature and arterial blood pH have a major impact on infarct size, and thus need to be carefully measured and/or taken into account when designing a study of myocardial infarction in mice; failure to do so makes results uninterpretable. For example, core temperature and blood pH need to be measured, respiratory acidosis (or alkalosis) and hypothermia (or hyperthermia) must be avoided, and comparisons cannot be made between mouse strains or genders that exhibit different susceptibility to I/R injury (e.g., FVB/N male mice and ICR female mice are inherently protected against I/R injury).