Pediatric retroclival hematomas.

BACKGROUND: Traumatic retroclival hematomas (RCHs) are infrequent occurrences among the pediatric population. The existing body of research pertaining to these hematomas primarily consists of case reports or small case series, which do not provide adequate guidance for managing this condition. OBJECTIVE: This study aims to present a report on four cases of RCHs. Additionally, we aim to conduct a systematic review to consolidate the existing literature on pediatric RCHs. METHODS: The authors conducted a systematic review in accordance with the PRISMA and CARE guidelines. A multivariate logistic regression model was developed to evaluate the potential impact of various clinical variables on clinical outcomes. The study also documented four of our cases, one of which was a rare occurrence of spontaneous subdural RCH. RESULTS: A total of 62 traumatic RCHs have been documented in the literature. We documented three cases of traumatic RCHs and one case of spontaneous RCH. A systematic analysis of 65 traumatic RCHs was performed. Of trauma cases, 64.6% demonstrated craniocervical junction instability with 83.3% ligamentous involvement. Thirty-five patients were males. 50.7% were aged between 5 and 9 years. Cranial nerve palsies occurred in 29 patients (27 had abducent palsy), 26 of which resolved within 6 months of trauma. 23.5% underwent surgery, and 76.5% were conservatively managed. Surgeries targeted hematomas, hydrocephalus, or craniocervical instability. Approaches to hematomas included transclival and far/extreme lateral suboccipital approaches. Clinical outcome was good in 75.4% and intermediate or poor in 24.6%. Logistic regression suggested an association between craniocervical junction injuries and poor or intermediate outcomes (OR 4.88, 95% CI (1.17, 27.19), p = 0.04). CONCLUSION: Pediatric RCHs are mostly traumatic and extradural. Children between 5 and 9 years old are most vulnerable. Craniocervical junction injuries, mainly ligamentous, are common in RCHs and are associated with intermediate or poor outcomes. Cervical MRI could be important in cases of trauma to rule out ligamentous injuries of the craniocervical junction. The small size of RCHs should not exempt the careful assessment of craniocervical junction instability. Cranial nerve palsies are common and usually resolve within 6 months. Conservative treatment is typical unless brainstem compression, hydrocephalus, or craniocervical junction instability exists.

Presentations and outcomes of familial hemophagocytic lymphohistiocytosis in the pediatric intensive care units (PICUs).

Objectives: We aimed to describe Familial Hemophagocytic Lymphohistiocytosis (F-HLH) patients' clinical features, intensive care courses, and outcomes. Methods: Multi-center retrospective cohort study of pediatric patients diagnosed with F-HLH from 2015 to 2020 in five tertiary centers in Saudi Arabia. Patients were classified as F-HLH based on their genetic confirmation of known mutation or on their clinical criteria, which include a constellation of abnormalities, early disease onset, recurrent HLH in the absence of other causes, or a family history of HLH. Results: Fifty-eight patients (28 male, 30 female), with a mean age of 21.0 ± 33.9 months, were included. The most common principal diagnosis was hematological or immune dysfunction (39.7%), followed by cardiovascular dysfunction in 13 (22.4%) patients. Fever was the most common clinical presentation in 27.6%, followed by convulsions (13.8%) and bleeding (13.8%). There were 20 patients (34.5%) who had splenomegaly, and more than 70% of patients had hyperferritinemia >500 mg/dl, hypertriglyceridemia >150 mg/dl and hemophagocytosis in bone marrow biopsy. Compared to deceased patients 18 (31%), survivors had significantly lower PT (p = 041), bilirubin level of <34.2 mmol/L (p = 0.042), higher serum triglyceride level (p = 0.036), and lesser bleeding within the initial 6 h of admission (p = 0.004). Risk factors for mortality included requirements of higher levels of hemodynamic (61.1% vs. 17.5%, p = 0.001) and respiratory (88.9% vs. 37.5%, p < 0.001) support, and positive fungal cultures (p = 0.046). Conclusions: Familial HLH still represents a challenge in the pediatric critical care setting. Earlier diagnosis and prompt initiation of appropriate treatment could improve F-HLH survival.

QIPS CURE: Implementing a Quality Improvement and Patient Safety Curriculum and Resident Experience.

BACKGROUND: Resident participation in quality improvement and patient safety (QIPS) programs is an essential training experience and Accreditation Council for Graduate Medical Education requirement. However, the most effective approach to achieve this is unclear. OBJECTIVE: We developed an experiential Quality Improvement and Patient Safety Curriculum and Resident Experience (QIPS CURE) program, which provides internal medicine (IM) residents with foundational QIPS knowledge, and evaluated its effectiveness. METHODS: After reviewing IM residency QIPS curricula and obtaining input from institutional stakeholders in 2013-2014, we launched a longitudinal QIPS curriculum for all 66 postgraduate year 1-3 IM residents in July 2014. The QIPS CURE included 2 major elements: didactics, delivered through a variety of sources, including online modules and workshops, and hands-on projects. We delivered this curriculum annually from 2014 to 2018. We used project completion and an attitude survey of participants to evaluate it. RESULTS: Six projects were completed in 2014-2015, and 10 projects completed yearly for the next 3 academic years. Residents presented all projects at regional meetings. Surveyed residents reported improvement in understanding (M = 5.71, SD = 1.07 pre- to M = 6.38, SD = 0.49 post-curriculum, P = .013) and competence (M = 3.31, SD = 1.18 pre- to M = 6.08, SD = 0.77, post-curriculum, P < .001) when comparing graduates of the curriculum with incoming interns. Qualitative analysis revealed perceived acquisition of skills needed to carry out successful QIPS projects. CONCLUSIONS: This QIPS program was sustainable over 4 years and generally well-received by residents, with many projects completed each year.

Serum Biomarkers for the Early Detection of the Early-Onset Neonatal Sepsis: A Single-Center Prospective Study.

BACKGROUND: Reducing the hazards of the early-onset neonatal sepsis (EONS) is a priority justifying the further investigation for potential biomarkers for its early diagnosis. PURPOSE: We aimed to investigate the diagnostic value of presepsin, procalcitonin, lactoferrin, interleukin (IL)-6, and IL-8 for the early diagnosis of EONS. METHODS: A prospective comparative study, including 30 cases with highly suspected EONS and 30 matched controls, was conducted. Besides the complete blood count and blood culture, C-reactive protein, procalcitonin, presepsin, IL-6, IL-8, and lactoferrin were measured at the admission and after 72 hours. RESULTS: At the time of the admission, presepsin, procalcitonin, C-reactive protein, and IL-8 were significantly higher in the sepsis group. The levels of presepsin, procalcitonin, and IL-8 significantly decreased after 72 hours of the admission. Presepsin, procalcitonin, IL-8, and IL-6 showed a high diagnostic ability for sepsis at admission with area under the curve of 0.934, 0.798, 0.775, and 0.751, respectively. The cutoff values of presepsin, procalcitonin, IL-8, and IL-6 were 821 pg/mL, 2.3 ng/mL, 54 pg/mL, and 24 pg/mL, with a sensitivity of 88.9%, 72.2%, 83.3%, and 94.4% and specificity of 85.7%, 80.9%, 71.4%, and 52.4%, respectively. Lactoferrin had the lowest diagnostic ability with area under the curve of 0.558. IMPLICATIONS FOR PRACTICE: Presepsin was the most accurate biomarker followed by procalcitonin, IL-8, and IL-6 regarding the early diagnosis and management of EONS. The combination between these biomarkers is highly recommended. IMPLICATIONS FOR RESEARCH: Further studies are needed to investigate the diagnostic ability of the combination of these biomarkers.

Do clinicians want recommendations? A multicenter study comparing evidence summaries with and without GRADE recommendations.

OBJECTIVES: Evidence-based clinical practice guidelines provide recommendations to assist clinicians in decision-making and to reduce the gap between best current research evidence and clinical practice. However, some argue that providing preappraised evidence summaries alone, rather than recommendations, is more appropriate. The objective of the study is to evaluate clinicians' preferences, and understanding of the evidence and intended course of action in response to evidence summaries with and without recommendations. STUDY DESIGN SETTING: We included practicing clinicians attending educational sessions across 10 countries. Clinicians were randomized to receive relevant clinical scenarios supported by research evidence of low or very low certainty and accompanied by either strong or weak recommendations developed with the GRADE system. Within each group, participants were further randomized to receive the recommendation plus the corresponding evidence summary or the evidence summary alone. We evaluated participants' preferences and understanding for the presentation strategy, as well as their intended course of action. RESULTS: One hundred eighty-nine of 219 (86%) and 201 of 248 (81%) participants preferred having recommendations accompanying evidence summaries for both strong and weak recommendations, respectively. Across all scenarios, less than half of participants correctly interpreted information provided in the evidences summaries (e.g., estimates of effect, certainty in the research evidence). The presence of a recommendation resulted in a more appropriate intended course of action for two scenarios involving strong recommendations. CONCLUSION: Evidence summaries alone are not enough to impact clinicians' course of action. Clinicians clearly prefer having recommendations accompanying evidence summaries in the context of low or very low certainty of evidence (Trial registration NCT02006017).

Takotsubo cardiomyopathy secondary to spontaneous right-sided pneumothorax.

Takotsubo cardiomyopathy (TCM) is a unique type of cardiomyopathy characterised by left ventricular systolic dysfunction in association with stressful conditions. Patients with this condition usually present with chest pain and dyspnoea, and the presentation can mimic acute coronary syndrome. We present a case of a woman aged 58 years who presented with progressive dyspnoea and cough. Her initial evaluation was suggestive of acute myocardial infarction with elevated serum troponin T and ST segment elevation. Her chest radiograph showed a large right-sided pneumothorax, which was treated with chest tube insertion. Coronary angiography and echocardiogram did not show any evidence of obstructive coronary artery disease but did show a large area of akinesis consistent with TCM. The patient was managed medically with supportive care. Her pneumothorax resolved, and her follow-up echocardiogram also showed improvement. The association between pneumothorax and TCM is rare, and only four other cases have been reported so far in the English literature.

Gut microbiome alterations in patients with stage 4 hepatitis C.

BACKGROUND: Hepatitis C virus (HCV) causes debilitating liver diseases, which may progress to cirrhosis and cancer, and claims 500,000 annual lives worldwide. While HCV epidemiology, pathophysiology, and therapy are being deeply studied, rare attention is given to reciprocal interactions between HCV infection , HCV-induced chronic liver diseases, and the human gut microbiome. As Egypt has the world's highest prevalence of HCV infections, we launched this study to monitor differences in the gut microbial community composition of Egyptian HCV patients that may affect, or result from, the patients' liver state. RESULTS: To this end, we analyzed stool samples from six stage 4-HCV patients and eight healthy individuals by high-throughput 16S rRNA gene sequencing using Illumina MiSeq. Overall, the alpha-diversity of the healthy persons' gut microbiomes was higher than those of the HCV patients. Whereas members of phylum Bacteroidetes were more abundant in HCV patients, healthy individuals had higher abundance of Firmicutes, Proteobacteria, and Actinobacteria. Genus-level analysis showed differential abundance of Prevotella and Faecalibacterium (higher in HCV patients) vs. Ruminococcus and Clostridium (healthy group), indicating that the higher abundance of Bacteroidetes in HCV patients is most likely due to Prevotella overabundance. The probiotic genus, Bifidobacterium, was only observed in the microbiotas of healthy individuals. CONCLUSIONS: To the best of our knowledge, this study provides a first overview of major phyla and genera differentiating stage 4-HCV patients from healthy individuals and suggests possible microbiome remodeling in chronic hepatitis C, possibly shaped by bacterial translocation as well as the liver's impaired role in digestion and protein synthesis. Future studies will investigate the microbiome composition and functional capabilities in more patients while tracing some potential biomarker taxa (e.g., Prevotella, Faecalibacterium vs. Bifidobacterium).

Capecitabine-Induced Takotsubo Cardiomyopathy: A Case Report and Literature Review.

Capecitabine is an orally administered chemotherapeutic agent that is metabolized at the tumor site to 5-fluorouracil and thought to be without significant cardiac toxicity. We report a rare case of takotsubo cardiomyopathy that is thought to be related to capecitabine where the patient presented with chest pain, and ST elevation within 48 hours of capecitabine therapy. Workup included cardiac catheterization and coronary angiogram that showed nonobstructive coronary artery disease and anteroapical left ventricular wall motion abnormality with left ventricular ejection fraction of 35%. The drug was stopped, and the patient was treated with beta-blocker and angiotensin-converting enzymes inhibitor. Six weeks later, she had a repeat echocardiogram that was normal. Capecitabine-related cardiomyopathy seems to be very rare because only 5 cases have been reported in the literature (including our case). The condition has to be anticipated and treated to prevent the serious consequence of cardiac dysfunction. All reported cases have eventually recovered after stopping capecitabine.

Ultrasound-guided hip joint injections are more accurate than landmark-guided injections: a systematic review and meta-analysis.

AIM: To compare the accuracy of ultrasound (US)-guided versus landmark-guided hip joint injections. METHODS: PubMed, Medline and Cochrane libraries were searched up to 31 July 2014. Two independent authors selected studies assessing accuracy of intra-articular hip injections based on predetermined inclusion and exclusion criteria. Selected papers were then evaluated for quality and a meta-analysis of accuracy was performed using random effects models. RESULTS: 4 US-guided (136 hip injections) and 5 landmark-guided (295 hip injections) studies were reviewed. The weighted means for US-guided and landmark-guided hip injection accuracies were 100% (95% CI 98% to 100%) and 72% (95% CI 56% to 85%), respectively. US-guided hip injection accuracy was significantly higher than landmark-guided accuracy (p<0.0001). SUMMARY: This is the first systematic review and meta-analysis of the accuracy of US-guided versus landmark-guided hip joint injections that has revealed that US-guided injections are significantly more accurate than those that are landmark guided. Future studies should compare US with fluoroscopic-guided hip joint injections for accuracy, efficacy, safety profile, cost-effectiveness and patient satisfaction.

Rhabdomyolysis as the first manifestation of human immunodeficiency virus infection.

Renal tubular acidosis (RTA) is a known complication of anti-retroviral medications. The presence of RTA in treatment naive-HIV patients is rare. A 49-year-old Caucasian woman presented with recurrent non-anion gap metabolic acidosis, AKI, rhabdomyolysis and hypokalemia on several occasions. Diagnosis of acquired distal RTA due to HIV was made given the history and laboratory data. To the best of our knowledge, this is the first case of HIV diagnosed with an initial presentation of rhabdomyolysis. We believe that acute renal failure was due to hypokalemia precipitating rhabdomyolysis caused by HIV-induced dRTA which was further exacerbated by amphetamine use.

Honorary authorship in postgraduate medical training.

OBJECTIVES: To determine whether postgraduate medical trainees are exposed to honorary authorship, whether they are aware of the topic and if they believe that further support and education concerning this issue is needed. METHODS: Postgraduate medical trainees were contacted by email with a link to our questionnaire on two occasions (2 and 26 February 2014) and then contacted in person (June-November 2014). The questionnaire topics included demographics, authorship practice beliefs and experience, and authorship policy-related questions. We also determined the proportion of perceived, International Committee of Medical Journal Editors (ICMJE)-defined and unperceived honorary authorship in the respondent group. RESULTS: The response rate was 27.7%. The prevalence of perceived, ICMJE-defined and unperceived honorary authorship was 38.1%, 57.3% and 24.2%, respectively; 90.1% were unaware of the ICMJE authorship criteria, 92.6% were unaware of a support system for authorship disputes, but 91.8% believed such a system should be implemented and 93.3% believed medical trainees and faculty should be instructed on authorship guidelines. CONCLUSIONS: A paradigm shift from the current system is needed, where enforcement of ethical authorship practices is shifted away from journal editors. Instruction on the topic should be provided to medical trainees throughout medical school and continued during further training. A process should also be outlined to resolve authorship disputes. These measures may encourage researchers to have an open discussion on the topic prior to the commencement of a research project, and to resolve authorship conflicts in a constructive manner. We also hope this paper encourages further work on the topic.

Azithromycin and Risk of Cardiovascular Death: A Meta-Analytic Review of Observational Studies.

Recent evidence, though conflicting, suggests an association between azithromycin use and cardiovascular death. We conducted a systematic review and meta-analysis to evaluate the effect of azithromycin on risk of death. Multiple databases were searched. Authors independently screened and extracted the data from studies. Primary outcome of interest was risk of death (cardiovascular and/or noncardiovascular). Subgroup analyses were conducted to explore the source of a possible heterogeneity. Random effects model meta-analysis and hazards ratio (HR) were used to pool the data and calculate the overall effect estimate, respectively. Eight hundred twenty-eight citations, identified with 5 cohort studies that involved 2,246,178 episodes of azithromycin use, met our inclusion criteria. Azithromycin use was not associated with higher risk of death from any cause, HR = 0.99 [confidence interval (CI), 0.82-1.19], I = 54%, or cardiovascular cause, HR = 1.15 (CI, 0.66-2.00), I = 64%, but there was a moderate degree of heterogeneity. Subgroup analyses have shown no increased risk of death with azithromycin use in younger population with zero degree of heterogeneity, HR = 0.85 (CI, 0.66-1.09), I = 0%. However, current use of azithromycin (within 1-5 days of therapy) was associated with a higher risk of death among older population with mild degree of heterogeneity, HR = 1.64 (CI, 1.23-2.19), I = 4%. In summary, azithromycin use was not associated with higher risk of death particularly in younger population. Nevertheless, older population might be at higher risk of death with current use of azithromycin, and an alternative therapy should probably be considered.

Acetabular anteversion is associated with gluteal tendinopathy at MRI.

OBJECTIVE: Gluteal tendinopathy and greater trochanteric pain syndrome (GTPS) remain incompletely understood despite their pervasiveness in clinical practice. To date, no study has analyzed the morphometric characteristics of the hip on magnetic resonance imaging (MRI) that may predispose to gluteal tendinopathy. This study aimed to evaluate whether acetabular anteversion (AA), femoral neck anteversion (FNA), and femoral neck-shaft angle (FNSA) are associated with MRI features of gluteal tendinopathy. MATERIALS AND METHODS: A total of 203 MRI examinations of the hip met our inclusion and exclusion criteria. A single blinded investigator measured AA, FNA, and FNSA according to validated MRI techniques. Two blinded subspecialty-trained musculoskeletal radiologists then independently evaluated the presence of gluteal tendinosis, trochanteric bursitis, and subgluteal bursitis. Statistical analysis was performed using a one-way analysis of variance (ANOVA; post-hoc Tukey's range test). RESULTS: At MRI, 57 patients had gluteal tendinosis with or without bursitis, 26 had isolated trochanteric bursitis, and 11 had isolated subgluteal bursitis. AA was significantly (p = 0.01) increased in patients with MRI evidence of gluteal tendinosis with or without bursitis [mean: 18.4°, 95 % confidence interval (CI): 17.2°-19.6°] compared with normal controls (mean: 15.7°, 95 % CI: 14.7°-16.8°). Similarly, AA was significantly (p = 0.04) increased in patients with isolated trochanteric bursitis (mean: 18.8°, 95 % CI: 16.2°-21.6°). No association was found between FNA or FNSA and the presence of gluteal tendinopathy. Interobserver agreement for the presence and categorization of gluteal tendinopathy was very good (kappa = 0.859, 95 % CI: 0.815-0.903). CONCLUSION: Our MRI study suggests that there is an association between increased AA and gluteal tendinopathy, which supports a growing body of evidence implicating abnormal biomechanics in the development of this condition.

Ultrasound-guided shoulder girdle injections are more accurate and more effective than landmark-guided injections: a systematic review and meta-analysis.

OBJECTIVE: To compare the accuracy and efficacy of ultrasound (US)-guided injections versus landmark-guided injections of the subacromial space, biceps tendon sheath, acromioclavicular (AC) joint and glenohumeral (GH) joint. METHODS: PubMed, Medline and Cochrane libraries were searched up to 31 July 2013. Two independent authors selected and evaluated randomised controlled trials comparing the accuracy and/or efficacy of US versus landmark-guided injection of the shoulder girdle. A meta-analysis of accuracy, pain Visual Analog Scale (VAS), function score and reported adverse events were performed. RESULT: Four cadaveric studies (300 cadaveric shoulders) and nine live human studies (514 patients) were reviewed. Based on three studies for AC joint, the accuracy of US versus a landmark-guided injection was 93.6% vs 68.2% (p<0.0001). Based on single studies, the accuracy of US versus a landmark-guided injection was 65% vs 70% for the subacromial space (p>0.05), 86.7% vs 26.7% for the biceps tendon sheath (p<0.05), and 92.5% vs 72.5% for the GH joint (p=0.025). Based on three studies for the subacromial space, the US group had a significantly greater reduction in pain (mean difference (MD)=1.47, 95% CI 1.0 to 1.93), and improvement in function (standardised MD=0.70, 95% CI 0.39 to 1.01) at 6 weeks postinjection. Based on a single study for the biceps tendon sheath, the US group had a significantly greater reduction in pain (MD 1.9, 95% CI 1.2 to 2.6) and improvement in function (MD=10.9, 95% CI 6.57 to 15.23). CONCLUSIONS: US-guided injections showed greater accuracy for all shoulder girdle injections, with the exception of the subacromial space. There was improved efficacy for the subacromial space and biceps tendon sheath injections.

Feasibility of ultrasound-guided percutaneous tenotomy of the long head of the biceps tendon--A pilot cadaveric study.

OBJECTIVE: To describe an ultrasound-guided proximal percutaneous tenotomy technique of long head of the biceps tendon (LHBT). METHODS: Three fresh cadavers with no prior shoulder surgery or LHBT tears were included in the study. A single experienced musculoskeletal radiologist completed six ultrasound-guided proximal percutaneous tenotomies of LHBT. A superficial to deep approach was performed on four shoulders using an arthroscopic banana blade or retractable blade. A deep to superficial approach was performed on two shoulders using an arthroscopic hook blade. A blinded anatomist dissected each specimen and graded the tenotomy, length of proximal LHBT stump, and evidence of iatrogenic injuries. RESULTS: Four of the six cadaveric LHBTs were fully transected. The two partially transected tenotomies were performed using the arthroscopic banana and retractable serrated blades (63% and 80% transections, respectively). The proximal LHBT stump mean length was 2.6 cm (95% CI, 1.8-3.4). There was no evidence of iatrogenic lesions. CONCLUSIONS: This cadaveric study showed that the ultrasound-guided percutaneous tenotomy of the LHBT is a feasible procedure. The deep to superficial approach using an arthroscopic hook blade resulted in complete transection. Further cadaveric studies with larger numbers are warranted to confirm this novel technique's applicability in clinical practice.

Bilateral ulnar neuropathy at the elbow secondary to neuropathic arthropathy associated with syringomyelia.

Neuropathic arthropathy (NA), also known as Charcot joint, refers to a chronic progressive degenerative arthritis that is associated with an underlying central or peripheral neurologic disorder. The elbow is rarely reported to be involved in NA, but when affected, it is commonly a result of a cervical syrinx or tabes dorsalis. Few reports in the literature describe ulnar neuropathy at the elbow (UNE) associated with NA of the elbow, and none describe bilateral UNE in association with a cervicothoracic syrinx. We present a unique case of bilateral UNE resulting from NA of the elbow associated with a cervicothoracic syrinx.

The utility of ultrasound in detecting anterior compartment thickness changes in chronic exertional compartment syndrome: a pilot study.

OBJECTIVE: To test the hypothesis that patients with chronic exertional compartment syndrome (CECS) of the anterior leg compartment have an increased anterior compartment thickness (ACT) compared with control subjects after exertion using ultrasound. DESIGN: Prospective comparison study. SETTING: Diagnostic imaging department of a tertiary care hospital. PATIENTS: Four patients with CECS and 9 control subjects. INTERVENTIONS: Patients with CECS and control subjects ran on a treadmill for up to 10 minutes. Anterior compartment thickness (both groups) and anterior compartment pressure (CECS patients) were measured before exertion and at scheduled intervals after exertion. MAIN OUTCOME MEASURES: Anterior compartment thickness, percentage change in ACT from rest, and compartment pressure. RESULTS: Anterior compartment pressures were diagnostic of CECS using the modified Pedowitz criteria in patients with CECS. Mean percentage change in ACT from rest in patients with CECS versus control subjects at 0.5 minutes was 21.3% versus 6.32% [95% confidence interval (CI), 6.92-35.6 and 0.094-12.5, respectively; P = 0.011]; at 2.5 minutes, it was 24.6% versus 4.22% (95% CI, 10.7-38.5 and -1.85-10.3, respectively; P = 0.003); and at 4.5 minutes, it was 24.9% versus 5.08% (95% CI, 14.3-35.5 and -0.813-11.0, respectively; P = 0.003). Mean ACT in patients with CECS versus control subjects significantly increased after exertion (P = 0.003) at 0.5 minutes, 2.5 minutes, and 4.5 minutes. CONCLUSIONS: Ultrasonography reveals a significant increase in ACT in patients with CECS of the anterior leg compartment. Further studies are warranted to validate these findings with the goal of developing anterior leg compartment CECS ultrasound diagnostic criteria and exploring the role of using ultrasound to diagnose CECS in other compartments.

DITPA, a thyroid hormone analog, reduces infarct size and attenuates the inflammatory response following myocardial ischemia.

BACKGROUND: Thyroid hormone can have positive effects on the cardiovascular system but its therapeutic potential is limited secondary to its adverse effects. DITPA (3,5-diiodothyroproprionic acid) is a synthetic thyroid hormone analog with positive inotropic effects similar to thyroid hormone but with minimal systemic effects. DITPA has previously been shown to reduce pathologic remodeling and improve cardiac output following myocardial infarction; however, few studies have examined the role of DITPA in determining infarct size or the early inflammatory response following myocardial ischemia. We examined the role of DITPA in the acute phase following infarction. MATERIALS AND METHODS: Mice were subjected to surgical induction of myocardial infarction and were then randomized to receive daily injections of DITPA or vehicle control. After 3 d, animals were sacrificed and infarct size was determined by H and E staining. Myocardial macrophage and neutrophil accumulation was determined by immunofluorescent staining. Immunoblotting and enzyme-linked immunosorbent assay (ELISA) were used to examine the levels of intercellular adhesion molecule-1 (ICAM-1), keratinocyte-derived chemokine (KC), monocyte chemoattractant protein (MCP-1), and interleukin 6 (IL-6) in homogenates from the ischemic tissue. RESULTS: Compared with vehicle control, DITPA treated animals had smaller infarcts (52.1%±5.7% versus 37.3%±3.6%, P<0.05) and decreased macrophage (32±4 versus 14±1 cells/HPF, P<0.05, and neutrophil (14±2 versus 7±1 cells/HPF, P<0.05) accumulation. Myocardial ICAM-1, (2.37±0.4 versus 1.1±0.2, P<0.05), KC levels (33.32±12.4 pg/mg, versus 21.24±8.9 pg/mg, P<0.05), and IL-6 levels (112.3±78 pg/mg versus 37.3±25.9 pg/mg, P<0.05) were also reduced in the DITPA treated group, while MCP-1 levels were equivalent between groups. CONCLUSIONS: Treatment with DITPA attenuates the acute inflammatory response and reduces myocardial infarct size. The reduction in myocardial ICAM-1, KC, and IL-6 levels in the DITPA group was associated with a decrease in macrophage and neutrophil accumulation.

Improved survival of mesenchymal stromal cell after hypoxia preconditioning: role of oxidative stress.

AIMS: To investigate the mechanisms underlying the beneficial effect of hypoxia preconditioning (HPC) on mesenchymal stromal cells (MSCs) and optimize novel non-invasive methods to assess the effect of biological interventions aimed to increased cell survival. MAIN METHODS: MSCs from rat femur, with or without HPC, were exposed to hypoxic conditions in cell culture (1% O(2) for 24h) and cell survival (by the LDH release assay and Annexin-V staining) was measured. Oxidant status (conversion of dichloro-fluorescein-DCF- and dihydro-ethidium-DHE-, protein expression of oxidant enzymes) was characterized, together with the mobility pattern of cells under stress. Furthermore, cell survival was assessed non-invasively using state-of-the-art molecular imaging. KEY FINDINGS: Compared to controls, Hypoxia resulted in increased expression of the oxidative stress enzyme NAD(P)H oxidase (subunit 67(phox): 0.05 ± 0.01AU and 0.48 ± 0.02AU, respectively, p<0.05) and in the amount of ROS (DCF: 13 ±1 and 42 ± 3 RFU/µg protein, respectively, p<0.05) which led to a decrease in stem cell viability. Hypoxia preconditioning preserved cell biology, as evidenced by preservation of oxidant status (16 ± 1 RFU/µg protein, p<0.05 vs. hypoxia), and cell viability. Most importantly, the beneficial effect of HPC can be assessed non-invasively using molecular imaging. SIGNIFICANCE: HPC preserves cell viability and function, in part through preservation of oxidant status, and its effects can be assessed using state-of-the-art molecular imaging. Understanding of the mechanisms underlying the fate of stem cells will be critical for the advancement of the field of stem cell therapy.