Acute Effect in Mechanical Efficiency by Pressure-Volume Loop Analysis after Transcatheter Aortic Valve Implantation.

Background: This study aimed to evaluate the immediate effect of transcatheter aortic valve implantation (TAVI) on mechanical efficiency. Methods: A total of 46 patients (25 females) with an average age of 83 ± 6.4 years underwent TAVI using the CoreValve system. During the same hospitalization, we conducted a comprehensive comparison of the patients before and after TAVI without inotropic support using echocardiography. The parameters encompassed left ventricular (LV) geometry, valvular load, global LV afterload and ventricular hemodynamics. The analysis using pressure-volume loops enabled the determination of load-independent contractility (Ees) and afterload, in addition to assessing potential energy, stroke work, and mechanical efficiency. Results: The immediate effect was an augmented aortic valve area accompanied by a reduction in the transvalvular pressure gradient. We observed reductions in left ventricular end-systolic volume and end-diastolic volume, and also reductions in global afterload and end-systolic meridional wall stress. The Ea index decreased, while the Ees index remained relatively stable. We noted increases in stroke volume and systemic arterial compliance, indicating more efficient blood transfer from the ventricle to aorta. These changes contributed to the normalization of ventricular-arterial coupling. In terms of mechanical work of the chamber, we observed significant decreases in potential energy, stroke work, and pressure-volume area. There was an increase in the mechanical efficiency of the chamber. Conclusions: The TAVI procedure immediately reduced global afterload and improved diastolic compliance of the chamber, resulting in enhanced ventricular function and mechanical efficiency.

An Update on Gene Therapy for Inherited Retinal Dystrophy: Experience in Leber Congenital Amaurosis Clinical Trials.

Inherited retinal dystrophies (IRDs) are a group of rare eye diseases caused by gene mutations that result in the degradation of cone and rod photoreceptors or the retinal pigment epithelium. Retinal degradation progress is often irreversible, with clinical manifestations including color or night blindness, peripheral visual defects and subsequent vision loss. Thus, gene therapies that restore functional retinal proteins by either replenishing unmutated genes or truncating mutated genes are needed. Coincidentally, the eye's accessibility and immune-privileged status along with major advances in gene identification and gene delivery systems heralded gene therapies for IRDs. Among these clinical trials, voretigene neparvovec-rzyl (Luxturna), an adeno-associated virus vector-based gene therapy drug, was approved by the FDA for treating patients with confirmed biallelic RPE65 mutation-associated Leber Congenital Amaurosis (LCA) in 2017. This review includes current IRD gene therapy clinical trials and further summarizes preclinical studies and therapeutic strategies for LCA, including adeno-associated virus-based gene augmentation therapy, 11-cis-retinal replacement, RNA-based antisense oligonucleotide therapy and CRISPR-Cas9 gene-editing therapy. Understanding the gene therapy development for LCA may accelerate and predict the potential hurdles of future therapeutics translation. It may also serve as the template for the research and development of treatment for other IRDs.

What is the impact of the COVID-19 pandemic on emergency medicine residency training: an observational study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has engendered difficulties for health systems globally; however, the effect of the pandemic on emergency medicine (EM) residency training programs is unknown. The pandemic has caused reduced volumes of emergency department (ED) patients, except for those with COVID-19 infections, and this may reduce the case exposure of EM residents. The primary objective of this study was to compare the clinical exposure of EM residents between the prepandemic and pandemic periods. METHODS: This was a retrospective study of EM resident physicians' training in a tertiary teaching hospital with two branch regional hospitals in Taiwan. We retrieved data regarding patients seen by EM residents in the ED between September 1, 2019, and April 30, 2020. The first confirmed COVID-19 case in Taiwan was reported on January 11, so the pandemic period in our study was defined as spanning from February 1, 2020, to April 30, 2020. The number and characteristics of patients seen by residents were recorded. We compared the data between the prepandemic and pandemic periods. RESULTS: The mean number of patients per hour (PPH) seen by EM residents in the adult ED decreased in all three hospitals during the pandemic. The average PPH of critical area of medical ED was 1.68 in the pre-epidemic period and decreased to 1.33 in the epidemic period (p value < 0.001). The average number of patients managed by residents decreased from 1.24 to 0.82 in the trauma ED (p value = 0.01) and 1.56 to 0.51 in the pediatric ED (p value = 0.003) during the pandemic, respectively. The severity of patient illness did not change significantly between the periods. CONCLUSIONS: The COVID-19 pandemic engendered a reduced ED volume and decreased EM residents' clinical exposure. All portion of EM residency training were affected by the pandemic, with pediatric EM being the most affected. The patient volume reduction may persist and in turn reduce patients' case exposure until the pandemic subsides. Adjustment of the training programs may be necessary and ancillary methods of learning should be used to ensure adequate EM residency training.

Is 15 minutes an appropriate resuscitation duration before termination of a traumatic cardiac arrest? A case-control study.

BACKGROUND: Previous guidelines suggest up to 15 minutes of cardiopulmonary resuscitation (CPR) accompanied by other resuscitative interventions before terminating resuscitation of a traumatic cardiac arrest. The current study evaluated the duration of CPR according to outcome using the model of a county-based emergency medical services (EMS) system in Taiwan. METHODS: This study was performed as a prospectively defined retrospective review from EMS records and cardiac arrest registration between June 2011 and November 2012 in Taoyuan, Taiwan. RESULTS: A total of 396 patients were enrolled. Among the blunt injuries, most incidents were traffic accidents (66.5%) followed by falls (31.5%). Bystander CPR was performed in 34 patients (8.6%). Of the patients, 18.4% were sent to intermediate to advanced level traumatic care hospitals. Although 4.8% of patients survived for 24 hours, only 2.3% survived to discharge, and 0.8% achieved cerebral performance category 1 or 2. Among all patients who developed return of spontaneous circulation (ROSC), 14.3% of ROSC was achieved within 15 minutes since CPR. Except for 1, most patients who developed ROSC over 24 hours but did not survive to discharge received CPR more than 15 minutes. Four of 6 patients who survived to discharge achieved ROSC after CPR for more than 15 minutes (16, 18, 22, and 24 minutes). Three patients discharged with cerebral performance category 1 or 2 received CPR for 6, 16, and 18 minutes, respectively. CONCLUSIONS: Fifteen minutes of CPR before terminating resuscitation is inappropriate for patients undergoing traumatic cardiac arrsests, as longer duration resuscitation increases ROSC and survival.

Reducing Left Ventricular Wall Stress through Aortic Valve Enlargement via Transcatheter Aortic Valve Implantation in Severe Aortic Stenosis.

Background: In aortic stenosis, the left ventricle exerts additional force to pump blood through the narrowed aortic valve into the downstream arterial vasculature. Adaptive hypertrophy helps to maintain wall stress homeostasis but at the expense of impaired compliance. Advanced ventricular deformation impacts the extent of functional recovery benefits achieved through transcatheter aortic valve implantation. Methods and Results: Subgroups were stratified based on output, with low-flow severe aortic stenosis defined as stroke volume index <35 mL· m-2. Before intervention, the low-flow subgroup exhibited worse effective orifice area index and arterial and global impedance, along with thinner wall thickness and larger chamber volume marginally. LV performance, including stroke volume index, ventricular elastance, and ventricular-arterial coupling, were notably inferior, consistent with worse adverse remodeling. Although the effective orifice area index was similarly augmented after TAVI, inferior recovery benefits were noted. Persistently higher wall stress and energy consumption were observed, along with poorer ventricular-arterial coupling. These changes in wall stress showed an inverse relationship with alterations in wall thickness and were proportional to changes in dimension and volume. Additionally, they were proportional to changes in left ventricular end-systolic pressure, pressure-volume area, and ventricular-arterial coupling but inversely related to ventricular end-systolic elastance. Conclusions: The study revealed that aortic valve enlargement through transcatheter aortic valve implantation reduces left ventricular wall stress in severe aortic stenosis. The reduced recovery benefits in the low-flow subgroup were evident. Wall stress could serve as a marker of mechanical benefit after the intervention.

The effects of topical anesthesia on outcomes and glucose control in diabetic patients treated with split-thickness skin graft surgery.

BACKGROUND: Using split-thickness skin grafting to treat diabetic foot and leg ulcers is common. Diabetic patients usually exhibit multiple comorbidities and high risks of adverse responses to general and spinal anesthesia. Topical anesthesia can be an alternative to avoid these risks. In this study, the clinical experience of split-thickness skin grafting under topical anesthesia was demonstrated, to evaluate its effectiveness and benefits in diabetic patients. METHODS: From 2018 to 2020, diabetic patients with foot or leg wounds undergoing split-thickness skin grafting were reviewed and categorized into two groups according to the anesthesia methods: topical anesthesia and general/spinal anesthesia. Patient demographics, wound characteristics and healing status, postoperative complications, and perioperative blood glucose levels were recorded and analyzed. RESULTS: During the study period, 28 patients underwent split-thickness skin grafting under topical anesthesia and 46 under general/spinal anesthesia. The rate of complete wound healing in 4 weeks was similar in both the groups. The topical anesthesia group suffered fewer postoperative infections (3.6% vs 21.7%, p = 0.044), required shorter postoperative hospitalization (8.3 ± 6.2 vs 11.1 ± 7.2 days, p = 0.048), and exhibited lower mean blood glucose levels and less glucose variability than the general/spinal anesthesia group. CONCLUSION: Conducting split-thickness skin grafting under topical anesthesia was shown to be a safe and effective means of treating leg and foot wounds in diabetic patients.

Association of In-Hospital Mortality and Dysglycemia in Septic Patients.

BACKGROUND: The associations between dysglycemia and mortality in septic patients with and without diabetes are yet to be confirmed. Our aim was to analyze the association of diabetes and sepsis mortality, and to examine how dysglycemia (hyperglycemia, hypoglycemia and glucose variability) affects in-hospital mortality of patients with suspected sepsis in emergency department (ED) and intensive care units. METHODS: Clinically suspected septic patients admitted to ED were included, and stratified into subgroups according to in-hospital mortality and the presence of diabetes. We analyzed patients' demographics, comorbidities, clinical and laboratory parameters, admission glucose levels and severity of sepsis. Odds ratio of mortality was assessed after adjusting for possible confounders. The correlations of admission glucose and CoV (blood glucose coefficients of variation) and mortality in diabetes and non-diabetes were also tested. RESULTS: Diabetes was present in 58.3% of the patients. Diabetic patients were older, more likely to have end-stage renal disease and undergoing hemodialysis, but had fewer malignancies, less sepsis severity (lower Mortality in Emergency Department Sepsis Score), less steroid usage in emergency department, and lower in-hospital mortality rate (aOR:0.83, 95% CI 0.65-0.99, p = 0.044). Hyperglycemia at admission (glucose≥200 mg/dL) was associated with higher risks of in-hospital mortality among the non-diabetes patients (OR:1.83 vs. diabetes, 95% CI 1.20-2.80, p = 0.005) with the same elevated glucose levels at admission. In addition, CoV>30% resulted in higher risk of death as well (aOR:1.88 vs. CoV between 10 and 30, 95%CI 1.24-2.86 p = 0.003). CONCLUSIONS: This study indicates that while diabetes mellitus seems to be a protective factor in sepsis patients, hyper- or hypoglycemia status on admission, and increased blood glucose variation during hospital stays, were independently associated with increased odds ratio of mortality.

Risk of gastrointestinal perforation in patients taking oral fluoroquinolone therapy: An analysis of nationally representative cohort.

BACKGROUND: Fluoroquinolone is a commonly prescribed antimicrobial agent, and up to 20% of its users registers adverse gastroenterological symptoms. We aimed to evaluate the association between use of fluoroquinolone and gastrointestinal tract perforation. METHODS: We conducted a nested case-control study on a national health insurance claims database between 1998 and 2011. The use of fluoroquinolones was classified into current (< 60 days), past (61-365 days prior to the index date) and any prior year use of fluoroquinolones. We used the conditional logistic regression model to estimate rate ratios (RRs), adjusting or matching by a disease risk score (DRS). RESULTS: We identified a cohort of 17,510 individuals diagnosed with gastrointestinal perforation and matched them to 1,751,000 controls. Current use of fluoroquinolone was associated with the greatest increase in risk of gastrointestinal perforations after DRS score adjustment (RR, 1.90; 95% CI, 1.62-2.22). The risk of gastrointestinal perforation was attenuated for past (RR, 1.33; 95% CI, 1.20-1.47) and any prior year use (RR, 1.46; 95% CI, 1.34-1.59). To gain insights into whether the observed association can be explained by unmeasured confounder, we compared the risk of gastrointestinal perforation between fluoroquinolone and macrolide. Use of macrolide, an active comparator, was not associated with a significant increased risk of gastrointestinal perforation (RR, 1.11, 95%CI, 0.15-7.99). Sensitivity analysis focusing on perforation requiring in-hospital procedures also demonstrated an increased risk associated with current use. To mitigate selection bias, we have also excluded people who have never used fluoroquinolone before or people with infectious colitis, enteritis or gastroenteritis. In both of the analysis, a higher risk of gastrointestinal perforation was still associated with the use of fluoroquinolone. CONCLUSIONS: We found that use of fluoroquinolones was associated with a non-negligible increased risk of gastrointestinal perforation, and physicians should be aware of this possible association.

STARD-compliant article: The utility of red cell distribution width to predict mortality for septic patients visiting the emergency department.

Sepsis is a common condition in the emergency department that is associated with high mortality. Red blood cell distribution width (RDW) has been used as a simple prognosis predictor for patients with community-acquired pneumonia, gram-negative bacteremia, and severe sepsis or septic shock. To evaluate the performance of RDW to predict in-hospital mortality among septic patients, we conducted a hospital-based retrospective cohort study in an emergency department of a tertiary teaching hospital. RDW was compared with other commonly used clinical prediction scores (Systemic Inflammatory Response Syndrome (SIRS), Mortality in Emergency Department Sepsis (MEDS) and the Confusion, Urea nitrogen, Respiratory rate, Blood pressure, 65 years of age and older (CURB65)). Of 6973 consecutive adult patients with a clinical diagnosis of sepsis and 2 sets of blood culture ordered by physicians, 477 (6.8%) died. The mortality group had higher RDW levels than the survival group (15.7% vs 13.8%). After dividing RDW into quartiles, the patients in the highest RDW quartile (RDW >15.6%; mortality, 16.7%) had more than twice the risk of in-hospital mortality compared with patients in the second highest quartile (RDW >14% and <15.6%; mortality, 7.3%), whereas the mortality rate in the lowest RDW quartile (<13.1%) was only 1.6%. The area under the receiver operating characteristic curve of RDW to predict mortality was 0.75 (95% confidence interval, 0.72-0.77), which is significantly higher than the areas under the curve of clinical prediction rules (SIRS, MEDS, and CURB65). After integrating RDW into these scores, all scores performed better in predicting mortality (0.73, 0.72, and 0.77, for SIRS, MEDS, and CURB65, respectively). RDW could be an independent predictor of mortality among septic patients. Clinicians could classify the septic patients into different risk groups according to RDW quartiles. For more accurate mortality prediction, RDW could be a potential parameter to be incorporated into clinical prediction rules.

Usefulness of natriuretic peptide for the diagnosis of Kawasaki disease: a systematic review and meta-analysis.

OBJECTIVE: To examine the diagnostic value of serum B-type natriuretic peptide (BNP) in acute Kawasaki disease (KD). DESIGN: Systematic review and meta-analysis. DATA SOURCES: A systematic literature search strategy was designed and carried out using MEDLINE, EMBASE and the Cochrane Library from inception to December 2013. We also performed manual screening of the bibliographies of primary studies and review articles, and contacted authors for additional data. STUDY ELIGIBILITY CRITERIA: We included all BNP and NT-pro (N-terminal prohormone) BNP assay studies that compared paediatric patients with KD to patients with febrile illness unrelated to KD. We excluded case reports, case series, review articles, editorials, congress abstracts, clinical guidelines and all studies that compared healthy controls. PRIMARY AND SECONDARY OUTCOME MEASURES: The performance characteristics of BNP were summarised using forest plots, hierarchical summary receiver operating characteristic (ROC) curves and bivariate random effects models. RESULTS: We found six eligible studies including 279 cases of patients with KD and 203 febrile controls. Six studies examined NT-proBNP and one examined BNP. In general, NT-proBNP is a specific and moderately sensitive test for identifying KD. The pooled sensitivity was 0.89 (95% CI 0.78 to 0.95) and the pooled specificity was 0.72 (95% CI 0.58 to 0.82). The area under the summary ROC curve was 0.87 (95% CI 0.83 to 0.89). The positive likelihood ratio (LR+ 3.20, 95% CI 2.10 to 4.80) was sufficiently high to be qualified as a rule-in diagnostic tool in the context of high pre-test probability and compatible clinical symptoms. A high degree of heterogeneity was found using the Cochran Q statistic. CONCLUSIONS: Current evidence suggests that NT-proBNP may be used as a diagnostic tool for KD. NT-proBNP has high diagnostic value for identifying KD in patients with protracted undifferentiated febrile illness. Prospective large cohort studies are needed to help determine best cut-off values and further clarify the role of NT-proBNP in the diagnosis process of KD.