Observation versus Cast Treatment of Toddler's Fracture: A Prospective Pilot Study.

"Toddler's fractures" are common in the pediatric population. Traditional treatment recommends casting these fractures, although with their inherent stability, may be unnecessary. This study evaluated if toddler's fractures can be treated with observation alone as opposed to casts. A prospective pilot study was performed with randomization and observational arms. Children were placed in short casts or observed without immobilization. A 21-day log was given to families to record walking. Follow up with radiographs occurred at 3 and 12 weeks. Twenty-one patients enrolled, three randomized and 18 chose their treatment. Thirteen patients were casted, and eight went without immobilization. Ambulation time was similar between groups (p = 0.260). Three without immobilization returned early but none converted to cast. All fractures healed uneventfully. There were no cast complications. Toddler's fractures treated with or without cast immobilization appears to be safe and effective but should be a shared decision between physician and parents. (Journal of Surgical Orthopaedic Advances 32(3):207-211, 2023).

Automated Data Cleanup for Mass Cytometry.

Mass cytometry is an emerging technology capable of 40 or more correlated measurements on a single cell. The complexity and volume of data generated by this platform have accelerated the creation of novel methods for high-dimensional data analysis and visualization. A key step in any high-level data analysis is the removal of unwanted events, a process often referred to as data cleanup. Data cleanup as applied to mass cytometry typically focuses on elimination of dead cells, debris, normalization beads, true aggregates, and coincident ion clouds from raw data. We describe a probability state modeling (PSM) method that automatically identifies and removes these elements, resulting in FCS files that contain mostly live and intact events. This approach not only leverages QC measurements such as DNA, live/dead, and event length but also four additional pulse-processing parameters that are available on Fluidigm Helios™ and CyTOF® (Fluidigm, Markham, Canada) 2 instruments with software versions of 6.3 or higher. These extra Gaussian-derived parameters are valuable for detecting well-formed pulses and eliminating coincident positive ion clouds. The automated nature of this new routine avoids the subjectivity of other gating methods and results in unbiased elimination of unwanted events. © 2019 International Society for Advancement of Cytometry.

A biomimetic approach towards phorone sesterterpenoids.

We report an investigation towards a unified total synthesis of the Korean sponge derived sesterterpenoids, phorones A (1) and B (2), via a biomimetic strategy. This work has established a new synthetic strategy to the parent ansellane sesterterpenoid skeleton with unanticipated diversion to a biogenetically related pathway.

Multivariate analysis of hypertension in general US adults based on the 2017 ACC/AHA guideline: data from the national health and nutrition examination survey 1999 to 2016.

PURPOSE: Since the publication of the 2017 ACC/AHA hypertension guideline, few studies have analyzed the epidemiology and management of hypertension across many heterogeneous subgroups in the US. MATERIALS AND METHODS: We analyzed the data collected by the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2016. Participants greater than 20 years of age, who had valid blood pressure measurements, were included in the study. A comprehensive analysis of 14 population subgroups was done to systematically examine how hypertension awareness, treatment, and control varied by subpopulations. RESULTS: Our study included 45,557 participants with a mean age of 47.1 years, 48.3% were male and 51.7% were female. 47.8% participants had hypertension, of which 59.9% were aware of their diagnosis. Among the participants who were aware of their hypertension, 90.3% were prescribed medication(s) to lower blood pressure, of which 39.2% had achieved control. Multivariate analysis showed age, gender, Race/ethnicity, annual family income, education level, BMI, waist to height ratio, diabetes, and previous cardiovascular events to be independent risk factors for hypertension. Lower likelihoods of awareness and treatment were associated with male sex, younger age, Mexican ethnicity, participants without health insurance, absence of previous cardiovascular events, diabetes, obesity, or smoking. Overall, hypertension control rate was suboptimal across most of subgroups (<40%). CONCLUSION: Based on the 2017 ACC/AHA guideline, almost half of the US adult population has hypertension. The suboptimal number of people with controlled blood pressure is pervasive in all subgroups and warrants greater efforts in prevention, as well as more effective treatment.

A new family of sesterterpenoids isolated around the Pacific Rim.

Covering: 2009 up to the end of 2017 There has been a recent eruption in the number of known marine sesterterpenoids which have been isolated from Pacific Rim marine organisms. These compounds have novel and unusual structures that exhibit incredibly potent and varied bioactivities. This review details the isolation, biological testing and prospects for this exciting new family with discussion of their potential biogenetic origins.

Race and ethnicity have significant influence on fractional exhaled nitric oxide.

BACKGROUND: Race and ethnicity have been shown to influence fractional exhaled nitric oxide (FeNO). There is a need to investigate cutoff points for different races and ethnicities to improve clinical application. OBJECTIVE: To investigate cutoff points for different races and ethnicities by analyzing the FeNO data collected by the National Health and Nutrition Examination Survey from 2007 to 2012. METHODS: This study included 23,433 participants. After excluding participants with confounding factors, 11,084 participants were eligible for data analysis. Based on age and the probability of having allergic airway inflammation, participants were divided into 4 groups. The geometric mean and 5th, 50th, and 95th percentiles of FeNO in Hispanic, white, black, and other races were analyzed in all groups. RESULTS: Compared with white participants, the geometric mean for FeNO in black participants was 36% to 41% higher in children and 5% to 8% higher in adults. Hispanic children had significantly higher FeNO values (14% to 19%) compared with non-Hispanic white children; however, those differences were not significant in adults. Other races had significantly higher FeNO values in children (24-54%) and adults (9-29%) compared with white participants. Further, for normal healthy black children, the 95th percentile was 40.2 parts per billion (ppb), which is significantly higher than the cutoff point recommended by current guidelines. CONCLUSION: Although there are significant differences in FeNO values among races and ethnicities, the current cutoff point at 50 ppb is sufficient to separate healthy from asthmatic populations in adults. However, for black children, we suggest increasing the cutoff point from 35 to 40 ppb to avoid unnecessary diagnosis and treatment.

Thromboembolic complications following a first isolated episode of superficial vein thrombosis: a cross-sectional retrospective study.

Superficial vein thrombosis (SVT) may be associated with complications such as venous thromboembolism (VTE) and recurrent SVT. The purpose of this study was to explore risk factors among patients with a first isolated episode of SVT (index SVT) involving upper and lower extremities and to estimate the prevalence of VTE complications within 1 year of index SVT. Retrospective chart review of electronic records at Marshfield Clinic in Wisconsin identified 381 subjects with a first isolated SVT diagnosis (male/female: 170/211; median age 59.4 years). Patients were stratified based on whether they did (n = 44; 11.5 %) or did not (n = 337; 88.5 %) experience VTE complications and whether they did (n = 25; 6.6 %) or did not (n = 356; 93.4 %) experience pulmonary embolism (PE) and/or deep vein thrombosis (DVT) within 1 year of index SVT. There were 49 complications among 44 patients; these included DVT (n = 18, 36.7 %), propagation of SVT (n = 18, 36.7 %), PE (n = 9, 18.4 %), new SVT at different location (n = 3, 6.1 %), and recurrent SVT (n = 1, 2.0 %). Univariate analysis of all VTE complications identified seven potential risk factors and similar analysis of PE/DVT complications identified eight potential risk factors, with six common risk factors identified in both analyses. Multivariate analysis identified indwelling venous catheter 30 days prior to SVT (p = 0.044), cancer history with treatment in the previous year (p = 0.001), and non-surgical trauma 7 days prior to SVT (p < 0.001) as independent risk factors for PE/DVT complications. Independent risk factors identified in the current study may convey greater risk for VTE complications, especially PE/DVT, following an initial isolated SVT episode.

Single-molecule in vivo imaging of bacterial respiratory complexes indicates delocalized oxidative phosphorylation.

Chemiosmotic energy coupling through oxidative phosphorylation (OXPHOS) is crucial to life, requiring coordinated enzymes whose membrane organization and dynamics are poorly understood. We quantitatively explore localization, stoichiometry, and dynamics of key OXPHOS complexes, functionally fluorescent protein-tagged, in Escherichia coli using low-angle fluorescence and superresolution microscopy, applying single-molecule analysis and novel nanoscale co-localization measurements. Mobile 100-200nm membrane domains containing tens to hundreds of complexes are indicated. Central to our results is that domains of different functional OXPHOS complexes do not co-localize, but ubiquinone diffusion in the membrane is rapid and long-range, consistent with a mobile carrier shuttling electrons between islands of different complexes. Our results categorically demonstrate that electron transport and proton circuitry in this model bacterium are spatially delocalized over the cell membrane, in stark contrast to mitochondrial bioenergetic supercomplexes. Different organisms use radically different strategies for OXPHOS membrane organization, likely depending on the stability of their environment.

Sultones and Sultines via a Julia-Kocienski Reaction of Epoxides.

The development of the homologous Julia-Kocienski reaction has led to the discovery of two new reaction modes of epoxides with sulfones. These pathways allow rapid and direct access to a range of γ-sultones and γ-sultines.

Dance of the SNAREs: assembly and rearrangements detected with FRET at neuronal synapses.

Soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptors (SNAREs) mediate vesicle fusion with the plasma membrane on activation by calcium binding to synaptotagmin. In the present study, we used fluorescence resonance energy transfer (FRET) and fluorescence lifetime imaging microscopy between fluorescently labeled SNARE proteins expressed in cultured rat hippocampal neurons to detect resting SNARE complexes, their conformational rearrangement on exocytosis, their disassembly before endocytosis of vesicular proteins, and SNARE assembly at newly docked vesicles. Assembled SNAREs are not only present in docked vesicles; unexpected residual "orphan SNARE complexes" also reside in para-active zone regions. Real-time changes in FRET between N-terminally labeled SNAP-25 and VAMP reported a reorientation of the SNARE motif upon exocytosis, SNARE disassembly in the active zone periphery, and SNARE reassembly in newly docked vesicles. With VAMP labeled C-terminally, decreased fluorescence in C-terminally labeled syntaxin (extracellular) reported trans-cis-conformational changes in SNAREs on vesicle fusion. After fusion SNAP-25 and syntaxin disperse along with VAMP, as well as the FRET signal itself, indicating diffusion of intact SNAREs after vesicle fusion but before their peripheral disassembly. Our measurements of spatiotemporal dynamics of SNARE conformational changes and movements refine models of SNARE function. Technical advances required to detect tiny changes in fluorescence in small fractions of labeled proteins in presynaptic boutons on a time scale of seconds permit the detection of rapid intermolecular interactions between small proportions of protein partners in cellular subcompartments.

Hypertension in Patients With Peripheral Artery Disease: An Updated Literature Review.

Peripheral artery disease (PAD), a condition where there is reduced blood flow due to narrowing or blockage of the arteries of the peripheral vasculature, is an epidemic that currently affects eight million people in the United States alone and is a major risk equivalent to having active coronary artery disease (CAD). However, it is commonly underdiagnosed in the general population. Hypertension is a common cardiovascular condition characterized by elevated blood pressure levels. There are several mitigating risk factors that can reduce the risk of complications of PAD, with hypertension playing a major role. This literature review aims to explore the relationship between hypertension and PAD, including their shared risk factors, pathophysiological mechanisms, and management strategies. In addition, we will analyze how this impacts major cardiovascular outcomes, such as critical limb ischemia, vascular amputation, myocardial infarction (MI), ischemic stroke, and cardiovascular-related death by examining relevant studies, current guidelines, and evidence. This literature review is intended to guide practitioners on ideal blood pressure parameters and evidence-based anti-hypertensives that provide overall cardiovascular benefit in both the primary care and hospital-based setting. By understanding the association between hypertension and PAD and the underlying pathophysiological mechanisms, healthcare professionals can improve diagnosis, treatment, and management strategies for affected individuals.

The changing landscape of geriatric care in acute myeloid leukemia: a 5-year analysis of inpatient mortality predictors, trends in mortality, and chemotherapy use.

Background: This study examined inpatient mortality factors in geriatric patients with acute myeloid leukemia (AML) using data from the 2016 to 2020 National Inpatient Sample. Methods: Identifying patients through ICD-10 codes, a total of 127,985 individuals with AML were classified into age categories as follows: 50.58% were 65 to 74 years, 37.74% were 75 to 84 years, and 11.68% were 85 years or older. Statistical analysis, conducted with STATA, involved Fisher's exact and Student's t tests for variable comparisons. Mortality predictors were identified through multivariate logistic regression. Results: Various hospital and patient-level factors, including an increase in age, race, a higher Charlson Comorbidity Index score, insurance status, and specific comorbidities such as atrial fibrillation and protein-calorie malnutrition, independently elevated the risk of inpatient mortality. Asthma, hyperlipidemia, and inpatient chemotherapy were linked to lower mortality. Although there was no statistically significant mortality rate change from 2016 to 2020, a decline in chemotherapy use in the eldest age group was noted. Conclusion: This study highlights the complexity of factors influencing inpatient mortality among geriatric patients with AML, emphasizing the need for personalized clinical approaches in this vulnerable population.

Independent predictors of mortality and 5-year trends in mortality and resource utilization in hospitalized patients with diffuse large B cell lymphoma.

Background: This retrospective study analyzed factors influencing all-cause inpatient mortality in 80,930 adult patients (2016-2020) with diffuse large B cell lymphoma using the National Inpatient Sample database. Methods: Utilizing ICD-10 codes, patients were identified, and statistical analysis was conducted using STATA. Fisher's exact and Student's t tests compared proportions and variables, multivariate logistic regression examined mortality predictors, and a 5-year longitudinal analysis identified mortality and resource utilization trends. Results: The inpatient mortality rate was found to be 6.56% with a mean age of 67.99 years. Several hospital- and patient-level factors including specific comorbidities such as congestive heart failure, atrial fibrillation, acute kidney injury, chronic obstructive pulmonary disease, liver failure, pancytopenia, tumor lysis syndrome, and severe protein-calorie malnutrition were independently associated with inpatient mortality. Hospitalization costs showed an increasing trend, impacting the overall population and survivors. Conclusion: These insights may refine risk assessment, treatment selection, and interventions.

Double Trouble: COVID-19 Infection Exacerbates Sickle Cell Crisis Outcomes in Hospitalized Patients-Insights from National Inpatient Sample 2020.

Background: This study investigated the impact of COVID-19 on patients with sickle cell crisis (SCC) using National Inpatient Sample (NIS) data for the year 2020. Methods: A retrospective cohort analysis was conducted utilizing International Classification of Diseases (ICD-10) codes to identify adults who were admitted with a principal diagnosis of sickle cell crisis. The primary outcomes examined were inpatient mortality, while the secondary outcomes assessed included morbidity, hospital length of stay, and resource utilization. Analyses were conducted with STATA. Multivariate logistic and linear regression analyses were used to adjust for confounding variables. Results: Of 66,415 adult patients with a primary SCC diagnosis, 875 were identified with a secondary diagnosis of COVID-19 infection. Unadjusted mortality rate was higher for SCC patients with COVID-19 (2.28%) compared to those without (0.33%), with an adjusted odds ratio (aOR) of 8.49 (p = 0.001). They also showed increased odds of developing acute respiratory failure (aOR = 2.37, p = 0.003) and acute kidney injury requiring dialysis (aOR = 8.66, p = 0.034). Additionally, these patients had longer hospital stays by an adjusted mean of 3.30 days (p < 0.001) and incurred higher hospitalization charges by an adjusted mean of USD 35,578 (p = 0.005). Conclusions: The SCC patients with COVID-19 presented higher mortality rates, increased morbidity indicators, longer hospital stays, and substantial economic burdens.

Aeromonas caviae-Associated Severe Bloody Diarrhea.

Aeromonas species are capable of inducing severe infections in both immunocompetent and immunocompromised individuals. Gastroenteritis is the most common infection associated with Aeromonas species in humans. We report a rare case of Aeromonas caviae severe gastroenteritis and bloody diarrhea that led to the development of sepsis in a 45-year-old female with no history of immunocompromising conditions. This patient required extensive medical support which included blood transfusions and antibiotics. Fortunately, with appropriate diagnostic measures and targeted antibiotic therapy, her symptoms resolved. Aeromonas species are becoming increasingly frequent among the pathogens isolated from patients suffering from gastroenteritis. As such, it is becoming increasingly important for clinicians to consider this pathogen when working up their patients for diarrhea.

Evaluating safe time to discharge after closed reduction and percutaneous pinning of uncomplicated type III supracondylar humerus fractures: a single-center retrospective review.

The purpose of this retrospective study was to review complications following closed reduction, percutaneous pinning of isolated, type III supracondylar fractures without associated injuries to evaluate if patients may be discharged safely on the day of surgery. We performed a retrospective chart and radiographic review of patients with isolated Gartland type III supracondylar humerus fractures who underwent closed reduction and percutaneous pinning over a 4-year period. We reviewed admission time to the emergency department, time and length of surgery, time to discharge, postoperative complications, readmission rate and office visits. Of the 110 patients included, 19 patients were discharged in less than 6 h, 45 patients between 6 and 12 h and 46 patients greater than 12 h. A total of 61 patients were discharged on the same day as surgery and 49 were discharged the next day. There were 11 postoperative complications. No postoperative complications were found in patients discharged less than 6 hours from surgery. For patients discharged between 6 and 12 hours postoperatively, one patient returned to the office earlier than scheduled. The result of our review suggests that patients can be safely discharged within the 12-h postoperative period with no increased risk of complications. This is contingent upon the patient having a stable neurovascular examination, pain control and caregiver's comfort level. This can decrease medical cost, family stress and burden to the hospital system. Time to discharge should still be evaluated on a case-by-case basis after evaluating medical and social barriers.

The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial.

BACKGROUND: Lowering LDL cholesterol with statin regimens reduces the risk of myocardial infarction, ischaemic stroke, and the need for coronary revascularisation in people without kidney disease, but its effects in people with moderate-to-severe kidney disease are uncertain. The SHARP trial aimed to assess the efficacy and safety of the combination of simvastatin plus ezetimibe in such patients. METHODS: This randomised double-blind trial included 9270 patients with chronic kidney disease (3023 on dialysis and 6247 not) with no known history of myocardial infarction or coronary revascularisation. Patients were randomly assigned to simvastatin 20 mg plus ezetimibe 10 mg daily versus matching placebo. The key prespecified outcome was first major atherosclerotic event (non-fatal myocardial infarction or coronary death, non-haemorrhagic stroke, or any arterial revascularisation procedure). All analyses were by intention to treat. This trial is registered at ClinicalTrials.gov, NCT00125593, and ISRCTN54137607. FINDINGS: 4650 patients were assigned to receive simvastatin plus ezetimibe and 4620 to placebo. Allocation to simvastatin plus ezetimibe yielded an average LDL cholesterol difference of 0·85 mmol/L (SE 0·02; with about two-thirds compliance) during a median follow-up of 4·9 years and produced a 17% proportional reduction in major atherosclerotic events (526 [11·3%] simvastatin plus ezetimibe vs 619 [13·4%] placebo; rate ratio [RR] 0·83, 95% CI 0·74-0·94; log-rank p=0·0021). Non-significantly fewer patients allocated to simvastatin plus ezetimibe had a non-fatal myocardial infarction or died from coronary heart disease (213 [4·6%] vs 230 [5·0%]; RR 0·92, 95% CI 0·76-1·11; p=0·37) and there were significant reductions in non-haemorrhagic stroke (131 [2·8%] vs 174 [3·8%]; RR 0·75, 95% CI 0·60-0·94; p=0·01) and arterial revascularisation procedures (284 [6·1%] vs 352 [7·6%]; RR 0·79, 95% CI 0·68-0·93; p=0·0036). After weighting for subgroup-specific reductions in LDL cholesterol, there was no good evidence that the proportional effects on major atherosclerotic events differed from the summary rate ratio in any subgroup examined, and, in particular, they were similar in patients on dialysis and those who were not. The excess risk of myopathy was only two per 10,000 patients per year of treatment with this combination (9 [0·2%] vs 5 [0·1%]). There was no evidence of excess risks of hepatitis (21 [0·5%] vs 18 [0·4%]), gallstones (106 [2·3%] vs 106 [2·3%]), or cancer (438 [9·4%] vs 439 [9·5%], p=0·89) and there was no significant excess of death from any non-vascular cause (668 [14·4%] vs 612 [13·2%], p=0·13). INTERPRETATION: Reduction of LDL cholesterol with simvastatin 20 mg plus ezetimibe 10 mg daily safely reduced the incidence of major atherosclerotic events in a wide range of patients with advanced chronic kidney disease. FUNDING: Merck/Schering-Plough Pharmaceuticals; Australian National Health and Medical Research Council; British Heart Foundation; UK Medical Research Council.

ortho-Quinone methides in natural product synthesis.

ortho-Quinone methides (o-QMs) are emerging as highly useful intermediates, the inherent reactivity of which can be used in linchpin reactions for the construction of complex natural products. This review encompasses the major contributions in this field, exemplifying the major strategies and reactivity modes which can be applied.

Validation of a scoliometer smartphone app to assess scoliosis.

BACKGROUND: Surgeons and software developers recognize that apps can improve patient care by replicating the function of existing medical devices. However, the incorporation of new tools requires that the clinical data being recorded is accurate and valid. This study attempts to validate a new iPhone app to measure scoliotic rotation. The objective of this study was to validate the scoliogauge iPhone application by comparing the results to simultaneous readings from a standard Scoliometer. METHODS: Four orthopaedic medical providers (attending surgeon, fellow, resident, and nurse practitioner) each read a standard scoliometer at 60 randomly selected angular measurements between -30 and 30 degrees, whereas a blinded observer simultaneously recorded the angular measurement derived from the scoligauge app. The correlation between the 2 measurements were calculated using a Pearson correlation coefficient with a P-value set to < 0.05 for significance. RESULTS: The Pearson correlation values ranged from 0.9994 to 0.9996 for all providers and all P-values < 0.001. There was no increase in time associated with using the app compared with the standard device. CONCLUSIONS: The scoligauge app is a convenient novel tool that replicates the function of a standard clinical scoliometer but with a potentially decreased financial cost and greater convenience for providers. CLINICAL RELEVANCE: Validation of this new device demonstrates the potential to increase the distribution of cost-effective scoliosis screening tools to a broad population of medical providers.