Altering Calcium Sensitivity in Heart Failure: A Crossroads of Disease Etiology and Therapeutic Innovation.

Heart failure (HF) presents a significant clinical challenge, with current treatments mainly easing symptoms without stopping disease progression. The targeting of calcium (Ca2+) regulation is emerging as a key area for innovative HF treatments that could significantly alter disease outcomes and enhance cardiac function. In this review, we aim to explore the implications of altered Ca2+ sensitivity, a key determinant of cardiac muscle force, in HF, including its roles during systole and diastole and its association with different HF types-HF with preserved and reduced ejection fraction (HFpEF and HFrEF, respectively). We further highlight the role of the two rate constants kon (Ca2+ binding to Troponin C) and koff (its dissociation) to fully comprehend how changes in Ca2+ sensitivity impact heart function. Additionally, we examine how increased Ca2+ sensitivity, while boosting systolic function, also presents diastolic risks, potentially leading to arrhythmias and sudden cardiac death. This suggests that strategies aimed at moderating myofilament Ca2+ sensitivity could revolutionize anti-arrhythmic approaches, reshaping the HF treatment landscape. In conclusion, we emphasize the need for precision in therapeutic approaches targeting Ca2+ sensitivity and call for comprehensive research into the complex interactions between Ca2+ regulation, myofilament sensitivity, and their clinical manifestations in HF.

Normal 24-hour urine calcium concentrations after long-term daily oral intake of vitamin D in doses ranging from 5000 to 50,000 international units in 14 adult hospitalized psychiatric patients.

Many controversies exist regarding vitamin D3 supplementation. These include not only diseases that are responsive to vitamin D supplementation, but also the long-term safety of prolonged daily oral vitamin D3 intake above 4000-10,000 International Units (IU). In particular, supplementation levels that do not result in adverse events, and the upper limits of safe serum 25-hydroxyvitamin D (25OHD) concentrations. Adverse reactions reported to occur with excessive vitamin D intake include hypercalcemia, renal failure, calcium crystal formation, undetectable parathyroid hormone concentrations, and hypercalciuria, all of which are reported to be reversible. To address the long-term safety of vitamin D supplementation, we previously reported data from patients in our hospital who have been voluntarily supplemented with vitamin D3 ranging from 5,000 to 10,000 IU/day since July 2011 as a standard of care for the prevention and treatment of vitamin D deficiency. Historically 90% of patients have agreed to daily supplementation, with most taking 10,000 IU/day. These data indicate no evidence for hypercalcemia, renal failure, calcium crystal formation, nephrolithiasis. or undetectable parathyroid hormone concentrations in patients taking 5000 or 10,000 IU/day for extended periods of time. As another measure for potential vitamin D toxicity, we retrospectively assessed 24-hour urine calcium excretion in 14 individuals on long-term daily oral vitamin D intake ranging from 5000 to 50,000 IU/day to further assess the safety of supplementation using these doses. This included patients taking either 5000 (4), 10,000 (9), or 50,000 (1) IU/day. Time on supplementation ranged from 10 to 102 months. A patient taking 400 IU/day and getting frequent sun exposure was also included. All fifteen 24-hour urine calcium measurements were normal. The current findings complement our experience with over 7000 patients in the past 13 years, indicating that prolonged daily oral intake of vitamin D3 ranging from 5000 to 10,000 IU/day is safe.

Clinician assessment of blood alcohol levels among emergency department patients.

INTRODUCTION: Alcohol intoxication is a significant public health concern and is commonly seen among emergency department (ED) patients. This study was undertaken to identify the accuracy of clinician assessment of blood alcohol levels among emergency department patients. METHODS: This prospective survey study was conducted at a Level 1 Trauma Center. Eligible study participants included physicians, nurses, and medical students involved in the care of patients who had BAC. Clinicians estimated the BAC prior to results availability. RESULTS: Among 243 clinicians, the mean difference between the estimated BAC and actual BAC was 17.4 (95% CI: 4.7 to 30.1). Providers tended to overestimate the actual BAC level. The accuracy between roles (attendings, residents, RNs, students) was not significant (ANOVA p-value 0.90). Accuracy was not correlated with age of the patient (Pearson correlation 0.04, p-value 0.54). Accuracy was not associated with the patient's gender (Student's t-test two-tailed p-value 0.90), ethnicity (White versus all others, t-test p-value 0.31), nor insurance (government versus not government, t-test p-value 0.81). The average accuracy value was associated with mode of arrival (t-test p-value 0.003). The average accuracy for walk-in subjects was -14.9 (CI: -32.8 to 3.1) compared to ambulance arrivals 28.3 (CI: 12.7 to 44.0). Providers underestimated BAC for walk-ins and overestimated BAC for ambulance arrivals. Among 107 patients with a BAC of 0, clinician estimates ranged from 0 to 350. Clinicians estimated non-zero BAC levels in 17% of patients with BAC of 0 (N = 18). CONCLUSIONS: Clinicians' estimates of BAC were often inaccurate, and often overestimated the BAC.

Perceptions of the SARS-CoV2 pandemic: a small comparative survey analysis between language preference populations in a United States community health center.

In 2019, a new variant of coronavirus, SARS-CoV-2 (COVID-19) created a global pandemic that has highlighted and exacerbated health disparities. Educating the general public about COVID-19 is one of the primary mitigation strategies amongst health professionals. English is not the preferred language for an estimated 22% of the United States population making effective mass communication efforts difficult to achieve. This study seeks to understand and compare several topics surrounding COVID-19 health communication and healthcare disparities between individuals with English language preference (ELP) and non-English language preference (NELP) within the United States. A survey available in seven languages asking about knowledge and opinions on COVID-19, vaccines, preferred sources of health information, and other questions, was administered February-April 2021 to patients at an urban federally qualified health center that also serves global refugees and immigrants. Descriptive statistics and comparative analysis were performed to identify differences between ELP and NELP individuals. Analysis of 144 surveys, 33 of which were NELP, showed 90.97% of all patients agreed that COVID-19 was a serious disease and 66.67% would receive the COVID-19 vaccine. There were numerous differences between ELP and NELP individuals, including trust in government, symptom identification, preferred source of health information, and feelings that cultural needs had been met. This study has identified several significant differences in patient perceptions relating to the COVID-19 pandemic when comparing NELP to ELP and highlighted areas where improvement can occur. Applying this information, easily utilized targeted resources can be created to quickly intervene and address health disparities among patients seeking care at an urban community health center.

Trauma-Specific Performance Improvement Activities for Emergency Medical Services Providers: A Statewide Perspective.

INTRODUCTION: Trauma-specific performance improvement (PI) activities are highly variable among Emergency Medical Services (EMS) providers. This study assesses the perception of the trauma PI activities of EMS providers in the state of Ohio and identifies potential barriers to conducting a successful program. METHODS: An institutional review board-approved, voluntary, and anonymous Qualtrics survey was disseminated to all EMS agencies registered under the Ohio Department of Public Safety throughout the 88 counties of Ohio. It included questions regarding what agencies considered trauma-specific PI activities, how frequently they completed those activities, and barriers related to conducting such PI activities. There were both open-ended and closed-ended questions in the survey, along with a follow-up interview. The data were descriptively and thematically analyzed. RESULTS: From the recorded responses (341), most the respondents (98.5%) either agreed or strongly agreed that trauma-specific PI activities improve performance of EMS providers, while only 63.8% (218) of the agencies performed them. Some activities considered as trauma PI and conducted at least once a month included (1) record keeping (74.6%), (2) confirmation on the use of correct triage protocols (66.9%), (3) measuring response time on trauma calls (60.0%), (4) PI reviews of trauma cases (56.9%), and (5) obtaining feedback from the receiving facility and or authorizing physicians (48.5%). Primary barriers to performing trauma PI activities included a lack of interest and financial resources, followed by system-level reasons such as unavailability of training centers and a lack of regional/state support. Thematic analysis of the data suggested that improved communication and awareness of trauma PI, sharing statewide data on trauma PI, better synchronization among EMS agencies and trauma centers, and enhanced EMS funding could potentially improve trauma-specific PI programs at the EMS level. CONCLUSIONS: Our results showed variability in the perception, execution, and availability of trauma-specific PI activities among EMS agencies in the state. Common barriers could potentially be mitigated by collaboration between agencies, trauma centers, and state-led initiatives. With the increased frequency of mass shootings and other large-scale trauma disasters, it is imperative from a state and regional level to address these inconsistencies and further elucidate effective measures of trauma PI for the EMS community.

Blunt traumatic coronary artery dissection: A case study.

BACKGROUND: Coronary artery dissection is an extremely rare but lethal complication of blunt chest trauma. Dissection may cause thrombus formation or vasospasm, leading to the clinical presentation of acute myocardial infarction. Diagnosis can be difficult as traumatic chest pain has several etiologies; therefore, an electrocardiogram (ECG) is necessary in all cases of thoracic trauma [1-3]. CASE REPORT: Thirty-eight-year old female, with no significant past medical history, presented to a freestanding emergency department with complaints of severe chest pain and right shoulder pain after a blunt trauma water sport accident. Upon selective angiography of left and right coronary artery and left heart catheterization, the patient was found to have an occluded distal left anterior descending artery (LAD). The patient underwent aspiration thrombectomy of the proximal LAD artery and percutaneous transluminal coronary angioplasty (PTCA) of distal LAD artery, which decreased the stenosis from 100% to less than 10%. The patient was discharged home on hospital day three with follow up in one month.Coronary artery dissection should be considered in blunt thoracic trauma particularly in cases of unexplained chest pain, regardless of the mechanism of injury, age of patient or comorbidities. Patients should be evaluated with an ECG, troponin, and possibly an echocardiogram to rule out this type of injury.

Incidence of central line associated bloodstream infection following central venous catheter placement in the emergency department.

INTRODUCTION: Central line-associated bloodstream infections (CLABSI) are costly and can be lifethreatening. Many efforts have been taken to minimize the rates of infection, including sterile technique, pre-packaged sterile kits, site selection, and replacing infected or potentially infected lines. This study aims to identify the incidence of CLABSI following catheter placement in the ED, and to compare rates of CLABSI among ED and ICU placed catheters. METHODS: This retrospective chart review was conducted at a Level 1 Trauma Center. Eligibility criteria included patients who had CVC placed in the ED or ICU from January 1st, 2018, through July 31st, 2019 who were 18 years or older. RESULTS: Among 1810 patients with central lines, 1254 met eligibility criteria. There was no significant difference in infection rates when comparing lines placed in the ED (2.5 per 1000 catheter days, 95% confidence interval [CI] 0.8 to 5.8) compared to those placed in the ICU (4.6 per 1000 catheter days, 95% CI 3.0 to 6.8). The odds of CLABSI was not associated with age, sex, indication, site, location nor which type of health care professional (HCP) placed the line. CONCLUSIONS: In this study, the incidence of infection was no different between lines placed in the ED compared to the ICU.

Vitamin D and Vitamin D Analogs as Adjuncts to Field Therapy Treatments for Actinic Keratoses: Current Research and Future Approaches.

Actinic keratoses (AK), also known as solar keratoses, are precancerous hyperkeratotic papules caused by long-term exposure to ultraviolet radiation. Management of AK prior to progression to cutaneous malignancy represents an important window of intervention. This is important on a population level, given the high incidence, morbidity, financial costs, and the low but measurable risk of mortality from cutaneous neoplasia. Treatments for AK have been refined for many years with significant progress over the past decade. Those recent advancements lead to questions about current treatment paradigms and the role of harnessing the immune system in field therapies. Recent studies suggest a key interplay between vitamin D and cancer immunity; in particular, the systemic and/or topical vitamin D analogs can augment field therapies used for severe actinic damage. In this review, we will examine the literature supporting the use of vitamin D-directed therapies to improve field therapy approaches. An enhanced understanding of these recent concepts with a focus on mechanisms is important in the optimized management of AK. These mechanisms will be critical in guiding whether selected populations, including those with immunosuppression, heritable cancer syndromes, and other risk factors for skin cancer, can benefit from these new concepts with vitamin D analogs and whether the approaches will be as effective in these populations as in immunocompetent patients.

Oral and Topical Vitamin D, Sunshine, and UVB Phototherapy Safely Control Psoriasis in Patients with Normal Pretreatment Serum 25-Hydroxyvitamin D Concentrations: A Literature Review and Discussion of Health Implications.

Vitamin D, sunshine and UVB phototherapy were first reported in the early 1900s to control psoriasis, cure rickets and cure tuberculosis (TB). Vitamin D also controlled asthma and rheumatoid arthritis with intakes ranging from 60,000 to 600,000 International Units (IU)/day. In the 1980s, interest in treating psoriasis with vitamin D rekindled. Since 1985 four different oral forms of vitamin D (D2, D3, 1-hydroxyvitaminD3 (1(OH)D3) and 1,25-dihydroxyvitaminD3 (calcitriol)) and several topical formulations have been reported safe and effective treatments for psoriasis-as has UVB phototherapy and sunshine. In this review we show that many pre-treatment serum 25(OH)D concentrations fall within the current range of normal, while many post-treatment concentrations fall outside the upper limit of this normal (100 ng/mL). Yet, psoriasis patients showed significant clinical improvement without complications using these treatments. Current estimates of vitamin D sufficiency appear to underestimate serum 25(OH)D concentrations required for optimal health in psoriasis patients, while concentrations associated with adverse events appear to be much higher than current estimates of safe serum 25(OH)D concentrations. Based on these observations, the therapeutic index for vitamin D needs to be reexamined in the treatment of psoriasis and other diseases strongly linked to vitamin D deficiency, including COVID-19 infections, which may also improve safely with sufficient vitamin D intake or UVB exposure.

Contraction-relaxation coupling is unaltered by exercise training and infarction in isolated canine myocardium.

The two main phases of the mammalian cardiac cycle are contraction and relaxation; however, whether there is a connection between them in humans is not well understood. Routine exercise has been shown to improve cardiac function, morphology, and molecular signatures. Likewise, the acute and chronic changes that occur in the heart in response to injury, disease, and stress are well characterized, albeit not fully understood. In this study, we investigated how exercise and myocardial injury affect contraction-relaxation coupling. We retrospectively analyzed the correlation between the maximal speed of contraction and the maximal speed of relaxation of canine myocardium after receiving surgically induced myocardial infarction, followed by either sedentary recovery or exercise training for 10-12 wk. We used isolated right ventricular trabeculae, which were electrically paced at different lengths, frequencies, and with increasing ß-adrenoceptor stimulation. In all conditions, contraction and relaxation were linearly correlated, irrespective of injury or training history. Based on these results and the available literature, we posit that contraction-relaxation coupling is a fundamental myocardial property that resides in the structural arrangement of proteins at the level of the sarcomere and that this may be regulated by the actions of cardiac myosin binding protein C (cMyBP-C) on actin and myosin.

Radiographic findings of SARS-CoV-2 infection.

STUDY OBJECTIVE: The 2019-20 coronavirus pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19). This study was undertaken to identify and compare findings of chest radiography and computed tomography among patients with SARS-CoV-2 infection. METHODS: This retrospective study was undertaken at a tertiary care center. Eligible subjects included consecutive patients age 18 and over with documented SARS-CoV-2 infection between March and July 2020. The primary outcome measures were results of chest radiography and computed tomography among patients with documented SARS-CoV-2 infection. RESULTS: Among 724 subjects, most were admitted to a medical floor (46.4%; N = 324) or admitted to an ICU (10.9%; N = 76). A substantial number of subjects were intubated during the emergency department visit or inpatient hospitalization (15.3%; N = 109). The majority of patients received a chest radiograph (80%; N = 579). The most common findings were normal, bilateral infiltrates, ground-glass opacities, or unilateral infiltrate. Among 128 patients who had both chest radiography and computed tomography, there was considerable disagreement between the 2 studies (52.3%; N = 67; 95% confidence interval: 43.7% to 61.0%).). The presence of bilateral infiltrates (infiltrates or ground-glass opacities) was associated with clinical factors including older age, ambulance arrivals, more urgent triage levels, higher heart rate, and lower oxygen saturation. Bilateral infiltrates were associated with poorer outcomes, including higher rate of intubation, greater number of inpatient days, and higher rate of death. CONCLUSIONS: Common radiographic findings of SARS-CoV-2 infection include infiltrates or ground-glass opacities. There was considerable disagreement between chest radiography and computed tomography. Computed tomography was more accurate in defining the extent of involved lung parenchyma. The presence of bilateral infiltrates was associated with morbidity and mortality.

Etiology-dependent impairment of relaxation kinetics in right ventricular end-stage failing human myocardium.

BACKGROUND: In patients with end-stage heart failure, the primary etiology often originates in the left ventricle, and eventually the contractile function of the right ventricle (RV) also becomes compromised. RV tissue-level deficits in contractile force and/or kinetics need quantification to understand involvement in ischemic and non-ischemic failing human myocardium. METHODS AND RESULTS: The human population suffering from heart failure is diverse, requiring many subjects to be studied in order to perform an adequately powered statistical analysis. From 2009-present we assessed live tissue-level contractile force and kinetics in isolated myocardial RV trabeculae from 44 non-failing and 41 failing human hearts. At 1 Hz stimulation rate (in vivo resting state) the developed active force was not different in non-failing compared to failing ischemic nor non-ischemic failing trabeculae. In sharp contrast, the kinetics of relaxation were significantly impacted by disease, with 50% relaxation time being significantly shorter in non-failing vs. non-ischemic failing, while the latter was still significantly shorter than ischemic failing. Gender did not significantly impact kinetics. Length-dependent activation was not impacted. Although baseline force was not impacted, contractile reserve was critically blunted. The force-frequency relation was positive in non-failing myocardium, but negative in both ischemic and non-ischemic myocardium, while the ß-adrenergic response to isoproterenol was depressed in both pathologies. CONCLUSIONS: Force development at resting heart rate is not impacted by cardiac pathology, but kinetics are impaired and the magnitude of the impairment depends on the underlying etiology. Focusing on restoration of myocardial kinetics will likely have greater therapeutic potential than targeting force of contraction.

Memantine, an NMDA Receptor Antagonist, Prevents Thyroxin-induced Hypertension, but Not Cardiac Remodeling.

Stimulation of glutamatergic tone has been causally linked to myocardial pathogenesis and amplified systemic blood pressure (BP). Memantine, a noncompetitive N-methyl-D-aspartate glutamatergic receptor (NMDA-R) antagonist, has been proposed to be an active cardioprotective drug. However, the efficacy of memantine and subsequently the possible involvement of the NMDA-R in the thyroxin (T4)-induced cardiovascular complications have never been investigated. We examined the effect of memantine (30 mg·kg·d) on the T4 (500 µg·kg·d)-provoked increase in mouse BP, cardiac hypertrophy indicated by enlarged overall myocardial mass, and reformed reactions of the contractile myocardium both in vivo and ex vivo after 2 weeks of treatment. Memantine alone did not result in any cardiovascular pathology in mice. Instead, memantine significantly prevented the T4-triggered systemic hypertension. But, it did not reverse cardiac hypertrophy, coupled in vivo left ventricular dysfunction (LV) or ex vivo right ventricular (RV) papillary muscle contractile alterations of the T4-treated mice. Our results openly direct the cardiovascular safety and tolerability of memantine therapy. Yet, extra research is necessary to endorse these prospective advantageous outcomes. Also, we believe that this is the first study to inspect the possible role of NMDA-R in the T4-stimulated cardiovascular disorders and concluded that NMDA-R could play a key role in the T4-induced hypertension.

Recovery following Thyroxine Treatment Withdrawal, but Not Propylthiouracil, Averts In Vivo and Ex Vivo Thyroxine-Provoked Cardiac Complications in Adult FVB/N Mice.

Persistent cardiovascular pathology has been described in hyperthyroid patients even with effective antithyroid treatment. Here, we studied the effect of a well-known antithyroid drug, propylthiouracil (PTU; 20 mg/kg/day), on thyroxine (T4; 500 µg/kg/day)-induced increase in blood pressure (BP), cardiac hypertrophy, and altered responses of the contractile myocardium both in vivo and ex vivo after 2 weeks of treatment. Furthermore, the potential recovery through 2 weeks of T4 treatment discontinuation was also investigated. PTU and T4 recovery partially reduced the T4-prompted increase in BP. Alternatively, PTU significantly improved the in vivo left ventricular (LV) function with no considerable effects on cardiac hypertrophy or ex vivo right ventricular (RV) contractile alterations subsequent to T4 treatment. Conversely, T4 recovery considerably enhanced the T4-provoked cardiac changes both in vivo and ex vivo. Altogether, our data is in agreement with the proposal that hyperthyroidism-induced cardiovascular pathology could persevere even with antithyroid treatments, such as PTU. However, this cannot be generalized and further investigation with different antithyroid treatments should be executed. Moreover, we reveal that recovery following experimental hyperthyroidism could potentially ameliorate cardiac function and decrease the risk for additional cardiac complications, yet, this appears to be model-dependent and should be cautiously construed.