Contraindications to tissue plasminogen activator thrombolysis for acute lower extremity ischemia.

OBJECTIVE: Previous randomized prospective trials have demonstrated the effectiveness of transcatheter tissue plasminogen activator (tPA) thrombolysis in treating acute limb ischemia (ALI) compared to conventional surgery. These pivotal trials have also highlighted contraindications for these procedures. Given recent advancements in techniques and technology, our aim is to reassess the relevance of these contraindications in contemporary practice. METHODS: A retrospective chart analysis was performed utilizing the inpatient medical records of consecutive individuals who underwent tPA treatment for acute limb ischemia (ALI) from September 2016 to April 2022. Inclusion criteria encompassed patients aged 18 and above displaying clinical symptoms and imaging evidence of ALI within 14 days. All patients received tPA with suction thrombectomy following the fast-track thrombolysis protocol. In cases where a persistent thrombus or stenosis was detected, catheter-directed thrombolysis was considered overnight, and patients underwent angiography and reassessment in the operating room subsequently. RESULTS: Patients were classified into two groups based on the STILE trial's established contraindications for endovascular treatment in acute limb ischemia (ALI). If a patient had any of these contraindications, they were placed in the contraindicated group. This resulted in 24 patients (32%) in the contraindicated group and 52 patients (68%) in the non-contraindicated group. No statistically significant demographic variations were observed between these groups. Contraindications in our study included uncontrolled hypertension (12/24, 50%), recent invasive procedures (7/27, 29%), history of cerebrovascular accident (CVA) within 6 months (3/24, 12%), and intracranial malformation/neoplasms (2/24, 8%). Three patients within the non-contraindicated group experienced bleeding complications: two with puncture site bleeds and one with nasal bleeding. In contrast, one patient in the contraindicated group had transient postoperative hematuria. There were no significant differences in bleeding complications observed between the two groups (p = .771). Additionally, no amputations were observed within our population. CONCLUSIONS: In light of our study results and advancements in endovascular therapies, we can now safely and efficiently treat patients who were previously considered contraindicated for such treatments. It is essential to individualize treatments and carefully balance the risks and benefits of endovascular versus open surgical revascularization for these patients. Additionally, we believe that the nearly 30-year-old guidelines for endovascular therapies need to be revisited and updated to align with modern technology.

Racial and Socioeconomic Determinants of Cardiovascular Health: A Comprehensive Review.

Cardiovascular diseases (CVDs) are the leading cause of death globally. Their prevalence and mortality rates continue to rise. This narrative review explores well-known risk factors for CVDs such as dyslipidemia, hypertension, diabetes, obesity, and smoking, and their prevalence among different racial and ethnic groups. In addition, we expand the discussion to include the impact of socioeconomic status (SES) on cardiovascular outcomes. The data demonstrate that non-Hispanic Black and Hispanic populations not only exhibit higher rates of hypertension, obesity, diabetes, and smoking but also face systemic barriers linked to lower SES, which worsen their cardiovascular outcomes. These barriers include a lack of education, lower income, higher rates of unemployment, and poor living conditions. Beyond these commonly studied factors, these groups also suffer from higher levels of food and housing insecurity and a lack of adequate insurance coverage, all of which contribute to poorer health. Additionally, there is a higher prevalence of mental health disorders, such as depression and anxiety, among these populations. This further compounds the risks and adverse outcomes associated with CVDs. It is essential to conduct further research into how SES and race influence cardiovascular health and to refine risk assessment methods. Concentrating on these aspects would make it possible to create interventions designed to meet the needs of diverse communities and strategies that could potentially reduce morbidity and mortality from CVD across populations. Moreover, this review advocates for integrating comprehensive socioeconomic data into cardiovascular health strategies, which is crucial for developing effective public health initiatives.

Obesity and Transcatheter Aortic Valve Replacement.

Amidst an aging population and escalating obesity prevalence, elucidating the impact of obesity on transcatheter aortic valve replacement (TAVR) outcomes becomes paramount. The so-called "obesity paradox"-a term denoting the counterintuitive association of obesity, typically a risk factor for cardiovascular diseases, with improved survival outcomes in TAVR patients relative to their leaner or normal-weight counterparts-merits rigorous examination. This review comprehensively investigates the complex relationship between obesity and the clinical outcomes associated with TAVR, with a specific focus on mortality and periprocedural complications. This study aims to deepen our understanding of obesity's role in TAVR and the underlying mechanisms of the obesity paradox, thereby optimizing management strategies for this patient demographic, tailored to their unique physiological and metabolic profiles.

Navigating Diagnostic Challenges in Acute Coronary Syndrome: A Case of Bezold-Jarisch Reflex and Wellens Pattern.

Acute coronary syndrome (ACS) presents significant diagnostic challenges, particularly in cases with atypical presentations and complex clinical scenarios. Here, we describe the case of a 59-year-old man who presented with presyncope, bradycardia, hypotension, and later syncope, attributed to the Bezold-Jarisch reflex. Electrocardiographic findings suggested both inferior and anterior wall infarction, with dynamic changes in T-wave morphology further complicating the diagnostic process. Despite a type A Wellens' pattern indicating critical stenosis in the proximal left anterior descending (LAD) artery, coronary angiography revealed a complete thrombotic lesion in the proximal right coronary artery (RCA), necessitating urgent intervention. Despite the Wellens pattern indicating LAD involvement, RCA revascularization took precedence due to immediate thrombotic risk. This case underscores the diagnostic challenges associated with conflicting clinical manifestations in ACS and highlights the importance of individualized management strategies integrating advanced diagnostic modalities to optimize outcomes. Understanding the interplay of complex clinical presentations and employing a nuanced approach to management are crucial in effectively navigating ACS scenarios.

The Association Between Oxidative Stress and the Progression of Heart Failure: A Systematic Review.

Chronic heart failure (CHF) is a progressive multifactorial condition where the role of oxidative stress may have implications in the pathogenesis of the disease. Despite growing interest among researchers and clinicians, the limited, unorganized, and divergent findings regarding the association between oxidative stress and the progression of heart failure (HF) have prompted us to conduct this study. Drawing upon the evolving nature of this research domain, this study is one of the first of its kind to present a systematic and comprehensive overview of the existing evidence regarding the role of oxidative stress production in the progression of HF. This study systematically reviews peer-reviewed empirical studies published in English, particularly focusing on the association between oxidative stress and the progression of HF. Parameters, such as publication year, study design, population demographics (size, age, and gender), types of HF, and characterization of markers in the existing studies, were reviewed. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) procedure, a thorough search was conducted on PubMed, Cochrane, Embase, and Sage databases, without any restrictions on the publication dates of articles, which yielded a total of 1,808 records on the association of oxidative stress production with clinical outcomes in HF patients. The analysis of the content of 17 articles offered a robust observation of this phenomenon, providing insights into the levels of oxidative stress, antioxidant markers, and the enzymes involved in the production of reactive oxygen species (ROS), and their association with the progression and severity of HF. The findings highlighted various knowledge gaps and future research priorities are recommended in the areas of interest and unexplored areas.

Integrating Cardiac Biomarkers and Electrocardiogram in Pulmonary Embolism Prognosis.

Pulmonary embolism (PE) represents a significant clinical challenge that substantially impacts healthcare systems. This case report focuses on the nuances of risk stratification in PE, highlighted through the presentation of a 64-year-old female patient. The uniqueness of this case lies in the patient's atypical presentation, where decreased exercise tolerance was the sole symptom leading to the diagnosis of PE. The patient was found to have new-onset atrial fibrillation, elevated levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), and signs of right ventricular strain on imaging. This scenario underscores the necessity for a comprehensive assessment in PE cases, particularly when classic symptoms (e.g., tachycardia, shortness of breath, chest pain) are absent. We explore the incidence of PE in patients diagnosed with deep vein thrombosis, examining the critical role of cardiac biomarkers, including B-type natriuretic peptide, NT-proBNP, and troponins, in prognostication and their potential use in risk assessment tools for PE patients. Additionally, the significance of electrocardiogram evaluation in these patients and its role in risk stratification is thoroughly assessed.

Advancements in Heart Transplantation: Donor-Derived Cell-Free DNA as Next-Generation Biomarker.

Heart failure, particularly in its advanced stages, significantly impacts quality of life. Despite progress in Guideline-Directed Medical Therapy (GDMT) and invasive treatments, heart transplantation (HT) remains the primary option for severe cases. However, complications such as graft rejection present significant challenges that necessitate effective monitoring. Endomyocardial biopsy (EMB) is the gold standard for detecting rejection, but its invasive nature, associated risks, and healthcare costs have shifted interest in non-invasive techniques. Donor-derived cell-free DNA (dd-cfDNA) has gained attention as a promising non-invasive biomarker for monitoring graft rejection. Compared to EMB, dd-cfDNA detects graft rejection early and enables clinicians to adjust immunosuppression promptly. Despite its advantages, dd-cfDNA testing faces challenges, such as the need for specialized technology and potential inaccuracies due to other clinical conditions. Additionally, dd-cfDNA cannot yet differentiate between types of graft rejection, and its effectiveness in chronic rejection remains unclear. Research is ongoing to set precise standards for dd-cfDNA levels, which would enhance its diagnostic accuracy and help in clinical decisions. The article also points to the future of HT monitoring, which may involve combining dd-cfDNA with other biomarkers and integrating artificial intelligence to improve diagnostic capabilities and personalize patient care. Furthermore, it emphasizes both global and racial inequalities in dd-cfDNA testing and the ethical issues related to its use in transplant medicine.

Activation of gp130 signaling in T cells drives TH17-mediated multi-organ autoimmunity.

The IL-6-gp130-STAT3 signaling axis is a major regulator of inflammation. Activating mutations in the gene encoding gp130 and germline gain-of-function mutations in STAT3 (STAT3GOF) are associated with multi-organ autoimmunity, severe morbidity, and adverse prognosis. To dissect crucial cellular subsets and disease biology involved in activated gp130 signaling, the gp130-JAK-STAT3 axis was constitutively activated using a transgene, L-gp130, specifically targeted to T cells. Activating gp130 signaling in T cells in vivo resulted in fatal, early onset, multi-organ autoimmunity in mice that resembled human STAT3GOF disease. Female mice had more rapid disease progression than male mice. On a cellular level, gp130 signaling induced the activation and effector cell differentiation of T cells, promoted the expansion of T helper type 17 (TH17) cells, and impaired the activity of regulatory T cells. Transcriptomic profiling of CD4+ and CD8+ T cells from these mice revealed commonly dysregulated genes and a gene signature that, when applied to human transcriptomic data, improved the segregation of patients with transcriptionally diverse STAT3GOF mutations from healthy controls. The findings demonstrate that increased gp130-STAT3 signaling leads to TH17-driven autoimmunity that phenotypically resembles human STAT3GOF disease.

Childhood verbal abuse as a child maltreatment subtype: A systematic review of the current evidence.

BACKGROUND: In recent years, the prevalence of childhood emotional abuse has surpassed other forms of maltreatment. Childhood verbal abuse (CVA) is a key attribute of emotional abuse, yet CVA is not recognized as its own form of maltreatment and thus, has not received adequate attention. Clear terminology, definitions, and measures are needed to aid in assessing the occurrence and impact of CVA for its recognition and prevention. OBJECTIVE: We aim to synthesize the evidence on the terms, definitions, and measurements of CVA and identify outcomes associated with CVA. PARTICIPANTS AND SETTING: A systematic review focused on adult perpetration of CVA among children and adolescents using clinical, community-based, and population-based samples. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed and four databases were utilized in May 2022: PsycINFO, MEDLINE, EMBASE, and ProQuest. A total of 149 quantitative and 17 qualitative studies were identified. RESULTS: Across studies reviewed, the most common perpetrators of CVA were parents, mothers, and teachers. Definitional themes for CVA included negative speech volume, tone, and speech content, and their immediate impact. The most frequent measures cited were Adverse Childhood Experiences Study (ACE) Questionnaire and the Conflict Tactics Scale (CTS); 50 % used self-created measures. CVA was associated with a range of internalizing and externalizing outcomes across the lifespan. CONCLUSIONS: Recognizing CVA as a form of maltreatment will be a starting point for its identification and prevention. Primary prevention of CVA using trauma-informed approaches must include adult training on the importance of safety, support, and nurturance during verbal communication with children.

Near-infrared hyperspectral image analysis for monitoring the cheese-ripening process.

Ripening is the most crucial process step in cheese manufacturing and constitutes multiple biochemical alterations that describe the final cheese quality and its perceived sensory attributes. The assessment of the cheese-ripening process is challenging and requires the effective analysis of a multitude of biochemical changes occurring during the process. This study monitored the biochemical and sensory attribute changes of paraffin wax-covered long-ripening hard cheeses (n = 79) during ripening by collecting samples at different stages of ripening. Near-infrared hyperspectral (NIR-HS) imaging, together with free amino acid, chemical composition, and sensory attributes, was studied to monitor the biochemical changes during the ripening process. Orthogonal projection-based multivariate calibration methods were used to characterize ripening-related and orthogonal components as well as the distribution map of chemical components. The results approve the NIR-HS imaging as a rapid tool for monitoring cheese maturity during ripening. Moreover, the pixelwise evaluation of images shows the homogeneity of cheese maturation at different stages of ripening. Among the chemical compositions, fat content and moisture are the most important variables correlating to NIR-HS images during the ripening process.

Expert Team in Your Back Pocket: Recommendations From a Pediatric Mental Health Access Program.

Nationwide challenges with the lack of access to mental health care for youth have prompted efforts to integrate mental health into pediatric primary care. Kansas Kids Mental Health Access Program (KSKidsMAP) was developed to promote mental health workforce development through primary-care practitioners (PCPs) by offering free access to consultations, training, and care coordination. Kansas Kids Mental Health Access Program, a federally funded pediatric mental health care access program (PMHCA), is highly interprofessional in nature, and recommendations reflect the team composition and collaboration efforts. Therefore, a mixed-methods study was conducted to assess the type of recommendations provided to PCPs who requested case consultation services. Seven themes were identified: (1) psychotherapy; (2) diagnostic evaluation; (3) community resources; (4) pharmacotherapy; (5) patient resources and toolkits; (6) education; and (7) other health recommendations. This study highlights the multifaceted approach of KSKidsMAP in addressing PCPs' pediatric mental health concerns.

3D face scan for fabrication of cranioplast: An applied innovative technique.

Cranial defects are repaired for esthetics, functional, morphological and psychological benefit of the affected patients. Purpose of a cranioplast is to prevent trauma to brain tissue, improve the cranial contour, symmetry and esthetics along with pain reduction. This technique describes the innovative use of a multicamera 3D face scanning software for obtaining a 3D face model of a road traffic accident patient for cranioplast fabrication. Advantage of this technique is that it is quick and easy and allows complete face scan under 10 s.

Seasonal variation in swelling of lower extremity edema in patients with chronic venous insufficiency.

OBJECTIVE: We had observed that some patients with chronic venous insufficiency (CVI) had reported their lower extremity edema was worse during warmer weather. Limited research is available regarding the seasonal variation in lower extremity edema. Patients with CVI were questioned to determine whether they had experienced significant seasonal variation in their lower extremity edema and which factors might be associated with such variation. METHODS: Consecutive patients with lower extremity edema were asked whether the edema was worse in the summer or warmer weather. Data was collected between June 2017 and August 2020. A total of 1683 patients (age range, 16-102 years; mean ± standard deviation, 62 ± 14.3 years). Of the 1683 patients, 1157 were female (mean age, 62 ± 14.13 years) and 526 were male (mean age, 62.5 ± 13.82 years). Data were also collected on the presenting symptoms, degree of venous reflux of the great saphenous vein (GSV) reported from the most recent duplex ultrasound, and the season at the time of questioning. For statistical analysis, χ2 goodness-of-fit tests and one-way analysis of variance tests were used. RESULTS: Of the 1683 patients, 56.6% had reported worsening of their lower extremity edema during warmer weather, including 62.7% of the female patients and 37.3% of the male patients. The female patients had reported significantly more worsening of their lower extremity edema (P = 7.06e-18). Female patient age was associated with whether they had experienced worsening (P = .02), with more younger patients reporting worsening. Male patient age was not associated with whether they had reported worsening (P = .97). No significant differences were found in the degree of presenting symptoms between those who had and had not reported worsening (P = .58). Also, no significant differences were found in the degree of venous reflux between the right (P = .61) and left (P = .89) GSV between those who had and had not reported worsening. The season in which the patients had presented during the study period was associated with whether they had reported worsening edema. The patients who had been questioned in the winter (December, January, February) and summer (June, July, August) had reported more worsening of their edema in the warmer months (P = .008 and P = .0002, respectively). The patients who had been questioned in the spring (March, April, May) and fall (September, October, November) had not reported significantly more worsening of their edema in the warmer months (P = .167 and P = .119, respectively). CONCLUSIONS: Of the 1683 patients surveyed, 56.6% had reported worsened edema in the warmer weather. The women (especially the younger women) in the present study had experienced significant worsening, although the men had not. The degree of GSV venous reflux and severity of the presenting symptoms of the patients was not associated with whether worse edema had been reported. However, the season in which the patients had been questioned was associated with the report of worsening edema. The patients questioned in the coldest and warmest months had reported significantly more worsening. The patients questioned in the milder months had not reported significantly more worsening. These findings suggest that a sex and age bias exists in the seasonal variation of lower extremity edema in patients with CVI.

Small-molecule SUMO inhibition for biomarker-informed B-cell lymphoma therapy.

Aberrant activity of the SUMOylation pathway has been associated with MYC overexpression and poor prognosis in aggressive B-cell lymphoma (BCL) and other malignancies. Recently developed small-molecule inhibitors of SUMOylation (SUMOi) target the heterodimeric E1 SUMO activation complex (SAE1/UBA2). Here, we report that activated MYC signaling is an actionable molecular vulnerability in vitro and in a preclinical murine in vivo model of MYC-driven BCL. While SUMOi conferred direct effects on MYC-driven lymphoma cells, SUMO inhibition also resulted in substantial remodeling of various subsets of the innate and specific immunity in vivo. Specifically, SUMOi increased the number of memory B cells as well as cytotoxic and memory T cells, subsets that are attributed a key role within a coordinated anti-tumor immune response. In summary, our data constitute pharmacologic SUMOi as a powerful therapy in a subset of BCL causing massive remodeling of the normal B-cell and T-cell compartment.

Atrial Flutter in the Elderly Patient: The Growing Role of Ablation in Treatment.

The prevalence of atrial flutter (AFL) is increasing among the elderly population, and managing this condition presents specific challenges within this demographic. As patients age, they often exhibit reduced responsiveness to conservative treatment, necessitating a more invasive approach. We present a case of a 93-year-old female who presented to the hospital with acute decompensated heart failure (ADHF) and AFL. A year prior, she was diagnosed with arrhythmia-induced cardiomyopathy. Despite recovering her ejection fraction (EF) through guideline-directed medical therapy (GDMT), her EF deteriorated again. The patient declined invasive management for her arrhythmia on multiple occasions. Managing such patients is challenging since the approach with pharmacotherapy alone often fails to maintain sinus rhythm or adequately control the ventricular rate. Growing evidence shows that invasive management, especially ablation, may be a safe and effective procedure for this patient population. Furthermore, the studies suggest that ablation may yield particular benefits for patients with simultaneous heart failure and atrial fibrillation/AFL (AF/AFL). Unfortunately, limited data exist regarding the invasive management of AFL in the elderly. Therefore, this case report aims to provide a comprehensive review of the current evidence regarding the safety and efficacy of ablation as a therapeutic option for AFL in elderly patients, with a particular focus on how patients with concomitant heart failure may benefit from ablation.

Role of Vitamin A Supplementation in Prevention and Control of Coronavirus Disease-19: A Narrative Review.

Coronavirus disease-19 (COVID-19) caused by SARS-CoV-2 is a novel viral infectious disease, which broke out in the end of winter season 2019 in China and soon became a pandemic. Characteristically there was severe local and systemic immune-inflammatory response to the virus, damaging the respiratory system and other organ systems. The morbidity and mortality caused by the disease are producing tremendous impact on health. The understanding about pathogenesis and manifestations of the disease was obscure. To date, no classic treatment or preventive measure was available for COVID-19 other than symptomatic and supportive care or few drugs under trial. A possibility exists that maintaining vitamin A adequate levels can protect the affected respiratory mucosa, increase antimicrobial activity, produce better antibody response, and have antiinflammatory effects, thereby promoting repair and healing as well. It has been discussed in the review that by various mechanisms, immune regulation through vitamin A supplementation is beneficial to boost immunity in the current outbreak situation when the population is susceptible to the disease. There is a high possibility that vitamin A supplementation to cases as well as population at risk of COVID-19 has a key role in prevention and control. Hence, it is believed that along with other therapeutic and preventive measures, maintaining vitamin A sufficiency during and prior to the development of active disease may act as an adjuvant in population at risk and cases to prevent and control COVID-19.

Stereophotogrammetric Method for Fabrication of Cranioplast Using Digital Facial Scan Technology - A Case Report.

Rationale: Traumatic brain injury is the most common cause of cranial defects. Cranioplasty is the surgical intervention performed to repair cranial defects. The purpose of a cranioplast is to protect the underlying brain tissues, reduce pain, and improve calvarial contour and symmetry. Patient Concerns: This case report describes the management of an ambulatory aided patient who met with a road traffic accident and had undergone decompressive craniectomy. Diagnosis: Noncontrast computed tomography confirmed the frontal cranial defect and was planned for decompressive craniectomy. Treatment Plan: An innovative multi-camera three-dimensional (3D) face-scanning software (Bellus 3D) was used for facial scanning to obtain a 3D face model and fabrication of 3D model using rich presence technology. Outcomes: The wax pattern was then fabricated on a 3D-prototyped model and a customised polymethylmethacrylate cranioplast was fabricated. Take-Away Lessons: his method with the added advantage of rapid prototyping technology resulted in prosthesis with good aesthetics and better fit.

Sphygmomanometer-induced hemostasis following iatrogenic guidewire perforation during lower extremity angioplasty.

OBJECTIVES: Iatrogenic guidewire perforation is a well-known complication of lower extremity angioplasty that is often benign or can be easily treated with endovascular techniques. However, perforations that occur in arterial side branches may be more challenging to manage. If bleeding persists, open surgery and fasciotomy may be required to evacuate the resulting hematoma and prevent compartment syndrome. These subsequent procedures increase morbidity and, if the angioplasty was performed in the outpatient setting, necessitate patient transfer to a hospital. To address these challenges, we describe a non-invasive hemostasis technique involving serial sphygmomanometer cuff inflations over the affected site in a series of five patients who experienced this complication at our office. METHODS: We retrospectively reviewed the medical records of consecutive patients undergoing lower extremity angioplasty that were found to have an arterial guidewire perforation on completion angiogram at our outpatient center between February 2012 and February 2017. Patients found to have iatrogenic guidewire perforations were administered intravenous protamine sulfate and were transferred to the surgical recovery room. Patients received ibuprofen or acetaminophen for pain management. A blood pressure cuff was placed around the site of perforation, and patients received serial cuff inflation cycles with repeated examinations of both limbs until patients reported cessation of pain and there were no signs of a developing hematoma. Patients were observed for two hours before they were discharged home. A follow-up duplex ultrasound examination was completed within one week of the intervention. RESULTS: Over the course of five years, 536 angioplasties were performed at our outpatient office. Five of these patients experienced iatrogenic guidewire perforation (0.93%). Perforations occurred in branches of the anterior or posterior tibial artery. All of these patients were successfully managed with the aforementioned hemostasis technique. None of these patients required transfer to a hospital for further management, and no complications were reported at follow-up. CONCLUSIONS: Complications of iatrogenic guidewire perforations in lower extremity arterial side branches can be safely and effectively managed by applying external compression around the affected site with an automatic blood pressure cuff.