Pre-existing Pathology Research Articles

Predictors of ventricular and atrial feature tracking-derived global longitudinal strain in healthy athletes and volunteers

Abstract Background Feature tracking (FT) strain analysis provides insights into the mechanics of the heart and carries essential prognostic and diagnostic information without prolonging image acquisition during cardiac magnetic resonance (CMR) scans. However, data regarding CMR-derived FT strain in athletes is scarce, especially in the atria. We explored the determinants of FT global longitudinal strain (GLS) values concerning all four cardiac chambers in healthy competitive athletes and less active volunteers. Methods Long- and short-axis cine sequences were analyzed with Medis Suite v4.0 (Leiden, The Netherlands) to assess FT strain. After excluding individuals with preexisting pathologies and images with quality issues, subjects were classified by sport types following the 2020 ESC Sports Cardiology Guidelines. Multiple linear regression models were constructed to assess the impact of age, sex (male=0, female=1), weekly training hours, and sports category (power coded as 0, mixed as 1, endurance as 2) on GLS values. Atrial strain values are positive, and ventricular ones are negative. Intercepts/constants are denoted as "baseline" for easier comprehension. Results Native CMR scans acquired at a tertiary cardiac centre of 596 healthy Caucasian subjects (411 athletes: 145 females, mean age 21±6, range 14-36 years; and 185 volunteers: 86 females, mean age 24±5, range 13-35 years) were included. Athletes had a high exercise load versus the controls who performed no or maximum recreational physical activity (19±7 vs. 3±2 hours/week, p<.001). When assessing athletes (weekly training≥6h), RA GLS (baseline: 34%, p<.001) is increased in females (β=2.0) but is expected to decrease with every one-hour increase in training hours (β=-0.2). LA GLS is notably affected by sex alone (baseline: 37%, β=3.6, p<.001), suggesting markedly higher values for females. RV GLS (baseline: -30%, p<.001) is associated with both age and training hours (β=0.1 for each), making it less negative. Conversely, LV GLS (baseline: -25%, p<.0001) is significantly modulated by all studied factors, with sports category (β=0.5), age, and training hours (β=0.1 each) increasing values and sex decreasing them (β=-0.9). In less active volunteers (weekly training<6h), sex (β=4.7) is the only significant factor for RA GLS (baseline: 33%, p=.04), and sports category (β=2.7, the group included 98 recreational athletes with low training loads) for LA GLS (baseline: 38%, p=.04). No variables were retained in the model for RV GLS, but sex (β=-1.4) remained a predictor in the LV GLS model (baseline: -21%, p=.002). Conclusion GLS shows significant variations influenced by age, sex, sports category, and training hours across all four heart chambers in athletes. These effects appear mostly inconclusive among less active individuals. This data calls for further advanced analyses of athlete's hearts to refine differentiation methods between healthy adaptation and cardiac pathologies.Left atrial FT analysisModel outputs for GLS predictions

Quantifying brain health in acute ischemic stroke through effective reserve.

To quantify brain health using a measure of reserve that incorporates pre-existing pathology. We analyzed two retrospective ischemic stroke cohorts (GASROS and SALVO) with neuroimaging and 90-day modified Rankin Scores (mRS) available. White matter hyperintensity (WMHv), brain, and intracranial volumes were automatically extracted, and brain parenchymal fraction (BPF) calculated. The latent variable effective reserve (eR) was modeled using age, WMHv, and BPF or brain volume in GASROS. Models were compared using Bayes Information Criterion (BIC). The best model's eR estimates were categorized into quartiles and evaluated in SALVO. GASROS included 476 (median age: 65.8; 65.3% male) and SALVO included 43 (median age: 69.2; 62.8% male) patients. Inverse associations between eR and mRS was seen in both models, with brain volume outperforming BPF (path coefficients: -0.67, -0.48, respectively; p < 0.001; |ΔBIC| = 362). Quartile-based eR stratification in SALVO showed a similar inverse trend, with worse outcomes in the low reserve group (mRS≤2 - highest vs lowest quartile: 85/90% vs 59/45% for GASROS/SALVO). Expanding the concept of eR, highlights its clinical translational potential. The strong link between higher eR and better outcomes underscores its value as a protective brain health metric.

6770 Graves’ disease induced by COVID-19 infection in a 49 year old male

Abstract Disclosure: N. Al-hosainat: None. A. Al Najada: None. T. Salar: None. S. Iqbal: None. K. Abdel Gadir: None. Introduction: Graves’ disease is an autoimmune disease causing hyperthyroidism, characterized by elevated thyrotropin-receptor antibodies. COVID-19 infection has been increasingly reported as a trigger of thyroid illness including Graves’ disease. We present a unique case of 49-year-old patient who was diagnosed with Graves’ disease after COVID-19 infection. Case description: A 49-year-old male patient with history of prediabetes presented with complaints of tremor, fatigue, generalized itching, and unintentional weight loss (30 Ibs in 6 months). He had COVID-19 infection 3 months prior. The remainder of review of systems was negative. No family history of thyroid disease. On exam, the patient had sinus tachycardia with otherwise normal vital signs. Diffuse thyromegaly was noted along with an intermittent fine tremor of the extremities. Blood work was notable for low TSH &amp;lt;0.01 uIU/mL, elevated free T4 (3.4 ng/dL), free T3 (17.6ng/dL), and TSH receptor antibody (12 IU/L). Thyroid ultrasound showed mild goiter with 2 nodules, one of which was TIRADS 4 and 1.5cm. This nodule was biopsied and found to be benign. Radioactive iodine uptake scan revealed homogeneous diffuse increased thyroid uptake. The diagnosis of Graves’ disease was made, and the patient was started on propranolol and methimazole with significant improvement of his symptoms and his laboratory tests normalizing. Discussion: Graves' disease is an autoimmune disease, characterized by hyperthyroidism, goiter, occasional orbitopathy and dermopathy. Caused by antibodies against thyroid-stimulating hormone receptors which stimulate thyroid hormone secretion and thyroid growth. Treatment is aimed to decrease thyroid hormone synthesis by either a Thionamide, radioiodine ablation, or surgery. Remission rates with antithyroid drugs average under 40 percent after one to two years of treatment and could exceed 80 percent after 5 to 10 years of treatment. COVID-19 is a multi-system disease, caused by SARS-CoV-2 virus, transmitted by large droplets and small particle aerosols, was declared a pandemic in 2020 and affected millions of people worldwide. There is emerging data showing the association of COVID-19 with various thyroid diseases including thyroiditis and relapse of known Graves' disease after the infection. We present a case of newly diagnosed Graves’ disease after COVID-19 infection in a patient with no personal or family history of such disease which raises the concern of autoimmune pathway activation induced by the infection. The onset of Graves’ disease after COVID-19 infection does not depend on the presence of pre-existing thyroid pathology and in this case responded well to antithyroid medication. Conclusion: COVID-19 can lead to the development of a range of medical illnesses. In patients who develop symptoms of thyrotoxicosis, Graves’ disease should be suspected, investigated, and treated appropriately Presentation: 6/3/2024

7988 A Case of Spontaneous Pituitary Hemorrhage in Late Pregnancy

Abstract Disclosure: D. Poudyal: None. G.L. Prince: None. Background: Pituitary apoplexy (PA), caused by hemorrhage into the pituitary gland, is rare. The prevalence in pregnancy is also quite rare, with PA complicating 1 in 10,000 pregnancies. PA usually occurs in patients with pre-existing pituitary adenomas. Spontaneous pituitary hemorrhage (PH) causing PA in the absence of a known adenoma or other precipitating factors is less frequently described. Presenting symptoms of PA are non-specific and can pose diagnostic challenges, yet PA must be managed urgently and decisively due to the risk of life-threatening hormonal deficiencies that can ensue. Physiologic changes in pregnancy pose additional challenges in evaluating and managing patients with possible PA. Here we present a case of spontaneous PH during the third trimester of pregnancy in the absence of pre-existing pituitary pathology or known precipitants. Case presentation: A 31-year-old female, G2P1, with an uncomplicated first pregnancy, presented with acute-onset headache and vision loss at 36 weeks gestation. Her symptoms resolved spontaneously in 45 minutes. MRI brain without contrast showed hemorrhage within the left aspect of the pituitary gland, a mildly displaced infundibulum, but no mass effect on the optic chiasm. MRI brain obtained 1 year prior for headache was unremarkable. Lab work showed an 8AM cortisol of 19 ug/dL (Ref range 3.7 - 19.4 ug/dL), and a total T4 of 11.3 ug/dL (Ref 4.9 - 11.7 ug/dL). Ultimately, interpretation of her cortisol testing was limited by: elevated cortisol-binding globulin in the high-estrogen state of pregnancy, elevated cortisol production by an intact hypothalamic-pituitary-adrenal (HPA) axis during the latter portion of pregnancy, and the lack of validated cutoff values for 8AM serum cortisol levels during pregnancy. In light of these factors and the risk of undiagnosed adrenal insufficiency (AI), she was treated empirically with oral hydrocortisone. Subsequently, she had an uneventful vaginal delivery, supported by stress dosing of her steroids. Postpartum, she had a normal 8AM cortisol level of 14 ug/dL, and she was noted to quickly begin breastfeeding without incident. Conclusion: PA remains a critical diagnosis that cannot be missed in patients presenting with concerning symptoms and signs, in order to identify and treat life-threatening hormonal deficiencies. Pregnancy poses unique challenges in diagnosing hormonal deficiencies such as AI due to normal physiologic changes affecting the HPA axis as well as other pituitary axes. Therefore, the benefit of empiric hydrocortisone treatment likely outweighs any associated treatment risk in cases with consistent symptomatology and radiographic findings. Presentation: 6/2/2024

Likelihood of Laryngeal Involvement in Autoimmune Thyroid Disorder Patients: A Meta-Analysis.

The involvement of the larynx in many situations can have a substantial impact on a person's voice, breathing, and general health. Individuals with autoimmune thyroid disorders can experience a variety of conditions affecting the larynx. Autoimmune thyroid disorders, such as Hashimoto's thyroiditis [HT] and Graves' disease [GD], are prevalent conditions affecting the thyroid gland. Beyond their established impact on thyroid function, these disorders have been associated with laryngeal involvement. The current study aims to explore the likelihood of laryngeal involvement in patients with Autoimmune Thyroid Disorders [AITD]. This study involved a retrospective analysis of medical records from patients diagnosed with autoimmune thyroid disorders. Inclusion criteria were a confirmed diagnosis through laboratory investigations and clinical assessment. Patients with pre-existing laryngeal pathologies or other conditions affecting the larynx were not considered. We collected data from 4 research articles and 3 clinical trials from Embase, PubMed, and NCBI-Trials portals, focusing on reported laryngeal symptoms. The severity of laryngeal involvement was assessed and categorized based on its extent and impact on vocal function. Preliminary analysis of the collected data indicated a significant proportion of patients with autoimmune thyroid disorders reporting laryngeal symptoms. Among these patients, various manifestations of laryngeal involvement were observed, including vocal changes, hoarseness, and throat discomfort. The findings show that laryngeal symptoms may be an underappreciated feature of these diseases, potentially impacting vocal function and quality of life in affected people. Further research is also needed for more precise projections in this direction.

The change in lumbar lordosis from the standing to the lateral position: implications for lateral interbody fusion.

The purpose of this cross-sectional, observational study was to establish the relationship between standing lumbar lordosis (LL) and lateral decubitus LL. Forty-nine subjects, 24 male and 25 female, were prospectively enrolled. Patients with pre-existing spinopelvic pathology were excluded. Standing, relaxed-seated, and lateral decubitus lateral radiographs were obtained. Radiographic variables measured included LL and lordosis change at each lumbar level (e.g. L1-L2). The change in LL when going from a standing to a lateral decubitus position (ΔLL), the correlation between standing and sitting LL compared to lateral decubitus LL, and the correlation between ΔLL and standing pelvic incidence (PI), pelvic tilt (PT), PI-LL mismatch, pelvic femoral angle (PFA), and sacral slope (SS) were calculated. Subjects had an average age of 25.7 ± 2.3 years and body mass index of 24.1 ± 3.0kg/m2. On average, 11.9°±8.2° (range - 7° to 29°) of LL was lost when transitioning from a standing to the lateral decubitus position. Lateral decubitus LL had a higher correlation with standing LL (R = 0.725, p < 0.001) than with relaxed-seated LL (R = 0.434, p < 0.001). Standing PT and PI-LL mismatch had moderately negative correlations with ΔLL (R=-0.58 and R=-0.59, respectively, both p < 0.05). Standing PI and standing PFA had a low negative correlation with ΔLL (R=-0.31 and R=-0.44, respectively, both p < 0.05) Standing SS and LL had no correlation with ΔLL. Standing LL was strongly correlated to lateral decubitus LL, although subjects lost an average of 11.9° from the standing to the lateral decubitus position. This has important implications for fusion in the lateral position.

Zein spray-dried microparticles loaded with chemically modified curcumin for active wound healing

Wound healing is a delicate process comprising various phases, of which inflammation constitutes the most critical one, as some wounds fail to evolve from this state due to pre-existing pathologies or medical conditions, becoming chronic and causing pain and serious consequences for the patients. Given this context, innovative strategies able to support the body in the transition through the inflammatory and the proliferative phases are needed. Here, we propose to deliver to the wound zein microparticles (ZμP) loaded with chemically modified curcumin (mCUR), a novel bioactive molecule with strong antioxidant properties. Derived from the classic curcumin, mCUR chemical structure has been modified with an amino phenyl carbonyl group on C4 to overcome the poor bioavailability in the human body and to reach stronger inhibition of inflammatory markers thanks to a higher in vitro efficacy (lower IC50). ZμP were fabricated via spray drying starting from various zein/mCUR ratios. An exhaustive characterization of the physico-chemical properties of ZμP, either empty or loaded, has been carried out, alongside with bioactivity assessments via human keratinocytes and Escherichia coli cultures. All the formulations presented average diameters of 1 μm, resulted biocompatible, and led to an encapsulation efficiency in the range of 78.1–83.0 %. Finally, antioxidant properties of loaded microparticles were assessed via DCFH-DA assay, where a fluorescence decrease proportional to mCUR concentration was clearly visible (down to 41.7 %). These promising results highlight our formulations’ ability to reduce oxidative stress inside the cells, representing a promising strategy to address the problem of chronic wounds, supporting the body in overcoming the inflammatory stage.

In-Hospital Mortality in Patients With Acute Myocardial Infarction: A Literature Overview.

Acute myocardial infarction (AMI) continues to be a predominant cause of global morbidity and mortality, with in-hospital mortality (IHM) serving as a pivotal metric for patient outcomes. This review explores the influence of several clinical variables on IHM in individuals with AMI. Factors such as age, gender, body mass index (BMI), smoking habits, existing comorbidities, prior coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI), and biomarkers, including high-sensitivity cardiac troponin T (hs-cTnT) and creatine kinase MB (CK-MB), significantly affect the prognosis of the patient. Advanced age and comorbid conditions such as diabetes and hypertension exacerbate myocardial damage and systemic impacts, thus increasing IHM. Gender and BMI are also critical, and women and patients with obesity face different risks. Smoking increases both the risk of AMI and IHM, underscoring the importance of cessation interventions. ST-elevation myocardial infarctionis associated with elevated IHM and requires immediate reperfusion therapy, while non-ST-elevation myocardial infarctionrequires customized management for risk assessment. Previous CABG and PCI add complexity to AMI treatment and elevate IHM due to pre-existing coronary pathology and the intricacies of the procedures involved. The application of biomarker-centered techniques facilitates the swift identification of individuals at elevated risk, improves therapeutic planning, and reduces IHM for patients with AMI. Understanding and incorporating these clinical determinants are essential to optimize the management of AMI, minimize IHM, and improve patient outcomes. This all-encompassing strategy requires ongoing research, quality improvement efforts, and personalized care approaches.

Diabetic myonecrosis complicated by emphysematous pyomyositis and abscess caused by Escherichia coli: a case report

BackgroundNecrotizing myopathies and muscle necrosis can be caused by immune-mediated mechanisms, drugs, ischemia, and infections, and differential diagnosis may be challenging.Case presentationWe describe a case of diabetic myonecrosis complicated by pyomyositis and abscess caused by Escherichia coli. A white woman in her late forties was admitted to the hospital with a 1.5 week history of bilateral swelling, weakness, and mild pain of the lower extremities and inability to walk. She had a history of type 1 diabetes complicated by diabetic retinopathy, neuropathy, nephropathy, and end-stage renal disease. C-reactive protein was 203 mg/l, while creatinine kinase was only mildly elevated to 700 IU/l. Magnetic resonance imaging of her lower limb muscles showed extensive edema, and muscle biopsy was suggestive of necrotizing myopathy with mild inflammation. No myositis-associated or myositis-specific antibodies were detected. Initially, she was suspected to have seronegative immune-mediated necrotizing myopathy, but later her condition was considered to be explained better by diabetic myonecrosis with multifocal involvement. Her symptoms alleviated without any immunosuppressive treatment. After a month, she developed new-onset and more severe symptoms in her right posterior thigh. She was diagnosed with emphysematous urinary tract infection and emphysematous myositis and abscess of the right hamstring muscle. Bacterial cultures of drained pus from abscess and urine were positive for Escherichia coli. In addition to abscess drainage, she received two 3–4-week courses of intravenous antibiotics. In the discussion, we compare the symptoms and findings typically found in pyomyositis, immune-mediated necrotizing myopathy, and diabetic myonecrosis (spontaneous ischemic necrosis of skeletal muscle among people with diabetes). All of these diseases may cause muscle weakness and pain, muscle edema in imaging, and muscle necrosis. However, many differences exist in their clinical presentation, imaging, histology, and extramuscular symptoms, which can be useful in determining diagnosis. As pyomyositis often occurs in muscles with pre-existing pathologies, the ischemic muscle has likely served as a favorable breeding ground for the E. coli in our case.ConclusionsIdentifying the etiology of necrotizing myopathy is a diagnostic challenge and often requires a multidisciplinary assessment of internists, pathologists, and radiologists. Moreover, the presence of two rare conditions concomitantly is possible in cases with atypical features.

Prevalence of preexisting articular bone pathology in patients with osteoarthritis screened for fasinumab clinical trials identified by X-ray or magnetic resonance imaging

ObjectiveTo examine the prevalence of preexisting articular bone pathology in patients with hip or knee pain due to osteoarthritis (OA) screened for fasinumab clinical trials. MethodThis post-hoc analysis included patients with OA screened for three phase 3 fasinumab studies (NCT02683239, NCT03161093, NCT03304379). During screening, participants who met other clinical inclusion/exclusion criteria underwent radiography of knees, hips, and shoulders. Those with Kellgren–Lawrence grade (KLG) ≥2 for index joint and without an exclusionary finding proceeded to magnetic resonance imaging (MRI) of index, contralateral, and KLG ≥3 joints. Exclusionary findings included bone fragmentation/collapse, bone loss/resorption, osteonecrosis, and fracture, by either X-ray or MRI. Participants with extensive subchondral cysts were also excluded. Prevalence of abnormalities on radiographs and MRIs are reported. ResultsOf 27,633 participants screened, 21,997 proceeded to imaging. Of these, 1203 (5.5%) were excluded due to the presence of ≥1 joint with severe articular bone pathology (X-ray or MRI): bone fragmentation/collapse (2.61%), subchondral insufficiency fracture (SIF; 1.67%), osteonecrosis (1.11%), and significant bone loss (0.32%). Additionally, 3.14% screen-failed due to extensive subchondral cysts. More than half of the exclusions due to bone fragmentation/collapse (386/572), osteonecrosis (141/245) and significant bone loss (59/71), and approximately one third of SIF (133/367) and extensive subchondral cysts (229/689) were evident on X-rays. ConclusionsApproximately one in 20 participants with OA who met the clinical screening criteria for fasinumab phase 3 trials were later excluded due to preexisting severe articular bone pathology findings by X-ray or MRI.

Inibidores da bomba de prótons e sua relação com a microbiota gastrointestinal: O benefício compensa o risco?

Background: This study aimed to investigate the impact of prolonged exposure to PPIs on the gastrointestinal microbiota, as well as to assess its potential implication on the development of gastrointestinal diseases. Methods: This literature review was based on the "National Library of Medicine” (PubMed) research platform, using the descriptors (intestinal microbiota OR gastrointestinal microbiomes OR gut microbiota OR gastrointestinal flora) AND (Proton pump inhibitors OR PPIs). The applied filters for work selection were: published within the last 5 years; written in Portuguese, English, or Spanish; excluding systematic reviews and meta-analyses. Results: Recent studies have revealed a series of alterations in the gastrointestinal microbiota, which have been associated with the exacerbation of pre-existing pathologies or the onset of new conditions. Prolonged use of PPIs has shown considerable impacts on the quantity of gastrointestinal microorganisms such as Streptococcus, Lactobacillus, Bacteroidetes, Veillonellaceae, among others. In addition, an increased incidence of diseases such as hepatic encephalopathy, gastroesophageal reflux disease (GERD), cirrhosis, spontaneous bacterial peritonitis, and intestinal infections have been found. Conclusion: The results showed that the dysbiosis triggered by chronic use of PPIs leads to an increased risk of gastrointestinal diseases. Therefore, it is crucial to adopt a rational prescription of these drugs, carefully considering the risks and benefits to ensure safe and effective use in clinical practice. Furthermore, there is a need for further research to define possible risk groups related to chronic use of PPIs, such as patients with hepatic cirrhosis or hepatitis B

Cervical Spine Manipulation and Causation of Cervical Artery Dissection: A Review of 10 Case Reports.

Recent media coverage of high-profile cases of cervical artery dissection (CAD) has ignited the discussion about the role of cervical spine manipulation (CSM) in causing cervical artery dissection. However, research does not support a causal association between cervical spine manipulation and cervical artery dissection in a healthy cervical spine. The objective of this study was to review the 10 most recent case reports of cervical spine manipulation and cervical artery dissection for convincing evidence of the causation of cervical artery dissection by cervical spine manipulation. Nine of 10 case reports showed no convincing evidence of a causal relationship between cervical spine manipulation and cervical artery dissection. The 10th case report was exceptional as the CSM was contraindicated by pre-existing cervical spine pathology. We conclude that these 10 case reports provide no convincing evidence of the causation of cervical artery dissection by cervical spine manipulation in a healthy cervical spine. One case report demonstrated that cervical spine manipulation can cause cervical artery dissection when performed in the presence of pre-existing cervical spine pathology. Therefore, we conclude that practitioners should exclude cervical spine pathology before performing cervical spine manipulation.

A retrospective study of the characteristics and toxicology of cases of lysergic acid diethylamide (LSD)- and psilocybin-related death in Australia.

Lysergic acid diethylamide (LSD) and psilocybin are used as recreational drugs, and there is renewed interest in their clinical use. The current study aimed to (1) determine the circumstances of death and case characteristics of LSD- and psilocybin-related death in Australia, 2000-23; and (2) determine the toxicological profile and major autopsy findings of these cases. This was a retrospective exploratory study of all cases of LSD- and psilocybin-related death in Australia, 2000-23, retrieved from the National Coronial Information System. A total of 43 cases were identified: 33 LSD and 10 psilocybin. The median ages were 24 years [interquartile range (IQR) = 13, range = 16-53] (LSD) and 26 years (IQR = 18.5, range = 20-58) (psilocybin), and fewer than five cases were female. The most common circumstance of death among both groups was traumatic accident (LSD 36.4%, psilocybin 40.0%). There were 12 cases of self-harm, all of which involved LSD, all by physical means. In a fifth, death was attributed to multiple drug toxicity (LSD 18.2%, psilocybin 20.0%). In one case, death was attributed solely to LSD toxicity, while in a further two cases death was attributed to a cardiovascular event following LSD consumption (one LSD only, one multiple drug toxicity). In four psilocybin cases, the cause of death was undetermined. The most common clinical presentation was severe agitation (LSD 27.3%, psilocybin 20.0%). Median blood concentrations were LSD 0.8μg/l (IQR = 1.7, range = 0.1-3), psilocin 20 μg/l (IQR = 53.5, range = 6-83). LSD was the only drug present in 25.0% of LSD cases and psilocybin in 20.0% of psilocybin cases. Pre-existing organ pathology was uncommon. Lysergic acid diethylamide (LSD)- and psilocybin-related death in Australia from 2000 to 2023 was primarily due to traumatic injury, whether through accident or self-harm. Cases of acute toxic reactions that were attributed solely to LSD were rare.

Long COVID in Children, Adults, and Vulnerable Populations: A Comprehensive Overview for an Integrated Approach.

Long COVID affects both children and adults, including subjects who experienced severe, mild, or even asymptomatic SARS-CoV-2 infection. We have provided a comprehensive overview of the incidence, clinical characteristics, risk factors, and outcomes of persistent COVID-19 symptoms in both children and adults, encompassing vulnerable populations, such as pregnant women and oncological patients. Our objective is to emphasize the critical significance of adopting an integrated approach for the early detection and appropriate management of long COVID. The incidence and severity of long COVID symptoms can have a significant impact on the quality of life of patients and the course of disease in the case of pre-existing pathologies. Particularly, in fragile and vulnerable patients, the presence of PASC is related to significantly worse survival, independent from pre-existing vulnerabilities and treatment. It is important try to achieve an early recognition and management. Various mechanisms are implicated, resulting in a wide range of clinical presentations. Understanding the specific mechanisms and risk factors involved in long COVID is crucial for tailoring effective interventions and support strategies. Management approaches involve comprehensive biopsychosocial assessments and treatment of symptoms and comorbidities, such as autonomic dysfunction, as well as multidisciplinary rehabilitation. The overall course of long COVID is one of gradual improvement, with recovery observed in the majority, though not all, of patients. As the research on long-COVID continues to evolve, ongoing studies are likely to shed more light on the intricate relationship between chronic diseases, such as oncological status, cardiovascular diseases, psychiatric disorders, and the persistent effects of SARS-CoV-2 infection. This information could guide healthcare providers, researchers, and policymakers in developing targeted interventions.

Novel benzimidazole angiotensin receptor blockers with anti-SARS-CoV-2 activity equipotent to that of nirmatrelvir: computational and enzymatic studies

ABSTRACT Background Hypertension worsens outcomes in SARS-CoV-2 patients. Sartans, a type of antihypertensive angiotensin receptor blocker-(ARB), reduce COVID-19 morbidity and mortality by targeting angiotensin-converting enzyme-2 (ACE2). This study aimed to evaluate the antiviral and antihypertensive effects of nirmatrelvir, commercial sartans (candesartan, losartan, and losartan carboxylic (Exp3174)), and newly synthesized sartans (benzimidazole-N-biphenyl carboxyl (ACC519C) and benzimidazole-N-biphenyl tetrazole (ACC519T)), compared to nirmatrelvir, the antiviral component of Paxlovid. Research design and methods Surface plasmon resonance (SPR) and enzymatic studies assessed drug effects on ACE2. Antiviral abilities were tested with SARS-CoV-2-infected Vero E6 cells, and antihypertensive effects were evaluated using angiotensin II-contracted rabbit iliac arteries. Results Benzimidazole-based candesartan and ACC519C showed antiviral activity comparable to nirmatrelvir (95% inhibition). Imidazole-based losartan, Exp3174, and ACC519T were less potent (75%–80% and 50%, respectively), with Exp3174 being the least effective. SPR analysis indicated high sartans-ACE2 binding affinity. Candesartan and nirmatrelvir combined had greater inhibitory and cytopathic effects (3.96%) than individually (6.10% and 5.08%). ACE2 enzymatic assays showed varying effects of novel sartans on ACE2. ACC519T significantly reduced angiotensin II-mediated contraction, unlike nirmatrelvir and ACC519T(2). Conclusion This study reports the discovery of a new class of benzimidazole-based sartans that significantly inhibit SARS-CoV-2, likely due to their interaction with ACE2.

Incident Dementia After Spontaneous Intracerebral Hemorrhage.

Post-stroke cognitive impairment and dementia (PSCID) is a complication that affects long-term functional outcomes after stroke. Studies on dementia after long-term follow-up in stroke have focused predominantly on ischemic stroke, which may be different from the development of dementia after spontaneous intracerebral hemorrhage (ICH). In this review, we summarize the existing data and hypotheses on the development of dementia after spontaneous ICH, review the management of post-ICH dementia, and suggest areas for future research. Dementia after spontaneous ICH has a cumulative incidence of up to 32.0-37.4% at 5 years post-ICH. Although the pathophysiology of post-ICH dementia has not been fully understood, two main theoretical frameworks can be considered: 1) the triggering role of ICH (both primary and secondary brain injury) in precipitating cognitive decline and dementia; and 2) the contributory role of pre-existing brain pathology (including small vessel disease and neurodegenerative pathology), reduced cognitive reserve, and genetic factors predisposing to cognitive dysfunction. These pathophysiological pathways may have synergistic effects that converge on dysfunction of the neurovascular unit and disruptions in functional connectivity leading to dementia post-ICH. Management of post-ICH dementia may include screening and monitoring, cognitive therapy, and pharmacotherapy. Non-invasive brain stimulation is an emerging therapeutic modality under investigation for safety and efficacy. Our review highlights that there remains a paucity of data and standardized reporting on incident dementia after spontaneous ICH. Further research is imperative for determining the incidence, risk factors, and pathophysiology of post-ICH dementia, in order to identify new therapies for the treatment of this debilitating condition.

Anatomical Structures at Risk in Percutaneous Distal Bunionette Correction

Introduction/Purpose: Bunionette deformity affects 23% of the population and has numerous surgical options, including a minimally invasive approach (MIA) to decrease complications. Percutaneous surgery is favored by patients as it decreases pain, inflammation, and noticeable incision sites. Three possible osteotomy sites have been identified: proximal, diaphyseal, and distal. The study investigates the anatomic structures at risk during distal osteotomy of bunionette deformity using a Shannon burr. The distal osteotomy site was on average greater than 8mm from the extensor digitorum longus and adductor digiti minimi while it was 1.64mm from the lateral dorsal cutaneous nerve. The study highlighted the challenges posed by minimally invasive approaches to treating bunionette deformity and the need for cautious consideration when utilizing percutaneous methods. Methods: Eleven fresh frozen below-knee amputated foot and ankle cadavers were used for this study. Cadavers were allowed to thaw for 12 hours at room temperature before performing any tissue handling. All cadavers were visually inspected for evidence of gross pathology. Fluoroscopic radiographs were used to inspect for evidence of preexisting pathology of the fifth metatarsal. All cadavers with gross pathology or radiographic fifth metatarsal pathology were excluded from the study. All procedures were performed by a fellowship trained orthopaedic foot and ankle surgeon. Results: All eleven cadavers met the inclusion criteria for this study. The average age of the patients was 66.6 +/- 20.1 years. There were five female feet and six male feet. There were seven right feet and four left feet. Distance from the percutaneous access site was measured to structures at potential risk. The closest structure at risk was the lateral dorsal cutaneous nerve (LDCN) (1.64 mm), which was contacted 2/11 times and transected both times. The extensor digitorum longus (EDL) and abductor digiti minimi (ADM) had no instances of contact during the procedure. Dissection allowed for the identification of structures at risk and the assessment of osteotomy. All procedures resulted in a complete osteotomy. Conclusion: Overall, distal percutaneous bunionette osteotomy is largely safe. Structures pertinent to the surgery were identified with ease and were intact after osteotomy with a Shannon burr. Anatomic variations of LDCN can present challenges to the procedure. Meticulous dissection and judicious use of fluoroscopy can help prevent further damage. Surgeons should be aware of anatomic variations in order to proceed safely.

Human and animal cells under influence of different lighting and stimulus

Circadian rhythms, are the basis of homeostasis of organisms like human and other mammals. Violation of circadian rhythms leads to the development of pathological conditions and severe course of preexisting pathologies. For example some work with B16-F1O cells (B16) has shown that molecules like opsins, Circadian Locomotor Output Cycles Kaput (CLOCK) and clock genes are changed after a white light pulse (WLP). Like this, melanopsin (OPN4) and rhodopsin (OPN2) through UVA irradiation induced B16 pigmentation. Thus, heat shock reduces secreted rhodopsin expression in normal Melan-a melanocytes, while the opposite effect is found in malignant B16 cells. In both cell lines UVA radiation increases the expression of melanopsin and melanin, interfering with several clock genes, and also increasing the DNA repair enzyme xeroderma pigmentosum, complementation group A (XPA). Furthermore, B16 are more responsive to UVA radiation when compared to normal cells. Thereby, opsins are involved in animal camouflage. And their functions in humans involve different wavelengths, for example in skin the keratinocyte differentiation by (410 nm) involved cone opsin (OPN1) and rhodopsin (OPN2), like this in epidermal keratinocytes irradiation by (447 nm) accelerates closure in wound-healing and violet light (415 nm) induced hyperpigmentation. Furthermore, in B16 cell culture certain wavelengths induce proliferation or inhibition like signs of apoptosis and necrosis. Finally understanding the response of opsins and clock genes to different wavelengths in the skin, we could attribute a therapeutic of photobiomodulation (PBM) to approach various dermatological conditions, such as psoriasis, atopic dermatitis, hair growth, wound healing and tissue regeneration.

Cardiovascular complications of COVID-19

Background. The problem of COVID-19 today is the most unresolved worldwide. Scientists and doctors all over the world are trying to study features of pathogenesis this disease to find the most effective treatment methods. Multiple organ complications COVID-19 lead to death and disability of patients. The disease manifests itself with symptoms of damage to the pulmonary system with subsequent damage other systems and organs. Considering that cardiovascular diseases remain the leading cause of death worldwide, it is necessary to study the features of flow COVID-19 against the background of existing cardiovascular pathology. Purpose – the purpose of the study was to analyze and summarize literature sources, which are devoted to the study of damage to the cardiovascular system as a result of COVID-19 affection. Materials and Methods. Publications were selected using keywords in PubMed (https://pubmed.ncbi.nlm.nih.gov/) and Google Scholar (https://scholar.google.com/) databases published over the period from 2020 to 2022. Results. The article analyzes the existing data of meta-analyzes regarding the incidence of cardiovascular disease, the effect of diabetes mellitus on the course of the disease, existing theories of the pathogenesis of cardiovascular disease in COVID-19. Clinical variants of heart damage in COVID-19 are also given, which are described in the literature today. Particular attention is paid to the peculiarities of development and the course of postcoid myocarditis, which is one of the most common complications of COVID-19 on the part of the cardiovascular system. Particularly noteworthy is the fact that according to the literature, some patients were diagnosed with myocarditis without clinical manifestations. Therefore, the data of histological examination of the myocardium of COVID-19 patients without myocarditis symptoms are of great interest. Difficulties also arise at the stage of diagnosing myocarditis, because the currently accepted methods are sometimes uninformative. Mass vaccination against COVID-19, unfortunately, also had such undesirable side effects as post-injection myocarditis. The literature data on the development of dilated cardiomyopathy after suffering from COVID-19 are presented. At the same time, dilated cardiomyopathy can be the result not only of the transferred myocarditis, but also a primary reaction to the effect of cytokines released by the virus. Conclusions. COVID-19 can exacerbate pre-existing cardiovascular pathology and provoke acute myocardial injury, deteriorating the course of the disease and the life prognosis for the patient.

Ocular Effects of MEK Inhibitor Therapy: Literature Review, Clinical Presentation, and Best Practices for Mitigation.

MEK signaling pathway targeting has emerged as a valuable addition to the options available for the treatment of advanced cancers including melanoma and non-small cell lung cancer. Ophthalmologic monitoring of patients taking part in clinical trials of MEK inhibitors has shown that while ocular effects are common, generally emerging during the first days to weeks of treatment, the majority are either asymptomatic or have minimal visual impact and are benign, resolving without intervention or the need to reduce or stop MEK inhibitor therapy. However rare cases of serious, potentially vision-threatening ocular toxicities have been reported during MEK inhibitor therapy. There is currently no recommendation for routine ophthalmologic screening or monitoring of patients with advanced cancer who are initiating MEK inhibitor therapy. However, baseline ophthalmologic examination may be useful for all patients initiating MEK inhibitor therapy to allow the differentiation of preexisting pathology versus the development of MEK inhibitor-associated retinopathy in the event of the emergence of symptomatic ocular events. Regular ophthalmologic examination may be appropriate for patients at increased risk for ocular events, such as patients with a history of ocular inflammation, infection, or underlying macular/retinal disease. All patients reporting visual disturbance should be referred for prompt ophthalmologic review to determine the potential seriousness of any underlying abnormalities and whether there is a need for treatment modification or specific intervention. Understanding the potential consequences of ocular toxicities is of particular importance in the context of decision-making for the continuation of potentially life-prolonging medications such as MEK inhibitors.