Epidermal inclusion cyst in an axillary lymph node with breast cancer: A case report.

Epidermal inclusion cyst (EIC) is a benign lesion rarely discovered within lymph nodes. The present case report introduces an EIC incidentally discovered during an axillary lymph node biopsy in a patient with invasive ductal carcinoma of the breast. A 55-year-old woman presented with a breast mass. Ultrasound revealed a suspicious mass, and a core needle biopsy confirmed the diagnosis of invasive ductal carcinoma. Lumpectomy and sentinel lymph node biopsies were performed. Histopathological examination revealed tumor-free lymph nodes, with one of them harboring a keratinous EIC. EICs typically arise from entrapped epidermal cells. Their presence in lymph nodes is exceptionally rare. While the origin of such inclusions remains unclear, various theories exist, including anomalous embryonic development, implantation, and metaplasia. This report highlights the unique presentation of an EIC within an axillary lymph node. Recognizing this entity is crucial to avoid misdiagnosis of malignancy and unnecessary interventions.

Intratesticular prepubertal­type mature teratoma in an infant: A case report and mini­review of the literature.

Testicular tumors are rare in children, representing a small percentage of pediatric solid tumors, with an incidence of 2 cases per 100,000 males. Teratomas, which are the most prevalent tumors in infants, may manifest in mature, immature, or malignant forms. While mature teratomas are typically found in the abdomen, intratesticular prepubertal-type teratomas in infants are infrequent. The present study describes the case of an infant with an intratesticular mature teratoma. A 6-month-old male infant presented with right-sided scrotal swelling, which was noted by his parents. There was no family history of similar conditions, and an investigation of his medical history did not reveal any notable findings. A physical examination revealed a non-reducible, solid mass indistinguishable from the right testicle, with no signs of inflammation or systemic symptoms. A scrotal sonography confirmed a large intratesticular cyst. The levels of α-fetoprotein and ß-human chorionic gonadotropin were normal. Surgical tumor enucleation was performed, and the histopathological examination revealed a benign, prepubertal-type teratoma composed entirely of mature elements. Surgical intervention is commonly used for the management of benign testicular tumors in pediatric patients, including prepubertal teratomas. This approach demonstrates an excellent prognosis as it does not elevate the likelihood of recurrence. Prepubertal-type teratomas have rarely been reported in the infantile testis. They may present as a solid mass indistinguishable from the testicle, with no signs of inflammation.

Novel Relaxin Receptor RXFP1 Agonist AZD3427 in the Treatment of Heart Failure: A Phase 1a/b, First-in-Human, Randomized, Single-Blind, Placebo-Controlled Study.

BACKGROUND: Heart failure mortality remains high despite recent progress in pharmacological treatment. AZD3427 is a selective long-acting analog of relaxin, a vasodilatory hormone with antifibrotic effects. We assessed the safety, pharmacokinetics, and pharmacodynamics of AZD3427 in healthy volunteers and patients with heart failure on standard-of-care therapy. METHODS AND RESULTS: In this first-in-human, phase 1a/b, randomized, single-blind, placebo-controlled study, healthy volunteers were randomized 6:2 to receive a single dose of AZD3427 or placebo by subcutaneous injection in 5 mixed-ethnicity cohorts (5, 10, 30, 90, or 270 mg) and 1 Japanese-descent cohort (270 mg), or by intravenous injection in 1 cohort (15 mg). After confirming safety and tolerability in healthy volunteers, 3 cohorts of patients with heart failure and left ventricular ejection fraction ≤40% and 3 cohorts with ejection fraction ≥41% were randomized 6:2 to receive 5 weekly doses of AZD3427 (5, 15, or 45 mg) or placebo by subcutaneous injection. In total, 56 healthy volunteers and 48 patients with heart failure were randomized. AZD3427 was well tolerated at all doses. After subcutaneous administration, AZD3427 was absorbed slowly, and exposure was approximately linear across the dose range. In patients with heart failure, AZD3427 terminal half-life was 13 to 14 days and there were numerical increases in stroke volume and estimated glomerular filtration rate. No treatment-emergent antidrug antibodies were detected. CONCLUSIONS: AZD3427 had favorable safety and pharmacokinetic profiles. Hemodynamic changes in patients with heart failure were consistent with the anticipated effects of a relaxin analog. These findings support further development of AZD3427 as a novel long-term treatment for patients with heart failure. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT04630067.

Whole­body MRI for metastatic workup in patients diagnosed with cancer.

Early diagnosis and appropriate staging workup are crucial for cancer patients. Whole-body magnetic resonance imaging (WB-MRI) has been proposed as another practical whole-body approach for assessing local invasiveness and distant metastases in patients newly diagnosed with cancer. The current study aimed to evaluate the efficacy of WB-MRI in assessing metastasis in patients newly diagnosed with cancer using histopathologic data as the reference method. A prospective observational study was performed from April 2018 to July 2020. MRI sequences were utilized to acquire anatomical and functional images in three orthogonal planes. The discovery was classified as nodal, skeletal and visceral metastases. Patient-based analysis was used for visceral metastasis and region-based for skeletal, systemic and lymph node metastases. A total of 43 consecutive patients (mean age, 56±15.2 years) were assessed successively. In 41 patients, there was a concordance between the WB-MRI and histological confirmation. The most prevalent site of metastasis was the skeletal system (18 patients). There were 12 individuals with liver metastasis, 10 with lung metastasis and 4 with peritoneal metastasis, with just one brain metastatic lesion found. On WB-MRI, 38 lymph node groups were deemed positive. Out of the total, 66 skeletal locations contained metastases. The accuracy of WB-MRI for nodal, skeletal and visceral metastases was (98.45, 100 and 100%, respectively). In conclusion, WB-MRI in three orthogonal planes, including the diffusion-weighted MRI with background body signal suppression sequence, may be utilized efficiently and accurately for assessing metastasis staging and may thus be utilized in patients with newly diagnosed cancer.

Randomized, Placebo-Controlled Phase 2b Study to Evaluate the Safety and Efficacy of Recombinant Human Lecithin Cholesterol Acyltransferase in Acute ST-Segment-Elevation Myocardial Infarction: Results of REAL-TIMI 63B.

BACKGROUND: High-density lipoprotein plays a key role in reverse cholesterol transport. In addition, high-density lipoprotein particles may be cardioprotective and reduce infarct size in the setting of myocardial injury. Lecithin-cholesterol acyltransferase is a rate-limiting enzyme in reverse cholesterol transport. MEDI6012 is a recombinant human lecithin-cholesterol acyltransferase that increases high-density lipoprotein cholesterol. Administration of lecithin-cholesterol acyltransferase has the potential to reduce infarct size and regress coronary plaque in acute ST-segment-elevation myocardial infarction. METHODS: REAL-TIMI 63B (A Randomized, Placebo­controlled Phase 2b Study to Evaluate the Safety and Efficacy of MEDI6012 in Acute ST Elevation Myocardial Infarction) was a phase 2B multinational, placebo-controlled, randomized trial. Patients with ST-segment-elevation myocardial infarction within 6 hours of symptom onset and planned for percutaneous intervention were randomly assigned 2:1 to MEDI6012 (2- or 6-dose regimen) or placebo and followed for 12 weeks. The primary outcome was infarct size as a percentage of left ventricular mass by cardiac MRI at 10 to 12 weeks, with the primary analysis in patients with TIMI Flow Grade 0 to 1 before percutaneous intervention who received at least 2 doses of MEDI6012. The secondary outcome was change in noncalcified plaque volume on coronary computed tomographic angiography from baseline to 10 to 12 weeks with the primary analysis in patients who received all 6 doses of MEDI6012. RESULTS: A total of 593 patients were randomly assigned. Patients were a median of 62 years old, 77.9% male, and 95.8% statin naive. Median time from symptom onset to randomization was 146 (interquartile range [IQR], 103-221) minutes and from hospitalization to randomization was 12.7 (IQR, 6.6-24.0) minutes, and the first dose of drug was administered a median of 8 (IQR, 3-13) minutes before percutaneous intervention. The index myocardial infarction was anterior in 69.6% and TIMI Flow Grade 0 to 1 in 65.1% of patients. At 12 weeks, infarct size did not differ between treatment groups (MEDI6012: 9.71%, IQR 4.79-16.38; placebo: 10.48%, [IQR, 4.92-16.61], 1-sided P=0.79. There was also no difference in noncalcified plaque volume (geometric mean ratio, 0.96 [95% CI, NA-1.10], 1-sided P=0.30). There was no significant difference in treatment emergent serious adverse events. CONCLUSIONS: Administration of MEDI6012 in patients with acute ST-segment-elevation myocardial infarction did not result in a significant reduction in infarct size or noncalcified plaque volume at 12 weeks. MEDI6012 was well tolerated with no excess in overall serious adverse events. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03578809.

Mammary analogue secretory carcinoma presenting with cervical lymphadenopathy: A rare case report with review of the literature.

INTRODUCTION: Mammary analogue secretory carcinoma is a rare malignant tumor of the salivary glands that typically involves the major glands. The aim of the current study is to report a rare case of mammary analogue secretory carcinoma that presented with left cervical lymphadenopathy. CASE REPORT: A 59-year-old lady presented with left cervical lymphadenopathy. Tissue biopsy and immunohistochemistry revealed metastatic carcinoma, favoring ovarian origin. Staging workup was performed and, ultimately, the patient was treated as having a carcinoma of unknown primary. After showing partial response to therapy, left side neck dissection was performed. Based on better assessment of the histologic picture and a broader panel of immunohistochemistry performed on the excision specimen, the final diagnosis was that of mammary analogue secretory carcinoma. DISCUSSION: Mammary analogue secretory carcinoma is usually an indolent salivary gland carcinoma, with the majority of patients presenting with a slow-growing, painless mass measuring approximately 2 cm in size, and a reported duration ranging from 2 months to several years. In certain cases, pain and facial paralysis have been reported. It could also be found incidentally during radiologic assessment for thyroid illness or routine dental screening. CONCLUSION: Diagnosing mammary analogue secretory carcinoma is challenging, and this should be in the differential diagnosis list of metastatic carcinomas to cervical lymph nodes.

Ductal carcinoma in situ arising from fibroadenoma; a rare case with review of literature.

Introduction: ibroadenoma (FA) is a common benign breast mass representing a group of hyperplastic breast lobules due to the deviation of normal development. This study aims to present a rare case of ductal carcinoma in situ (DCIS) associated with fibroadenoma. Case report: A 49-year-old married female presents with a right breast mass for five years. Core needle biopsy diagnosed the specimen as cellular complex fibroadenoma. A breast-lumpectomy and the histopathological examination of the surgical specimen confirmed ductal carcinoma in-situ. Discussion: Malignant changes within fibroadenomas typically happen at an older age, with the age of detection in the fifth decade. Complex fibroadenomas are more related to malignant transformation. Old age and strong family history are risk factors for malignant transformation of fibroadenomas. Conclusion: Fibroadenomas are common benign tumors. They can rarely be associated with DCIS. Therefore, the risk of malignancy should always be kept in mind.

Thyroid collision tumors; A case series with literature review.

Background: Collision tumors are two histologically distinct types of malignancies within the same mass and organ. The aim of this study is to present a case series of thyroid collisions. Methods: This was a multicenter retrospective case series study. The participants were consecutive in order. Socio-demographic and clinical data were obtained from hospital records. Results: The study included eight cases comprising six (75%) females and two (25%) males. The patients had different presentations, including neck swelling, dyspnea, and dizziness. The pathology was successfully determined through fine-needle aspiration. Four patients (50%) underwent lobectomy, whereas the other half (four patients) underwent total thyroidectomy. Conclusion: Collision tumors of papillary thyroid cancer (PTC) and follicular thyroid carcinoma (FTA) or medullary thyroid carcinoma (MTC) and FTA are exceedingly rare phenomena that most commonly affect females. Complete or partial thyroidectomy is the ideal management of choice for these cases and is associated with good survival.

Clinical Characteristics and Prognosis of Young Middle Eastern Adults with ST-Elevation Myocardial Infarction: One-Year Follow-Up.

AIMS: Few studies have investigated premature ST-elevation myocardial infarction (STEMI) in the Middle East. We aimed to compare the clinical characteristics and one-year prognosis of young (<45 years) and older (≥45 years) Middle Eastern adults with STEMI. METHODS AND MATERIAL: A total of 706 patients with STEMI, who were prospectively enrolled in the First Jordanian Percutaneous Coronary Intervention Registry, were stratified into two groups (<45 or ≥45 years). Baseline clinical variables and one-year major adverse cardiovascular events (MACE) were evaluated. RESULTS: Young patients (<45 years) comprised 17.4% of STEMI patients (123 of 706). Compared with older patients (≥45 years), young patients were mostly male (96% vs 82%, P<0.001), smokers (86% vs 49%, P<0.001) and less likely to have multi-vessel disease (26% vs 44%, P=0.001). Anterior STEMI was the most common diagnosis and left anterior descending artery was the most common culprit vessel in both groups. There were no significant differences between the younger and older patients in in-hospital (20% vs 19%, P=0.12) and one-year MACE (24% vs 26%, P=0.68). However, none (0%) of the young died during one-year follow-up while 21 (4%) of the older patients died (P=0.036). CONCLUSIONS: Young adult patients in the Middle East with STEMI are more likely to be smoking men with multiple risk factors and single vessel disease by angiography. Although, younger patients had similar one-year MACE to older patients, their mortality rate appears to be better. A larger study is warranted to investigate this vulnerable group of patients to prevent future events.

Awareness of Parents About the Emergency Management of Avulsed Tooth in Eastern Province and Riyadh.

Objective: To assess the level of parents knowledge about the emergency management of tooth avulsion in Eastern Province and Riyadh. Methods: A cross-sectional study was carried out by means of a questionnaire-based internet survey in which 1201 parents from Eastern Province and Riyadh participated. The questionnaire contained 10 closed-ended questions and was used to assess the knowledge of parents about the emergency management of avulsed teeth in Eastern Province and Riyadh. Chi-square test was used for data analysis. Results: In response to closed-ended questions, the statistically significant result was obtained for the history of child dental trauma in which 35% (P=0.04) of parents reported history of dental trauma in their children. These parents were belong to Eastern province (51%) and Riyadh (49%). Furthermore, only 31.3% of the parents were aware of possible storage media for transportation of avulsed tooth while 68.7% (49.5% in Eastern Province and 50.5% in Riyadh) were unaware (P=0.02) of it. Conclusion: That the majority of the parents were unaware of emergency management for tooth avulsion in two densely populated regions of Saudi Arabia. Education of parents should be initiated at a national level.

Acute interaction between oral glucose (75 g as Lucozade) and inorganic nitrate: Decreased insulin clearance, but lack of blood pressure-lowering.

AIMS: Dietary inorganic nitrate (NO3- ) lowers peripheral blood pressure (BP) in healthy volunteers, but lacks such effect in individuals with, or at risk of, type 2 diabetes mellitus (T2DM). Whilst this is commonly assumed to be a consequence of chronic hyperglycaemia/hyperinsulinaemia, we hypothesized that acute physiological elevations in plasma [glucose]/[insulin] blunt the haemodynamic responses to NO3- , a pertinent question for carbohydrate-rich Western diets. METHODS: We conducted an acute, randomized, placebo-controlled, double-blind, crossover study on the haemodynamic and metabolic effects of potassium nitrate (8 or 24 mmol KNO3 ) vs. potassium chloride (KCl; placebo) administered 1 hour prior to an oral glucose tolerance test in 33 healthy volunteers. RESULTS: Compared to placebo, there were no significant differences in systolic or diastolic BP (P = 0.27 and P = 0.30 on ANOVA, respectively) with KNO3 , nor in pulse wave velocity or central systolic BP (P = 0.99 and P = 0.54 on ANOVA, respectively). Whilst there were significant elevations from baseline for plasma [glucose] and [C-peptide], no differences between interventions were observed. A significant increase in plasma [insulin] was observed with KNO3 vs. KCl (n = 33; P = 0.014 on ANOVA) with the effect driven by the high-dose cohort (24 mmol, n = 13; P < 0.001 on ANOVA; at T = 0.75 h mean difference 210.4 pmol/L (95% CI 28.5 to 392.3), P = 0.012). CONCLUSIONS: In healthy adults, acute physiological elevations of plasma [glucose] and [insulin] result in a lack of BP-lowering with dietary nitrate. The increase in plasma [insulin] without a corresponding change in [C-peptide] or [glucose] suggests that high-dose NO3- decreases insulin clearance. A likely mechanism is via NO-dependent inhibition of insulin-degrading enzyme.

Remote ischaemic preconditioning suppresses endogenous plasma nitrite during ischaemia-reperfusion: a randomized controlled crossover pilot study.

AIM: The aim of this article is to test the hypothesis that remote ischaemic preconditioning (RIPC) increases circulating endogenous local and systemic plasma (nitrite) during RIPC and ischaemia-reperfusion (IR) as a potential protective mechanism against ischaemia-reperfusion injury (IRI). METHODS: Six healthy male volunteers (mean age 29.5 ± 7.6 years) were randomized in a crossover study to initially receive either RIPC (4 × 5 min cycles) to the left arm, or no RIPC (control), both followed by an ischaemia-reperfusion (IR) sequence (20 min cuff inflation to 200 mmHg, 20 min reperfusion) to the right arm. The volunteers returned at least 7 days later for the alternate intervention. The primary outcome was the effect of RIPC vs. control on local and systemic plasma (nitrite). RESULTS: RIPC did not significantly change plasma (nitrite) in either the left or the right arm during the RIPC sequence. However, compared to control, RIPC decreased plasma (nitrite) during the subsequent IR sequence by ~26% (from 118 ± 9 to 87 ± 5 nmol l-1 ) locally in the left arm (P = 0.008) overall, with an independent effect of -58.70 nmol l-1 (95% confidence intervals -116.1 to -1.33) at 15 min reperfusion, and by ~24% (from 109 ± 9 to 83 ± 7 nmol l-1 ) systemically in the right arm (P = 0.03). CONCLUSIONS: RIPC had no effect on plasma (nitrite) during the RIPC sequence, but instead decreased plasma (nitrite) by ~25% during IR. This would likely counteract the protective mechanisms of RIPC, and contribute to RIPC's lack of efficacy, as observed in recent clinical trials. A combined approach of RIPC with nitrite administration may be required.

Expert Opinion Percutaneous Coronary Intervention in Older People: Does Age Make a Difference?

As many people are living longer, much older patients are now commonly being seen in clinical practice. The management of coronary disease in this group presents formidable challenges. We review the epidemiology of coronary disease in this population and report on the burden of comorbidity, influence of frailty, problems with polypharmacy, interactions and compliance for the older patient. We discuss the management of stable and acute coronary syndromes, the specific anatomical challenges of the older coronary artery, the outcomes of the limited number of trials involving older patients, and review the guidelines available.

Paradoxical normoxia-dependent selective actions of inorganic nitrite in human muscular conduit arteries and related selective actions on central blood pressures.

BACKGROUND: Inorganic nitrite dilates small resistance arterioles via hypoxia-facilitated reduction to vasodilating nitric oxide. The effects of nitrite in human conduit arteries have not been investigated. In contrast to nitrite, organic nitrates are established selective dilators of conduit arteries. METHODS AND RESULTS: We examined the effects of local and systemic administration of sodium nitrite on the radial artery (a muscular conduit artery), forearm resistance vessels (forearm blood flow), and systemic hemodynamics in healthy male volunteers (n=43). Intrabrachial sodium nitrite (8.7 µmol/min) increased radial artery diameter by a median of 28.0% (25th and 75th percentiles, 25.7% and 40.1%; P<0.001). Nitrite (0.087-87 µmol/min) displayed conduit artery selectivity similar to that of glyceryl trinitrate (0.013-4.4 nmol/min) over resistance arterioles. Nitrite dose-dependently increased local cGMP production at the dose of 2.6 µmol/min by 1.1 pmol·min(-1)·100 mL(-1) tissue (95% confidence interval, 0.5-1.8). Nitrite-induced radial artery dilation was enhanced by administration of acetazolamide (oral or intra-arterial) and oral raloxifene (P=0.0248, P<0.0001, and P=0.0006, respectively) but was inhibited under hypoxia (P<0.0001) and hyperoxia (P=0.0006) compared with normoxia. Systemic intravenous administration of sodium nitrite (8.7 µmol/min) dilated the radial artery by 10.7% (95% confidence interval, 6.8-14.7) and reduced central systolic blood pressure by 11.6 mm Hg (95% confidence interval, 2.4-20.7), augmentation index, and pulse wave velocity without changing peripheral blood pressure. CONCLUSIONS: Nitrite selectively dilates conduit arteries at supraphysiological and near-physiological concentrations via a normoxia-dependent mechanism that is associated with cGMP production and is enhanced by acetazolamide and raloxifene. The selective central blood pressure-lowering effects of nitrite have therapeutic potential to reduce cardiovascular events.

Nitrite reduction and cardiovascular protection.

Inorganic nitrite, a metabolite of endogenously produced nitric oxide (NO) from NO synthases (NOS), provides the largest endocrine source of directly bioavailable NO. The conversion of nitrite to NO occurs mainly through enzymatic reduction, mediated by a range of proteins, including haem-globins, molybdo-flavoproteins, mitochondrial proteins, cytochrome P450 enzymes, and NOS. Such nitrite reduction is particularly favoured under hypoxia, when endogenous formation of NO from NOS is impaired. Under normoxic conditions, the majority of these nitrite reductases also scavenge NO, or diminish its bioavailability via reactive oxygen species (ROS) production, suggesting an intricate balance. Moreover, nitrite, whether produced endogenously, or derived from exogenous nitrite or nitrate administration (including dietary sources via the Nitrate-Nitrite-NO pathway) beneficially modulates many key cardiovascular pathological processes. In this review, we highlight the landmark studies which revealed nitrite's function in biological systems, and inspect its evolving role in cardiovascular protection. Whilst these effects have mainly been ascribed to the activity of one or more nitrite reductases, we also discuss newly-identified mechanisms, including nitrite anhydration, the involvement of s-nitrosothiols, nitro-fatty acids, and direct nitrite normoxic signalling, involving modification of mitochondrial structure and function, and ROS production. This article is part of a Special Issue entitled "Redox Signalling in the Cardiovascular System".

A comparison of organic and inorganic nitrates/nitrites.

Although both organic and inorganic nitrates/nitrites mediate their principal effects via nitric oxide, there are many important differences. Inorganic nitrate and nitrite have simple ionic structures and are produced endogenously and are present in the diet, whereas their organic counterparts are far more complex, and, with the exception of ethyl nitrite, are all medicinally synthesised products. These chemical differences underlie the differences in pharmacokinetic properties allowing for different modalities of administration, particularly of organic nitrates, due to the differences in their bioavailability and metabolic profiles. Whilst the enterosalivary circulation is a key pathway for orally ingested inorganic nitrate, preventing an abrupt effect or toxic levels of nitrite and prolonging the effects, this is not used by organic nitrates. The pharmacodynamic differences are even greater; while organic nitrates have potent acute effects causing vasodilation, inorganic nitrite's effects are more subtle and dependent on certain conditions. However, in chronic use, organic nitrates are considerably limited by the development of tolerance and endothelial dysfunction, whereas inorganic nitrate/nitrite may compensate for diminished endothelial function, and tolerance has not been reported. Also, while inorganic nitrate/nitrite has important cytoprotective effects against ischaemia-reperfusion injury, continuous use of organic nitrates may increase injury. While there are concerns that inorganic nitrate/nitrite may induce carcinogenesis, direct evidence of this in humans is lacking. While organic nitrates may continue to dominate the therapeutic arena, this may well change with the increasing recognition of their limitations, and ongoing discovery of beneficial effects and specific advantages of inorganic nitrate/nitrite.