Blocking FSH induces thermogenic adipose tissue and reduces body fat.

Menopause is associated with bone loss and enhanced visceral adiposity. A polyclonal antibody that targets the ß-subunit of the pituitary hormone follicle-stimulating hormone (Fsh) increases bone mass in mice. Here, we report that this antibody sharply reduces adipose tissue in wild-type mice, phenocopying genetic haploinsufficiency for the Fsh receptor gene Fshr. The antibody also causes profound beiging, increases cellular mitochondrial density, activates brown adipose tissue and enhances thermogenesis. These actions result from the specific binding of the antibody to the ß-subunit of Fsh to block its action. Our studies uncover opportunities for simultaneously treating obesity and osteoporosis.

Leapfrog dynamics in phage-bacteria coevolution revealed by joint analysis of cross-infection phenotypes and whole genome sequencing.

Viruses and their hosts can undergo coevolutionary arms races where hosts evolve increased resistance and viruses evolve counter-resistance. Given these arms race dynamics (ARD), both players are predicted to evolve along a single trajectory as more recently evolved genotypes replace their predecessors. By coupling phenotypic and genomic analyses of coevolving populations of bacteriophage λ and Escherichia coli, we find conflicting evidence for ARD. Virus-host infection phenotypes fit the ARD model, yet genomic analyses revealed fluctuating selection dynamics. Rather than coevolution unfolding along a single trajectory, cryptic genetic variation emerges and is maintained at low frequency for generations until it eventually supplants dominant lineages. These observations suggest a hybrid 'leapfrog' dynamic, revealing weaknesses in the predictive power of standard coevolutionary models. The findings shed light on the mechanisms that structure coevolving ecological networks and reveal the limits of using phenotypic or genomic data alone to differentiate coevolutionary dynamics.

Leaky resistance and the conditions for the existence of lytic bacteriophage.

In experimental cultures, when bacteria are mixed with lytic (virulent) bacteriophage, bacterial cells resistant to the phage commonly emerge and become the dominant population of bacteria. Following the ascent of resistant mutants, the densities of bacteria in these simple communities become limited by resources rather than the phage. Despite the evolution of resistant hosts, upon which the phage cannot replicate, the lytic phage population is most commonly maintained in an apparently stable state with the resistant bacteria. Several mechanisms have been put forward to account for this result. Here we report the results of population dynamic/evolution experiments with a virulent mutant of phage Lambda, λVIR, and Escherichia coli in serial transfer cultures. We show that, following the ascent of λVIR-resistant bacteria, λVIR is maintained in the majority of cases in maltose-limited minimal media and in all cases in nutrient-rich broth. Using mathematical models and experiments, we show that the dominant mechanism responsible for maintenance of λVIR in these resource-limited populations dominated by resistant E. coli is a high rate of either phenotypic or genetic transition from resistance to susceptibility-a hitherto undemonstrated mechanism we term "leaky resistance." We discuss the implications of leaky resistance to our understanding of the conditions for the maintenance of phage in populations of bacteria-their "existence conditions."

Safety and Outcomes of Intravenous Thrombolytic Therapy in Ischemic Stroke Patients with COVID-19: CASCADE Initiative.

BACKGROUND: There is little information regarding the safety of intravenous tissue plasminogen activator (IV-tPA) in patients with stroke and COVID-19. METHODS: This multicenter study included consecutive stroke patients with and without COVID-19 treated with IV-tPA between February 18, 2019, to December 31, 2020, at 9 centers participating in the CASCADE initiative. Clinical outcomes included modified Rankin Scale (mRS) at hospital discharge, in-hospital mortality, the rate of hemorrhagic transformation. Using Bayesian multiple regression and after adjusting for variables with significant value in univariable analysis, we reported the posterior adjusted odds ratio (OR, with 95% Credible Intervals [CrI]) of the main outcomes. RESULTS: A total of 545 stroke patients, including 101 patients with COVID-19 were evaluated. Patients with COVID-19 had a more severe stroke at admission. In the study cohort, 85 (15.9%) patients had a hemorrhagic transformation, and 72 (13.1%) died in the hospital. After adjustment for confounding variables, discharge mRS score ≥2 (OR: 0.73, 95% CrI: 0.16, 3.05), in-hospital mortality (OR: 2.06, 95% CrI: 0.76, 5.53), and hemorrhagic transformation (OR: 1.514, 95% CrI: 0.66, 3.31) were similar in COVID-19 and non COVID-19 patients. High-sensitivity C reactive protein level was a predictor of hemorrhagic transformation in all cases (OR:1.01, 95%CI: 1.0026, 1.018), including those with COVID-19 (OR:1.024, 95%CI:1.002, 1.054). CONCLUSION: IV-tPA treatment in patients with acute ischemic stroke and COVID-19 was not associated with an increased risk of disability, mortality, and hemorrhagic transformation compared to those without COVID-19. IV-tPA should continue to be considered as the standard of care in patients with hyper acute stroke and COVID-19.

FSIP1 binds HER2 directly to regulate breast cancer growth and invasiveness.

Fibrous sheath interacting protein 1 (FSIP1), a spermatogenesis-related testicular antigen, is expressed in abundance in breast cancers, particularly in those overexpressing human epidermal growth factor receptor 2 (HER2); however, little is known about its role in regulating the growth and metastasis of breast cancer cells. We and others have shown previously that FSIP1 expression in breast cancer correlates positively with HER2-positivity, recurrence, and metastases and negatively with survival. Here, using coimmunoprecipitation and microscale thermophoresis, we find that FSIP1 binds to the intracellular domain of HER2 directly. We further show that shRNA-induced FSIP1 knockdown in SKBR3 and MCF-7 breast cancer cells inhibits proliferation, stimulates apoptosis, attenuates epithelial-mesenchymal transition, and impairs migration and invasiveness. Consistent with reduced proliferation and enhanced apoptosis, xenotransplantation of SKBR3 cells stably transfected with sh-FSIP1 into nu/nu mice results in reduced tumor volumes compared with sh-NC transplants. Furthermore, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) mapping using sh-FSIP1 gene signature yielded associations with extracellular matrix protein pathways, and a reduction in SNAI2 protein expression was confirmed on Western blot analysis. Complementarily, interrogation of the Connectivity Map using the same gene signature yielded, as top hits, chemicals known to inhibit epithelial-mesenchymal transition, including rapamycin, 17-N-allylamino-17-demethoxygeldanamycin, and LY294002. These compounds phenocopy the effects of sh-FSIP1 on SKBR3 cell viability. Thus, FSIP1 suppression limits oncogenesis and invasiveness in breast cancer cells and, considering its absence in most other tissues, including normal breast, may become a potential target for breast cancer therapy.

Stroke Care Trends During COVID-19 Pandemic in Zanjan Province, Iran. From the CASCADE Initiative: Statistical Analysis Plan and Preliminary Results.

BACKGROUND: The emergence of the COVID-19 pandemic has significantly impacted global healthcare systems and this may affect stroke care and outcomes. This study examines the changes in stroke epidemiology and care during the COVID-19 pandemic in Zanjan Province, Iran. METHODS: This study is part of the CASCADE international initiative. From February 18, 2019, to July 18, 2020, we followed ischemic and hemorrhagic stroke hospitalization rates and outcomes in Valiasr Hospital, Zanjan, Iran. We used a Bayesian hierarchical model and an interrupted time series analysis (ITS) to identify changes in stroke hospitalization rate, baseline stroke severity [measured by the National Institutes of Health Stroke Scale (NIHSS)], disability [measured by the modified Rankin Scale (mRS)], presentation time (last seen normal to hospital presentation), thrombolytic therapy rate, median door-to-needle time, length of hospital stay, and in-hospital mortality. We compared in-hospital mortality between study periods using Cox-regression model. RESULTS: During the study period, 1,026 stroke patients were hospitalized. Stroke hospitalization rates per 100,000 population decreased from 68.09 before the pandemic to 44.50 during the pandemic, with a significant decline in both Bayesian [Beta: -1.034; Standard Error (SE): 0.22, 95% CrI: -1.48, -0.59] and ITS analysis (estimate: -1.03, SE = 0.24, p < 0.0001). Furthermore, we observed lower admission rates for patients with mild (NIHSS < 5) ischemic stroke (p < 0.0001). Although, the presentation time and door-to-needle time did not change during the pandemic, a lower proportion of patients received thrombolysis (-10.1%; p = 0.004). We did not see significant changes in admission rate to the stroke unit and in-hospital mortality rate; however, disability at discharge increased (p < 0.0001). CONCLUSION: In Zanjan, Iran, the COVID-19 pandemic has significantly impacted stroke outcomes and altered the delivery of stroke care. Observed lower admission rates for milder stroke may possibly be due to fear of exposure related to COVID-19. The decrease in patients treated with thrombolysis and the increased disability at discharge may indicate changes in the delivery of stroke care and increased pressure on existing stroke acute and subacute services. The results of this research will contribute to a similar analysis of the larger CASCADE dataset in order to confirm findings at a global scale and improve measures to ensure the best quality of care for stroke patients during the COVID-19 pandemic.

Coherent Motion of Monolayer Sheets under Confinement and Its Pathological Implications.

Coherent angular rotation of epithelial cells is thought to contribute to many vital physiological processes including tissue morphogenesis and glandular formation. However, factors regulating this motion, and the implications of this motion if perturbed, remain incompletely understood. In the current study, we address these questions using a cell-center based model in which cells are polarized, motile, and interact with the neighboring cells via harmonic forces. We demonstrate that, a simple evolution rule in which the polarization of any cell tends to orient with its velocity vector can induce coherent motion in geometrically confined environments. In addition to recapitulating coherent rotational motion observed in experiments, our results also show the presence of radial movements and tissue behavior that can vary between solid-like and fluid-like. We show that the pattern of coherent motion is dictated by the combination of different physical parameters including number density, cell motility, system size, bulk cell stiffness and stiffness of cell-cell adhesions. We further observe that perturbations in the form of cell division can induce a reversal in the direction of motion when cell division occurs synchronously. Moreover, when the confinement is removed, we see that the existing coherent motion leads to cell scattering, with bulk cell stiffness and stiffness of cell-cell contacts dictating the invasion pattern. In summary, our study provides an in-depth understanding of the origin of coherent rotation in confined tissues, and extracts useful insights into the influence of various physical parameters on the pattern of such movements.

Inferring strain-level mutational drivers of phage-bacteria interaction phenotypes.

The enormous diversity of bacteriophages and their bacterial hosts presents a significant challenge to predict which phages infect a focal set of bacteria. Infection is largely determined by complementary -and largely uncharacterized- genetics of adsorption, injection, and cell take-over. Here we present a machine learning (ML) approach to predict phage-bacteria interactions trained on genome sequences of and phenotypic interactions amongst 51 Escherichia coli strains and 45 phage λ strains that coevolved in laboratory conditions for 37 days. Leveraging multiple inference strategies and without a priori knowledge of driver mutations, this framework predicts both who infects whom and the quantitative levels of infections across a suite of 2,295 potential interactions. The most effective ML approach inferred interaction phenotypes from independent contributions from phage and bacteria mutations, predicting phage host range with 86% mean classification accuracy while reducing the relative error in the estimated strength of the infection phenotype by 40%. Further, transparent feature selection in the predictive model revealed 18 of 176 phage λ and 6 of 18 E. coli mutations that have a significant influence on the outcome of phage-bacteria interactions, corroborating sites previously known to affect phage λ infections, as well as identifying mutations in genes of unknown function not previously shown to influence bacterial resistance. While the genetic variation studied was limited to a focal, coevolved phage-bacteria system, the method's success at recapitulating strain-level infection outcomes provides a path forward towards developing strategies for inferring interactions in non-model systems, including those of therapeutic significance.

Statins As Anti-Hypertensive Therapy: A Systematic Review and Meta-Analysis.

Hypertension is the most prevalent condition in clinical practice. Hypertension, diabetes, and hypercholesterolaemia are major contributing factors to cardiovascular diseases. They commonly coexist in a single patient. Statins have been used as prominent medicines for the reduction of cardiovascular events. Statins have been shown to reduce blood pressure in patients with hypertension and have lipid-lowering properties in recent articles. Statins reduce blood pressure because of their impact on endothelial function, their interactions with the renin-angiotensin system, and their influence on major artery compliance. This meta-analysis aimed to ascertain the effectiveness and efficacy of statins for managing hypertension in patients with hypertension. Systematic searches were conducted on PubMed, Science Direct, Embase, Cochrane Library, and Google Scholar. Randomized controlled trials, systematic trials, and cohort studies were retrieved using keywords on statins and their use in patients with hypertension. Exclusion criteria included studies that were not in the English language, studies that did not include patients on statins with hypertension, studies that did not provide enough information, technical reports, opinions, or editorials, and studies involving patients < 18 years old. The inclusion criteria were randomized controlled trials, meta-analyses, adult patients aged > 18 years old, and studies that were freely available or through institutional login. This meta-analysis scrutinized 9361 randomized controlled trials, clinical trials, meta-analyses, and systematic reviews, of which 32 articles including 25 randomized controlled trials and seven meta-analyses were included in the final analysis. This meta-analysis of the role of statins in hypertensive patients aimed to determine the outcome of hypertension control along with antihypertensive medication. Our study showed that statins are useful in reducing both systolic and diastolic blood pressure. We used a heterogeneous model for analysis due to variations in the study characteristics. The I2 value was 0.33 (0.76, 0.10) for systolic blood pressure and 0/88 (0.86, 0.90) for diastolic blood pressure. The I2 value for the seven meta-analyses included in the study was 1.79 (2.88, 0.69).

Competition-driven eco-evolutionary feedback reshapes bacteriophage lambda's fitness landscape and enables speciation.

A major challenge in evolutionary biology is explaining how populations navigate rugged fitness landscapes without getting trapped on local optima. One idea illustrated by adaptive dynamics theory is that as populations adapt, their newly enhanced capacities to exploit resources alter fitness payoffs and restructure the landscape in ways that promote speciation by opening new adaptive pathways. While there have been indirect tests of this theory, to our knowledge none have measured how fitness landscapes deform during adaptation, or test whether these shifts promote diversification. Here, we achieve this by studying bacteriophage [Formula: see text], a virus that readily speciates into co-existing receptor specialists under controlled laboratory conditions. We use a high-throughput gene editing-phenotyping technology to measure [Formula: see text]'s fitness landscape in the presence of different evolved-[Formula: see text] competitors and find that the fitness effects of individual mutations, and their epistatic interactions, depend on the competitor. Using these empirical data, we simulate [Formula: see text]'s evolution on an unchanging landscape and one that recapitulates how the landscape deforms during evolution. [Formula: see text] heterogeneity only evolves in the shifting landscape regime. This study provides a test of adaptive dynamics, and, more broadly, shows how fitness landscapes dynamically change during adaptation, potentiating phenomena like speciation by opening new adaptive pathways.

A Systematic Review of Lipid Management in Secondary Prevention and Comparison of International Lipid Management Pathways.

Acute coronary syndrome remains a major cause of morbidity and mortality despite significant improvements in its prevention and management. Lipid management and other risk factors such as hypertension, diabetes, obesity, smoking and sedentary lifestyle stratification is the key to minimising this risk. Lipid management is an important part of secondary prevention and patients are historically undertreated after post-acute coronary syndrome. We performed a narrative review on observational studies on lipid management pathways post ACS on PubMed, Google Scholar, Journal Storage and ScienceDirect and excluded case reports, case series and randomized controlled trials. Our review showed that most patients following acute coronary syndrome receive suboptimal treatment for hypercholesterolemia. The role of statin in reducing future cardiac events risk is undisputable, however, statin intolerance remains a major concern. There is substantial variation in the management of lipids in patients following an acute cardiac event and patients were followed up in primary care in some countries and secondary care in others. The mortality risk is significantly high in patients with second or recurrent cardiac events and future cardiac events are associated with higher morbidity and mortality risk. There is significant variation in lipid management pathways in patients who suffer from cardiac events across the globe and lipid therapy optimization remains suboptimal in these patients, putting them at future risk of cardiovascular events. It is therefore imperative to optimally manage dyslipidemia in these patients in order to minimize the risk of subsequent cardiac events. Cardiac rehabilitation programs might be a way forward to incorporate lipid management for patients discharged from the hospital after having acute coronary events for lipid therapy optimization.

Determinants of menstrual hygiene among adolescent school girls in a rural area of Patna, Bihar, India: A cross-sectional study.

Background: Adolescence is a transitional phase marked by the onset of menarche. Most adolescent girls have incomplete or inaccurate information about menstrual physiology and hygiene. There are several misconceptions and taboos linked with it, resulting in adverse health outcomes. However, numerous factors associated with menstrual hygiene are modifiable. If these are adequately identified and addressed, it can empower young girls to lead healthy life in a positive environment. Aims and Objectives: (1) To assess the knowledge and practices regarding menstrual hygiene among adolescent school girls. (2) To determine the association of menstrual hygiene practices with sociodemographic and related factors. Materials and Methods: A descriptive cross-sectional study was conducted in rural Patna, Bihar, in which 300 eligible adolescent school-going menstruating girls (13-17 years) were recruited from four schools. They were interviewed using a predesigned questionnaire, and relevant information on sociodemographic profiles and menorrhoeal characteristics was obtained. Median scores were calculated for the knowledge and practices domain. Multiple logistic regression was used to determine the associated factors of menstrual hygiene practice. Results: The mean age of girls was 14 ± 1.07 years, while the mean age of menarche was 12.37 ± 0.92 years. More than half (59.3%) were found to possess good knowledge (scores 7 and above) regarding menstruation and its physiology. Half (50.3%) of the girls had good menstrual hygiene practices (scores 9 and above). Multiple logistic regression model revealed that adolescent girls studying in government schools (AOR = 0.05, CI = 0.02-0.12) and those living in nuclear families (AOR = 0.05, CI = 0.02-0.12) were likely to be significantly associated with poor menstrual hygiene practices. Conclusion: Menstrual hygiene is still far from satisfactory; hence, it should be a vital aspect of the school health educational curriculum. There is an imperative need to design acceptable awareness/advocacy programs for adolescent girls in the future.

The Effect of Vitamin D Supplementation on Incidence of Type 2 Diabetes: A Systematic Review.

With the clinical increase in Type 2 Diabetes worldwide, several interventions to decrease its incidence have been investigated. One such intervention is Vitamin D supplementation, as it affects Insulin secretion from the pancreas and Insulin receptors in the cells of the body. This systematic review addresses whether or not Vitamin D supplementation has a role in reducing the risk of developing Type 2 Diabetes. Systematic searches were conducted on PubMed, and Cochrane Library mainly but also checked Google Scholar. Randomized controlled trials, systematic trials and cohort studies were retrieved that included keywords pertaining to Vitamin D supplementation and the incidence of Type 2 Diabetes. Exclusion criteria included studies that looked at different forms of Diabetes, studies including patients aged less than 18 or more than 85 years of age and studies that were not English language. For all the trials identified, the incidence of Type 2 Diabetes among the cohort receiving vitamin D supplementation was compared to the cohort receiving placebo medication. Additionally, the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) was analyzed to observe if there was a difference between Insulin resistance among these two cohorts between the start of the trials and the end. Thirteen randomized controlled trials were identified. Seven of these identified incidences of Type 2 Diabetes as a research outcome, out of which six showed no statistically significant impact of vitamin D on the incidence of Type 2 Diabetes. Out of the 13 trials, 10 analyzed the impact of vitamin D supplementation on patients' HOMA-IR. In six of these trials, patients receiving vitamin D supplementation had a decrease in their HOMA-IR, while it increased in 4 trials. In seven of the ten trials that analyzed for HOMA-IR, the HOMA-IR was less in the vitamin D cohort than the placebo cohort. There is insufficient evidence to suggest that vitamin D supplementation significantly reduces the incidence of Type 2 Diabetes despite its effects on insulin resistance. Further research in this area would be helpful in order to influence clinical guidelines on vitamin D supplementation among patients at risk of Type 2 Diabetes.

Competition-driven eco-evolutionary feedback reshapes bacteriophage lambda's fitness landscape and enables speciation.

A major challenge in evolutionary biology is explaining how populations navigate rugged fitness landscapes without getting trapped on local optima. One idea illustrated by adaptive dynamics theory is that as populations adapt, their newly enhanced capacities to exploit resources alter fitness payoffs and restructure the landscape in ways that promote speciation by opening new adaptive pathways. While there have been indirect tests of this theory, none have measured how fitness landscapes deform during adaptation, or test whether these shifts promote diversification. Here, we achieve this by studying bacteriophage λ, a virus that readily speciates into co-existing receptor specialists under controlled laboratory conditions. We used a high-throughput gene editing-phenotyping technology to measure λ's fitness landscape in the presence of different evolved-λ competitors and found that the fitness effects of individual mutations, and their epistatic interactions, depend on the competitor. Using these empirical data, we simulated λ's evolution on an unchanging landscape and one that recapitulates how the landscape deforms during evolution. λ heterogeneity only evolved in the shifting landscape regime. This study provides a test of adaptive dynamics, and, more broadly, shows how fitness landscapes dynamically change during adaptation, potentiating phenomena like speciation by opening new adaptive pathways.

An Unusual Presentation of Type B Aortic Dissection as Out-of-Hospital Cardiac Arrest Complicated by Spinal and Renal Ischaemia Along With Atrial Fibrillation, Stroke, and Severe Stenosis in Obtuse Marginal Branch: A Therapeutic Dilemma.

Aortic dissection (AD) is a catastrophic cardiovascular problem that can be challenging to diagnose sometimes. Despite diagnostic challenges, it requires a high degree of suspicion and prompt treatment is vital to its successful management. AD can be divided into type A aortic dissection (TAAD) and type B aortic dissection (TBAD). TAAD is characterised by dissection in the ascending aorta whereas TBAD does not have dissection in the ascending aorta. TBAD is usually managed conservatively, and patients receive medical therapy such as antihypertensive medications, analgesia, and rehabilitation. This, however, is complicated by malperfusion of certain organs, which can be life-threatening. Patients who have malperfusion of certain organs should be managed aggressively and endovascular aortic repair should be considered in such cases. We present a case of a 63-year-old patient who presented with out-of-hospital pulseless electrical activity cardiac arrest and was successfully resuscitated. An electrocardiogram showed new-onset atrial fibrillation with ST-segment depression and a coronary angiogram showed severe stenosis in the obtuse marginal branch of the left circumflex artery. A computed tomography scan of the thorax and abdomen showed TBAD with an occluded right renal artery and the patient was conservatively managed. The patient was discharged home after prolonged hospital admission and was conservatively managed for TBAD. This case was complicated by the fact that the patient had an out-of-hospital cardiac arrest and a coronary angiogram showed severe stenosis in the obtuse marginal branch of the left circumflex artery. The patient also had new-onset atrial fibrillation, which made his clinical management very challenging. It is important to avoid unnecessary coronary intervention that can create more challenges in managing such patients.

EkoSonic™ Endovascular System-Directed Thrombolysis in a Patient With COVID-19 Infection Presenting With Bilateral Large Pulmonary Embolism Causing Right Ventricular Strain: A Case Report.

We discuss a case of a 31-year-old male patient who presented to the accident and emergency department with shortness of breath and chest pain since the morning of the day of presentation. His polymerase chain reaction (PCR) test had returned positive for severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2), which causes coronavirus disease 2019 (COVID-19), two weeks ago and his main symptoms had been shortness of breath, dry cough, generalized body pain, and fever. He was not vaccinated against the COVID-19 virus. He had not required hospitalization for COVID-19 and his symptoms had improved on day 10 from the date of diagnosis; however, he developed pleuritic chest pain with shortness of breath on the day of presentation. He was found to have tachypnoea, hypoxia, and tachycardia on assessment. His electrocardiogram showed a right bundle branch block with sinus tachycardia. He underwent a CT pulmonary angiography (CTPA) that showed bilateral large pulmonary emboli extending from the main pulmonary arteries bilaterally extending to the sub-segmental level. There was evidence of right heart strain on the scan. He also had a bedside echocardiogram performed after the CT scan, which showed an enlarged right ventricle but no left ventricular thrombus. His blood results showed D-dimer levels of 14,000 ng/mL and troponin T of 255 ng/L. He received treatment with low molecular weight heparin (LMWH) and underwent emergency EkoSonic™ Endovascular System (EKOS) thrombolysis (Boston Scientific, Marlborough, MA). He remained on ultrasound-accelerated thrombolysis (USAT) for the next 12 hours and showed significant improvement and was taken off oxygen post-EKOS thrombolysis. He was discharged home on oral rivaroxaban after 48 hours of hospital stay; follow-up after two months showed normal-sized right ventricle with no evidence of pulmonary hypertension.

A Case Presentation Based on Incidental Diagnosis of Atrial Myxoma in a Patient Presenting With Atrial Fibrillation and Suspected Carney Complex.

We present the case of a 54-year-old lady who presented to hospital with palpitations and was diagnosed with atrial fibrillation with rapid ventricular response. She was given intravenous metoprolol 5 mg initially followed by a further 5 mg and was commenced on bisoprolol 2.5 mg once daily. She reverted back to normal sinus rhythm and was referred for echocardiography following an episode of paroxysmal atrial fibrillation. The echocardiogram showed a large mobile atrial myxoma in the left atrium and mild-to-moderate mitral regurgitation with preserved left ventricular function. Her past medical history includes transsphenoidal surgery for acromegaly in 1979, followed by radiotherapy and partial thyroidectomy for goitre. Her chest radiograph was normal and blood results were unremarkable. She was accepted for inpatient transfer to a cardiothoracic centre for surgical removal of atrial myxoma. She underwent surgery with successful excision of the atrial myxoma, and biopsies confirmed the mass to be atrial myxoma. The surgery was complicated by the patient developing atrial fibrillation with fast ventricular response that was chemically cardioverted with an intravenous loading dose of amiodarone 300 mg over 2 hours followed by 900 mg infusion over 24 hours. She had follow-up in the outpatient clinic with cardiology and endocrine specialists for a year and no recurrence of myxoma was noted. Her blood tests including growth hormone and thyroid function tests were normal.

A Case Report on the Incidental Diagnosis of a Left Atrial Myxoma in a Patient Presenting With Right Shoulder Pain and Inter-scapular Back Pain.

Primary cardiac tumors are rare, and myxoma is a rare benign primary cardiac tumor in adults, commonly found within the left atrium. The presentation can vary from patients being asymptomatic to pulmonary embolism or stroke. Smaller atrial myxomas are usually asymptomatic, however, larger ones can cause symptoms such as dyspnea, orthopnea, cough, peripheral edema, palpitations, and fatigue. We present a case report of a 72-year-old patient presenting with right shoulder pain and chest pain on breathing to the accident and emergency department. The patient was complaining of right shoulder pain for five days and pleuritic chest pain for the last 48 hours. Initial electrocardiogram showed normal sinus rhythm, however, repeat electrocardiograms showed atrial fibrillation. An echocardiogram showed a homogeneous, relatively round mass seen in the left atrium, close to the inter-atrial septum, and close to the roof of the left atrium, and the patient underwent surgical removal of the benign tumor.

Resolution of Thyrotoxicosis-Associated Pulmonary Hypertension With Treatment of Thyrotoxicosis: A Case-Based Report and Literature Review.

We present a case of a 41-year-old Afro-Caribbean female, who was diagnosed with thyrotoxic Graves' disease. She had a past medical history of hypertension and was on amlodipine and valsartan. There was no significant family history of note. She initially presented to Emergency Department with palpitations and excessive sweating. Her thyroid-stimulating hormone was <0.02mu/L and free triiodothyronine (T3) 29.5pmol/L at the time of diagnosis. The thyroid peroxidase antibody test was negative. She was started on carbimazole 15mg once daily and propranolol 40mg twice daily. She remained non-compliant to treatment for over two years and missed most outpatient clinic appointments and her condition remained poorly controlled during this time period. She was re-admitted to the hospital after 18 months, with high output congestive cardiac failure. An echocardiogram showed pulmonary hypertension and her right ventricular systolic pressure was measured to be 70-75mmHg. She was started on Lugol's iodine 0.2mls three times daily, propranolol 40mg three times daily, cholestyramine 4 gram four times a day, propylthiouracil 100mg four times a day. After 3 weeks of treatment, she became euthyroid and her pulmonary hypertension improved dramatically with treatment. She underwent total thyroidectomy after a few weeks and biopsies confirmed the findings of Graves' disease.

Systemic Manifestation of Miliary Tuberculosis in Patient With Advanced Diabetic Retinopathy Presenting With Electrolyte Imbalance, Seizures, and Adrenal Insufficiency.

Extra-pulmonary manifestations of tuberculosis can have diverse presentations depending on the affected organs. In this case report, we describe a case of a 50-year-old man of South Asian origin who presented with acute adrenal crisis on a background of undiagnosed miliary tuberculosis. Imaging after repeated episodes of adrenal crisis and seizures revealed bilaterally enlarged adrenals and cerebral tuberculomas, suggesting adrenal and central nervous system involvement. CT chest, abdomen and pelvis showed apical lung nodules and tree-in-bud appearance suggestive of tuberculosis. Due to high endogenous levels of adrenocorticotropic hormone and a flat response after a short synacthen test, a diagnosis of primary adrenal insufficiency secondary to tuberculosis infection was made. He remains well on anti-tuberculous chemotherapy, corticosteroids, and anti-epileptic medication. This case report exemplifies the unusual but life-threatening presentations of extra-pulmonary tuberculosis that may become increasingly common with immunosuppression because of the human immunodeficiency virus global epidemic and immunosuppressant therapies; therefore, a low index of suspicion is needed in these cases.