Extreme Elevation Research Articles

Focal myocarditis, an unusual imitator: Case report and short literature review

Introduction. Acute myocarditis is a serious inflammatory condition of the myocardium. Clinically, symptoms may differ from case to case, and as such can pose a significant diagnostic dilemma. Here we present a case of acute focal myocarditis with markedly elevated troponins, in which diagnosis was finally made using cardiac magnetic resonance (CMR). Case outline. A male patient, 26-year-old, without cardiovascular risk factors presented with severe chest pain, diaphoresis, pallor, and dyspnea. Blood pressure was 160/110 mmHg, and electrocardiogram (ECG) showed ST-segment elevation in inferior leads. In laboratory there was an extreme elevation of Troponin. Inferior-posterior-lateral STEMI was suspected, and initial treatment was given according to that suspicion. The patient was then sent to catheterization laboratory for further evaluation, which showed absence of coronary artery disease. A working diagnosis of myocardial infarction with non-obstructive coronary arteries (MINOCA) was established. To distinguish MINOCA from other causes of myocardial injury with elevated troponins, a CMR was done, and its finding was consistent with focal myocarditis of inferolateral localization. Further treatment consisted of beta blockers, angiotensin-converting-enzyme inhibitors and avoidance of strenuous activity for the next six months. The patient fully recovered and had no further complications with ECG only showing flat T-wave in D3 lead. Conclusion. Focal myocarditis is an unusual manifestation of myocardial disease and can confuse physicians, especially if it occurs along with elevated cardiac markers and ST-elevation, but in a young patient, without any known comorbidity, this diagnosis must be considered. Here, a CMR may be a useful tool.

A data-driven spatial approach to characterize the flood hazard.

Model output of localized flood grids are useful in characterizing flood hazards for properties located in the Special Flood Hazard Area (SFHA-areas expected to experience a 1% or greater annual chance of flooding). However, due to the unavailability of higher return-period [i.e., recurrence interval, or the reciprocal of the annual exceedance probability (AEP)] flood grids, the flood risk of properties located outside the SFHA cannot be quantified. Here, we present a method to estimate flood hazards that are located both inside and outside the SFHA using existing AEP surfaces. Flood hazards are characterized by the Gumbel extreme value distribution to project extreme flood event elevations for which an entire area is assumed to be submerged. Spatial interpolation techniques impute flood elevation values and are used to estimate flood hazards for areas outside the SFHA. The proposed method has the potential to improve the assessment of flood risk for properties located both inside and outside the SFHA and therefore to improve the decision-making process regarding flood insurance purchases, mitigation strategies, and long-term planning for enhanced resilience to one of the world's most ubiquitous natural hazards.

Feasibility of Utilizing Transforming Growth Factor Beta as a Biomarker of Depression in Hospitalized Patients

Several mental conditions and depression, have been linked to immune response disorganization. However, it is unclear if particular immune mediators play a part in the etiopathogenesis of depression. Although there are no definite biomarkers to diagnose depression, the current study sought to logically evaluate the possibility and feasibility of checking a biomarker for depression to be utilized for hospitalized patients suspected of depression. In this narrative review, related articles were gathered through a search of PubMed, Scopus, and ScienceDirect databases as well as a manual search of full-text paper references. The reviewed studies demonstrated the potential role of the transforming growth factor beta (TGF-β) in depressive disorders. Previous studies represented a negative role for TGF-β in depression pathophysiology and an increase in TGF-β after depression treatment. Elevated plasma TGF-alpha acted controversial to TGF-β. The level of TGF-β in maternal plasma increased getting close to delivery, and researchers found that it might be associated with postpartum depression. In addition, researchers reported extreme elevations in TGF-β levels in the brain cells of subjects who died by suicide. Although the results of this study revealed a plausible link between TGF-β and depression based on the literature, sensitivity and specificity studies needed before TGF-β as a biomarker may be extensively employed in clinical practice. Depression appears to be down-regulating TGF-β and its signaling or the underlying mechanisms of the pathogenesis of consequent neurological disorders, while further studies are required for the application of the TGF-β assessment in clinical practice.

Phylogenomics and plastome evolution of a Brazilian mycoheterotrophic orchid, Pogoniopsis schenckii.

Pogoniopsis likely represents an independent photosynthesis loss in orchids. We use phylogenomic data to better identify the phylogenetic placement of this fully mycoheterotrophic taxon, and investigate its molecular evolution. We performed likelihood analysis of plastid and mitochondrial phylogenomic data to localize the position of Pogoniopsis schenckii in orchid phylogeny, and investigated the evolution of its plastid genome. All analyses place Pogoniopsis in subfamily Epidendroideae, with strongest support from mitochondrial data, which also place it near tribe Sobralieae with moderately strong support. Extreme rate elevation in Pogoniopsis plastid genes broadly depresses branch support; in contrast, mitochondrial genes are only mildly rate elevated and display very modest and localized reductions in bootstrap support. Despite considerable genome reduction, including loss of photosynthesis genes and multiple translation apparatus genes, gene order in Pogoniopsis plastomes is identical to related autotrophs, apart from moderately shifted inverted repeat (IR) boundaries. All cis-spliced introns have been lost in retained genes. Two plastid genes (accD, rpl2) show significant strengthening of purifying selection. A retained plastid tRNA gene (trnE-UUC) of Pogoniopsis lacks an anticodon; we predict that it no longer functions in translation but retains a secondary role in heme biosynthesis. Slowly evolving mitochondrial genes clarify the placement of Pogoniopsis in orchid phylogeny, a strong contrast with analysis of rate-elevated plastome data. We documented the effects of the novel loss of photosynthesis: for example, despite massive gene loss, its plastome is fully colinear with other orchids, and it displays only moderate shifts in selective pressure in retained genes.

ODP015 "Malignant" Hypertension in an Older Male

Abstract Background Malignant hypertension connotates extreme elevation of blood pressure with associated acute target organ injury. Secondary causes of hypertension should always be considered in patients presenting with acute organ dysfunction especially when the hypertension is also resistant. Clinical case: A 66-year-old male was transferred to our hospital after two successive admissions to a local hospital with acute confusion. Importantly, he was noted to have acute kidney injury and hypokalemia in the course of those admissions. On review of his records, it was noted that he had been evaluated recently for chest pain with a contrast enhanced chest CT which incidentally detected a left adrenal mass. Biopsy of the mass had been performed and returned positive for adrenocortical carcinoma. Past history was also notable for chronic hypertension, type 2 diabetes and hypothyroidism for which he was on appropriate therapy. On physical examination, the patient was noted to be hypertensive. Other pertinent findings included facial plethora, extensive bruising and supraclavicular fat pad fullness. Abdominal striae were not seen. Laboratory investigations showed hyperglycemia (glucose: 201 mg/dL), hypokalemia (potassium: 3. 0 mmol/L) and metabolic alkalosis (bicarbonate: 30 mmol/L). Endocrine work up showed suppressed aldosterone (<4. 0 ng/dL, n: <21 ng/dL), total testosterone (31 ng/dL, n: 240-950 ng/dL) and ACTH (<5. 0 pg/mL, n: 7.2-63 pg/mL). Dehydroepiandrosterone (474 mcg/dL, n: 12-227 mcg/dL) and androstenedione (219 ng/dL, n: 40-150 ng/dL) levels were elevated. Cortisol levels did not suppress with overnight dexamethasone suppression test (29.8 mcg/dL). A diagnosis of Cushing's syndrome secondary to adrenocortical carcinoma was made. The patient was initiated on chemotherapy with carboplatin and etoposide. He was planned for mitotane therapy but passed away unexpectedly before the drug could be arranged. Conclusion Adrenocortical carcinoma can present with rapid onset of Cushingoid symptoms as well as sudden decompensation of previously controlled chronic hypertension, both of which were seen in this case. Although relatively uncommon, it remains a treatable and yet deadly cause for secondary hypertension, and should be considered in the appropriate clinical and biochemical settings. Presentation: No date and time listed

RF32 | PSUN65 Effect of Oral Contraceptive Medication on Blood Pressure, Plasma Renin, and Aldosterone Levels

Abstract Background Combination oral contraceptive medications may cause elevations of plasma renin activity and aldosterone levels. Clinical Case A 20-year-old female with a past medical history of chronic migraines and allergic rhinitis was referred to endocrinology for evaluation of secondary hypertension after she was found to have elevated renin levels by her primary care physician. The patient was noted to be hypertensive during a tonsillectomy 4 months prior and had also experienced an increased frequency of headaches prompting an evaluation for secondary hypertension and the initiation of lisinopril 10 mg daily. Her other medications included levocetirizine, biotin, and the combined oral contraceptive pill (OCP) norgestimate-ethinyl estradiol (0.25 mg/0.035 mg). Physical examination was remarkable for blood pressure 130/85mmHg, Pulse rate 77, BMI 30 kg/m2, pale striae on upper arms, lower back and abdomen, and a slight fat pad on the posterior nape of her neck. Initial lab results revealed normal plasma sodium, potassium, metanephrines and normetanephrines, plasma renin activity (PRA) 70.657 ng/mL/h (0.167-5.380 ng/mL/h), aldosterone 18.9 ng/dL (0.0-30.0 ng/dL), and 8: 00 amcortisol 30.3 mcg/dL (6.2-19.4mcg/dL). Doppler ultrasound and magnetic resonance angiography excluded renal artery stenosis and abdominal renin-secreting tumors. Owing to concern about OCP interference with the measurements of PRA and aldosterone levels, these tests were repeated at the end of a seven-day OCP placebo pills and biotin withdrawal. Lab results revealed: PRA >178 ng/mL/h, aldosterone 15.3 ng/dL, 1 mg overnight dexamethasone suppression test cortisol 1.1 mcg/dL, and 24-hour urinary cortisol 22.4 mcg/L (normal value <24mcg/L). Subsequently, the patient agreed to discontinue OCP and biotin and have labs redrawn 6 weeks later, which revealed PRA of 0.9 ng/mL/h and aldosterone of 5.9 ng/dL. Her blood pressure also normalized off the oral contraceptive and lisinopril was successfully discontinued. Conclusion This case report demonstrates the clinically significant impact of oral contraceptive medication on blood pressure, plasma renin activity and aldosterone levels. It's well known that oral contraceptives may cause elevations in PRA and aldosterone1 likely due to an upregulation of angiotensin mediated by the effect of ethinyl estradiol on the hepatocytes1, albeit not previously reported of the magnitude found in our patient. The extreme elevations of PRA and aldosterone in our patient suggested a diagnosis of either renovascular hypertension, renin secreting neoplasm or coarctation of aorta all of which were excluded. The subsequent normalization of blood pressure, PRA and Aldosterone off oral contraception×6 weeks confirmed that the OCP was the source of her hypertension and lab abnormalities. This case highlights the importance of identifying and omitting interfering medications when evaluating patients for secondary causes of hypertension. References Oelkers WK. Effects of estrogens and progestogens on the renin- aldosterone system and blood pressure. Steroids 1996;61: 166–71. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Monday, June 13, 2022 12:36 p.m. - 12:41 p.m.

The effect of burosumab on intact and C-terminal FGF23 measurements.

To investigate the effect of CRYSVITA® (burosumab-twza) on FGF23 measurements in an intact and a C-terminal immunoassay. An intact serum FGF23 (MedFrontier) and a C-terminal plasma FGF23 assay (Immutopics) were used. Serum/plasma pools were spiked to span the burosumab therapeutic range (1.4-11.3 μg/ml) and FGF23 recovery was assessed. Patient serum and plasma samples obtained pre and post-burosumab treatment were evaluated on both assays and compared with corresponding phosphorus measurements RESULTS: Spiking burosumab (1.4-11.3 μg/ml) into sample pools resulted in a dose-dependent negative analytical interference on intact FGF23 measurements and no significant interference for C-terminal FGF23 measurements. However, more than a 500-fold median increase (post- vs. pre-burosumab administration) in in vivo FGF23 concentrations were observed by both assays. Therapeutic concentrations of burosumab result in a negative analytical interference of the intact, but not the C-terminal FGF23 immunoassay. Despite this in vitro analytical interference in the intact assay, relatively large elevations of both intact FGF23 and C-terminal FGF23 measurements were observed in vivo following burosumab administration. Following burosumab administration, FGF23 measurements must be interpreted within the clinical context of the patient and other relevant biomarker results. This article describes a negative analytical interference by burosumab in an intact FGF23 immunoassay. The recovery of C-terminal FGF23 is not significantly affected by the presence of burosumab. In vivo, both assays demonstrate extreme FGF23 elevations in the presence of the drug. Furthermore, the measurement of FGF23 blocked by burosumab is not clinically useful regarding hypophosphataemia.

Pulmonary artery dissection following pulmonary balloon valvuloplasty in dogs

Introduction/objectivesPulmonary artery dissection is a rare complication following balloon valvuloplasty for pulmonic stenosis. We sought to report the rate of this complication in dogs and describe the demographic, clinical, procedural, and outcome data in affected dogs. Animals, materials and methodsMedical records at a single academic institution between 2002 and 2021 were reviewed for dogs with pulmonic stenosis treated by a balloon valvuloplasty. Dogs were included for evaluation if there was evidence of pulmonary artery dissection on echocardiography or necropsy following balloon valvuloplasty. The demographic, clinical, surgical, and follow-up information were then recorded. ResultsSix dogs were included from 210 balloon valvuloplasty procedures for pulmonic stenosis giving a 3.9% rate of pulmonary dissection. There was a variety of signalment, pulmonary valve morphologies, and balloon catheter types used in each dog. All dogs had severe pulmonic stenosis (median pressure gradient of 208 mmHg, range 94–220 mmHg) with 5/6 dogs having a pressure gradient >144 mmHg. The median balloon to pulmonary valve annulus ratio was 1.35 (range 1.25–1.5). Three dogs died perioperatively, and three dogs were alive at follow up 3.3, 4.0, and 4.1 years postoperatively. ConclusionPulmonary artery dissection is a rare complication following balloon valvuloplasty for pulmonic stenosis. Extreme elevations in preoperative pulmonary valve flow velocity were common. Prognosis is variable, with a potential 50% perioperative survival rate, but extended survival times were noted in those patients discharged from hospital.

Clinicoepidemiologic considerations in the diagnosis of tuberculous lymphadenitis: evidence from a high burden country

ObjectivesTuberculosis is the biggest health issue worldwide, with tuberculous lymphadenitis (TBL) being its most common extrapulmonary manifestation. Clinical diagnoses of TBL often pose challenges; thus, this study aimed to analyze the clinical, epidemiologic, and laboratory aspects of TBL in Debre Markos Specialized Comprehensive Hospital, northwest Ethiopia. MethodsThe study was conducted at Debre Markos Specialized Comprehensive Hospital from October 2019 to March 2021. Patients with lymphadenitis displaying cytomorphologic features of tuberculosis were enrolled. A checklist was used to collect clinicodemographic data. ResultsAmong a total of 294 patients with TBL, 237 (80.61%) were adults aged 15-45 years. A fluctuant consistency (177; 60.20%; n = 294) with predominant involvement of cervical lymph nodes (229; 77.8%) was the most frequent presentation. Most patients did not have either HIV infection (235; 94.37%; n = 261) or known chronic medical illnesses (250; 95.8%). Constitutional symptoms (113; 41.85%; n = 270) and chronic cough (56; 20.74%; n = 270) were infrequent. The erythrocyte sedimentation rate (ESR) was increased in the majority of patients (133; 80%; n = 165), of whom extreme elevation (≥100 mm/hour) seen in 63 (38.18 %) patients and the mean ESR for our participants was 78.64 mm/hour. ConclusionTBL typically presents as a fluctuant neck mass, predominantly in young adults. The majority of patients have no constitutional symptoms or cough. HIV infection or chronic medical illnesses are uncommon. The raised erythrocyte sedimentation rate is a fairly consistent finding.

Metoprolol Inhibits Developmental Brain Sterol Biosynthesis in Mice.

De novo sterol synthesis is a critical homeostatic mechanism in the brain that begins during early embryonic development and continues throughout life. Multiple medications have sterol-biosynthesis-inhibiting side effects, with potentially detrimental effects on brain health. Using LC-MS/MS, we investigated the effects of six commonly used beta-blockers on brain sterol biosynthesis in vitro using cell lines. Two beta-blockers, metoprolol (MTP) and nebivolol, showed extreme elevations of the highly oxidizable cholesterol precursor 7-dehydrocholesterol (7-DHC) in vitro across multiple cell lines. We followed up on the MTP findings using a maternal exposure model in mice. We found that 7-DHC was significantly elevated in all maternal brain regions analyzed as well as in the heart, liver and brain of the maternally exposed offspring. Since DHCR7-inhibiting/7-DHC elevating compounds can be considered teratogens, these findings suggest that MTP utilization during pregnancy might be detrimental for the development of offspring, and alternative beta-blockers should be considered.

Aortic stenosis in homozygous familial hypercholesterolaemia: a paradigm shift over a century.

Homozygous familial hypercholesterolaemia (HoFH) is an orphan disease defined by extreme elevations in low-density lipoprotein cholesterol, cutaneous xanthomas, and pre-mature atherosclerotic cardiovascular disease. Survival has more than doubled over the past three decades. Aortic stenosis (AS) [supravalvular aortic stenosis (SVAS) or valvular aortic stenosis (VAS)] is commonly encountered. There are no medical treatments available and complex high-risk surgeries represent the only available option in severe cases. A systematic review was performed to summarize the current evidence on AS in HoFH and to determine whether pharmacological treatment (statins) have had an impact on clinical presentation, phenotype and clinical course over the past nine decades (PROSPERO CRD42021250565). MEDLINE, Embase Classic + Embase, Cochrane Central Register of Controlled Trials, PubMed, AfricaWide, and Scopus were searched from inception to 10 November 2021. Searches identified 381 publications, of which 19 were retained; they were cross-sectional or retrospective studies. Separately, 108 individual case reports were described. Within the 424 HoFH cases, AS was identified in 57% of patients in the pre-statin era vs. 35% in patients reported more recently (>2000, long-term statin period). With an increase in longevity due to statins and lipoprotein apheresis, a change in the proportion of patients with SVAS and VAS with a SVAS:VAS ratio of 47:53 and 10:90 for HoFH patients not on statin and on long-term statin, respectively, was noted. These data suggest that SVAS and VAS are frequent in HoFH and that the phenotype has shifted towards calcific VAS as statins and lipoprotein apheresis improve survival in these patients.

Practical management of the haemorrhagic complications of myeloproliferative neoplasms.

Myeloproliferative neoplasms can be associated with bleeding manifestations which can cause significant morbidities. Although haematologists are aware of the likelihood of this complication in the setting of myeloproliferative neoplasms, it may often be overlooked especially in patients with no extreme elevation of blood counts and those with myelofibrosis. Acquired von Willebrand syndrome and platelet dysfunction are the two common diagnoses to be considered in this regard. In this review article, we discuss the mechanisms for the development of these rare bleeding disorders, their diagnosis and practical management.

Sonification enables continuous surveillance of the ST segment in the electrocardiogram

IntroductionST segment elevation myocardial infarction is a common reason for out-of-hospital cardiac arrest in adult patients. The surveillance of the ST segment in the electrocardiogram is limited to visual presentation. However, the ST segment can change during the course of treatment. If ST elevation is present immediate coronary revascularization is needed, therefore detecting ST elevation changes the treatment fundamentally. Sonification of the ST segment is a new method which enables the emergency team to detect intermediate changes of the ST segment. Material and methodsWe have chosen two sonification designs which were introduced to two groups, medical students and computer science students. Twenty-one participants took part in the study. The sonification was designed for evaluation of the ST segment. The user was supposed to become empowered to distinguish between no, medium–low, medium–high or extreme ST elevation by listening to the sonification. The two groups were asked to evaluate the sounds for possible ST elevation as well as for aesthetics and usability. In a second study twenty-five medical students were taking part in a medical scenario in which sonification was played during a simulated case. The patient was suffering from a myocardial infarction, ST elevation was transient and sonification sounds were changing appropriately. The students were supposed to detect these changes and act accordingly by modifying the treatment. ResultsBoth groups were able to classify ST segment elevation by listening to the sonification samples. The higher the ST segment, the better was the detection rate overall. In all of the three categories (pleasantness, informativeness and long-term listening) the Water Ambience sonification was rated higher compared to the Polarity sonification. Moreover, in the two groups that took part in the study, we found a significant difference when comparing classification performance using both sonification designs. For the group of medical students as t(20) = 4.31, p = 3.44 × 10−4, p < 0.01 and for the computer science students as t(19) = 3.40, p = 9.39 × 10−6, p < 0.01. In the simulated medical scenario participants indicated that 96% detected the ST elevation. 60% stated that sonification played a role whereas for 32% it did not play a role for the detection of ST elevation. ConclusionsSonification has the potential to play an important role as a new supporting tool for the surveillance of the ST segment during the care of patients with suspicion of myocardial infarction. It can be helpful to differentiate between ST segment elevation myocardial infarction and non-ST segment myocardial infarction especially if ST elevation is transient. Furthermore, sonification is viewed as pleasant to listen to and might not contribute to alarm fatigue.

ST segment elevation: the lost measure of early ischemic preconditioning in the landmark study of Murry et al. 1986

BackgroundIn their landmark study Murry et al. (Circulation 74:1124, 1986) showed dramatic ST segment elevation of the ECG during the first occlusion of a dog coronary artery. They made the insightful observation that “… in subsequent occlusions, these changes were slower to develop and frequently did not reach the magnitude seen during the first occlusion.” This electrophysiological preconditioning has been almost completely dismissed as irrelevant to ischemic preconditioning in animal models. We found in the Ossabaw miniature swine model of metabolic syndrome that brief coronary occlusion often led to ST elevation that quickly progressed to ventricular tachycardia and fibrillation.HypothesisAn AMPKγ3 mutation in Ossabaw swine will explain the extreme ST elevation and provide evidence for the relevance of ST segment ischemic preconditioning.Methods and ResultsLean mutants had impaired glucose tolerance compared to wild type Ossabaw swine. Myocardial ischemia induced by balloon occlusion of the circumflex artery elicited profound electrocardiographic ST elevation in lean mutant compared to wild type swine. Infusion of an AMPK agonist, AICAR (0.5 mM), prior to occlusion significantly reduced ST elevation in lean mutants, while completely preventing ST segment elevation in wild type. Ischemic preconditioning of the ST segment changes occurred in wild type pigs during the course of 5 occlusions, but only occurred in mutant pigs with AICAR infusion. Infusion of compound C (30 μM), an AMPK antagonist, prior to occlusion blocked the AICAR‐induced attenuation of ST elevation in lean mutants. The KATP channel agonist pinacidil increased ST elevation and the antagonist glibenclamide attenuated ST elevation during occlusion. While the degree of diet‐induced MetS (obesity, further impaired glucose tolerance, insulin resistance, and hypertension) was not different between mutant and wild type swine, except for greater plasma lipids in mutants, there was no difference in ST elevation during myocardial occlusion.ConclusionsLean Ossabaw swine with the V199l AMPK mutation have impaired glucose tolerance and exacerbated KATP channel‐mediated ST elevation during myocardial ischemia. Excess calorie diet induces MetS and abolishes cardioprotection in wild type AMPK swine. ST segment changes are an excellent measure of ischemic preconditioning in this model, thus showing the relevance of Murry’s landmark discovery.

Advancements in the Treatment of Homozygous Familial Hypercholesterolemia.

Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder with extreme elevations of low-density lipoprotein cholesterol (LDL-C) leading to premature atherosclerotic cardiovascular disease (ASCVD) as early as in childhood. Management of HoFH centers around aggressive and adequate reduction of LDL-C levels to slow the trajectory of ASCVD development. Historically, lowering LDL-C levels in HoFH has been challenging because of both the markedly elevated LDL-C levels (often ＞400 mg/dL) and reduced response to treatment options, such as statins, for which the mechanism of action requires a functional LDL receptor. However, the treatment landscape for HoFH has rapidly progressed over the last decade. While statins and ezetimibe remain first-line treatment, patients often require addition of multiple therapies to achieve goal LDL-C levels. The PCSK9 inhibitors are an important recent addition to the available treatment options, along with lomitapide, bile acid sequestrants, and, possibly, bempedoic acid. Additionally, ANGPTL3 has emerged as an important therapeutic target, with evinacumab being the first available ANGPTL3 inhibitor on the market for the treatment of patients with HoFH. For patients who cannot achieve adequate LDL-C reduction, lipoprotein apheresis may be necessary, with the added benefit of reducing lipoprotein(a) levels that carries an added risk if also elevated in patients with HoFH. Finally, gene therapy and genome editing using CRISPR/Cas-9 are moving through clinical development and may dramatically alter the future landscape of treatment for HoFH.

Severe thyrotoxicosis as initial presentation of gastric choriocarcinoma: a case report

BackgroundExtragonadal choriocarcinoma is rare and can be associated with hyperthyroidism when producing very high levels of human chorionic gonadotropin.Case presentationA 62-year-old Hispanic female presented with a 3-week history of shortness of breath, palpitations, extreme weakness, new-onset hot flashes, and right flank pain. Her physical examination was remarkable for tachycardia, hepatomegaly, hyperreflexia, and tremor; goiter was absent. Laboratory studies revealed increased lactate dehydrogenase, alkaline phosphatase, suppressed thyroid stimulating hormone, very elevated T4, and absent thyroid stimulating immunoglobulin. 18F-fluorodeoxyglucose positron emission tomography-computed tomography exhibited hepatomegaly with multiple large fluorodeoxyglucose-avid liver masses and a focus of fluorodeoxyglucose avidity in the stomach with no structural correlate. A thyroid scan (99mTcO4−) showed diffusely increased tracer uptake. She was started on propranolol and methimazole. Upon stabilization of severe thyrotoxicosis, upper endoscopy was performed, showing a ~ 5 cm bleeding lesion in the greater stomach curvature body; biopsy was consistent with choriocarcinoma; beta-human chorionic gonadotropin hormone was 2,408,171 mIU/mL. The patient received methotrexate followed by etoposide and cisplatin. Methimazole was titrated down, and upon liver failure the medication was stopped. The thyrotoxicosis was effectively controlled with antithyroid drug and concurrent chemotherapy. At ~ 1.5 months after initial diagnosis, the patient died due to bleeding/acute liver failure with coagulation defects followed by multiple organ failure.ConclusionsSevere thyrotoxicosis can represent an unusual initial presentation of metastatic choriocarcinoma in the setting of extreme elevation of beta-human chorionic gonadotropin. Primary gastric choriocarcinoma is an aggressive malignancy with very poor outcomes. The co-occurrence of severe thyrotoxicosis with advanced primary gastric choriocarcinoma and imminent liver failure complicates management options.

The Diagnostic Value of Extremely Elevated Erythrocyte Sedimentation Rate in A Tertiary Pediatric Hospital

Objective: The aim of this study was to evaluate the frequency, demographic and clinical characteristics of pediatric patients with extremely elevated erythrocyte sedimentation rate (ESR) in a reference children's hospital, and to improve clinicians' ability to use extremely elevated ESR in the differential diagnosis. Material and Methods: A retrospective cohort study was conducted to examine the clinical data of pediatric patients with extremely elevated ESR ( ≥100 mm/h). The patients were divided into 6 main groups according to their diagnosis as infectious, non-infectious inflammatory disease (NIID), malignancy, nephrologic, miscellaneus and unknown. Then, the specific sub-diagnoses of the patients were determined and evaluated. Clinical and laboratory data of the patients were recorded. Results: We analyzed the results of a total of 3166 patients with high ESR (≥20 mm/h) and 189 (5.96%) patients with extremely elevated ESR were included in the final analysis. The most common etiology of extremely elevated ESR was NIID (35.9%), followed by infections (33.3%), malignancies (19.0%) nephrologic (2.6%), miscellaneus (4.7%) and unknown (4.2%). The most common specific diagnosis was acute rheumatic fever, Kawasaki disease, lymphadenitis and leukemia. The high ESR was only negatively correlated with hemoglobin and albumin levels. Conclusion: Identifying the most common diseases that cause extreme ESR elevation in children can help clinicians in the differential diagnosis of diseases but it cannot be used as a screening tool for diseases.

Evidence of a population of leaf-eared mice Phyllotis vaccarum above 6,000 m in the Andes and a survey of high-elevation mammals.

Biologists have long pondered the extreme limits of life on Earth, including the maximum elevation at which species can live and reproduce. Here we review evidence of a self-sustaining population of mice at an elevation that exceeds that of all previously reported for mammals. Five expeditions over 10 years to Volcán Llullaillaco on the Argentina/Chile border observed and collected mice at elevations ranging from 5,070 m at the mountain's base to the summit at 6,739 m (22,110 feet). Previously unreported evidence includes observations and photographs of live animals and mummified remains, environmental DNA, and a soil microbial community reflecting animal activity that are evaluated in combination with previously reported video recordings and capture of live mice. All of the evidence identifies the mouse as the leaf-eared mouse Phyllotis vaccarum, and it robustly places the population within a haplotype group containing individuals from the Chilean Atacama Desert and nearby regions of Argentina. A critical review of the literature affirms that this population is not only an elevational record for mammals but for all terrestrial vertebrates to date, and we further find that many extreme elevations previously reported for mammals are based on scant or dubious evidence.

Temporary Increased LDL-C in Offspring with Extreme Elevation of Maternal Preconception Estradiol: A Retrospective Cohort Study.

ObjectiveTo investigate the effect of maternal estradiol (E2) elevation on long-term metabolic manifestations in the offspring.Study Design and SettingThis was a retrospective cohort study. Overall, 3690 children conceived by in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) between July 2014 and December 2017 were recruited and divided into four groups categorized by maternal E2 quartiles (Q1, <2420; Q2, 2420–3839; Q3, 3839–5599; and Q4, ≥5599 pg/mL). The metabolic profiles were measured during childhood. Linear mixed models were used to evaluate the association between maternal E2 elevation and metabolic phenotypes of the offspring.ResultsLipoprotein cholesterol (LDL-C) was significantly higher in the highest quartile group than in the lowest quartile group during infancy (adjusted mean difference [95% confidence interval, CI]): 0.11 [0.02, 0.20], P = 0.005), but the difference disappeared in the later childhood phase. In children born after fresh embryo transfer, LDL-C showed an increasing trend with the increase in maternal E2 level (adjusted mean difference [95% CI]: Q2 vs Q1, −0.01 [−0.11, 0.08], Q3 vs Q1, 0.06 [−0.04, 0.15], Q4 vs Q1, 0.10 [0, 0.20]). Other metabolic variables were comparable across increasing quartiles of maternal E2 levels.ConclusionThis study demonstrates a temporary increase in LDL-C levels in infants with higher levels of maternal preconception E2 levels. However, the long-term safety of hyperestrogens after ovarian stimulation in the next generation is favorable. The mechanism underlying the transiently increased metabolic dysfunction risk in infants conceived by IVF/ICSI requires investigation in future studies.

Geomorphology of the Beqaa Valley, Lebanon and Anti-Lebanon Mountains

Abstract Geomorphology of Lebanon presents a unique pattern of contrasting landforms. These include two notable mountain ranges, the Lebanon and Anti-Lebanon Mountains, the Beqaa Valley, the elongated coastal area and a significant amount of karst relief forms. This study focuses on the investigation of the topographic and geologic setting of Lebanon by visualizing datasets covering Lebanon and Anti-Lebanon mountains and the Beqaa Valley. Data were collected using the open source repositories of the high-resolution data (GEBCO, ETOPO1, DEM embedded in R). Three 3D models of the relief of the country are presented based on the ‘grdview’ package of GMT with azimuth rotations of the view point at 205°/30° and 165°/30°. The geologic map is based on the compiled datasets of the USGS. The R based modelling allowed division of the raster grid into several geomorphological zones according to the slope steepness and aspect orientation. The extreme elevations of the study area range from -2007 m and 2973 m. The key contribution of this work is the topographic and geologic data synthesis for 2D and 3D modelling of Lebanon. Another aspect concerns technical integration of GMT and R scripting approaches with QGIS mapping into the cartographic framework for visualizing of the Lebanese topography as a multi-tool approach. For the future similar studies on Lebanon this paper can serve as a guide for completing a project on the multi-source 2D and 3D data mapping as a conceptual foundation for research on Lebanese environment.