Takotsubo syndrome in association with pheochromocytoma: clinical and practical considerations.

In clinical practice, pathophysiology of Takotsubo syndrome (TTS) has been attributed to adrenergic discharge mostly associated with a variety of stressors. Occasionally, organic sources of adrenergic discharge (including pheochromocytoma) might also account for this phenomenon and are not considered as exclusion criteria for the diagnosis of TTS (as opposed to previous suggestions). We read with great interest the recently published article by Maffè et al. that describes a case of fatal TTS due to a ruptured pheochromocytoma in a middle-aged male. In this context, we would like to comment on this interesting case and potential implications of TTS associated with pheochromocytoma....

Cardiac myxoma as a potential trigger of takotsubo cardiomyopathy: A brief review on mechanistic and clinical perspectives.

In clinical practice, cardiac myxomas constitute the majority of benign cardiac neoplasms, and might potentially present with a variety of embolic, obstructive as well as constitutional symptoms. On the other hand, these neoplasms might be potentially associated with the evolution of takotsubo cardiomyopathy (TTC) that is universally considered as a transient form of acute myocardial dysfunction. Accordingly, the present paper primarily aims to focus on potential mechanisms and associated clinical implications of TTC evolution in the setting of cardiac myxomas.

Systemic inflammation in patients with Takotsubo syndrome: a review of mechanistic and clinical implications.

Over recent decades, systemic inflammation  as  quantified  with  inflammation  markers  or  indices has been extensively  investigated  in the setting of  various  cardiovascular  conditions  including heart failure (HF),  acute coronary syndromes (ACS). In contrast, systemic inflammation  in patients with  takotsubo syndrome (TTS) has been an underrated  phenomenon in clinical practice. On the other hand, experimental and clinical data  have been  rapidly  accumulating  in the recent years  regarding   pathogenetic, prognostic as well as therapeutic implications of  systemic inflammation in TTS.  Accordingly, the present article  aims to provide a general perspective  on mechanistic and  clinical aspects of  systemic  inflammation in the setting of  TTS.

Cardiac Biomarkers in the Setting of Asthma Exacerbations: a Review of Clinical Implications and Practical Considerations.

PURPOSE OF REVIEW: The present paper aims to highlight clinical implications of elevated cardiac biomarkers and associated myocardial dysfunction in a variety of cardiac and non-cardiac scenarios in patients with an asthma exacerbation, and to propose a basic algorithm for cardiovascular evaluation and triage (and hence, for further management) of these patients primarily based on evaluation of cardiac biomarkers along with basic diagnostic modalities and specific cardiac symptoms in the hospital setting. RECENT FINDINGS: Elevation of cardiac biomarkers in the setting of an asthma exacerbation mostly signifies a new-onset subclinical myocardial dysfunction/injury generally associated with certain asthma-related factors including acute hypoxemia and bronchodilator therapy, and usually has a limited prognostic value in these patients. On the other hand, elevation of these biomarkers in patients with an asthma exacerbation might also denote a variety of certain life-threatening cardiac or non-cardiac conditions associated with significant myocardial dysfunction (acute coronary syndromes (ACSs), sepsis, etc.) that might be masked by the rampant course of the asthma exacerbation, and hence, might possibly go undetected potentially aggravating the prognosis in a portion of these patients. In patients with an asthma exacerbation, it seems imperative to timely diagnose and manage emerging diverse clinical conditions particularly through the guidance of cardiac biomarkers and associated myocardial dysfunction patterns in an effort to improve overall prognosis in these patients.

Takotsubo cardiomyopathy in the setting of multiple sclerosis: a multifaceted phenomenon with important implications.

Dear Editor, Takotsubo cardiomyopathy (TTC) has been universally regarded as a unique form of reversible myocardial dysfunction associated with a variety of emotional and physical stressors. In their recently published elegant article, Dell'Aquila et al. have reported an interesting case of TTC triggered by an exacerbation of relapsing-remitting multiple sclerosis (MS). However, we would like to comment on this interesting case and its particular implications...

Combined Effectiveness of Honey and Immunonutrition on Bacterial Translocation Secondary to Obstructive Jaundice in Rats: Experimental Study.

BACKGROUND Obstructive jaundice is a serious, life-threatening condition that can lead to death as a result of sepsis and multiorgan failure due to bacterial translocation. Treatment should be started as soon as possible after diagnosis. MATERIAL AND METHODS Forty 24-week-old male Sprague Dawley rats, with an average weight of 250 g to 300 g, were included in this study. The rats were randomly placed into five groups, each group consisted of eight rats. The sham group underwent only common bile duct (CBD) dissection and no ligation was performed. CBD ligation was applied to the other groups. After the operation, one CBD group was fed with rat chow only, the others were fed with rat chow supplemented with honey, or immunonutrients, or honey plus immunonutrients. After 10 to 12 days, all rats were sacrificed; blood and tissue samples were collected for biochemical, microbiological, and histopathological evaluation. RESULTS In the groups that were fed with honey and immunonutrients, alanine aminotransferase (ALT) levels were decreased significantly compared to the other groups. Statistically significant differences were detected in terms of bacterial translocation (BT) rates among liver and spleen samples, and laboratory values of serum, except for MLNs of the BDL+HI group, when compared to other groups. We found mean mucosal thickness of ileum samples have been improved notably in the BDL+HI group compared to the other groups, especially compared to the C/BDL group. CONCLUSIONS Immunonutrition applied with honey had immunostimulant effects, decreased BT due to an additive effect, and had positive effects on intestinal mucosa.

Importance of Ki-67 in human epidermal growth factor receptor 2 positive breast cancer.

PURPOSE: The aim of this study was to evaluate the importance of Ki-67 in Human Epidermal Growth Factor Receptor 2 (Her-2) positive breast cancer patients. METHODS: We reviewed the records of patients diagnosed with Her-2-positive non-metastatic breast cancer between 2005 and 2011. Paraffin-embedded tissue samples were stained with MIB-1 mouse monoclonal antibody to find Ki-67 levels. Patients were grouped as low Ki-67<20% and high Ki-67≥20%. Demographic and clinical features were compared. RESULTS: One hundred and six patients were included in the study. Median follow up time was 41 months (range 15-100). Median age was 49.5 years (range 29-79). Twenty-nine patients (27.4%) were in the Ki-67 low group. Demographic features were similar in both groups. Lymphovas cular invasion was more frequent in the Ki-67 high group, and hormone receptor (HR) positivity was more frequent in the Ki-67 low group (p=0.03, p=0.03, respectively). Recurrence rate was not significantly different in both groups (p=0.36). T stage (p=0.02), stage (p<0.01), lymphovascular invasion (p=0.02), ER status (p=0.02), and HR status (p<0.01) were related with recurrence. In multivariate analysis, stage and HR negativity were independent factors for recurrence (p<0.01, p=0.01, respectively). Recurrence sites were also similar in both groups. Survival rates at the third year for Ki-67 low group and Ki-67 high group were 94% and 92%, respectively. CONCLUSION: Her-2 positive patients with low Ki-67 and high Ki-67 had similar demographic and pathologic features except lymphovascular invasion and HR status. HR status was an important factor for disease course. Clinical course was determined by HR status rather than Ki-67.

An experimental model of aortic surgery and the effect of Iloprost on lung injury.

OBJECTIVES: Ischemia/reperfusion (I/R) damage of the lung is a frequently encountered complication following aortic surgery. The aim of the present study is to investigate the histopathological effects of Iloprost on pulmonary damage developed after I/R. DESIGN: Twenty-four Sprague-Dawley rats were randomly divided into 3 groups. In the control group, aortas were not clamped. In the I/R group, aortas were occluded, and after 1 h of ischemia, clamps were removed. After 2 h of reperfusion period, lungs of the rats were extracted. In the I/R + Iloprost group after 1 h of ischemia, Iloprost infusion was initiated, and maintained for the duration of 2 h reperfusion period. For histopathological scoring, density of polymorphonuclear leucocytes, congestion, interstitial edema, and bleeding were semiquantitatively evaluated, and histopathological changes were scored. RESULTS: In the I/R group, multifocal-marked histopathological changes in 5 (62.5%), and multifocal-moderate histopathological changes in 3 (37.5%) rats were detected. In the I/R + Iloprost group, multifocal-moderate histopathological changes in 4 (50%), and multifocal-mild changes in 4 (50%) rats were detected. CONCLUSIONS: In the experimental rat model, administration of Iloprost has been shown to have preventive effects for pulmonary damage occurring after I/R generated by infrarenal aortic occlusion.

Serum Copeptin in Cardiooncology Practice: Review of Pathophysiological and Clinical Implications.

In cardiooncology practice, "early cardiotoxicity" refers to an emerging subclinical myocardial dysfunction/injury in response to certain chemotherapeutic regimens. This condition can progress to overt cardiotoxicity in time and hence warrants proper and timely diagnostic and preventive strategies. Current diagnostic strategies for "early cardiotoxicity" are largely based on conventional biomarkers and certain echocardiographic indices. However, a significant gap still exists in this setting, warranting further strategies to improve diagnosis and overall prognosis in cancer survivors. Copeptin (surrogate marker of the arginine vasopressine axis) might serve as a promising adjunctive guide for the timely detection, risk stratification, and management of early cardiotoxicity on top of conventional strategies largely due to its multifaceted pathophysiological implications in the clinical setting. This work aims to focus on serum copeptin as a marker of "early cardiotoxicity" and its general clinical implications in patients with cancer.

Clinicopathological and molecular analyses of uterine carcinosarcomas using next-generation sequencing: A single-center experience.

Background: Uterine carcinosarcomas (UCS) constitute 3-4% of all uterine malignancies and 16% of deaths caused due to uterine neoplasms. Aim: In this study, we aimed to perform DNA-based mutation analysis in 12 genes (KRAS, NRAS, EGFR, C-KIT, BRAF, PDGFRA, ALK, ERBB2, ERBB3, ESR1, RAF1, PIK3CA) to determine the molecular subtypes of UCS using next-generation sequencing (NGS) in patients with aggressive UCS and poor prognosis. We aimed to compare the results of our analysis with clinicopathological data to contribute to the development of targeted therapy approaches related to the molecular changes of UCS. Materials and Methods: In this study, we included 12 cases diagnosed with uterine carcinosarcomas and examined the changes in oncogenes that play a role in UCS pathogenesis. For the analysis of mutation, the clinicopathological data were compared with the variations in the DNA-based gene panel consisting of 12 genes and 1237 variants in the UCS using the NGS method. Results: EGFR mutation was found in 91.7% of the cases, mutation in 41.7%, PDGFRA mutation in 25%, KRAS and PIK3CA mutation in 16.7%, and C-KIT mutation in 8.3% of the cases. Although no statistical significance was found between the detected mutation and clinicopathological data, it was concluded that PDGFRA mutation might be associated with advanced-stage disease development. Conclusion: This study's findings regarding different molecular types of UCS and information on oncogenesis of UCS can provide inferences for targeted therapies in the future by identifying targetable mutations representing early oncogenic events and thereby contribute toward further studies on this subject.

The effects of sirolimus on target organs during mesenteric ischemia and reperfusion damage in an experimental rat model.

BACKGROUND: Mesenteric ischemia and reperfusion (I/R) syndrome (MIRS) has been considered a clinicopathologic entity associated with a variety of clinically severe conditions with decreased intestinal blood flow and has been known to induce I/R damage in various organs. Sirolimus (SRL), a macrolide antibiotic isolated from a strain of Streptomyces hygroscopicus, is a potent and nonnephrotoxic immunosuppressant. OBJECTIVE: This study was designed to investigate the potential impact of sirolimus on MIRS-induced I/R damage in renal, intestinal, pulmonary, and hepatic tissues in an experimental rat model. METHODS: Twenty-four male Sprague-Dawley rats, aged 6 to 8 weeks and weighing 280 (±20 g), were studied. Using computer-generated random numbers, rats were assigned to 1 of the following 3 groups: group 1 (I/R group, n = 8), group 2 (I/R + sirolimus group, n = 8), and group 3 (control group, n = 8). Sirolimus, in a 1 mg/mL (60 mL) solution, was administered intraperitoneally in a dose of 1.5 mg/kg/d to the rats assigned to group 2 starting from 3 days before the surgical procedure. In surgery, a laparotomy was performed to clamp the superior mesenteric artery and, thus, induce bowel ischemia in groups 1 and 2. After 60 minutes of ischemia, the microvascular clamp on the superior mesenteric artery was removed for 3 hours of reperfusion. Soon after experimental induction of MIRS, bowel, lung, kidney, and liver specimens from each animal were harvested for both biochemical and histopathologic analysis. RESULTS: There were statistically significant differences between groups 1 and 3 with regard to degrees of intestinal (P < 0.001), hepatic (P = 0.001), renal (P < 0.001), and pulmonary (P = 0.01) I/R damage. The lung specimens from group 2 had less inflammation and perivascular edema formation compared with specimens from group 1, but no statistical significance was observed between the groups (P < 0.33). There were statistically significant differences between groups 1 and 2 with regard to degrees of intestinal, hepatic, and renal I/R damage (P = 0.001 for all). CONCLUSION: The findings of the present study demonstrate the attenuating effects of sirolimus on I/R damage in the intestine and remote organs, including the liver and kidney in the setting of MIRS in an experimental rat model. As a therapeutic implication, the utility of sirolimus may be of clinical value in procedures associated with a high likelihood of I/R damage, including major abdominal operations and renal transplantation. However, whether these results apply to humans is unclear. Additional experimental and clinical studies are warranted to confirm the clinical utility of sirolimus in conditions potentially associated with I/R damage.

Late Coronary Aneurysm Formation after Kawasaki Disease: a Review of Mechanistic and Clinical Aspects.

In patients with Kawasaki disease (KD), evolution of coronary artery aneurysms (CAAs) generally emerges within the first few weeks after disease onset. However, CAA formation in these patients might occasionally arise as a late-onset phenomenon after a long latent period. Characteristically, late CAAs manifest as new-onset vascular pathologies or expansion of long-stable CAAs on coronary imaging modalities, and might have diverse mechanistic and clinical implications. Accordingly, the present paper aims to focus on late CAA formation and its implications in the setting of KD.

Contrary effects of coenzyme Q10 and vitamin E after testicular ischemia/reperfusion in a rat model validated with glucose metabolism imaging.

OBJECTIVE: To evaluate the efficacy of antioxidants in cellular-level post-ischemia/reperfusion injury of the testis and to validate these effects with 18F-fluorodeoxyglucose positron emission tomography. METHODS: Fifty-six adult male rats were randomly divided into seven groups-Group 1: sham; Group 2: ischemia/reperfusion only group; Group 3: ischemia was induced and vitamin E (100 mg/kg) was administered intraperitoneally 30 min before reperfusion; Group 4: vitamin E was given intraperitoneally without ischemia/reperfusion; Group 5: ischemia was induced and coenzyme Q10 (10 mg/body weight) was administered intraperitoneally 30 min before reperfusion; Group 6: coenzyme Q10 was administered intraperitoneally without ischemia/reperfusion; Group 7: ischemia was induced and coenzyme Q10 + vitamin E was administered intraperitoneally 30 min before reperfusion. After detorsion, fluorodeoxyglucose was applied to all groups according to the animals' weight and fluorodeoxyglucose positron emission tomography was performed after 1 h. In pursuit of imaging, orchiectomy was performed for histopathological and biochemical evaluations. RESULTS: A significant effect of group on catalase, maximum standardized uptake value, and seminiferous tubule diameters (p < 0.005) was observed. According to this, combining ischemia/reperfusion with vitamin E increased the maximum standardized uptake value significantly higher than in all other groups; in addition, catalase was significantly higher than in Groups 4-6. Histopathological outcomes revealed that "sham" had significantly larger seminiferous tubule diameter than Groups 2-4. Also, "ischemia/reperfusion" was the only group which had significantly smaller seminiferous tubule diameters than Groups 6 and 7. CONCLUSION: In contrast to vitamin E, coenzyme Q10 provided remarkable regression of oxidative stress-induced enzymes and revealed consistent effects on histopathological outcomes, which were validated with fluorodeoxyglucose positron emission tomography imaging.

Signet ring cell adenoma of the thyroid: a very rare entity.

OBJECTIVES: To report a case of signet ring cell adenoma of the thyroid which is an extremely rare thyroid lesion. CLINICAL PRESENTATION AND INTERVENTION: A 25-year-old female patient presented with a goiter and dysphagia that had been present for the last 1 year before admission. Physical examination revealed a palpable solitary nodule in the right lobe of the thyroid. The ultrasonogram demonstrated multiple nodules among which the most remarkable one was 15 x 24 mm in size, in the right lobe of the thyroid. After surgical excision, the lesion was found to be consistent withsignet ring cell adenomacharacterized by the presence of round to oval signet ring cells with large cytoplasmic vacuoles and hyperchromatic eccentric nuclei. Intracytoplasmic thyroglobulin, periodic acid-Schiff (PAS) with and without diastase and combined Alcian-blue-PAS were all positive. CONCLUSIONS: Pathologists should keep this rare primary tumor of the thyroid in mind when examining thyroid lesions and should not confound it with metastatic signet ring cell carcinoma of the thyroid.

Late Versus Early Myocardial Remodeling After Acute Myocardial Infarction: A Comparative Review on Mechanistic Insights and Clinical Implications.

In the setting of acute myocardial infarction (AMI), adverse myocardial remodeling (AMR) has been universally regarded as an early-onset phenomenon generally arising within the first few weeks (usually within days in the infarct zone) following myocardial injury. On the other hand, onset of cardiac morphological changes in this setting may potentially extend far beyond this time frame (usually beyond several months after the index AMI), suggesting a prolonged latent period in certain cases. In clinical practice, this delayed form of post-AMI remodeling, namely late AMR, has emerged as an interesting and underrecognized phenomenon with poorly understood mechanisms. Notably, systemic inflammation and associated growth factors seem to play a pivotal role in this setting. Accordingly, the present article primarily aims to discuss potential mechanisms and clinical implications of late AMR (in a comparative manner with its classical early counterpart) among AMI survivors along with a particular emphasis on potential benefits of certain anti-inflammatory strategies in this setting.

Sesamin ameliorates mucosal tissue injury of mesenteric ischemia and reperfusion in an experimental rat model.

INTRODUCTION: Mesenteric ischemia/reperfusion (I/R) injury is a serious clinical condition. There were a lot of experimental studies performed in the treatment of I/R injury. To our knowledge, this is the first experimental study with effects of sesamin on I/R injury model. We aimed to investigate the protective effect of sesamin on mesenteric I/R injury model. MATERIAL AND METHODS: A total of 32 male Sprague-Dawley rats were divided into four groups. Control group: superior mesenteric artery (SMA) exposed without clamping. I/R group: SMA was clamped for 60 min and then reperfused for 2 h. Sesamin group (S): 30 mg/kg sesamin were given for 5 days, and SMA exposed without clamping. I/R + S group: 30 mg/kg sesamin were given for 5 days, SMA was clamped for 60 min, and then reperfused for 2 h. Plasma and tissue oxidant parameters were investigated as well as histopathological evaluation. RESULTS: Plasma and tissue total antioxidant status (TAS) levels were significantly higher in I/R + S group compared to the rest (p < 0.005). The plasma TAS levels in I/R group was significantly low. The highest tissue TAS levels were detected in I/R + S group. The high levels of plasma and tissue TOS were found in I/R + S group. Plasma and tissue OSI levels were significantly higher in I/R group. Histopathologic evaluation showed that the mean level of intestinal tissue injury score in I/R group was 2.75 and 1.38 in I/R + S group. CONCLUSIONS: Sesamin helps to protect the intestinal tissue at the cellular level by reducing the oxidative stress and inflammation at both the plasma and tissue levels in the experimental I/R model.

Systemic Inflammation and Arrhythmogenesis: A Review of Mechanistic and Clinical Perspectives.

In the recent decades, systemic inflammation, as a clinical phenomenon, has been the focus of extensive research particularly with regard to its potential association with a variety of cardiovascular diseases including atherogenesis and acute coronary syndromes. Within this context, there also exists a potential link between systemic inflammation and cardiac arrhythmogenesis in various aspects. Accordingly, systemic inflammation response as measured with inflammation markers (cytokines, etc) has been investigated in the setting of well-known cardiac arrhythmias including atrial fibrillation and ventricular tachycardia. Based on current literature, clinical utility of these markers might potentially yield important prognostic implications in the setting of certain arrhythmogenic conditions. On the other hand, there exists limited data regarding therapeutic implications including clinical benefit of primary anti-inflammatory agents (corticosteroids, colchicine, etc) in the setting of arrhythmia management. The present review primarily aims to discuss potential triggers and fundamental mechanisms of inflammation-related arrhythmias along with a particular emphasis on clinical implications of systemic inflammation in the setting of cardiac arrhythmogenesis.