Idiopathic myointimal hyperplasia of the mesenteric veins, an uncommon cause of intestinal ischemia.

Idiopathic myointimal hyperplasia of the mesenteric veins (IMHMV) is an uncommon cause of intestinal ischemia. It was firstly described by Genta and Haggit in 1991. Only a few cases have been reported and it is difficult to know the true incidence.

Ultrasound findings associated to gallbladder carcinoma.

OBJECTIVE: This article reviews the most relevant ultrasound findings associated with gallbladder cancer. MATERIAL AND METHOD: A descriptive and retrospective study was made of clinical features and imaging studies in patients subjected to surgery for gallbladder neoplasm in the Reina Sofía General University Hospital (Murcia) during the time period 2000-2011. RESULTS: A total of 15 cases of gallbladder cancer were found during the study period, 9 of whom were women. The mean age was 77 years (range 61-96). Pain was the principal complaint. The patients had cholelithiasis in 13 cases, smoking in 2 cases, and obesity in 3 cases. The ultrasound showed gallbladder wall thickening (>4mm) in 8 cases, intraluminal mass in 4, scleroatrophic gallbladder in 2, and mass replacing the gallbladder in one. Only in 4 cases was the suspicion of gallbladder carcinoma established preoperatively. According to the pTNM staging, 4 patients were carcinoma in situ (Tis), one case T1a, 6 cases T2, 3 cases T3 and one case T4. In 7 cases, the only evidence was the preoperative ultrasound, and in 8 the study was completed with an abdominal CT. CONCLUSION: Early diagnosis of gallbladder cancer is rare. The ultrasound diagnostic approach is difficult; only a localized thickening coexisting with gallstones seems to be significant, and requires a biopsy. The image of a mass and a stone occupying the gallbladder is associated with later stages of the disease.

Association of anthracycline-related cardiac histological lesions with NADPH oxidase functional polymorphisms.

OBJECTIVE: Treatment with anthracyclines may cause cardiac dysfunction, but the sequence of anthracycline-induced heart lesions has been incompletely characterized. NADPH oxidase, a key mediator of oxidative cardiac damage and remodeling, modulates anthracycline clinical cardiotoxicity. Our aim was to determine which cardiac histological lesions are specifically induced by anthracycline treatment and to investigate the role of NADPH functional genetic polymorphisms in their development. PATIENTS AND METHODS: Using a retrospective case-control design, we evaluated cardiac histological lesions and NADPH genotype (polymorphisms rs1883112, rs4673, and rs13058338) in 97 consecutive decedents with a cancer diagnosis (48 treated with anthracyclines). RESULTS: Myocytolysis (60%), patched myocardial necrosis (19%), and myocardial fibrosis (diffuse and patched; 62% and 23%, respectively) were associated with anthracycline treatment. In patients receiving anthracyclines, NADPH oxidase polymorphism rs4673 protected against focal myocardial necrosis (odds ratio [OR], 0.11; 95% confidence interval [CI], 0.20-0.63) whereas rs1883112 was strongly associated with cardiac fibrosis (OR, 5.11; 95% CI, 1.59-16.43), which was present in all homozygotes. CONCLUSION: Anthracyclines induce a cardiac remodeling pattern characterized by interstitial or patched fibrosis. The contribution of the functionally relevant NADPH polymorphisms rs1883112 and rs4673 to anthracycline-related heart lesions provides a plausible explanation for their modulation of cardiotoxicity. If confirmed, these findings may lead to better individualized strategies for early detection and prevention of anthracycline cardiotoxicity.

[Cardiac sarcoidosis as an infrequent cause of sudden death in asymptomatic young patients]. / Sarcoidosis cardíaca como causa muy infrecuente de muerte súbita en pacientes jóvenes asintomáticos.

Cardiac involvement in sarcoidosis has been described in both symptomatic and asymptomatic patients. The aim of this report is to further the understanding of sarcoidosis and its clinical presentation. We report the autopsy and toxicology results of two cases of sudden death in young men. A 37-year-old male had generalized sarcoidosis, in mediastinal glands and intramyocardial sarcoid granulomas in the left ventricle, which had caused a 14mm thickening of the ventricular wall and a secondary dilated myocardiopathy causing sudden death. A 27-year-old male had extensive sarcoidosis of the lungs and mediastinum. Granulomas with a fibrotic background were found in the cardiac wall which could have originated an arrhythmogenic mechanism causing sudden death. Post-mortem study including careful examination of cardiac conduction pathways are vital to ascertain the cause of sudden death.

Prevented Sudden Cardiac Death and Neurologic Recovery in Inherited Heart Diseases.

Introduction: Inherited cardiovascular diseases are an important cause of sudden cardiac death (SD). The use of risk scores identify high risk patients who would benefit from an implantable cardioverter-defibrillators (ICDs). The development of automated devices for out-of-hospital cardiac arrest improves early resuscitation. The objective of the study is to quantify prevented SD and the neurological recovery of patients with inherited cardiovascular diseases. Methods: Two hundred fifty-seven cases of SD (age 42 ± 18 years, 79.4% men) of non-ischemic cardiac cause were prospectively collected during the study period (2009-17). Fifty three (20.6%) had a resuscitated cardiac arrest (RCA) (age 40 ± 18 years, 64.2% male). Epidemiological, clinical and autopsy aspects were analyzed. Prevented SD was defined as a combination of RCA and appropriate ICD therapy cases. Results: An autopsy was performed in 157/204 (77.0%) cases who died. There were 19 (12.1%) cases with a negative autopsy. The diagnosis of cardiomyopathy and channelopathy was 58.0 and 18.7%, respectively. Female sex and confirmed or suspected channelopathy were associated with successful resuscitation. The percentage of prevented SD remained low during the study period (mean 35.6%). 60.4% of RCA cases presented good neurological outcome. There was no association between neurological recovery and therapeutic hypothermia, but there was association with time of resuscitation (min). Conclusion: A fifth part of non-ischemic cardiac arrests were resuscitated. Female sex and channelopathies were more prevalent among RCA. Two thirds of RCA had a good neurological recovery.

Genotype of Null Polymorphisms in Genes GSTM1, GSTT1, CYP1A1, and CYP1A1*2A (rs4646903 T>C)/CYP1A1*2C (rs1048943 A>G) in Patients with Larynx Cancer in Southeast Spain.

BACKGROUND: some types of cancer have been associated with the presence of single nucleotide polymorphisms (SNPs) of some genes that encode enzymes: glutathione-S transferase (GST), whose alteration leads to loss of function and a lower capacity to eliminate toxic GSTM1 and GSTT1 null genotypes; SNPs causing loss of function of CYP1A1 or CYP1A1-2 cytochrome P450 enzymes related with a lower capacity to deactivate hydrocarbons related to smoking, which involves a higher risk of developing some smoking-dependent cancers including larynx cancer. OBJECTIVE: to compare the presence of null SNPs in genes GSTM1, GSTT1, and CYP1A1 rs 4646903 T>C, and CYP1A1-2 RS1048943 A>G in patients with hypopharyngeal and larynx cancer with a healthy control group. MATERIALS AND METHOD: The study included a total of 80 patients with hypopharyngeal and laryngeal cancer and 23 healthy subjects. Genomic DNA was obtained from saliva samples, determining genotype GSTM1 (present +, or null -), GSTT1 (present + or null -). Polymorphisms (SNP) in CYP1A1 T>C (present + CC, or absent - TC/TT), and CYP1A1-2 A>G (present + GG, or absent - AG/AA). RESULTS: the mean age of patients with larynx cancer was 62 years and of control subjects 63 years. Of the total sample, over 95% were men, and over 90% were smokers. The presence of null genotypes for GTM1 was 50% in patients with larynx cancer (p = 0.042), while GSTT1 was 88.75% (p = 0.002). CYP1A1 rs4646903 T>C polymorphisms were detected in 100% of cases of larynx cancer and 17.39% of healthy subjects (p > 0.001). CONCLUSIONS: patients with larynx cancer present more gene GSTM1 and GSTT1 null polymorphisms, and CYP1A1 rs4646903 T>C polymorphisms.

Gene expression changes in colon tissues from colorectal cancer patients following the intake of an ellagitannin-containing pomegranate extract: a randomized clinical trial.

The clinical evidence of dietary polyphenols as colorectal cancer (CRC) chemopreventive compounds is very weak. Verification in humans of tissue-specific molecular regulation by the intake of polyphenols requires complex clinical trials that allow for the procurement of sufficient pre- and postsupplementation tissue samples. Ellagitannins (ETs), ellagic acid (EA) and their gut microbiota-derived metabolites, the urolithins, modify gene expression in colon normal and cancer cultured cells. We conducted here the first clinical trial with 35 CRC patients daily supplemented with 900 mg of an ET-containing pomegranate extract (PE) and evaluated the expression of various CRC-related genes in normal and cancerous colon tissues before (biopsies) and after (surgical specimens) 5-35 days of supplementation. Tissues were also obtained from 10 control patients (no supplementation) that confirmed a large, gene- and tissue-specific interindividual variability and impact of the experimental protocol on gene expression, with some genes induced (MYC, CD44, CDKN1A, CTNNB1), some repressed (CASP3) and others not affected (KRAS). Despite these issues, the consumption of the PE was significantly associated with a counterbalance effect in the expression of CD44, CTNNB1, CDKN1A, EGFR and TYMs, suggesting that the intake of this PE modulated the impact of the protocol on gene expression in a gene- and tissue-specific manner. These effects were not associated with the individuals' capacity to produce specific urolithins (i.e., metabotypes) or the levels of urolithins and EA in the colon tissues and did not reproduce in vitro effects evidencing the difficulty of demonstrating in vivo the in vitro results.

Acute sarcoid myopathy: a case report and literature review.

Sarcoidosis is a worldwide spread disease with brad clinical spectrum, in which the pulmonary involvement is the main manifestation (more than 90% of cases); nevertheless, extrathoracic symptoms can predominate in the clinical picture and they may even be the first manifestation. One of them is the skeletal muscle involvement that normally is chronic and silent, with poor response to treatment with glucocorticoids. However, in some cases, it has an acute presentation. We present a case of a 61-year-old man with diagnosis of sarcoidosis whe were evaluated for proximal lower limb weakness within few days of evolution.

Genetics of myocarditis in arrhythmogenic right ventricular dysplasia.

BACKGROUND: Myocarditis occasionally is related to arrhythmogenic right ventricular dysplasia (ARVD) and sometimes overlaps during the early stages, which may lead to misdiagnosis. Acute myocarditis may reflect an active phase of ARVD. OBJECTIVE: The purpose of this study was to evaluate the genetic basis of myocarditis in ARVD and to investigate the association with a poorer prognosis and a higher risk of ventricular arrhythmias. METHODS: Two groups were analyzed: group A, which consisted of 131 affected patients-84 with ARVD (62% male, age 45 years [range 33-55 years]) and 47 with left-sided forms (arrhythmogenic left ventricular dysplasia [ALVD]) (47% male, age 45 years [range 25-61 years]); and group B, which consisted of 64 nonaffected mutation-carrying relatives (36% male, age 42 years [range 22-56 years]; 23 from classic ARVD families and 41 from ALVD families). RESULTS: Seven patients (3.5%) presented with a clinical diagnosis of acute myocarditis over median follow-up of 34 months. Myocarditis was the first clinical presentation in 6 of 7 cases. In 2 patients, acute myocarditis preceded worsening of left ventricular systolic function. In 1 case, myocarditis was associated with an increased gadolinium pattern in cardiac magnetic resonance. Two patients presented with ECG changes weeks after myocarditis resolution. Myocarditis preceded the development of ventricular tachycardia in 2 other patients. Myocarditis clustered in families bearing DSP Q447* and LDB3 c.1051A>G. CONCLUSION: Acute myocarditis reflects an active phase of ARVD that leads to changes in phenotype and abrupt progression of the disease. An active phase should be suspected in a patient with myocarditis associated with a family history of ARVD. Certain mutations may increase the susceptibility to superimposed myocarditis in ARVD.

MicroRNAs expression in normal and malignant colon tissues as biomarkers of colorectal cancer and in response to pomegranate extracts consumption: Critical issues to discern between modulatory effects and potential artefacts.

SCOPE: MicroRNAs (miRs) are proposed as colorectal cancer (CRC) biomarkers. Pomegranate ellagic acid and their microbiota metabolites urolithins exert anticancer effects in preclinical CRC models, and target normal and malignant colon tissues in CRC patients. Herein, we investigated whether the intake of pomegranate extract (PE) modified miRs expression in surgical colon tissues versus biopsies from CRC patients. METHODS AND RESULTS: We conducted a randomized, double-blind, controlled trial. Thirty-five CRC patients consumed 900 mg PE daily before surgery. Control CRC patients (no PE intake, n = 10) were included. Our results revealed: (1) significant differences for specific miRs between malignant and normal tissues modifiable by the surgical protocols; (2) opposed trends between -5p and -3p isomolecules; (3) general induction of miRs attributable to the surgery; (4) moderate modulation of various miRs following the PE intake, and (5) no association between tissue urolithins and the observed miRs changes. CONCLUSION: PE consumption appears to affect specific colon tissue miRs but surgery critically alters miRs levels hindering the discrimination of significant changes caused by dietary factors and the establishment of genuine differences between malignant and normal tissues as biomarkers. The components responsible for the PE effects and the clinical relevance of these observations deserve further research.

[Peritoneal gliomatosis]. / Gliomatosis peritoneal.

BACKGROUND: Peritoneal gliomatosis is characterized by the presence of miliary implants of mature glia on the peritoneum of patients with ovarian teratomas, usually immature. CLINICAL CASE: We report the case of a woman operated on 5 years earlier due to a right mature ovarian teratoma. When she was operated on due to left ovarian tumor she presented a miliary glial dissemination in omentum and peritoneum. CONCLUSION: The association of peritoneal gliomatosis ovarian teratomas is rare. Although the primary treatment and patient monitoring is focused on the teratoma, control should be maintained of peritoneal implants because of the possibility of malignancy. We believe it would be beneficial to establish a protocol for monitoring these lesions.

ANTECEDENTES: la gliomatosis peritoneal se caracteriza por la existencia de implantes miliares de tejido glial diseminados dentro de la cavidad abdominal de pacientes con teratomas ováricos, generalmente inmaduros. Caso clínico: paciente femenina intervenida cinco años antes de un teratoma maduro del ovario derecho, que al ser operada de un tumor en el ovario izquierdo se encontró diseminación miliar de tejido glial en el epiplón y el peritoneo. CONCLUSIÓN: la asociación de gliomatosis peritoneal con teratomas ováricos es infrecuente y, aunque el tratamiento principal y seguimiento de los pacientes está enfocado al teratoma deben controlarse los implantes peritoneales, por la posibilidad de malignización. Consideramos que sería benéfico establecer un protocolo para el seguimiento de pacientes con estas lesiones.

Targeted metabolic profiling of pomegranate polyphenols and urolithins in plasma, urine and colon tissues from colorectal cancer patients.

SCOPE: Urolithins are bioactive metabolites produced by the gut microbiota from ellagitannins (ETs) and ellagic acid (EA). We investigated whether urolithins could be detected in colon tissues from colorectal cancer (CRC) patients after pomegranate extract (PE) intake. METHODS AND RESULTS: CRC patients (n = 52) were divided into controls and PEs consumers (900 mg/day for 15 days) before surgical resection. PEs with low (PE-1) and high (PE-2) punicalagin:EA ratio were administered. Twenty-three metabolites, but no ellagitannins, were detected in urine, plasma, normal (NT) or malignant (MT) colon tissues using UPLC-ESI-QTOF-MS/MS (UPLC, ultra performance liquid chromatography; QTOF, quadrupole TOF). Free EA, five EA conjugates, gallic acid and 12 urolithin derivatives were found in colon tissues. Individual and total metabolites levels were higher in NT than in MT, independently of the PE consumed. The maximal mean concentration (1671 ± 367 ng/g) was found in NT after consumption of PE-1 and the lowest concentration (42.4 ± 10.2 ng/g) in MT with PE-2. Urolithin A or isourolithin A were the main urolithins produced (54 and 46% patients with urolithin A or isourolithin A phenotype, respectively). High punicalagin content (PE-2) hampered urolithins formation. CONCLUSION: Significant levels of EA derivatives and urolithins are found in human colon tissues from CRC patients after consumption of pomegranate. Further studies are warranted to elucidate their biological activity.

Clinical and genetic determinants of anthracycline-induced cardiac iron accumulation.

BACKGROUND: The involvement of iron in anthracycline cardiotoxicity is supported by extensive experimental data, and by the preventive efficacy of dexrazoxane, an iron chelator. However, no clinical evidence of anthracycline-induced cardiac iron accumulation is available and the influence of previous iron overload or of genetic factors in human-induced heart disease is largely unknown. Our aim was to test the hypothesis that anthracyclines increase iron heart concentration and that HFE genotype modulates this iron deposit. METHODS: We retrospectively evaluated cardiac events, cardiac iron and HFE genotype in 97 consecutive necropsies from patients with solid and hematological neoplasms. Heart and liver iron concentration was determined by atomic absorption spectroscopy. HFE gene mutations (C282Y and H63D) linked to hereditary hemochromatosis were analyzed by Fluorescence Resonance Energy Transfer (FRET) genotyping. RESULTS: Heart iron concentration was increased in cases treated with a cumulative doxorubicin dose greater than 200mg/m(2) (490 vs 240 µg/g; p=0.01), independently of liver iron load or transfusion history. HFE mutated haplotypes 282C/63D (p=0.049) and 282Y/63H (p=0.027) were associated to higher cardiac iron deposits. The haplotype C282Y-Y/H63D-H interacted with anthracyclines for increasing cardiac iron load. In a multivariate linear regression analysis both HFE genotypes and anthracyclines contributed to heart iron concentration (R(2)=0.284). CONCLUSIONS: Our data support the occurrence of an HFE-modulated heart iron accumulation in individuals treated with anthracyclines, independently of systemic iron load. If prospectively confirmed, iron-related parameters might be useful as predictive factors for anthracycline cardiotoxicity.

Fatal heat stroke in a schizophrenic patient.

Objective. The case of a patient who developed a fatal post-exertional heat stroke is reported. Case Report. A 20-year-old man with a history of morbid obesity, hypertension, and schizophrenia was admitted to our intensive care unit because of multiorgan failure due to severe heat stroke. He had been working under the sun. Treatment included aggressive body cooling but, in spite of the best supportive care, the patient succumbed in a few hours. We concluded that the adverse event was possibly associated with his obesity and the use of antipsychotics. Histological evaluation revealed lesions consistent with severe hyperthermia and shock. Conclusions. Heat stroke is an uncommon clinical entity characterized by systemic heat and loss of the body's normal mechanisms for dealing with heat stress, such as sweating and temperature control. When heat stroke is diagnosed early and supportive care begins promptly the prognosis is optimal but it becomes a life-threatening disease when treatment is delayed. Lack of physical acclimatization and the use of certain medications that interfere with salt and water balance can impair thermoregulation under conditions of high environmental temperature. Health professionals must be adequately prepared to prevent, recognise, and treat them urgently.