Faster perfusate instillation time results in more systemic leakage of amikacin sulfate when performing intravenous regional limb perfusion in horses.

OBJECTIVE: To evaluate if a difference in synovial amikacin concentrations exists in the radiocarpal joint (RCJ) following different durations of instillation of an IV regional limb perfusion (IVRLP) perfusate. ANIMALS: 7 healthy horses. METHODS: Horses received 2 IVRLPs with 2 g amikacin diluted to 60 mL with 0.9% NaCl via the cephalic vein in a crossover study design with a wash-out period between procedures. Instillation of the perfusate was administered over a 1-minute (technique 1) and 5-minute (technique 5) period. Concentrations of amikacin within the RCJ were measured at time (T) 5, 10, 15, 20, 25, and 30 minutes after instillation of the perfusate. Systemic concentrations of amikacin were measured at T0, 5, 10, 15, 20, 25, 29 minutes, and 1 minute after tourniquet removal (T31). Amikacin concentrations were determined by fluorescence polarization immunoassay. RESULTS: The median maximum concentration (CMAX) of amikacin within the RCJ for technique 1 was 338.4 µg/mL (range, 60 to 4,925 µg/mL), while the median CMAX for technique 5 was higher at 694.8 µg/mL (range, 169.2 to 3,410 µg/mL; P = .398). There was a higher amikacin blood concentration over time for technique 1 compared to technique 5 (P = .004). CLINICAL RELEVANCE: Administration of perfusate at different rates did not significantly affect synovial concentration of amikacin within the RCJ when performing IVRLP. However, increased systemic leakage was noted when the perfusate was administered over 1 minute, which might affect synovial concentrations in a larger group of horses.

Massive Pulmonary Embolism Related to a Patient With Heart Failure Secondary to Stress Cardiomyopathy: A Case Report.

Venous thromboembolism (VTE) is a common disease, which includes deep venous thrombosis (DVT) and pulmonary embolism (PE). It is the third most common cardiovascular disorder, affecting predominantly the male elderly population. Stress cardiomyopathy (SC) is a transitorily cardiovascular condition produced after an emotional or physical trigger, and it features signs and symptoms of acute coronary syndrome. Its pathophysiological mechanisms remain unclear, and SC has also been related to critical complications such as heart failure, arrhythmias, left ventricular outflow obstruction, and thromboembolic events. This case report highlights the association of PE and SC that might play a pathophysiological role.

Largest comparison between onset and relapses of acquired thrombotic thrombocytopenic purpura reveals severe neurological involvement and worse analytic parameters at debut.

It has been proposed that the onset of Acquired Thrombotic Thrombocytopenic Purpura (iTTP) is more severe than subsequent relapses; however, existing studies have limitations. We conducted a retrospective observational study to compare analytical and clinical severity of onset and relapse aTTP cases between 2012 and 2023. A total of 370 episodes of aTTP were analyzed, comprising 272 at initial diagnosis and 98 relapses. At onset, analytical parameters indicative of severity (low hemoglobin, low platelet count, and increased LDH) were significantly worse; patients had severe neurological symptoms (p<0.001) and ≥ 3 points in the TMA mortality score (p<0.001). In conclusion, the onset of aTTP is associated with worse analytical parameters and severe neurological involvement.

ADAMTS13 recovery in acute thrombotic thrombocytopenic purpura after caplacizumab therapy.

ABSTRACT: Caplacizumab prevents the interaction between von Willebrand factor and platelets and is used to treat immune thrombotic thrombocytopenic purpura (iTTP). Its administration has been associated with a delay in ADAMTS13 activity restoration after plasma exchange (PEX) suspension. We analyzed the outcomes of 113 iTTP episodes, 75 of which were treated with caplacizumab, in 108 patients from the Spanish Registry of Thrombotic Thrombocytopenic Purpura. Caplacizumab shortened the time to platelet count normalization and reduced PEX requirement, exacerbations, and relapses. There was no difference in the time to achieve ADAMTS13 activity ≥20% after PEX end between caplacizumab-treated and nontreated episodes (median [interquartile range], 14.5 [7.7-27.2] vs 13.0 [8.0-29.0] days, P = .653). However, considering the 36 episodes in which caplacizumab was started ≤3 days after iTTP diagnosis, the time for ADAMTS13 restoration from PEX end was higher than in those episodes in which caplacizumab was started >3 days after iTTP diagnosis (20.0 [12.0-43.0] vs 11.0 [3.5-20.0] days, P = .003) or than in non-caplacizumab-treated episodes (P = .033). This finding could be related to a significantly shorter duration of PEX in early caplacizumab-treated episodes than in late caplacizumab-treated episodes (5.5 [4.0-9.0] vs 15.0 [11.0-21.5] days, P < .001) or non-caplacizumab-treated episodes (11.0 [6.0-26.0] days, P < .001). There were no differences in time to ADAMTS-13 restoration from PEX start (28.0 [17.2-47.5], 27.0 [19.0-37.5] and 29.5 [15.2-45.0] days in early caplacizumab-treated, late caplacizumab-treated and non-caplacizumab-treated episodes). Early administered caplacizumab does not prevent the requirement for immunosuppression but has beneficial effects by shortening PEX requirement without major safety concerns.

[Treatment of cardiogenic shock due to right ventricular involvement]. / Tratamiento del choque cardiogénico con compromiso ventricular derecho.

The right ventricle is susceptible to changes in preload, afterload, and contractility. The answer is its dilation with dysfunction/acute failure; filling is limited to the left ventricle and cardiac output. Systemic venous congestion is retrograde to the right heart, it is involved in the genesis of cardiogenic shock due to right ventricle involvement. This form of shock is less well known than that which occurs due to left ventricular failure, therefore, treatment may differ. Once the primary treatment has been carried out, since no response is obtained, supportive treatment aimed at ventricular pathophysiology will be the next option. It is suggested to evaluate the preload for the reasoned indication of liquids, diuretics or even ultrafiltration. Restore or maintain heart rate and sinus rhythm, treat symptomatic bradycardia, arrhythmias that make patients unstable, use of temporary pacing or cardioversion procedures. Improving contractility and vasomotility, using vasopressors and inotropes, alone or in combination, the objective will be to improve right coronary perfusion pressure. Balance the effect of drugs and maneuvers on preload and/or afterload, such as mechanical ventilation, atrial septostomy and pulmonary vasodilators. And the increasing utility of mechanical support of the circulation that has become a useful tool to preserve/restore right heart function.

El ventrículo derecho es susceptible a cambios en la precarga, poscarga y la contractilidad y la respuesta fisiopatológica es la dilatación con disfunción/falla aguda lo que limita el llenado del ventrículo izquierdo y el gasto cardiaco. La congestión venosa sistémica, está implicada en la génesis del choque cardiogénico con compromiso del ventrículo derecho. Esta forma de choque es menos conocida que la que sucede por falla ventricular izquierda, por ende, el tratamiento puede diferir. La primera línea de tratamiento son las medidas de soporte y en caso de no funcionar, el tratamiento dirigido a la fisiopatología ventricular será la siguiente opción. Se sugiere evaluar la precarga para la indicación razonada de líquidos, diuréticos o la ultrafiltración. Restaurar o mantener la frecuencia cardiaca y el ritmo sinusal, tratar la bradicardia sintomática, las arritmias que inestabilizan a los pacientes, el uso de marcapaso temporal o procedimientos de cardioversión. Mejorar la contractilidad y vasomotilidad a través del uso de vasopresores e inotrópicos, solos o combinados, el objetivo será mejorar la presión de perfusión coronaria derecha. Balancear el efecto de fármacos y maniobras en la precarga y/o poscarga, como la ventilación mecánica, septostomía atrial y vasodilatadores pulmonares. Y la creciente utilidad del soporte mecánico de la circulación que se ha convertido en una herramienta útil para preservar/restaurar la función cardiaca derecha.

Clinical Characteristics and Outcomes in Adults With Moderate-to-Severe Complexity Congenital Heart Disease Undergoing Palliation or Surgical Repair.

Background: Congenital heart disease (CHD) survival rate has improved dramatically due to advances in diagnostic and therapeutic techniques. However, concerning the unrepaired CHD population of moderate and severe complexity, the data regarding risk predictors and surgical outcomes are scarce. Our aim was to describe the surgical results and predictors of in-hospital outcomes in adult patients with moderate-to-severe complexity CHD that were not repaired in childhood. Methods: We conducted a retrospective cohort study that included 49 adult patients with moderate-to-complex CHD who were treated in a single medical centre. Clinical and echocardiographic variables were obtained on admission, after surgical procedures and during follow-up. Results: Most of the patients were female (66%). Left ventricular ejection fraction and right ventricular outflow tract fractional shortening were within the normal range. The median pulmonary artery systolic pressure was 37 (27-55) mm Hg. The median time was 118 (80-181) minutes for extracorporeal circulation and 76 (49-121) minutes for aortic cross-clamping. The most frequent complication was postoperative complete atrioventricular block (12.2%). In-hospital survival rate was 87.7%. The development of low cardiac output syndrome with predominant right ventricle failure in the postoperative period was the most important predictor of in-hospital death (P = 0.03). Conclusions: Deciding to treat adults with CHD is challenging in moderate and severe unrepaired cases. Adequate clinical, functional, and imaging evaluation is essential to determine each patient's suitability for surgical management and to achieve the best clinical outcome for this population.

Contexte: Grâce aux avancées réalisées en matière de techniques diagnostiques et thérapeutiques, la survie des patients atteints d'une cardiopathie congénitale s'est considérablement améliorée. Cependant, en ce qui concerne les personnes atteintes d'une cardiopathie congénitale non corrigée présentant une complexité modérée ou extrême, les données portant sur les facteurs de risque prédictifs ainsi que sur les résultats chirurgicaux sont rares. Notre objectif était de décrire les résultats chirurgicaux ainsi que les facteurs prédictifs des résultats obtenus en milieu hospitalier chez les patients adultes atteints d'une cardiopathie congénitale présentant une complexité modérée ou extrême qui n'a pas été corrigée pendant l'enfance. Méthodologie: Nous avons mené une étude de cohorte rétrospective comprenant 49 patients adultes atteints d'une cardiopathie congénitale modérée ou complexe qui ont reçu leurs traitements dans un seul centre médical. Les variables cliniques et échocardiographiques ont été obtenues au moment de l'admission, après les interventions chirurgicales et pendant la période de suivi. Résultats: Les patients étaient en majorité des femmes (66 %). La fraction d'éjection du ventricule gauche ainsi que la fraction de raccourcissement de la voie d'éjection ventriculaire droite sont demeurées dans les limites de la normale. La pression systolique médiane de l'artère pulmonaire a été de 37 mmHg (27-55 mmHg). Le temps médian écoulé pour la circulation extracorporelle a été de 118 minutes (80-181 minutes) et pour le clampage de la crosse aortique, de 76 minutes (49-121 minutes). Le bloc auriculo-ventriculaire postopératoire complet a été la complication la plus fréquente (12,2 %). Le taux de survie en milieu hospitalier a été de 87,7 %. Le développement du syndrome du faible débit cardiaque accompagné d'une insuffisance prédominante du ventricule droit durant la période postopératoire a constitué le principal facteur prédictif de décès à l'hôpital (p = 0,03). Conclusion: Il est difficile de traiter les adultes qui présentent une cardiopathie congénitale modérée ou sévère non corrigée. Il est essentiel que les évaluations cliniques, fonctionnelles et par imagerie soient réalisées de façon adéquate pour déterminer si une prise en charge chirurgicale convient aux patients et pour garantir les meilleurs résultats cliniques chez ces derniers.

A Single Transradial Guiding Catheter in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Percutaneous Coronary Intervention: A Door-to-Balloon Optimized Strategy.

Background Acute coronary syndrome (ACS) is the leading cause of morbidity and mortality worldwide. The different reperfusion strategies have evolved over the years, and efforts have been directed to reduce its complications. Among these strategies, the one that has shown the best results is percutaneous coronary intervention, which has significantly improved the survival and prognosis of these patients; however, this procedure is not free of complications since multiple factors are involved. Among them is the time of patient care from the time of diagnosis until the coronary reperfusion therapy is performed. Methodology In this study, we describe the experience in our center with the 6-French Ikari Left guide catheter as a strategy of radial angiography-angioplasty with a single catheter to reduce the care times of patients with acute ST-elevation myocardial infarction (STEMI) in our center and compare it with the series reported by other international centers since. To establish an alternative to the usual approach that consists of the use of Judkins catheters, diagnosis, and guiding. Results Our study showed a success rate for diagnostic angiography and percutaneous coronary intervention (PCI) with the 6- French Ikari Left catheter comparable to those obtained in other centers, even with lower complication rates than the usual approach with Judkins' Catheters. Conclusions The use of the 6-French Ikari Left catheter demonstrated shorter needle-device time and compared to other international series, it was shown to be shorter and related to shorter fluoroscopy time. Our study has a small sample and only included a highly selected population, which represents a limitation. This study is vulnerable to the different practices of the operators, with involvement in procedure time and use of contrast volume.

Efficacy of the oral supplement, Equine Omega Complete, for the prevention of gastric ulcers and alpha-tocopherol supplementation in horses.

BACKGROUND: Omega-3 fatty acid and alpha-tocopherol supplementation reduces gastric ulcer formation in humans and rodents; however, efficacy of prevention in horses is unknown. Equine Omega Complete (EOC) is an oral supplement containing omega-3 fatty acids and alpha-tocopherol. HYPOTHESIS/OBJECTIVE: Determine if EOC supplementation prevents gastric ulcers and increases serum alpha-tocopherol concentrations in healthy horses. ANIMALS: Nine thoroughbred geldings; 5-13 years old. METHODS: Prospective randomized block design, repeated in crossover model. Horses were administered EOC, omeprazole, or water PO for 28 days. Horses underwent an established gastric ulcer induction protocol from days 21-28 via intermittent feed deprivation. Gastroscopies were performed on days 0, 21, and 28. Serum alpha-tocopherol concentrations were measured on days 0 and 28. The effects of treatment and time on ulcer grades were assessed with ordinal logistic regression, with significance at P-value <.05. RESULTS: Ulcer grades increased during ulcer induction in control and EOC but not omeprazole groups (P = .02). Grades increased in EOC-treated horses after ulcer induction from a median of 1 [95% confidence interval 0-2.5] (day 0) to 2.5 [1.5-3.5] (day 28) and were similar to the control group (P = .54). Serum alpha-tocopherol increased in EOC-treated horses from day 0 to day 28 (mean 2.2 ± 0.43 µg/mL to 2.96 ± 0.89 µg/mL; P < .001) with high individual variation; this increase was not different from omeprazole or control groups. CONCLUSION AND CLINICAL IMPORTANCE: Supplementation with EOC for 28 days did not prevent gastric ulcer formation nor increase alpha-tocopherol concentrations relative to the control group.

[Anatomy-physiology considerations for cardiogenic shock with right ventricular involvement].

Since the discovery of right ventricular infarction, interest in the characteristics of the right ventricle has been increasing. Right ventricular function is now known to be a predictor of mortality in different settings. The right ventricle is a low-pressure, high-compliance, high-volume chamber. To carry out its normal function, it is coupled to the pulmonary circulation and the left ventricle. In the face of acute changes in pressure, volume overload and ischemia, it dilates to adapt to its new load. Its manifestation may be ventricular dysfunction and/or failure that will progress to cardiogenic shock due to right ventricular involvement. Various entities may be the cause of acute dysfunction: right ventricular infarction (alterations in contractility due to ischemia) and high-risk pulmonary thromboembolism (increased afterload). Both share a similar ventricular pathophysiology and high mortality without treatment. Understanding anatomy and physiology, dysfunction and acute ventricular failure are important to define a convenient diagnosis and treatment oriented towards pathophysiology. In this first part, the anatomy and physiology, acute right ventricular dysfunction/failure and cardiogenic shock are taken into consideration, from the perspective of these two entities. In another paper, treatment aimed at cardiogenic shock due to right ventricular involvement will be reviewed.

Desde el conocimiento del infarto del ventrículo derecho, el interés por las características del ventrículo derecho ha sido cada vez mayor. Ahora se sabe que la función ventricular derecha es un predictor de mortalidad en diferentes contextos. El ventrículo derecho es una cavidad de baja presión, alta compliancia y alto volumen. Para llevar a cabo su función normal se encuentra acoplado a la circulación pulmonar y al ventrículo izquierdo. Ante alteraciones agudas de sobrecarga de presión, volumen e isquemia, se dilata para adaptarse a su nueva carga. Su manifestación puede ser disfunción o falla ventricular que progresará a choque cardiogénico por involucro del ventrículo derecho. Diversas entidades pueden ser la causa de la disfunción aguda: el infarto del ventrículo derecho (alteraciones de la contractilidad por isquemia) y la tromboembolia pulmonar de alto riesgo (aumento de la poscarga). Ambas comparten una fisiopatología ventricular similar y alta mortalidad sin tratamiento. Entender la anatomía fisiológica, la disfunción y la falla ventricular aguda es importante para definir un diagnóstico oportuno y un tratamiento orientado a la fisiopatología. En esta primera parte se toma en consideración la anatomía fisiológica y la disfunción/falla aguda ventricular derecha y su desenlace en el choque cardiogénico, desde la perspectiva de estas dos entidades. En otro trabajo se revisará el tratamiento orientado al choque cardiogénico por involucro ventricular derecho.

Effects of a 10% dimethyl sulfoxide solution on radiocarpal joint amikacin pharmacokinetics during intravenous regional limb perfusion in standing sedated horses.

OBJECTIVE: To determine the effect of a 10% dimethyl sulfoxide (DMSO) solution on the peak concentration (CMAX ) of amikacin in the radiocarpal joint (RCJ) during intravenous regional limb perfusion (IVRLP) compared with 0.9% NaCl. STUDY DESIGN: Randomized crossover study. ANIMALS: Seven healthy adult horses. METHODS: The horses underwent IVRLP with 2 g of amikacin sulfate diluted to 60 mL using a 10% DMSO or 0.9% NaCl solution. Synovial fluid was collected from the RCJ at 5, 10, 15, 20, 25, and 30 minutes after IVRLP. The wide rubber tourniquet placed on the antebrachium was removed after the 30 min sample. Amikacin concentrations were quantified by a fluorescence polarization immunoassay. The mean CMAX and time to peak concentration (TMAX ) of amikacin within the RCJ were determined. A one-sided paired t-test was used to determine the differences between treatments. The significance level was p < .05. RESULTS: The mean ± SD CMAX in the DMSO group was 1361.8 ± 593 µg/mL and in the 0.9% NaCl group it was 860 ± 481.6 µg/mL (p = .058). Mean TMAX using the 10% DMSO solution was 23 and 18 min using the 0.9% NaCl perfusate (p = .161). No adverse effects were associated with use of the 10% DMSO solution. CONCLUSION: Although there were higher mean peak synovial concentrations using the 10% DMSO solution no difference in synovial amikacin CMAX between perfusate type was detected (p = .058). CLINICAL SIGNIFICANCE: Use of a 10% DMSO solution in conjunction with amikacin during IVRLP is a feasible technique and does not negatively affect the synovial amikacin levels achieved. Further research is warranted to determine other effects of using DMSO during IVRLP.

Pseudo-Normalization of the T-wave During Stress and Its Relationship With Myocardial Ischemia: Evaluation by Myocardial Perfusion Single Photon Emission Computed Tomography (SPECT).

Background The T-wave alterations are suggestive of ischemia, among them there is the pseudo-normalization (positivization of the T-wave, previously negative, during stress exercise). Myocardial single photon emission computed tomography (SPECT) at rest and stress is usually performed with Technetium 99 (Tc-99), which has high sensitivity and specificity for the detection of ischemic heart disease. In this study, we decided to investigate the patients who pseudo-normalized the T-wave in the stress test to correlate with the existence of ischemia diagnosed by myocardial perfusion study, specifically myocardial SPECT in perfusion and rest with Tc-99. Methodology T - wave pseudo-normalization patients who underwent a myocardial perfusion SPECT between January 2018 and June 2019 were included in this retrospective study. We analyzed 81 patients: 50 patients with pseudo-normalization of T-waves and 31 patients, as a control group, without pseudo-normalization. A descriptive analysis of the quantitative variables was performed using Student's t-test or Mann-Whitney U test, and for the qualitative variables, the χ2 test or Fisher's exact test was performed. Results The degree of ischemia according to the presence or absence of pseudo-normalization of the T-wave. The pseudo-normalization of the T-wave in the group without ischemia (48.4% vs. 36%), for the mild degree the proportions were the same (38.7% vs. 38%), the moderate degree it was slightly higher in the pseudo-normalization of the T-wave (9.7% vs. 18%) and severe (3.2% vs. 6%). Conclusions In this study, the relationship between pseudo-normalization of the T waveform and ischemia, predominantly moderate to severe, was demonstrated. However, it was not statistically significant due to the size of the sample studied.

[Epithelioid hemangioendothelioma as a cause of intestinal intussusception in an adult female patient: case report]. / Hemangioendotelioma epitelioide como causa de intususcepción intestinal en una paciente adulta: caso clínico.

Introduction: Epithelioid hemangioendothelioma is a rare vascular tumor with an epithelioid and histiocytoid appearance. Intestinal intussusception can manifest as chronic abdominal pain, representing only 1-5% of intestinal obstructions in adults. Case report: 65-year-old female who is attended with chronic abdominal pain. We performed a computed tomography showing the incursion of the ileum into the right colon. She was taken to the operating table, with the finding of ileo-colic intestinal intussusception due to small bowel tumor, with subsequent anatomopathological results of epithelioid hemangioendothelioma. Conclusions: The diagnosis and management process with an appropriate postoperative outcome is described.

Introducción: El hemangioendotelioma epitelioide es un tumor vascular poco frecuente de aspecto epitelioide e histiocitoide. La intususcepción intestinal suele ser causa de dolor abdominal crónico y corresponde al 1-5% de las obstrucciones intestinales en el adulto. Caso clínico: Mujer de 65 años que acude con dolor abdominal crónico. Se realiza tomografía computarizada y se observa incursión del íleon en el colon derecho. Es llevada a mesa operatoria con hallazgo de intususcepción intestinal ileocólica por tumoración de intestino delgado, con resultado anatomopatológico de hemangioendotelioma epitelioide. Conclusiones: Se describe el proceso de diagnóstico y manejo, con apropiado desenlace posoperatorio.

Coronary Artery Disease in Systemic Lupus Erythematosus: What Do the Facts Say?

Systemic lupus erythematosus (SLE) is an autoimmune disease that can affect any organ with a predisposition for women of reproductive age. It is related to a higher risk of cardiovascular events, increasing it up to 50 times in young people, and 30% of deaths are attributed to coronary artery disease. The risk of developing cardiovascular disease in SLE is related not only to traditional cardiovascular risks factors such as advanced age, hypertension, dyslipidemia, and diabetes but also to disease-specific factors, such as degree of activity, autoantibodies, organ damage, and treatment. Accelerated atherosclerosis is one of the main contributors to pathogenesis. Manifestations range from angina to acute myocardial infarction and sudden death. Markers have been studied for the detection of subclinical disease and stratification of these patients, as well as different treatment options to improve the cardiovascular prognosis of the disease.

Changes in Heart Rate Variability with Induction of Gastric Ulcers in Adult Horses.

Gastric ulceration can be induced by athletic training and is a significant welfare concern. The objective of this study was to evaluate the effect of gastric ulcer induction on heart rate variability (HRV) in the horse. We hypothesized that induction of gastric ulcers would decrease HRV and increase low frequency fluctuations, consistent with increased sympathetic tone. A convenience sample of 8 horses in a larger study were enrolled. Horses were randomly assigned to receive water or 2 mg/kg omeprazole orally once daily for 28 days. Gastric ulcers were induced through intermittent feed withholding on days 21 to 28. Gastroscopy was performed and gastric ulcers were graded (0-IV) by three blinded reviewers on days 21 and 28. Continuous electrocardiograms were obtained for one hour at the start and end of ulcer induction. HRV was assessed in 1-hour recordings for time domain variables and 5 minute sections for frequency domain analysis. HRV and ulcer grade across treatments were compared by a mixed effect model, with treatment and time as fixed effects and horse as a random effect. Gastric ulcer grade increased with induction protocol (P < .0001) and decreased with omeprazole treatment (P = .0007). Omeprazole treatment increased R-R intervals (P = .01) and decreased ratio of low frequency/high frequency signal (P = .008) as compared to horses receiving water. This was attributable to decreasing low frequency fluctuations (P = .05). While limited by the small sample size (four horses/treatment), this study suggests that omeprazole treatment decreases heart rate, and LF/HF ratio during ulcer induction, consistent with a decrease in sympathetic tone.

Case Report: α-Spectrin Mutation Associated with αLELY Polymorphism Responsible for Hereditary Pyropoikilocytosis.

Hereditary pyropoikilocytosis (HPP) is characterised by severe hemolytic anemia due to membrane instability. We report the case of a 13-day-old boy with neonatal jaundice and severe hemolytic anemia. A peripheral smear examination showed severe anisopoikylocytosis. DNA sequencing revealed compound double heterozygous for mutant α-spectrin SPTA1 (Arg28His) and homozygous αLELY polymorphism (low expression α-spectrin allele), compatible with diagnosis of HPP.The patient required a blood transfusion initially, but spontaneously improved after two years. Our case illustrates that, despite the presence of the allele αLELY in homozygous, the clinical phenotype is similar to cases with a mutation in SPTA1 associated with αLELY in trans.

Acute heart failure due to a giant left atrial myxoma: a case report.

Background: Cardiac myxomas are the most common primary benign tumour of the heart. Most of them occur between the 4th and 6th decade of life, are most frequent in the woman, and most frequently localized in the left atrium. Case summary: We present a case of a 41-year-old female who presented with a history of left-sided heart failure. A left atrial mass of 87 × 88 × 65 mm was documented by cardiac magnetic resonance. She was taken to surgical resection of the mass. Histopathologic findings were diagnostic of cardiac myxoma. Generally, myxomas that are bigger than 6 cm are associated with the worst prognosis. Discussion: Primary cardiac tumours are mostly benign, being in 50% of the cases a cardiac myxoma. The rest of them correspond to papillary fibroelastoma (26%), fibromas (6%), lipomas (4%), and others including calcified tumours, haemangiomas, teratomas, cysts, and rhabdomyomas. Our clinical case illustrates an unusual and rare presentation of cardiac myxoma with a double mitral lesion.

Does size matter? Two new deletions in the HBB gene cause ß0-thalassemia.

Most ß-thalassemias are caused by mutations involving one or a limited number of nucleotides within the gene or its adjacent regions. They can be substitutions or deletions; in these cases, the loss ranges from a single nucleotide to even the entire HBB gene, so we wonder if the phenotype is due to the size of the deletion or the location of the mutation. To clarify this, we present two new deletions in the ß-globin gene that cause ß0-thalassemia. The hematological parameters were determined with an automated cell counter; the Hb A2 and Hb F levels were measured by performance liquid chromatography. Hemoglobins were analyzed by capillary zone electrophoresis (Sebia Capillarys Flex system) and ion-exchange HPLC (BioRad Variant II ß-thalassemia Short Program). Molecular characterization was performed by automatic Sanger sequencing. The screening of common α-thalassemia point mutations and deletions in the world (21 in total) were carried out using multiplex PCR followed by reverse-hybridization with a commercial Alpha-Globin StripAssay kit. We have characterized two new mutations-(1) 1-bp deletion [CD61/62(-G)] [HBB:c.186_187delG], (2) 105-bp deletion [IVS-2-nt767-CD111] [HBB:c.316-84_333del]-and we have described, for first time in Spain, the 25-bp deletion [ß nts 252 - 276 deleted] [HBB:c.93-22_95del] mutation. These mutations were classified as pathogenic by UniProt Variants confirmed according to the American College of Medical Genetics and Genomics guidelines. These mutations present a phenotype compatible with ß0-thalassemia, supported by hematological parameters that correlate the degree of reduction in the synthesis of the ß-globin chain. Identification of this type of mutation is important for genetic counselling of partners where both are carriers, so that they are aware of the genetic risk of having affected children, allowing them to take an informed decision about their reproductive choices.

ß-Thalassemia Intermedia: Interaction of α-Globin Gene Triplication With ß-thalassemia Heterozygous in Spain.

Objectives: To verify with hematimetric data that the diagnosis and clinical grade of ß-TI can be established when a triplication of alpha genes (αααanti 3.7) and heterozygous ß-thalassemia coexist. Materials and Methods: Retrospective study in which 73 patients of Caucasian origin participated, who simultaneously showed a triplication or quadruplication of genes α and ß-thalassemia.Screening for the most frequent α-thalassemia mutations as well as gene triplication (αααanti 3.7) was carried out by multiplex PCR followed by reverse hybridization with a commercial Alpha-Globin StripAssay kit and confirmed by MLPA (Multiplex ligation-dependent probe amplification). The molecular diagnosis of ß-thalassemia was carried out by automatic sequencing according to the Sanger method. Results: The genotypes have been classified into three groups according to the number of α globin genes and the severity of the alteration in the ß globin gene. All had a mutation in the HBB gene (ß0-thalassemia, ß+-thalassemia severe, and ß+-thalassemia mild). Group I patients who have coherent 6 α genes and groups II and III with 5 α globin genes. In group III, the patients were carriers of mutations affecting the ß and δ globin genes. The most significant hematological parameters were hemoglobin levels, MCV, RDW, and the percentage of Hb F. Conclusions: In group I, regardless of the distribution of the 6 α globin genes, homozygous triplication (ααα/ααα) or heterozygous quadruplication (αααα/αα), the association with heterozygous ß-thalassemia results in severe to moderate anemia that may or may not require transfusion therapy, is the severity of the HBB gene mutation that would determine the clinical variation. Group II patients phenotypically behaved like mild thalassemia intermedia, except for one case that presented thalassemic trait because it also presented an associated α-thalassemia (ααα/-α3.7). Finally, group III patients behaved as a thalassemic trait since all were carriers of mutations that increase the overexpression of γ genes.

Next generation sequencing for diagnosis of hereditary anemia: Experience in a Spanish reference center.

BACKGROUND AND AIMS: Hereditary anemia (HA) encloses a wide group of rare inherited disorders with clinical and hematologic overlaps that complicate diagnosis. MATERIALS AND METHODS: A 48-gene panel was developed to diagnose HA by Next Generation Sequencing (NGS) in a large cohort of 165 patients from 160 unrelated families. RESULTS: Patients were divided in: A) patients who had a suspicion of a specific type of HA (n = 109), and B) patients who had a suspicion of HA but with no clear type (n = 56). Diagnostic performance was 83.5% in group A and a change of the initial diagnosis occurred in 11% of these patients. In group B, 35.7% of patients achieved a genetic diagnosis. NGS identified 6 cases of xerocytosis, 6 of pyruvate kinase (PK) deficiency, 4 of G6PD, and 1 case of phytosterolemia with no initial suspicion of these pathologies, which is clinically relevant since they have specific treatment. Five patients were found to carry variants associated to two different pathologies (4 of them combining a metabolic deficiency and a membrane defect), and 44 new variants were identified in 41 patients. CONCLUSION: The use of NGS is a sensitive technique to diagnose HA and it shows better performance when patients are better characterized.