Early focal electroencephalogram and neuroimaging findings predict epilepsy development after aneurysmal subarachnoid hemorrhage.

INTRODUCTION: Seizures are a common complication of subarachnoid hemorrhage (SAH) in both acute and late stages: 10-20 % acute symptomatic seizures, 12-25 % epilepsy rate at five years. Our aim was to identify early electroencephalogram (EEG) and computed tomography (CT) findings that could predict long-term epilepsy after SAH. MATERIAL AND METHODS: This is a multicenter, retrospective, longitudinal study of adult patients with aneurysmal SAH admitted to two tertiary care hospitals between January 2011 to December 2022. Routine 30-minute EEG recording was performed in all subjects during admission period. Exclusion criteria were the presence of prior structural brain lesions and/or known epilepsy. We documented the presence of SAH-related cortical involvement in brain CT and focal electrographic abnormalities (epileptiform and non-epileptiform). Post-SAH epilepsy was defined as the occurrence of remote unprovoked seizures ≥ 7 days from the bleeding. RESULTS: We included 278 patients with a median follow-up of 2.4 years. The mean age was 57 (+/-12) years, 188 (68 %) were female and 49 (17.6 %) developed epilepsy with a median latency of 174 days (IQR 49-479). Cortical brain lesions were present in 189 (68 %) and focal EEG abnormalities were detected in 158 patients (39 epileptiform discharges, 119 non-epileptiform abnormalities). The median delay to the first EEG recording was 6 days (IQR 2-12). Multiple Cox regression analysis showed higher risk of long-term epilepsy in those patients with CT cortical involvement (HR 2.6 [1.3-5.2], p 0.009), EEG focal non-epileptiform abnormalities (HR 3.7 [1.6-8.2], p 0.002) and epileptiform discharges (HR 6.7 [2.8-15.8], p < 0.001). Concomitant use of anesthetics and/or antiseizure medication during EEG recording had no influence over its predictive capacity. ROC-curve analysis of the model showed good predictive capability at 5 years (AUC 0.80, 95 %CI 0.74-0.87). CONCLUSIONS: Focal electrographic abnormalities (both epileptiform and non-epileptiform abnormalities) and cortical involvement in neuroimaging predict the development of long-term epilepsy. In-patient EEG and CT findings could allow an early risk stratification and facilitate a personalized follow-up and management of SAH patients.

Cognitive decline in adult-onset temporal lobe epilepsy: Insights from aetiology.

PURPOSE: To identify patients with adult-onset temporal lobe epilepsy (TLE) at risk of developing cognitive decline. Detecting which patients, aetiologies, or factors are most closely related with memory decline would allow us to identify patients that would eventually benefit from more specific treatment. METHODS: Single centre, retrospective analysis of a prospectively followed-up cohort study, including all patients with the diagnosis of adult-onset TLE during 2013, with a minimum follow-up of five years. Memory and cognitive decline were analysed at 5 years and at last follow-up. RESULTS: Of 89 initially selected patients, 71 were included. After 5 years, 11/71 (15.5%) patients suffered cognitive decline, of which 1/71 (4%) developed dementia. At last follow-up (range 65-596 m) a total of 34/71 (47.8%) patients were diagnosed with cognitive decline, specifically either memory decline or dementia. Cognitive decline at 5 years was related to: 1. Age at onset: 62.65 years (SD 9.04) in the group with cognitive decline vs 50.33 y. (SD 13.02 in the group without cognitive decline; p=0.004); 2. Onset as status epilepticus (3/6 in patients with memory decline vs 8/65 in patients without cognitive decline; p=0.04); 3. Immune aetiology: 42% compared with unknown (10%) and structural (10%) aetiologies; p=0.036; 4. Hippocampal sclerosis on MRI: 5/11 patients with cognitive decline vs 9/51 patients without cognitive decline; p=0.035. Cognitive decline was not related to seizure frequency, sex, or age (p=0.78; p=0.40; p=0.95, respectively). CONCLUSIONS: Older age at epilepsy onset, onset as status epilepticus, immune aetiology, and hippocampal sclerosis are risk factors for developing cognitive decline in patients with adult-onset temporal lobe epilepsy.

Patients with initial nodal involvement due to breast cancer who have received neoadjuvant chemotherapy: Combined sentinel node-radioguided surgery of the pathological node.

OBJECTIVE: To study the feasibility and usefulness of ultrasound-guided pre-chemotherapy marking of pathologic lymph node followed by sentinel lymph node biopsy (SLNB)-pathologic node radioguided biopsy (ROLL) combined technique, in axillary involvement breast cancer patients undergoing neoadjuvant chemotherapy (NACT). MATERIAL AND METHODS: Prospective diagnostic study of 30 patients with breast cancer and cN1 axillary staging with NACT indication. Before NACT, the biopsied node was marked with a clip (MBN). After NACT an ultrasound was performed and in case of good response a SLNB (99mTc-nanocolloids) plus targeted axillary dissection MBN ROLL biopsy (99mTc-albumin macroaggregates) was performed. Axillary lymph node dissection (ALND) was performed if SLNB and/or MBN were positive for tumor cells. The localization-removal rate of the sentinel lymph node (SLN) and MBN were evaluated. False-negative rate (FNR) and positive predictive value (PPV) of SLNB alone were also evaluated. RESULTS: Thirty patients were included in the study. SLN could be detected in all patients while MBN was successfully removed in 27 (90%). The SLN coincided with MBN in 15 patients (50%). In 12 patients SLNB was negative while MBN positive, leading to a FNR of 44.4% for SLNB alone. We found a PPV of 37% for the SLNB. In 5 patients (18.5%) both SLNB and MBN were negative, avoiding ALND. CONCLUSIONS: SLNB-MBN radioguided biopsy ROLL combined technique is a useful and accessible procedure for accurate axillary restaging after NACT, avoiding the high rate of FNR of SLNB alone in this group of patients and avoiding a great number of ALND.

Mitogenomic analysis of extant condor species provides insight into the molecular evolution of vultures.

The evolution of large vultures linked to mountainous habitats was accompanied by extreme physiological and behavioral specializations for energetically efficient flights. However, little is known on the genetic traits associated with the evolution of these obligate soaring scavengers. Mitochondrial DNA plays a vital role in regulating oxidative stress and energy production, and hence may be an important target of selection for flight performance. Herein, we characterized the first mitogenomes of the Andean and California condors, the world's heaviest flying birds and the only living representatives of the Vultur and Gymnogyps genus. We reconstructed the phylogenetic relationships and evaluated possible footprints of convergent evolution associated to the life-history traits and distributional range of vultures. Our phylogenomic analyses supported the independent evolution of vultures, with the origin of Cathartidae in the early Paleogene (~ 61 Mya), and estimated the radiation of extant condors during the late Miocene (~ 11 Mya). Selection analyses indicated that vultures exhibit signals of relaxation of purifying selection relative to other accipitrimorph raptors, possibly indicating the degeneration of flapping flight ability. Overall, our results suggest that the extreme specialization of vultures for efficient soaring flight has compensated the evolution of large body sizes mitigating the selection pressure on mtDNA.

Evaluation of MR imaging-targeted biopsies of the prostate in biopsy-naïve patients. A single centre study.

PURPOSE: To evaluate the differences in prostate cancer detection rate and biopsy effectiveness between magnetic resonance imaging (MRI) target biopsy (TB) and transperineal standard biopsy (SB) in biopsy-naïve patients. MATERIAL AND METHODS: Between October 2014 and April 2016, 60 men with a mean age of 64.1±6.7 (SD) years (range: 53-82 years) were prospectively enrolled. All patients underwent a prostate MRI study, evaluated by two radiologists, before undergoing the biopsy. A transperineal 12-core SB was carried out before TB, without the information from the MRI. The detection rate for all tumors and for clinically significant tumors (CS) was recorded. Sampling variables such as the proportion of cores positive for CS cancer (PCP-CS) and the maximum cancer core length (MCCL) were also calculated. The ability of MRI to predict the presence of a CS tumor at biopsy was studied using a sector analysis. Patients with negative biopsies were followed during a minimum of 12 months. RESULTS: The detection rate for SB and TB was 53.3% (32/60) and 46.7% (28/60) respectively for all tumors (P=0.289) and 45% (27/60) in both techniques for CS tumors. TB obtained a larger PCP-CS (P<0.001) and MCCL (P=0.018). The sensitivity, specificity, positive predictive value, negative predictive value and cancer prevalence was 83.3%, 92.9%, 83.3%, 92.9% and 30% for peripheral zone sectors and 43.8%, 97.1%, 70.0%, 91.8% and 13,3% for transitional zone sectors. The proportion of patients that showed an increase of PSA faster than 0.75ng/mL/year after a negative biopsy was 26.1%. CONCLUSION: Detection rate of prostate cancer did not show significant differences between a TB and a SB technique in biopsy-naïve patients. However, targeted prostate biopsies demonstrated a better sampling effectiveness thus reducing the cores needed to diagnose clinically significant tumors.

[Classification of idiopathic generalised epilepsies in patients over 16 years of age]. / Clasificacion de las epilepsias generalizadas idiopaticas en mayores de 16 años.

INTRODUCTION: Idiopathic generalised epilepsies (IGE) are a set of electroclinical syndromes with different phenotypes. Our aim is to analyse those phenotypes in patients over 16 years of age. PATIENTS AND METHODS: We conducted a retrospective analysis of a series of patients with IGE. They were classified as childhood absence epilepsy (CAE), juvenile absence epilepsy (JAE), juvenile myoclonic epilepsy (JME), epilepsy with tonic-clonic seizures only (TCSE), epilepsy with eyelid myoclonias and absences (EMA) and pure photogenic epilepsy (PE). RESULTS: We included 308 patients, the majority females (56.8%), in our study. JME was the most prevalent (40.9%), followed by TCSE (30%), JAE (10%), EMA (8.7%), CAE (7.7%) and PE (1.6%). The types of seizures presented by the most patients were tonic-clonic (89.6%), myoclonic (45.4%), absence (31.4%), reflex seizures (13.3%), eyelid myoclonias (12.6%), non-epileptic psychogenic seizures (3.6%) and status epilepticus (1.9%). They all had generalised spike-and-wave discharges in the electroencephalogram (EEG). 19.2% presented asymmetrical discharges and 28.2% showed a photoparoxysmal response. We observed differences between syndromes in polytherapy (p < 0.0001), withdrawal of therapy (p = 0.01) and being seizure-free beyond the age of 50 (p = 0.004). CONCLUSIONS: JME was the most frequent. Generalised tonic-clonic seizures were the type of seizures presented by the most patients, followed by myoclonic, absent and reflex seizures. The EEG showed a photoparoxysmal response in over a quarter of the patients, and one in five displayed asymmetrical anomalies. Differences were observed according to the syndrome in polytherapy, persistence of seizures and withdrawal of treatment.

TITLE: Clasificacion de las epilepsias generalizadas idiopaticas en mayores de 16 años.Introduccion. Las epilepsias generalizadas idiopaticas (EGI) son un conjunto de sindromes electroclinicos con distintos fenotipos. Nuestro objetivo es analizar dichos fenotipos en pacientes mayores de 16 años. Pacientes y metodos. Analizamos retrospectivamente una serie de pacientes con EGI. Los clasificamos en epilepsia de ausencias infantil (EAI), epilepsia de ausencias juvenil (EAJ), epilepsia mioclonica juvenil (EMJ), epilepsia con crisis tonicoclonicas solo (ECTC), epilepsia con ausencias y mioclonias palpebrales (EAM) y epilepsia fotogenica pura (EF). Resultados. Incluimos 308 pacientes, mayoritariamente mujeres (56,8%). La EMJ fue mas prevalente (40,9%), seguida de la ECTC (30%), la EAJ (10%), la EAM (8,7%), la EAI (7,7%) y la EF (1,6%). Los tipos de crisis que presentaron mas pacientes fueron las tonicoclonicas (89,6%), las mioclonicas (45,4%), las ausencias (31,4%), las crisis reflejas (13,3%), las mioclonias palpebrales (12,6%), las crisis psicogenas no epilepticas (3,6%) y el estado epileptico (1,9%). Todos tenian descargas punta-onda generalizada en el electroencefalograma (EEG). El 19,2% presento descargas asimetricas y el 28,2%, respuesta fotoparoxistica. Observamos diferencias entre sindromes en politerapia (p < 0,0001), retirada de tratamiento (p = 0,01) y estar libres de crisis por encima de los 50 años (p = 0,004). Conclusiones. La EMJ fue la EGI mas frecuente. Las crisis tonicoclonicas generalizadas fueron el tipo de crisis que presentaron mas pacientes, seguidas de las mioclonicas, las ausencias y las crisis reflejas. El EEG mostro en mas de una cuarta parte de los pacientes una respuesta fotoparoxistica, y en uno de cada cinco, anomalias asimetricas. Se observaron diferencias segun el sindrome en politerapia, persistencia de crisis y retirada de tratamiento.

Enantiomeric analysis of overlapped chromatographic profiles in the presence of interferences. Determination of ibuprofen in a pharmaceutical formulation containing homatropine.

In this work, we studied the combination of chemometric methods with chromatographic separations as a strategy applied to the analysis of enantiomers when complete enantioseparation is difficult or requires long analysis times and, in addition, the target signals have interference from the matrix. We present the determination of ibuprofen enantiomers in pharmaceutical formulations containing homatropine as interference by chiral HPLC-DAD detection in combination with partial least-squares algorithms. The method has been applied to samples containing enantiomeric ratios from 95:5 to 99.5:0.5 and coelution of interferents. The results were validated using univariate calibration and without homatropine. Relative error of the method was less than 4.0%, for both enantiomers. Limits of detection (LOD) and quantification (LOQ) for (S)-(+)-ibuprofen were 4.96×10-10 and 1.50×10-9mol, respectively. LOD and LOQ for the R-(-)-ibuprofen were LOD=1.60×10-11mol and LOQ=4.85×10-11mol, respectively. Finally, the chemometric method was applied to the determination of enantiomeric purity of commercial pharmaceuticals. The ultimate goal of this research was the development of rapid, reliable, and robust methods for assessing enantiomeric purity by conventional diode array detector assisted by chemometric tools.

SEOM clinical guidelines for the treatment of Hodgkin’s lymphoma

Hodgkin lymphoma (HL) is an uncommon B cell lymphoid malignancy representing approximately 10-15 % of all lymphomas. HL is composed of two distinct disease entities; the more commonly diagnosed classical HL and the rare nodular lymphocyte-predominant HL. An accurate assessment of the stage of disease and prognostic factors that identify patients at low or high risk for recurrence are used to optimize therapy. Patients with early stage disease are treated with combined modality strategies using abbreviated courses of combination chemotherapy followed by involved-field radiation therapy, while those with advanced stage disease receive a longer course of chemotherapy often without radiation therapy. High-dose chemotherapy (HDCT) followed by an autologous stem cell transplant (ASCT) is the standard of care for most patients who relapse following initial therapy. Brentuximab vedotin should be considered for patients who fail HDCT with ASCT (AU)

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SEOM clinical guidelines for the treatment of follicular non-Hodgkin’s lymphoma

Follicular non-Hodgkin's lymphoma (FL) is a nodal B lymphoid malignancy that originates from the germinal center of a lymph node. FL is the second most frequent lymphoma subtype. The course of the disease is usually characterised by a typically indolent clinical course, with a median survival rate of 8-10 years, although most patients relapse after treatment. Diagnosis should always be based on a surgical specimen like an excisional node lymph biopsy. The first-line treatment of FL will depend of extension disease, tumour burden, patient symptoms, performance status and also patient decision. The addition of rituximab to conventional chemotherapy has improved ORR, PFS and OS. As first line in patients that need treatment, a combination of chemotherapy with rituximab induction followed by 2 years of rituximab maintenance is the best option. High-dose chemotherapy with autologous stem-cell transplantation in first line has not shown improvement and is not recommended as first-line therapy. Before any treatment decision in relapsed patients, a repeat biopsy is mandatory to rule out a transformation into large cell aggressive lymphoma. Standard treatment is controversial, depends on the efficacy of prior treatment, duration of the time-to-relapse, patient’s age and histological findings at relapse (AU)

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SEOM clinical guidelines for the treatment of follicular non-Hodgkin's lymphoma.

Follicular non-Hodgkin's lymphoma (FL) is a nodal B lymphoid malignancy that originates from the germinal center of a lymph node. FL is the second most frequent lymphoma subtype. The course of the disease is usually characterised by a typically indolent clinical course, with a median survival rate of 8-10 years, although most patients relapse after treatment. Diagnosis should always be based on a surgical specimen like an excisional node lymph biopsy. The first-line treatment of FL will depend of extension disease, tumour burden, patient symptoms, performance status and also patient decision. The addition of rituximab to conventional chemotherapy has improved ORR, PFS and OS. As first line in patients that need treatment, a combination of chemotherapy with rituximab induction followed by 2 years of rituximab maintenance is the best option. High-dose chemotherapy with autologous stem-cell transplantation in first line has not shown improvement and is not recommended as first-line therapy. Before any treatment decision in relapsed patients, a repeat biopsy is mandatory to rule out a transformation into large cell aggressive lymphoma. Standard treatment is controversial, depends on the efficacy of prior treatment, duration of the time-to-relapse, patient's age and histological findings at relapse.

Reflex seizures triggered by cutaneous stimuli.

PURPOSE: Among the different precipitating stimuli for reflex seizures, Touch-Induced Seizures (TIS) and Hot Water Seizures (HWS) are consistently described in different reports. The aim of this study was to analyze the clinical, EEG and image data of patients with TIS and HWS. METHODS: We retrospectively analyzed patients who were followed up in our Epilepsy Unit and had seizures triggered by these stimuli. All patients were studied with electroencephalography (EEG) and magnetic resonance (MR). RESULTS: We recruited six patients, including five men, with an age range of 30-64 years-old. Four patients had TIS; all them had focal motor seizures after the stimuli, with epileptic foci in the fronto-central regions associated with peri-central gyri lesions on MR. One patient had HWS related to a septo-optic dysplasia with periopercular polymicrogyria, and one patient had focal seizures that evolved into bilateral convulsions triggered by washing the mouth with cold water. We considered this last patient to have water contact-induced seizures (WCIS). CONCLUSIONS: Seizures in TIS are most likely focal, without impairment of awareness, and refractory to medical treatment. Antiepileptic drugs can prevent the progression to bilateral convulsion. The origins of such seizures seem to be related to small lesions or epileptogenic zones in the perirolandic areas. Lesional HWS and WCIS are focal seizures that involve impairment of consciousness or focal seizures that evolve to bilateral convulsion, are not such location specific and involve larger ictogenic areas. In both epilepsies, stimulus avoidance is the most effective treatment.

SEOM clinical guidelines for the treatment of Hodgkin's lymphoma.

Hodgkin lymphoma (HL) is an uncommon B cell lymphoid malignancy representing approximately 10-15 % of all lymphomas. HL is composed of two distinct disease entities; the more commonly diagnosed classical HL and the rare nodular lymphocyte-predominant HL. An accurate assessment of the stage of disease and prognostic factors that identify patients at low or high risk for recurrence are used to optimize therapy. Patients with early stage disease are treated with combined modality strategies using abbreviated courses of combination chemotherapy followed by involved-field radiation therapy, while those with advanced stage disease receive a longer course of chemotherapy often without radiation therapy. High-dose chemotherapy (HDCT) followed by an autologous stem cell transplant (ASCT) is the standard of care for most patients who relapse following initial therapy. Brentuximab vedotin should be considered for patients who fail HDCT with ASCT.

Host alkaloids differentially affect developmental stability and wing vein canalization in cactophilic Drosophila buzzatii.

Host shifts cause drastic consequences on fitness in cactophilic species of Drosophila. It has been argued that changes in the nutritional values accompanying host shifts may elicit these fitness responses, but they may also reflect the presence of potentially toxic secondary compounds that affect resource quality. Recent studies reported that alkaloids extracted from the columnar cactus Trichocereus terscheckii are toxic for the developing larvae of Drosophila buzzatii. In this study, we tested the effect of artificial diets including increasing doses of host alkaloids on developmental stability and wing morphology in D. buzzatii. We found that alkaloids disrupt normal wing venation patterning and affect viability, wing size and fluctuating asymmetry, suggesting the involvement of stress-response mechanisms. Theoretical implications are discussed in the context of developmental stability, stress, fitness and their relationship with robustness, canalization and phenotypic plasticity.

Automatized sspKa measurements of dihydrogen phosphate and Tris(hydroxymethyl) aminomethane in acetonitrile/water mixtures from 20 to 60°C.

We measured pKa values of Tris(hydroxymethyl)aminomethane and dihydrogen phosphate; both are commonly used to prepare buffers for reverse-phase liquid chromatography (RPLC), in acetonitrile/water mixtures from 0% to 70% (v/v) (64.6% (w/w)) acetonitrile and at 20, 30, 40, 50, and 60°C. The procedure is based on potentiometric measurements of pH of buffer solutions of variable solvent compositions using a glass electrode and a novel automated system. The method consists in the controlled additions of small volumes of a thermostated solution from an automatic buret into another isothermal solution containing exactly the same buffer-component concentrations, but a different solvent composition. The continuous changes in the solvent composition induce changes in the potentials. Thus, only two sequences of additions are needed: increasing the amount of acetonitrile from pure water and decreasing the content of acetonitrile from 70% (v/v) (64.6% (w/w)). In the procedure with homemade apparatus, times for additions, stirring, homogenization, and data acquisition are entirely controlled by software programmed for this specific routine. This rapid, fully automated method was applied to acquire more than 40 potential data covering the whole composition range (at each temperature) in about two hours and allowed a systematic study of the effect of temperature and acetonitrile composition on acid-base equilibria of two widely used substances to control pH close to 7. The experimental pKa results were fitted to empirical functions between pKa and temperature and acetonitrile composition. These equations allowed predictions of pKa to estimate the pH of mixtures at any composition and temperature, which would be very useful, for instance, during chromatographic method development.

Development of an ionic liquid-based dispersive liquid-liquid microextraction method for the determination of nifurtimox and benznidazole in human plasma.

Dispersive ionic liquid-liquid microextraction combined with liquid chromatography and UV detection was used for the determination of two antichagasic drugs in human plasma: nifurtimox and benznidazole. The effects of experimental parameters on extraction efficiency-the type and volume of ionic liquid and disperser solvent, pH, nature and concentration of salt, and the time for centrifugation and extraction-were investigated and optimized. Matrix effects were detected and thus the standard addition method was used for quantification. This microextraction procedure yielded significant improvements over those previously reported in the literature and has several advantages, including high inter-day reproducibility (relative standard deviation=1.02% and 3.66% for nifurtimox and benznidazole, respectively), extremely low detection limits (15.7 ng mL(-1) and 26.5 ng mL(-1) for nifurtimox and benznidazole, respectively), and minimal amounts of sample and extraction solvent required. Recoveries were high (98.0% and 79.8% for nifurtimox and benznidazole, respectively). The proposed methodology offers the advantage of highly satisfactory performance in addition to being inexpensive, simple, and fast in the extraction and preconcentration of these antichagasic drugs from human-plasma samples, with these characteristics being consistent with the practicability requirements in current clinical research or within the context of therapeutic monitoring.

[Massive haemorrhage after bivalirudin anticoagulation in two heart transplant patients]. / Hemorragia masiva después de anticoagulación con bivalirudina en 2 casos de pacientes con trasplante cardiaco.

Heparin-induced thrombopenia is a common autoimmune complication. It is a prothrombotic state due to the formation of antibodies against heparin/platelet factor 4 complexes. In this situation drugs other than heparin must be used for anticoagulation during extracorporeal circulation (bypass) surgery. Two cases of heart transplantation are presented in whom bivalirudin was used as an anticoagulant during the cardiopulmonary bypass. Severe bleeding complications were observed in both patients. The diagnosis of heparin-induced thrombopenia needs to be improved, as well as the development of protocols for using new drugs other than heparin. For this reason, we have reviewed current protocols and alternative therapies to heparin.

Correlation of immunological markers with graft vasculopathy development in heart transplantation.

This study examined the imbalance between T effector cells (Th1 defined as CD3+ interferonγ+) and T regulatory cells (Treg defined as CD4+CD25(high)FoxP3+) as a valuable albeit limited marker of cardiac allograft vasculopathy (CAV) after heart transplantation (HTx). CAV remains, with neoplasms, the most important cause of death in patients surviving the first year after HTx. It is an immune-mediated pathology, although nonimmune factors may also play a role. The process included concentric fibrous intima hyperplasia that narrows the entire length of the affected arteries. Coronary angiography is the usual method of diagnosis. Because a transplanted heart is a denervated organ, CAV is not diagnosed until the disease reaches an advanced stage, in which case transplantation is the only option for treatment. Although the host's immune response against an allogeneic graft is the major cause of endothelial dysfunction, the objective of this study was to detect anti-allogeneic responses on peripheral blood, seeking to identify signs of CAV before classical methods to predict outcomes in HTx recipients. CD3, CD4, CD8, CD19, CD56, Th1, and the Treg mononuclear cell populations were studied in 37 de novo and 20 long-term (more than 3 years) HTx patients as well as 20 healthy volunteers using flow cytometry. A progressive increase in CD8 and Th1 percentages and decrease in the CD4 population were detected during follow-up. Although Th1 changes also reflect processes not related to CAV receiver operating characteristics analysis of Th1/Treg ratio showed an area under the curve of 0.976, with an estimated sensitivity of 100% and specificity of 90%. The positive prediction value was 58.8% and the negative prediction value, 100%. These results prove that the Th1/Treg ratio was an important marker to following host immune response after HTx. The results confirm the need to test other T lymphocyte subsets.

Assessment of immunological markers as mediators of graft vasculopathy development in heart transplantation.

Heart transplantation (HT) remains the treatment of choice for patients with end-stage heart failure. Cardiac allograft vasculopathy (CAV), a diffuse form of coronary atherosclerosis, is the major cause of death after the first year of HT. CAV is thought to be multifactorial in origin. Although nonimmune factors may play a role in CAV development, it is primarily an immune-mediated disease. CAV is diagnosed by routine annual coronary angiography, and usually when diagnosed, the disease is advanced. There is a need to develop noninvasive surrogate markers for early detection. For this purpose, careful immune monitoring and graft histologic assessment are mandatory. The main objective of this study was the assessment of immunologic markers as mediators of CAV development in HT. Flow cytometry was performed to assess peripheral blood mononuclear cell populations forming CD3, CD4, CD8, CD19, CD56, Th1 (CD3+IFNγ+) or Treg (CD4+CD25(high)FoxP3+) markers among 20 de novo HT recipients. The control group included 13 patients who were more than 2 years post-HT (four with and nine without CAV) as well as 20 healthy subjects. CAV-related events over 2 years' follow-up correlated with the Th1/Treg ratio. An increased Th1 lymphocyte percentage was detected over the follow-up. Patients with medium and high Th1/Treg ratios showed higher acute rejection scores as well as greater incidences of CAV. These results indicated that the Th1/Treg ratio may represent a valuable marker to monitor allospecific T-cell responses in peripheral blood. Changes in the Th1/Treg ratio may help in the early detection of patients at risk for CAV. More studies with longer follow-up are needed to confirm these preliminary results.

Inferior vena cava obstruction by a cardiac mass: unusual presentation of primary antiphospholipid syndrome.

We present a previously healthy 43-year-old woman with a cardiac mass that caused almost total occlusion of the inferior vena cava at its junction with the right atrium. The resected mass proved to be a thrombus. Preoperative imaging tests could not distinguish it from other intracardiac tumors such as myxoma. A postoperative immunological study revealed a primary antiphospholipid syndrome. This case presents an unusual diagnosis of antiphospholipid syndrome and a rare location of a cardiac thrombus.