Monitoring with circulating tumor cells in the perioperative setting of patients with surgically treated stages I-IIIA NSCLC.

Background: Surgery is regarded as the treatment's cornerstone for early stage and locally advanced non-small cell lung cancer (NSCLC) whenever the tumor is considered resectable. Liquid biopsy is one of the most promising research areas in oncology in the last 10 years, providing a useful non-invasive tool to detect and monitor cancer. The prognostic value of circulating tumor cells (CTCs) has been studied in different cancer types and had been related with a higher risk of relapse and worse prognosis. The aim of this study is to evaluate the prognostic value of CTC detection in patients with stage I-IIIA NSCLC treated with surgery. Methods: We conducted a prospective, single-center study of 180 consecutive patients with resected and pathological confirmed stage I to IIIA (TNM AJCC/UICC 8th edition) NSCLC. Patients' blood samples were processed and CTCs were characterized before and after the surgery. A cohort of patients had CTC determination after chemotherapy and surgery. Cut-off points were established in 1 and 5 CTCs for statistical analysis. Results: A proportion of 76.7% had at least 1 CTC before the surgery, and 30.6% had 5 or more, while 55.9% had at least 1 CTC after surgery, and 8.3% had 5 or more. We found no correlation between preoperative CTC detection for a cut-off of 5 with neither overall survival (OS) [hazard ratio (HR): 0.99, P=0.887], disease-free survival (DFS) (HR: 0.95, P=0.39) nor relapse (32.7% vs. 28.8%, P=0.596). We also did not find a correlation between postoperative CTCs detection for a cut-off of 5 with either OS (HR: 1.01, P=0.808), DFS (HR: 0.95, P=0.952) or relapse (26.7% vs. 29.5%, P=0.83). The mean change in the number of CTCs over time between preoperative and postoperative samples was 2.13, with a standard deviation of 6.78. Conclusions: Despite the large cohort of patients included in this study, CTC monitoring in the perioperative setting was not correlated with relapse, DFS or OS in our study, and therefore cannot be recommended as a reliable biomarker for minimal residual disease (MRD) after surgery.

New software application for clarifying tear film lipid layer patterns.

PURPOSE: The lipid layer of the tear film limits evaporation during the interblink interval and also affects tear stability. This study was designed to validate a new software application designed to characterize the tear film lipid layer through texture and color pattern recognition. METHODS: Using the Tearscope-plus (slit-lamp magnification ×200), the lipid layer was examined in 105 healthy young adults, and interference photographs were acquired with a Topcon DV-3 digital camera. The photographs were classified by a clinician experienced in examining lipid layer patterns (LLPs), and these classifications were used as the reference standard (reference examiner). Next, LLPs were graded using the new software and further by 2 observers (observer 1 and observer 2) with experience in examining the ocular surface. RESULTS: Strong correlation was detected between the categories determined by the new application and reference examiner (Cramer V 0.85-0.93, P < 0.001). The classifications made using the new application and by observer 1 and observer 2 were also consistent although correlation was weaker (Cramer V 0.56-0.87, P < 0.001). For thinner LLPs, greatest correspondence with the reference was observed using the new software (96.6%), whereas the 2 observers showed better agreement when grading thicker patterns. Notwithstanding, agreement between the 2 observers and the reference examiner was good with at least 81% matched classifications. Best agreement (96.2%) was noted between the new method and observers 1 and 2 for recognizing meshwork patterns, whereas observers 1 and 2 showed greatest correspondence when classifying color fringe patterns. CONCLUSIONS: The new application can objectively categorize LLPs using the Tearscope-plus.

[Hyperhomocysteinemia and treatment with antiepileptic drugs. Effects of different doses of folic acid]. / Hiperhomocisteinemia en pacientes tratados con antiepilépticos. Efecto de diferentes dosis de ácido fólico.

BACKGROUND AND OBJECTIVE: An increase homocysteine values, which is an independent risk factor for atherotrombotic disease, can be produced with antiepileptic treatment. The aims of this study were: 1) to assess the frequency and determinant factors of hyperhomocysteinemia in adult patients receiving antiepileptic drugs, and 2) to know the effect of different doses of folic acid. PATIENTS AND METHOD: Ninety eight patients and 100 healthy controls similar in age and gender were studied. Eighty six patients were treated with hepatic enzyme inductors (diphenylhydantoine and/or phenobarbital and/or primidone and/or carbamazepine), 5 received non inductors (valproate) and 7 were treated with both in combination. Thirty eight patients were randomized to receive in an open and concurrent way folic acid, 0.2 mg (n = 18) or 5.2 mg (n = 20) daily for 3 months. RESULTS: Homocysteine values were increased in patients in relation with controls (mean [SD]12.2 [6.7] 95% confidence interval [CI],10.0-13.5 vs 8.8[2.2] 95% CI, 8.3-9.2 micromol/l; p < 0.001). Hyperhomocysteinemia was found in 28 patients and 4 controls (28.6% vs 4.0%; p < 0.001). In a multivariate analysis hyperhomocysteinemia was positively associated with treatment with antiepileptic inductors and negatively with folate values and female gender. Homocysteine values decreased after treatment with folic acid at high and low doses (p < 0.001 for both groups), and the values observed in the latter group were similar to those in healthy controls. CONCLUSIONS: Hyperhomocysteinemia is frequent in patients treated with antiepileptic drugs. Treatment with hepatic enzyme inductors and low folate values are predictors of hyperhomocysteinemia. Administration of folic acid, even at very low doses, produces a significant decrease of homocysteinemia in these patients.

Hiperhomocisteinemia en pacientes tratados con antiepilépticos. Efecto de diferentes dosis de ácido fólico / Hyperhomocysteinemia and treatment with antiepileptic drugs. Effects of different doses of folic acid

FUNDAMENTO Y OBJETIVO: La elevación de la homocisteína, que es un factor de riesgo de enfermedad aterotrombótica, puede producirse con la administración de antiepilépticos. Los objetivos de este estudio han sido: a) evaluar la frecuencia y los factores determinantes de hiperhomocisteinemia en pacientes adultos tratados con antiepilépticos, y b) conocer el efecto de diferentes dosis de ácido fólico sobre los valores de homocisteína plasmática. PACIENTES Y MÉTODO: Se estudió a 98 pacientes y a 100 controles sanos con edad y sexo similares. De los pacientes, 86 recibían tratamiento con inductores de enzimas hepáticas (difenilhidantoínay/o fenobarbital y/o primidona y/o carbamacepina), 5 con no inductores (valproato) y 7 con combinación de ambos. Treinta y ocho pacientes se trataron aleatoriamente de forma abierta y concurrente con 0,2 mg (n = 18) o 5,2 mg (n = 20) de ácido fólico diariamente durante 3 meses. RESULTADOS: Las concentraciones de homocisteína estaban aumentadas en los pacientes en relación con los controles (media [desviación estándar] 12,2 [6,7] µmol/l intervalo de confianza del 95%,10,0-13,5, frente a 8,8 [2,2] µmol/l; intervalo de confianza del 95%, 8,3-9,2 µmol/l;p < 0,001). En 28 pacientes y en 4 controles existía hiperhomocisteinemia (el 28,6 frente al4,0%; p < 0,001). En el análisis multivariante, la hiperhomocisteinemia se asoció positivamente al tratamiento con antiepilépticos inductores y negativamente a los valores de folato y al sexo femenino. La homocisteinemia descendió significativamente tras el tratamiento con ácido fólico, tanto en dosis altas como bajas (p < 0,001 para ambos grupos), y en este último grupo se obtuvieron concentraciones similares a las de los controles sanos. CONCLUSIONES: La hiperhomocisteinemia es frecuente en los pacientes tratados con antiepilépticos. El tratamiento con inductores de las enzimas hepáticas y los valores bajos de folato son predictores de hiperhomocisteinemia. El tratamiento con ácido fólico, incluso a dosis muy bajas, disminuye significativamente la homocisteinemia en estos pacientes

BACKGROUND AND OBJECTIVE: An increase homocysteine values, wich is an independent risk factor for atherotrombotic disease, can be produced with antiepileptic treatment. The aims of this study were: 1) to assess the frequency and determinant factors of hyperhomocysteinemia in adult patients receiving antiepileptic drugs, and 2) to know the effect of different doses of folic acid. PATIENTS AND METHOD: Ninety eight patients and 100 healthy controls similar in age and gender were studied. Eigthy six patients were treated with hepatic enzyme inductors (diphenylhydantoine and/or phenobarbital and/or prim done and/or carbamazepine), 5 received non inductors (valproate)and 7 were treated with both in combination. Thirty eight patients were randomized to receive in an open and concurrent way folic acid, 0.2 mg (n = 18) or 5.2 mg (n = 20) daily for 3 months. RESULTS: Homocysteine values were increased in patients in relation with controls (mean[SD]12.2 [6.7] 95% confidence interval [CI],10,0-13,5 vs 8.8[2.2] 95% CI, 8,3-9,2 µmol/l;p < 0.001). Hyperhomocysteinemia was found in 28 patients and 4 controls (28.6% vs 4.0%;p < 0.001). In a multivariate analysis hyperhomocysteinemia was positively associated with treatment with antiepileptic inductors and negatively with folate values and female gender. Homocysteine values decreased after treatment with folic acid at high and low doses (p < 0.001 for both groups), and the values observed in the latter group were similar to those in healthy controls. CONCLUSIONS: Hyperhomocysteinemia is frequent in patients treated with antiepileptic drugs. Treatment with hepatic enzyme inductors and low folate values are predictors of hyperhomocysteinemia. Administration of folic acid, even at very low doses, produces a significant decrease of homocysteinemia in these patients

Lateral medullary infarction secondary to vertebral artery dissection presenting as a trigeminal autonomic cephalalgia.

A 51-year-old woman had an attack of severe hemifacial pain with autonomic features as the presenting symptom of a lateral medullary infarction. A bilateral vertebral artery dissection was demonstrated. The existence of secondary cases may lead to a better understanding of the pathophysiology of trigeminal autonomic cephalalgias.

Cholinergic-dopaminergic imbalance in Pisa syndrome.

Pisa syndrome is a rare type of truncal dystonia. Its development is associated commonly with neuroleptic treatment, but there are rare idiopathic cases or those related to neurodegenerative disorders. Recently, an association between cholinesterase inhibitors and Pisa syndrome has been described. The authors report two patients, one with Alzheimer's disease treated with risperidone and another with Parkinson's disease who presented this kind of dystonia after donepezil initiation. In the first patient the condition resolved after discontinuation of risperidone, and in the second one the condition resolved when donepezil was withdrawn. In patients with pharmacologic or degenerative dopaminergic neurotransmission disorders, cholinergic excess may induce this peculiar type of dystonia.

Meningitis autoinmune simulando una meningitis bacteriana / Autoimmune meningitis simulating bacterial meningitis

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