Functional patterns of cytomegalovirus (CMV) pp65 and immediate early-1-specific CD8(+) T cells that are associated with protection from and control of CMV DNAemia after allogeneic stem cell transplantation.

BACKGROUND: The functional profile of cytomegalovirus (CMV)-specific CD8(+) T cells that associate with protection from and control of CMV DNAemia in allogeneic stem cell transplant (allo-SCT) recipients remains incompletely characterized. METHODS: We enumerated pp65 and immediate early (IE)-1-specific CD8(+) T cells expressing interferon-gamma, tumor necrosis factor-alpha, and CD107a, by flow cytometry in 94 patients at days +30 and +60 after allo-SCT. RESULTS: Fifty of 94 patients had CMV DNAemia within the first 100 days after transplant. CMV-specific CD8(+) T-cell responses (of any functional type) were more likely to be detected in patients who did not display CMV DNAemia than in those who did (P = 0.04). Qualitatively, no major differences in the functional signature of CMV-specific CD8(+) T cells were noted between patients who had or did not have CMV DNAemia. Patients displaying levels of polyfunctional CD8(+) T cells at day +30 >0.30 cell/µL had a lower risk of CMV DNAemia (positive predictive value 76%, and negative predictive value 43%). CONCLUSION: The presence of polyfunctional CD8(+) T cells (either expressing CD107a or not) was associated with lower levels of CMV replication, and higher frequency of self-resolved episodes. The data reported further clarify the role of polyfunctional CD8(+) T cells in control of CMV DNAemia in allo-SCT recipients.

Effect of long-term prophylaxis in the development of cytomegalovirus-specific T-cell immunity in D+/R- solid organ transplant recipients.

BACKGROUND: This study aimed to characterize the dynamics of acquisition of cytomegalovirus (CMV)-specific cell-mediated immunity (CMI) in CMV donor positive/recipient negative solid organ transplant (SOT) patients receiving long-term antiviral prophylaxis, and to determine whether development of CMI confers protection against CMV disease. METHODS: A prospective multicenter study was conducted in Spain from September 2009 to September 2012. Whole blood specimens were prospectively collected at 30, 90, 120, 200, and 365 days after SOT, and CMI was determined by enumeration of CMV pp65 and IE-1-specific CD69(+) /interferon-γ-producing CD8(+) and CD4(+) T cells by flow cytometry for intracellular cytokine staining. As part of a simultaneous clinical trial, patients received either early prophylaxis (in the first 3 days after transplantation) in the first period of the study or delayed prophylaxis (initiated at day 14) during the second period of the study. The impact of the dynamics of acquisition of CMV-specific CMI on the incidence of CMV disease was evaluated by Kaplan-Meier survival analysis. RESULTS: A total of 95 SOT recipients were recruited. CMV infection and disease occurred in 38 (40%) and 26 (27.4%) patients, respectively. The proportion of patients achieving any detectable CMV-specific CMI response at each of the different monitoring points was higher in liver transplant recipients, as compared to kidney or heart transplant recipients. The presence of any detectable response at day 120 or 200 was protective against the development of CMV disease (positive predictive values 92% and 93%, respectively). CONCLUSIONS: The rate of acquisition of CMV-specific CMI in SOT recipients undergoing antiviral prophylaxis differed significantly between different SOT populations. Patients developing any detectable CMI response were protected against the occurrence of CMV disease.

Intragastric balloon and multidisciplinary team.

BACKGROUND: The intragastric balloon is widely used for weight reduction in obese patients, but results are variable. We describe our results enhancing the importance of a Multidisciplinary Team (MT) taking part in the treatment. METHODS: A retrospective review was done concerning a total of 119 balloons , placed in 116 patients, under endoscopic control and conscious sedation, from May 2001 until August 2006. 49 patients were prepared and recommended to be followed by a MT in a physical unit, at least every 15 days during 6 months. 67 were indicated and followed by other colleagues, without MT. Removal was performed 6 months later. RESULTS: Concerning our 49 patients, mean age was 38, 1 years, 31 female and 18 males, with BMI ranged between 32 and 63, average of 42. The average decrease of weight excess was 31, 85% (-4, 45-80, 4%), and the BMI diminished 5,3 points (from 13,6 to gain of 0,9). The treatment failed in 34,6 % of our patients -including 4 patients lost of follow-up (8, 16%)-, compared with 53, 8% of patients without structured MT for selection and follow-up. Physical exercise enhanced markedly the results with 45, 8% of excess of weight loss in women and 39, 7% in males, compared with 14, 6 and 15, 6% in patients who didn't follow the program. The weight loss was mostly fat mass, 89,9% in men and 75,6% in women.- The results maintenance was obtained in 40% of patients one year later. There were no major complications; one balloon had to be removed at 3 weeks because of intolerance, another at 5 months because of gastroesophageal reflux. CONCLUSIONS: BIB is an effective help to achieve a short term weight loss in obese patients; nevertheless, good and long lasting results will depend on the modification of life style obtained by a multidisciplinary approach.

[Comparison of two gentamicin dosing schedules in the newborn]. / Comparación de dos pautas de dosificación de gentamicina en el recién nacido.

INTRODUCTION: Gentamicin is widely used in full-term neonates as empirical therapy for early-onset suspected or proven sepsis. Several dosing schedules for gentamicin have been recommended for this neonatal population. OBJECTIVE: To compare gentamicin serum levels, efficacy and toxicity of two dosing schedules in term and preterm newborns. MATERIAL AND METHODS: The study included 200 newborns who were started on gentamicin therapy. Group A (N=100) was prescribed a multiple-daily dosing regimen and Group B (N=100) on a once-daily dosing regimen. Newborns in Group A received gentamicin at 2.5-3.5 mg/kg/dose q12-18 h depending on postnatal age and serum creatinine levels, and newborns in Group B received 4-5 mg/kg/dose q24-48 h depending on postconceptional and postnatal age. All peak and trough serum drug levels, demographic data, and markers of potential nephrotoxicity and ototoxicity were compared. RESULTS: Peak serum gentamicin levels were significantly higher (8.2+/-0.22 microg/ml vs. 5.9+/-0.13 microg/ml; p

[Physical activity and bariatric surgery]. / Ejercicio físico y cirugía bariátrica.

Obesity is a very serious problem at the 21st Century essentially affecting developed countries. It may be considered a pandemicity. Among predisposing factors for obesity here are, on the one hand, the new feeding habits with fat-and carbohydrate-rich pre-cooked foods, and in the other hand sedentary lifestyle due to occidental society lifestyles. Although obesity is considered a chronic disease, it would really represent a normal and physiologic adaptation mechanism to an "obesogenic" environment. Bariatric surgery represents a solution for morbid obesity when all the other conservative measures have failed, achieving the modification of nutritional habits and nutrients absorption. However, it is paramount to modify lifestyle concerning sedentary lifestyle. Individualized exercise monitoring offers the advantage of motivating and rejection to exercise. It is necessary to study and assess the efficacy of aerobic and anaerobic physical activity at both pre-surgical preparation and further course of these patients.

[Use of somatostatin in five neonates with chylothorax]. / Tratamiento con somatostatina en cinco recién nacidos con quilotórax de diferentes etiologías.

BACKGROUND: The addition of somatostatin to the conventional treatment of neonatal chylothorax has been described in isolated cases. OBJECTIVE: To describe the results obtained in a series of five patients with neonatal chylothorax treated with somatostatin. PATIENTS: Five neonates (gestational age range: 29-39 weeks) diagnosed with chylothorax of various etiologies were included. Chylothorax was congenital in two neonates, secondary to congenital diaphragmatic hernia repair in two neonates and secondary to thrombosis in the superior vein cava in one neonate. All the neonates were started on conservative therapy and intravenous somatostatin in distinct doses ranging from a bolus of 2 microg/kg/12 h to continuous perfusion at 10 microg/kg/h. RESULTS: In all patients the chylous drainage was stopped. No adverse effects were observed. CONCLUSIONS: Somatostatin can be a safe and effective option in the treatment of both primary and secondary neonatal chylothorax refractory to conservative treatment.

Effect of delaying prophylaxis against CMV in D+/R- solid organ transplant recipients in the development of CMV-specific cellular immunity and occurrence of late CMV disease.

OBJECTIVES: Evaluate the protective effect against late CMV disease of delaying antiviral prophylaxis initiation in D+/R- patients receiving solid organ transplant (SOT). METHODS: Prospective multicenter study in D+/R- SOT recipients in Spain (Sept/09-Sept/12). Whole blood specimens were prospectively collected after Tx for CMV-specific cell-mediated immunity (CMI) determination. Two prophylaxis strategies were compared: early prophylaxis (EP; starting within the first 3 days after Tx) and delayed prophylaxis (DP; starting 14 days after Tx). Risk factors for the occurrence of CMV disease were determined by survival analysis and proportional risk Cox regression models. RESULTS: We included 95 patients (50 EP V 45 DP). Twenty six patients (27.4%) developed CMV disease: 32.7% EP vs. 20% DP; (p = 0.2). No cases of CMV disease were reported previously to beginning delayed prophylaxis. The percentage of individuals with detectable CMI response was higher in patients with DP although differences did not reach statistic significance (42% vs 29.6% at day 200 after Tx; p = 0.4). There was a clear trend towards less end-organ CMV disease in patients receiving DP (18.2% EP vs 5% DP; p = 0.09) and DP was the only protective factor in the multivariate analysis (HR: 0.26; CI: 0.05-1.2; p = 0.09). CONCLUSIONS: A 14-day delay in CMV prophylaxis in D+/R- SOT recipients is safe and may reduce the incidence of late CMV end-organ disease although correlation of this effect with CMI responses was not complete.

Reconstitution of CMV pp65 and IE-1-specific IFN-γ CD8(+) and CD4(+) T-cell responses affording protection from CMV DNAemia following allogeneic hematopoietic SCT.

Threshold levels of CMV-specific T-cell populations presumably affording protection from active CMV infection in allo-SCT recipients have been proposed, but lack extensive validation. We quantified CMV pp65 and immediate-early 1-specific IFN-γ CD8(+) and CD4(+) T cell responses at days +30, +60 and +90 after transplantation in 133 patients, and established cutoff cell levels protecting from CMV DNAemia within the first 120 days after transplantation. No patients showing IFN-γ CD8(+) or IFN-γ CD4(+) T-cell counts >1.0 and >1.2 cells/µL, respectively, developed a subsequent episode of CMV DNAemia. Initial or recurrent episodes of CMV DNAemia occurred in the face of IFN-γ T-cell levels below defined thresholds. Negative predictive values at day +30 for the IFN-γ CD8(+) and CD4(+) T-cell markers were 68.1 and 61.8%, respectively. Recipients of grafts from CMV seropositive, related or HLA-matched donors, or receiving non-myeloablative conditioning had nonsignificant tendencies to reach more frequently protective levels of both T-cell subsets at early and late (day +365) times after transplantation. The use of anti-thymocyte globulin and umbilical cord blood transplantation were associated with impaired CMV-specific T-cell reconstitution. CMV-specific IFN-γ CD8(+) and CD4(+) T-cell recovery occurred irrespective of detectable CMV DNAemia.

Rupture of intracranial arterial aneurysms in neonates: case report and review of the literature.

The rupture of cerebral arterial aneurysm is an extremely rare cause of intracranial hemorrhage in infants. Brain magnetic resonance imaging is an excellent technique commonly used to suggest the diagnosis. In this article, we propose color flow Doppler ultrasound as a useful, simple, inexpensive, noninvasive, and accessible option for confirming the lesion.We report one case of cerebral aneurysm in a neonate admitted to our unit. Furthermore, we performed a thorough review of the literature on cerebral aneurysm that led us to the observation that the vast majority of untreated patients suffered a second bleeding that caused death. Thus, we insist on the benefits of a timely treatment.

Anomalous polarization profiles in sunspots: possible origin of umbral flashes

We present time-series spectropolarimetric observations of sunspots in the Ca II infrared triplet lines, which show a periodic occurrence of anomalous, asymmetric, circular polarization profiles in the umbral chromosphere. The profiles may be caused by the periodic development of an unresolved atmospheric component in a downward flowing magnetized environment. This active component with upward directed velocities as high as 10 kilometers per second is connected to the umbral flash (UF) phenomenon. We can explain the observations with a semiempirical model of the chromospheric oscillation and of the sunspot magnetized atmospheric plasma during a UF event.

69,XXX karyotype in a malformed liveborn female. Maternal origin of triploidy.

A liveborn female with a 69,XXX karyotype and clinical features of triploidy syndrome is reported. Main phenotypical features are: intrauterine growth retardation, hypotonicity, micrognathism, low-set ears, ocular anomalies, syndactyly and atrophy of the cerebral cortex and corpus callosum. Study of chromosomal heteromorphisms revealed that triploidy might have arisen through fertilization of a diploid ovum by a haploid sperm (diginy).

Low prevalence of complications of delayed herniotomy in the extremely premature infant.

AIM: To study the relationship between the delay of herniotomy in the extremely premature infant and the rate of complications in comparison with full-term children. METHODS: A follow-up study of three groups of neonates operated on for inguinal hernia was performed. The groups were defined as: a) the short-waiting group (SWG): prematures (mean gestational age: 32.56 +/- 0.62; n = 9) operated on within 2 wk of diagnosis (median: 5 d); b) the long-waiting group (LWG): prematures (mean gestational age: 28.38 +/- 1; n = 21) operated on after more than 2 wk (median: 39 d); and c) control group of full-term children (FTG); (mean gestational age: 38.18 +/- 0.29; median of timing: 3 d; n = 11). Several variables (gestational age, weight at birth and at surgery, side of the inguinal herrnia, timing, duration of surgery, type of anaesthesia, length of hospitalization), as well as the occurrence of apnoea, incarceration and testicular atrophy were compared between groups. RESULTS: Timing was the only variable that was different between the LWG and the other two groups (p < 0.001, ANOVA). Seven preoperative episodes of incarceration occurred: one in the SWG, two in the LWG and four in the FTG (p = 0.138, chi2). In the follow-up study two testicular atrophies, related to previous episodes of incarceration, were found: one in the FTG and the other in the SWG (p = 0.221, chi2). CONCLUSION: The deferral of herniotomy in the extremely premature infant, until the child is ready to be discharged from the neonatal unit, does not seem to increase the risk of incarceration episodes or testicular atrophy.

[Neonatal septicemia: incidence and risk factors]. / Sepsis neonatal: incidencia y factores de riesgo.

The cases of 131 newborns with positive blood cultures have been reviewed. These children were born in our hospital between 1985 and 1990. We found that the incidence of sepsis was 4.3/1000 newborns. Early neonatal sepsis was the most frequent, representing 58% of the cases. Late sepsis in hospitalized infants represented 1.34% of the cases. Streptococcus B was the microorganism most frequently isolated (26.7%), followed by S. epidermidis (19.8%), E. coli (13.7%) and S. aureus (10.68%). In over 50% of the cases of early sepsis, maternal-fetal risk factors were present. Mortality was 7.6%, with half of these cases due to Streptococcus B.

A comparison of 0.0625% bupivacaine with fentanyl and 0.1% ropivacaine with fentanyl for continuous epidural labor analgesia.

UNLABELLED: We compared the analgesic efficacy and the degree of motor block achieved with epidural infusion of 0.0625% bupivacaine (Group B) versus 0.1% ropivacaine (Group R), both with 0.0002% fentanyl (2 microg/mL) in laboring patients. A prospective, double-blinded study was performed in 98 ASA physical status I-II parturients who were divided randomly into two groups to receive either bupivacaine or ropivacaine after catheter location had been tested with an initial bolus of lidocaine and fentanyl. The infusion rate was 15 mL/h in every case. When pain was perceived, 5-mL boluses of the assigned epidural analgesic were administered every 10 min until analgesia was achieved. We recorded pain intensity, level of sensory block, degree of motor block, hemodynamic variables, secondary effects, mode of delivery, neonatal outcome, and patient satisfaction. There were no statistically significant differences in any of the factors analyzed. Highly effective analgesia was achieved in both groups with a small incidence of motor block. These findings suggest that bupivacaine may be more potent than ropivacaine. IMPLICATIONS: We compared different concentrations of epidural bupivacaine and ropivacaine thought to be equipotent. Both solutions were equally efficient in providing highly effective epidural analgesia for labor with minimal motor block. These findings suggest that bupivacaine may be more potent than ropivacaine.

[Fatal nanism: 3 different entities]. / Enanismos letales: tres entidades diferentes.

Three cases of congenital dwarfism are presented. All of them are lethal and represent the three better known nonviable nosologic entities: Achondrogenesis I, Achondrogesis II and Thanatophoric dwarfism. According to clinical features and radiologic data it is possible to approach the diagnosis accurately. We comment genetic, clinic, radiologic and histologic aspects of these processes. It is important to establish a differential diagnosis as these entities have different genetic basis, what influences genetic counsel.

[Clinical course and prognostic factors in newborns with very low birth weight]. / Evolución y factores pronósticos en recién nacidos de muy bajo peso.

OBJECTIVE: We report the results of survival and incidence of neurodevelopmental sequelae in a group of 249 infants treated in our hospital between 1986-91, whose birth weight was under 1,500 grams. METHOD: We perform a follow-up at corrected ages of 3, 6, 10, 18, 36 months and 5 years thought results only included children followed until 18. Sequelae were classified in three groups, according to the disability degree. RESULTS: Survival resulted to be 69.87% (174), 38.7% for the group under 1,000 grams and 84.7% for those over 1,000 grams. Sequelae were present in 22.6% (11.6% moderate and 10.9% severe). The incidence of severe sequelae was very different on basis of the birth weight, 25.8% for children under 1,000 grams, 13.9% for 1,000-1,249 grams and 1.6% for 1,250-1,500 grams. CONCLUSIONS: Intracranial haemorrhage, hyperbilirubinemia, assisted ventilation and persistence of ductus arteriosus were significantly associated sequelae. We didn't find differences with respect to multiple pregnancy, seizures, sepsis or neonatal hypoxia.