Disease-free survival and response to therapy of clinically node- negative Papillary Thyroid Cancer treated without central neck dissection: Retrospective study of 321 patients.

BACKGROUND AND OBJECTIVE: Nodal metastases in the central compartment are frequent in papillary thyroid cancer (PTC). However, they are mostly micrometastases with no impact on survival and their relevance on the risk of locoregional relapse is controversial. There is no consensus regarding optimal management of the central neck in patients with PTC cN0. In our center, we do not perform prophylactic central neck dissection (pCND). The objective of this study is to review our long-term results and compare them with the most recent literature. PATIENTS AND METHODS: Retrospective review of patients with PTC who underwent total thyroidectomy (TT) without CND between 2005 and 2017. Primary result was disease-free survival in the neck (DFS). RESULTS: 321 patients were identified, mostly T1-T2 tumors (94.1%). Median follow-up was 90 months. DFS in the central compartment was excellent (96.1% at 10 year's follow-up). 19 patients had cervical recurrence, of which 15 underwent salvage surgery. On their last visit, including salvage surgery when appropriate, 77% of patients had excellent response, 18.7% had indeterminate response, 3.1% had biochemically incomplete response and 1.2% had morphologically incomplete response. Recurrent laryngeal nerve (RLN) paralysis after TT was transient in 4.7% of patients and permanent in 0.9% of patients. There were no RLN paralysis after salvage surgery. Permanent hypoparathyroidism occurred in 3.4% of patients. Only one patient had hypoparathyroidism after salvage surgery and it was permanent. CONCLUSIONS: Based on long-term results and low rate of complications associated with salvage surgery in our experience, we consider routine pCND is not justified.

Relationship between hair cortisol concentrations and cognitive functioning in adolescents with ADHD.

Background: Our study aimed to explore whether the hair cortisol concentration (HCC), a measure of long-term cortisol output, is associated with poorer cognitive functioning in adolescents with attention deficit and hyperactivity disorder (ADHD). We further aimed to test the potential moderating effects of sex and childhood maltreatment.Methods: In this cross-sectional study, fifty-three adolescents with ADHD were studied. The ADHD Rating Scale (ADHD-RS) and Childhood Trauma Questionnaire (CTQ) were administered. Seven cognitive tasks from the Cambridge Neuropsychological Test Automated Battery (CANTAB) were administered, and two cognitive factors (attention and memory and executive functioning) were identified by confirmatory factor analysis. A 3-cm hair sample from the posterior vertex region of the head was obtained. HCCs were determined by a high-sensitivity enzyme immunoassay kit. Multiple linear regression analyses were used to explore the association between HCCs and either cognitive performance or ADHD severity while adjusting for sex, childhood maltreatment and the ADHD-RS total score.Results: Sex moderated the relationship between HCCs and attention/memory confirmatory factor analysis (CFA) scores, with better performance in boys with higher HCCs. HCCs were not associated with executive functioning or ADHD symptoms. Childhood maltreatment was associated with inattention symptoms in adolescents with ADHD.Conclusions: Our study suggests that HCCs are positively associated with attention and memory performance in adolescents with ADHD, with a moderating effect of sex (the relationship is strongest in boys).

We studied the relationship between cortisol and cognition in adolescents with ADHD.Hair cortisol concentrations (HCCs) were determined.We explored the moderating effects of sex and childhood trauma.Sex moderated the relationship between HCCs and attention and memory.Childhood trauma did not moderate the relationship between HCCs and cognition.

Comparison of obstetrical outcomes in patients undergoing cerclage with or without amniocentesis.

OBJECTIVE: We sought to compare the obstetrical outcomes in patients who underwent midtrimester cerclage placement with or without prior amniocentesis in a single center cohort. METHODS: A retrospective medical record review in a single academic institution was undertaken of all patients who underwent either an exam or ultrasound indicated cerclage. This group was then divided into two groups: amniocentesis or no amniocentesis groups. Detailed maternal data was abstracted from the prenatal and hospital records. Amniocentesis fluid specimens were sent for Gram stain, aerobic and anaerobic bacterial culture, including mycoplasma and ureaplasma, as well as for glucose. Comparisons were performed utilizing Parametric 2-sample t-test for continuous variables and Fisher's exact test was utilized to compare categorical variables. RESULTS: A total of 160 patients who underwent a cerclage were utilized for comparison. Sixty-five patients who had an amniocentesis performed prior to the cerclage were compared with 95 patients who underwent a cerclage without an amniocentesis. None of the amniocentesis results were positive for infection in those that received a cerclage. Patients that had an amniocentesis before cerclage were found to have an earlier gestational age at time of the procedure (20.30 ± 2.29 weeks versus 21.32 ± 1.81 weeks, p < .001), a shorter cervical length on presentation (0.93 ± 0.61 cm versus 1.45 ± 0.66 cm, p < .001), delivered at an earlier gestational age (GA 32.2 [30.3 to 34.2] versus 36.3 [35.2 to 37.3] weeks, p < .001) with shorter time from cerclage placement until delivery (13.9 [0.0 to 24.0] versus 16.3 [0.3 to 23.2] weeks, p = .010). The rates of chorioamnionitis and PPROM were significantly higher in the amniocentesis group (17 versus 2%, p = .0008 and 26 versus 13%, p = .03 respectively). Five patients who underwent an amniocentesis did not receive a cerclage, with one having a positive Gram stain and culture. CONCLUSION: Amniocentesis use prior to cerclage placement in this single institution cohort was utilized in patients who presented earlier in gestation with shorter cervical length and more cervical dilation. The severity of presentation was the determining factor in the decision to perform an amniocentesis prior to cerclage placement, and, because of this difference in severity, outcomes for the amniocentesis group were predictably worse than those who did not undergo amniocentesis.

HLA association with the susceptibility to anti-synthetase syndrome.

OBJECTIVE: To investigate the human leukocyte antigen (HLA) association with anti-synthetase syndrome (ASSD). METHODS: We conducted the largest immunogenetic HLA-DRB1 and HLA-B study to date in a homogeneous cohort of 168 Caucasian patients with ASSD and 486 ethnically matched healthy controls by sequencing-based-typing. RESULTS: A statistically significant increase of HLA-DRB1*03:01 and HLA-B*08:01 alleles in patients with ASSD compared to healthy controls was disclosed (26.2% versus 12.2%, P=1.56E-09, odds ratio-OR [95% confidence interval-CI]=2.54 [1.84-3.50] and 21.4% versus 5.5%, P=18.95E-18, OR [95% CI]=4.73 [3.18-7.05]; respectively). Additionally, HLA-DRB1*07:01 allele was significantly decreased in patients with ASSD compared to controls (9.2% versus 17.5%, P=0.0003, OR [95% CI]=0.48 [0.31-0.72]). Moreover, a statistically significant increase of HLA-DRB1*03:01 allele in anti-Jo-1 positive compared to anti-Jo-1 negative patients with ASSD was observed (31.8% versus 15.5%, P=0.001, OR [95% CI]=2.54 [1.39-4.81]). Similar findings were observed when HLA carrier frequencies were assessed. The HLA-DRB1*03:01 association with anti-Jo-1 was unrelated to smoking history. No HLA differences in patients with ASSD stratified according to the presence/absence of the most representative non-anti-Jo-1 anti-synthetase autoantibodies (anti-PL-12 and anti-PL-7), arthritis, myositis or interstitial lung disease were observed. CONCLUSIONS: Our results support the association of the HLA complex with the susceptibility to ASSD.

Detection of antibodies to denatured human leucocyte antigen molecules by single antigen Luminex.

The anti-HLA antibody detection has been improved in sensitivity and specificity with solid-phase antigen bead (SAB) assays based on Luminex. However, false positive results due to denatured HLA (dHLA) may arise after single antigen test. The aim of this study was to compare the performance of the two Luminex technology-based anti-HLA detection kits available in the market in showing undesired anti-HLA antibody results. A prospective cohort was assessed for anti-HLA antibodies with single antigen A manufacturer (AM) kit and a comparison cohort with single antigen B manufacturer (BM) kit. A total of 11 out of 90 patients in a prospective cohort presented monospecific HLA-I antibodies with AM, and 5 out of 11 confirmed monospecific reaction with BM. Despite the confirmation of monospecific reaction with both manufacturers, 80% were assigned as dHLA reaction by specific crossmatch. Further comparative cohorts detected four out of six monospecific reactions with BM that were confirmed as possible dHLA reactions. A positive SAB test should rule out a reaction against a dHLA molecule, thus avoidance of prolonged waitlist periods or misattribution of anti-HLA reactions after transplantation.

Regulatory T-cell Number in Peripheral Blood at 1 Year Posttransplant as Predictor of Long-term Kidney Graft Survival.

BACKGROUND: Regulatory T (Treg) cells play a role in limiting kidney transplant rejection and can potentially promote long-term transplant tolerance. There are no large prospective studies demonstrating the utility of peripheral blood Treg cells as biomarkers for long-term graft outcome in kidney transplantation. The aim of our study was to analyze the influence of the absolute number of peripheral blood Treg cells after transplantation on long-term death-censored graft survival. METHODS: We monitored the absolute numbers of Treg cells by flow cytometry in nonfrozen samples of peripheral blood in 133 kidney transplant recipients, who were prospectively followed up to 2 years after transplantation. Death-censored graft survival was determined retrospectively in January 2017. RESULTS: The mean time of clinical follow-up was 7.4 ± 2.9 years and 24.1% patients suffered death-censored graft loss (DCGL). Patients with high Treg cells 1 year after transplantation and above the median value (14.57 cells/mm3), showed better death-censored graft survival (5-year survival, 92.5% vs 81.4%, Log-rank P = .030). One-year Treg cells showed a receiver operating characteristic - area under curve of 63.1% (95% confidence interval, 52.9-73.2%, P = 0.026) for predicting DCGL. After multivariate Cox regression analysis, an increased number of peripheral blood Treg cells was a protective factor for DCGL (hazard ratio, 0.961, 95% confidence interval, 0.924-0.998, P = 0.041), irrespectively of 1-year proteinuria and renal function. CONCLUSIONS: Peripheral blood absolute numbers of Treg cells 1 year after kidney transplantation predict a better long-term graft outcome and may be used as prognostic biomarkers.

Anti-perlecan antibodies and acute humoral rejection in hypersensitized patients without forbidden HLA specificities after kidney transplantation.

BACKGROUND: The improvement in the definition of serum anti-HLA antibodies (HLA-Abs) profiles after Luminex-assay implementation in transplant patients follow-up is clear. This success has permitted the development of hypersensitized-recipient allocation and donor-paired exchange programs improving the access to transplantation. However, non-HLA Abs have been described in transplanted patients but their effect in hypersensitized transplanted recipients is unclear. METHODS: Twenty-seven HLA hypersensitized patients awaiting for kidney transplantation (KT) were studied and 11 of them were followed after KT. The HLA Abs profile was confirmed in serum by Single Antigen Luminex assay and panel reactive of antigens >98% was achieved in all patients. Subsequently, the ability to fix complement by C1q test was also assessed. Serum non-HLA Abs before and 1 month after transplantation were measured in the 11 hypersensitized recipients. RESULTS: 95.2% of the hypersensitized on waiting list had concomitant serum anti-HLA and non-HLA Abs. The more frequent specificity in non-HLA Abs were found against Glutathione S-transferase theta-1 (GSST-1) (in 62%) and C-terminal fragment of perlecan (LG3) (in 52%). Four out of 11 transplanted patients presented early antibody-mediated rejection (ABMR) confirmed by biopsy and had serum anti-LG3 antibodies, two of them with concomitant anti-anti-angiotensin II type I receptor. Only one patient developed de novo-donor specific HLA antibodies. CONCLUSIONS: The incidence of non-HLA antibodies in patients in the waiting list is largely underestimated. The concomitance anti-HLA and non-HLA Abs in hypersensitized patients is very common and the detection of non-HLA Abs in this population could allow to identify patients with an increased risk of humoral rejection.

Immunomodulatory effect of Polypodium leucotomos (Anapsos) in child palatine tonsil model.

BACKGROUND: Recurrent tonsillitis might reduce the immunological capability of fighting against the infection of tonsil tissue. Polypodium leucotomos (Anapsos) immunomodulating effect has been subject of research in the last years. The aim of this research is to test the in vitro immunomodulating capacity of Anapsos in a child palatine tonsil explants model. METHODS: Palatine tonsils explants of children undergoing amigdalectomy were stimulated with mononuclear cells obtained from their own blood by density gradient centrifugation. Some were then treated with Anapsos while others rest untreated. Cytokines were measured by ELISA, immune cells activation was measured by flow cytometry and activation of immunoglobulins was appreciated by indirect immunofluorescence in tonsils tissue. RESULTS: Anapsos activates Natural Killers cells. It increases IL-2 and IFN-γ levels by the activation of Th2 lymphocytes, and IL-10, by the Th1 lymphocytes. Anapsos also increases immunoglobulins IgM, IgD and IgG4 by B-lymphocyte activation in tonsils tissue. CONCLUSION: Anapsos has an immunomodulating effect, both in humoral and cellular responses, which might benefit children suffering of recurrent tonsillitis as it could enhance their immune system. This effect might reduce the number of episodes suffered and therefore the number of children undergoing surgery.

Avoiding Inadequate Intrapartum Antibiotic Prophylaxis for Group B Streptococci.

OBJECTIVE: To estimate the frequency and reasons for inadequate group B streptococci (GBS) prophylaxis at our institution and to estimate what proportion of cases can be avoided with perfect protocol adherence. METHODS: This was a retrospective cohort study of neonates born to GBS-colonized women who received inadequate prophylaxis between April 30, 2013, and May 1, 2014. The maternal chart was analyzed to categorize each case as avoidable (adequate time on labor and delivery to receive antibiotics 4 hours before birth and ß-lactam antibiotic-eligible) or unavoidable and to determine whether a violation of the 2010 Centers for Disease Control and Prevention (CDC) protocol (delayed or incorrect antibiotics) occurred. RESULTS: A total of 197 of 488 (40.4%, 95% confidence interval 36.1-44.8%) newborns of group B-colonized women received inadequate prophylaxis. Of these, 157 cases (79.7%, 73.4-84.8%) were unavoidable and would have occurred even with perfect protocol adherence. The 40 (20.3%, 15.3-26.5%) avoidable cases due to protocol violations resulted from delayed antibiotic administration (first dose of antibiotics more than 1 hour after admission [median 9.33 hours, range 3.83-25 hours] in 25 patients; no antibiotics in four patients; total 29 patients, 72.5%) or incorrect antibiotic selection (11 patients, 27.5%). CONCLUSIONS: Forty percent of patients received inadequate prophylaxis, and four of five cases are unavoidable with our current labor management and the 2010 CDC guidelines. Timeliness and selection of antibiotics remain areas for improvement, but the overall effects on sepsis prevention will be modest.

Transitory effect on endolymphatic hydrops of the intratympanic steroids for Ménière's disease.

OBJECTIVES/HYPOTHESIS: This study aimed to evaluate the changes in electrocochleography (EcohG) measurements after intratympanic (IT) dexamethasone therapy and to correlate them with the long-term effects on the control of vertigo. STUDY DESIGN: Prospective outcomes research. METHODS: This study included 62 patients with unilateral Ménière's Disease (MD) refractory to medical therapy for at least 1 year. Each patient was treated with a fixed protocol of three consecutive weekly injections of a commercial 4 mg/mL dexamethasone preparation. The 1995 American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) criteria for reporting treatment outcomes for MD were used. Electrocochleography (EcohG) measurements were performed 1 month before and 1 and 12 months after IT steroid therapy. Caloric test and vestibular evoked myogenic potential (VEMPs) were performed before the IT treatment. The summating potential/action potential (SP/AP) ratio was measured before and after the IT treatment. A Kaplan-Meier analysis was used to evaluate the control of vertigo over a 2-year period. RESULTS: Complete vertigo control (class A) was achieved in 26 patients (41.9%) at the 12-month follow-up and in 12 patients (19.3%) at the 24-month follow-up. A significant reduction (P < 0.01) in the SP/AP ratio after the IT steroid treatment was observed in the first-month determination, but no significant differences were found when the initial and 12-month determination were compared. CONCLUSIONS: IT dexamethasone provides an alternative treatment for patients with Ménière's Disease. A transitory reduction of the endolymphatic hydrops is detected by the EcohG 1 month after treatment. The hydrops levels returned to their initial values in the 1-year EcohG follow-up. LEVEL OF EVIDENCE: 2b.

The use of electrocochleography to monitor the response of Ménière's disease patients to intratympanic steroids.

CONCLUSIONS: Intratympanic (IT) dexamethasone provides an alternative for patients with Ménière's disease (MD). A reduction of the endolymphatic hydrops is detected by the EcohG 1 month after the treatment. OBJECTIVE: The use of intratympanic corticoid injections for MD has become popular due to the lack of reported adverse effects, but the mechanism of action is not well established. This study aimed to evaluate the changes in electrocochleography (EcohG) measurements during IT dexamethasone therapy. METHODS: This study included 53 patients with unilateral MD refractory to medical therapy for at least 1 year. Each patient was treated with a fixed protocol of three consecutive weekly injections of a commercial 4 mg/ml dexamethasone preparation. EcohG measurements were performed 1 month before and 1 month after IT steroid therapy. The SP/AP ratio was measured before and after the IT treatment. A Kaplan-Meier analysis was used to evaluate the control of vertigo over a 2-year period. RESULTS: Complete vertigo control (class A) was achieved in 22 patients (41.5%) at the 12-month follow-up and 8 patients (15.1%) at the 24-month follow-up. A significant reduction (p < 0.01) in the SP/AP ratio after the IT steroid treatment was observed.

Rapid and sustained autologous neutralizing response leading to early spontaneous recovery after HCV infection.

After HCV infection, the association between the humoral response and viral sequence evolution remains unclear. We investigated the mechanisms leading to early HCV clearance and spontaneous recovery in two patients. The early evolution of the HCV envelope glycoproteins, and the infectivity spectrum of variants were explored using retroviral pseudoparticles bearing HCV envelopes. Ability of the autologous neutralizing response to control these variants was analyzed. For the first case, the maximum neutralizing activity was for serum collected between two and three months post ALT peak, this activity was still detectable after 30 months. For the second case, autologous neutralizing activity against the variant isolated at the ALT peak was detected in every serum collected between 4 days and 13 months after. The neutralizing response was sustained beyond the time at which the virus was cleared. This raise interesting questions about the role of such antibodies in case of re-exposure.

[Extratympanic electrocochleography in Ménière's disease]. / Electrococleografía extratimpánica en la enfermedad de Ménière.

INTRODUCTION: Electrocochleography is the registration of an electrophysiological event which takes place in the cochlea after an acoustical stimulus. Most of the authors consider an increased summating potential (SP)/action potential (AP) ratio as characteristic of endolymphatic hydrops. METHODS: A longitudinal, prospective study of a unilateral Ménière's population diagnosed according to the American Academy of Otolaryngology-Head and Neck Surgery classification was carried out. A complete clinical history and bedside examination were performed, in addition to complete auditory and vestibular testing and an extratympanic electrocochleography. We selected 20 normal hearing subjects with no history of vestibular and otological pathology as a control group. RESULTS: Of the 100 patients included in the study, 62 were diagnosed as definite Ménière's disease, and 13 and 25 as probable and possible Ménière's disease, respectively. In the electrocochleography, 85% of all the patients had an SP/AP ratio above 0.5. A sensibility of 92%, 78% and 75% was obtained in the definite, probable and possible Ménière's disease patients respectively. DISCUSSION AND CONCLUSIONS: Electrocochleography is a useful method for diagnosing and evaluating patients with Ménière's disease syndrome. It provides information about the progression of the process and shows a significant correlation with the clinical stage.