HPV genotype distribution according to severity of cervical neoplasia using the digene HPV genotyping LQ test

A new genotyping-based DNA assay (Digene LQ^®) was developed recently. The primary aim was to assess the distribution of HPV types using this new assay in atypical squamous cells of undeterminate significance (ASCUS). The secondary aim was to correlate the HPV types with the severity of the disease. The study population comprised 376 ASCUS women. The women were all Hybrid Capture II (HCII) positive and were admitted in three European referral gynecology clinics between 2007 and 2010. A colposcopy with histological examination was performed in all these patients. HPV 16 was typed in 40 % of patients, HPV 18 in 7 %, and HPV 31 in 17 %, and 18 % of patients had mixed genotypes. Patients aged over 30 more often had the HPV 16 genotype than patients aged under 30 (29 % vs. 11 %, chi-square test p < 0.001). The risk of cervical intra-epithelial neoplasia of grade 2 or more (CIN2 +) when HPV 18 positive is lower than the probability associated with HPV 16 or HPV 31: 28 % vs. 58 % and 52 %, respectively (chi-square test, p = 0.005 and p = 0.05, respectively). The Digene LQ^®, a new sequence-specific hybrid capture sample preparation, is fast and efficient and allows high-throughput genotyping of 18 HR HPV types by PCR compared to traditional non-sequence-specific sample preparation methods.     

Cognitive-behavioral therapy versus other therapies: Redux

Despite the evidence suggesting that all treatments intended to be therapeutic are equally efficacious, the conjecture that one form of treatment, namely cognitive-behavioral therapy (CBT), is superior to all other treatment persists. The purpose of the current study was to (a) reanalyze the clinical trials from an earlier meta-analysis that compared CBT to ‘other therapies’ for depression and anxiety (viz., Tolin, 2010) and (b) conduct a methodologically rigorous and comprehensive meta-analysis to determine the relative efficacy of CBT and bona fide non-CBT treatments for adult anxiety disorders. Although the reanalysis was consistent with the earlier meta-analysis' findings of small to medium effect sizes for disorder-specific symptom measures, the reanalysis revealed no evidence for the superiority of CBT for depression and anxiety for outcomes that were not disorder-specific. Following the reanalysis, a comprehensive anxiety meta-analysis that utilized a survey of 91 CBT experts from the Association of Behavioral and Cognitive Therapists (ABCT) to consensually identify CBT treatments was conducted. Thirteen clinical trials met the inclusion criteria. There were no differences between CBT treatments and bona fide non-CBT treatments across disorder-specific and non-disorder specific symptom measures. These analyses, in combination with previous meta-analytic findings, fail to provide corroborative evidence for the conjecture that CBT is superior to bona fide non-CBT treatments.     

The assessment of the effect of different intraabdominal pressures used for laparoscopic cholecystectomy surgery on optic nerve sheath diameter: a prospective observational cohort study

Background/aimDuring laparoscopic cholecystectomy operations, increases in intraabdominal, intrathoracic, and intracranial pressures (ICP) can be seen after pneumoperitoneum created for surgical imaging. Orbital ultrasonography (USG), which has been developed in recent years, is a method that can evaluate the ICP by measuring the optic nerve sheath diameter (ONSD) from the eyeball.In our study, we aimed to evaluate whether different intraabdominal pressure values created during laparoscopic cholecystectomy operations correlate with ICP by measuring ONSD.Materials and methodsThe study included a total of 90 patients with American Society of Anesthesiologists (ASA) physical status classification I (ASA I) and II (ASA II) and ages from 18 to 65 years with laparoscopic cholecystectomy planned.After the patients were intubated, at the 5th min, bilateral ONSD measurements were performed. The same measurements were performed at the 15th and 30th min after CO2 insufflation and additionally 10 min after CO2 was released at the end of the operation. During intrabdominal CO2 insufflation, patients with 10 mmHg pressure applied comprised Group 1, patients with 12 mmHg pressure applied comprised Group 2, and patients with 14 mmHg pressure applied comprised Group 3.Results The study was completed with 89 patients, 51 female and 38 males. One patient was excluded from the study due to erroneous values. The variations in ONSD measured in the right-left eye before pneumoperitoneum and at the 15th and 30th min after abdominal CO2 insufflation were observed to be statistically significant (p < 0.01). In all three groups, the right and left eye ONSD values were not identified to be statistically significantly different (p > 0.01).A significant increase was observed in ONSD values in direct proportion to the increase in intraabdominal pressure in patients undergoing laparoscopic cholecystectomy surgery.Conclusion USG-guided ONSD measurements appear be a guide to ensure optimization of intraabdominal pressures and safe anesthesia administration for patients, especially those at risk of ICP increase, during laparoscopic surgery.     

Assessment of psychometric properties,cross-cultural adaptation,and translation of the Turkish version of the ICU mobility scale

Background/aim The aim of the study was to carry out the cultural adaptation and translation of the ICU mobility scale (IMS) into Turkish and research the psychometric properties.Materials and methods This study was based on methodological design. The IMS was translated from English to the Turkish through a regularised translation process. Two physiotherapists assessed patients independently in the coronary intensive care unit. The measures such as construct validity, intra and interrater reliability, and internal consistency of the IMS Turkish version were assessed. Results A total of 70 intensive care patients were included in the study. The intrarater and interrater reliability of the IMS was excellent. The weighted Kappa value was 0.92 (0.87–0.96) for the intrarater reliability, and 0.87 (0.80–0.93) for the interrater reliability. There were significant correlations between the IMS and functional status score for the intensive care unit (r = 0.83), Perme intensive care unit mobility score (r = 0.84), Katz activities of daily living (r = 0.73), handgrip strength (r = 0.62), knee extension strength (r = 0.46), and age (r = –0.44).Conclusion This study suggests that the IMS Turkish version is a reliable and valid scale for assessing functional status and mobility level in ICU patients.     

Circulating miR-29c-3p is downregulated in patients with acromegaly

Background/aimmiRNAs control various biological functions, such as cell proliferation, differentiation, signaling pathways, apoptosis and metabolism. Recently, it has been shown that there is a relationship between changes in miRNA expression and the development of acromegaly. Studies are needed to identify new disease-specific miRNAs. The aim of the current study is to evaluate plasma miR-29c-3p, miR-31-5p and miR-18a-5p steady-state levels in acromegaly. Another aim is to investigate whether there is a difference in the levels of these miRNAs in patients with inadequate control and controlled acromegaly with somatostatin analog (SSA) therapy. These miRNAs targeting the IGF-1 gene were determined by in silico estimation.Materials and methodsThe study included 30 healthy controls (HC) and 20 patients with acromegaly. Anterior pituitary functions and disease activities of patients with acromegaly were evaluated at the time of study. The miR-29c-3p, miR-31-5p and miR-18a-5p levels were measured using quantitative real-time PCR (RT-qPCR).ResultsThe expression level of miR-29c-3p was significantly lower in patients with acromegaly compared to the HC group (p < 0.001). This downregulation was more pronounced in patients with inadequately controlled acromegaly than in patients with acromegaly controlled with somatostatin analogues (SSA) therapy (p = 0.016). Univariate logistic regression analysis results showed that down regulation of miR-29c-3p expression increases the risk of developing acromegaly [OR (95% Cl) = 1.605 (1.142-2.257), p = 0.006]. There was no significant difference between the groups in terms of miR-31-5p and miR-18a-5p expression levels (p = 0.375 and p = 0.649, respectively). ConclusionPlasma miR-29c-3p expression level is downregulated in patients with acromegaly, and this is more pronounced in patients with inadequate control.     

Functional characterization of CD8(+) antigen-specific cytotoxic T lymphocytes after enrichment based on cytokine secretion: comparison with the MHC-tetramer technology

Cell therapy with antigen-specific T cells holds promise for various diseases including cancer and viral infections. The powerful enrichment procedure based on major histocompatibility complex (MHC)-tetramers, however, is of limited applicability so far. Therefore, the recently developed cell surface affinity matrix technology that allows direct identification and enrichment of life antigen-specific T cells based on cytokine secretion was evaluated in this respect. To this end, CD8(+) T cells directed against the HLA-A(*)0201-restricted melanoma-associated peptide Melan-A (aa26-35) were generated by combining stimulation of peptide-pulsed autologous dendritic cells (DC) with antigen-independent expansion with anti-CD3/anti-CD28 monoclonal antibodies (MoAb). Antigen-specific cytotoxic T lymphocyte (CTL) were detected based on stimulation-induced interferon (IFN)-gamma and interleukin (IL)-4 secretion and enriched > 100-fold using the cell surface affinity matrix technology. The resulting IFN-gamma- and IL-4-secreting CTL lines contained > 80% and > 70% cytokine positive T cells, respectively. They exhibited a cytotoxic activity against Melan-A expressing target cells that was significantly higher as compared to nonpurified CTL. Direct staining of enriched CTL with HLA-A2-Melan-A-tetramers revealed a high correlation between the results obtained from the cell surface affinity matrix technology and those obtained from tetrameric complexes. Altogether, our study demonstrates that cytokine-driven enrichment based on the cell surface affinity matrix technology enables selective isolation of functionally active antigen-specific CTL that may be used for an adoptive T cell transfer in immunotherapy.     

Pancreas divisum: thin-section CT

Twelve patients with known pancreas divisum underwent thin-section computed tomography (CT) to determine the capability of CT to depict this pancreatic anomaly. Focal pancreatic enlargement was present in five patients. Two distinct pancreatic moieties separated by a fat cleft were noted in three patients; a fourth patient had focal atrophy in the distribution of the dorsal pancreas. The two pancreatic moieties were identified at the same craniocaudal level in all four of these patients. The dorsal duct was depicted in all 12 patients, while the short ventral duct was seen in only five of the 12 patients. Failure of the ventral and dorsal pancreatic ducts to fuse was identified in all five patients in whom both ducts were seen. CT may not enable specific diagnosis of pancreas divisum in the majority of patients. If, however, distinct pancreatic moieties or unfused ductal systems are evident, the diagnosis may be confidently suggested.     

Clinical validation of a novel enzyme‐linked immunosorbent spot assay‐based in vitro diagnostic assay to monitor cytomegalovirus‐specific cell‐mediated immunity in kidney transplant recipients: a multicenter,longitudinal, prospective,observational study

Impaired cytomegalovirus (CMV)‐specific cell‐mediated immunity (CMV‐CMI) is a major cause of CMV reactivation and associated complications in solid‐organ transplantation. Reliably assessing CMV‐CMI is desirable to individually adjust antiviral and immunosuppressive therapy. This study aimed to evaluate the suitability of T‐Track^® CMV, a novel IFN‐γ ELISpot assay based on the stimulation of peripheral blood mononuclear cells with pp65 and IE‐I CMV proteins, to monitor CMV‐CMI following kidney transplantation. A prospective longitudinal multicenter study was conducted in 86 intermediate‐risk renal transplant recipients. CMV‐CMI, CMV viral load, and clinical complications were monitored over 6 months post‐transplantation. Ninety‐five percent and 88–92% ELISpot assays were positive pre‐ and post‐transplantation, respectively. CMV‐specific response was reduced following immunosuppressive treatment and increased in patients with graft rejection, indicating the ability of the ELISpot assay to monitor patients' immunosuppressive state. Interestingly, median pp65‐specific response was ninefold higher in patients with self‐clearing viral load compared to antivirally treated patients prior to first viral load detection (P < 0.001), suggesting that reactivity to pp65 represents a potential immunocompetence marker. Altogether, T‐Track^® CMV is a highly sensitive IFN‐γ ELISpot assay, suitable for the immunomonitoring of CMV‐seropositive renal transplant recipients, and with a potential use for the risk assessment of CMV‐related clinical complications (ClinicalTrials.gov Identifier: NCT02083042).     

Delayed hepatic CT scanning: increased confidence and improved detection of hepatic metastases

Fifty oncologic patients with suspected hepatic metastases were prospectively evaluated by dynamic sequential hepatic computed tomography (DSHCT) and by delayed iodine hepatic computed tomography (DICT) scanning. DICT scanning was performed 4-6 hours following administration of 60 g of intravenous iodine. Both techniques were evaluated for lesion definition relative to the adjacent hepatic parenchyma and for numbers of metastases detected. Metastases were detected by both techniques in 26 patients. Fifteen patients (58%) had lesions better defined by DICT. DICT scanning detected more metastases in seven of these 15 patients. In eight patients (31%), there was no difference between the two techniques in numbers of masses detected or lesion definition. In three cases (11%), metastases were more confidently identified on the initial or DSHCT scan. DICT scanning, as described, is useful in defining and detecting hepatic metastases, especially where there is questionable hepatic involvement or better quantification of size is necessary.