Phase I dose escalation and expansion study of golidocitinib, a highly selective JAK1 inhibitor, in relapsed or refractory peripheral T-cell lymphomas.

BACKGROUND: Relapsed or refractory peripheral T-cell lymphomas (r/r PTCLs) are a group of rare and aggressive diseases that lack effective therapies. Constitutive activation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway is reported to be associated with PTCLs. Golidocitinib is an oral, potent JAK1 selective inhibitor evaluated in a phase I/II multinational study in patients with r/r PTCLs. PATIENTS AND METHODS: Patients with r/r PTCLs were eligible. The primary objectives were to assess safety and tolerability of golidocitinib and to define its recommended phase II dose (RP2D). The secondary objectives were to evaluate its antitumor activity and pharmacokinetics (PK). RESULTS: A total of 51 patients were enrolled and received golidocitinib treatment at 150 or 250 mg once daily (QD). The median prior lines of therapies were 2 (range: 1-8). Golidocitinib was tolerated at both doses tested, while a higher incidence of serious adverse events and dose modifications at 250 mg were observed. The most common grade ≥3 drug-related treatment-emergent adverse events were neutropenia (27.5%) and thrombocytopenia (11.8%). An objective response rate of 39.2% and a complete response rate of 21.6% were observed. With median follow-up time of 14.7 and 15.9 months, the median duration of response (DoR) and progression-free survival were 8.0 and 3.3 months, respectively. Based on these data, 150 mg QD was defined as the RP2D. Golidocitinib demonstrated a favorable PK profile as an oral agent. Biomarker analysis suggested a potential correlation between JAK/STAT pathway aberrations and clinical activity of golidocitinib. CONCLUSIONS: In this phase I study, golidocitinib demonstrated an acceptable safety profile and encouraging antitumor efficacy in heavily pretreated patients with r/r PTCLs. These results support the initiation of the multinational pivotal study in patients with r/r PTCLs.

Analysis of Brachypodium distachyon UVR8 reveals conservation in UV-B receptors.

The Ultraviolet Resistance Locus 8 (UVR8) in plants recognizes ultraviolet-B (UV-B) light and plays a crucial role in regulating plant growth through a series of signal transduction events. However, the UVR8 in monocotyledon crops has not yet been systematically analysed. We identified BdUVR8 (BRADI_3g45740) from the genome of Brachypodium distachyon, a relative of wheat, by analysing the phylogenetic tree, the gene expression pattern, detecting accumulation of UV-B response metabolites, and checking for phenotype recovery. The BdUVR8 protein sequence is similar to the known UVR8 of other species. The phylogenetic tree of UVR8 shows clear divergence between dicotyledons and monocotyledons. Expression analysis revealed that UV-B downregulates BdUVR8 by 70% and upregulates the chalcone synthase (BdCHS) gene 3.4-fold in B. distachyon. The pCAMBIA1300::BdUVR8-mCherry construct introduced into Arabidopsis uvr8 mutants showed that the BdUVR8 protein is localized in the cytoplasm and translocates into the nucleus in response to UV-B irradiation. The introduction of BdUVR8 into uvr8 rescued hypocotyl elongation caused by UV-B and restored expression of HY5, Chalcone synthase, and Flavanone 3-hydroxylase, as well as accumulation of total flavonoids. Together, our results show that BdUVR8 is a photoreceptor that perceives UV-B in B. distachyon.

Effectiveness of transarterial embolisation for intractable postpartum haemorrhage in a disseminated intravascular coagulation state, despite emergency hysterectomy.

PURPOSE: We evaluated the effectiveness of transarterial embolization (TAE) for intractable postpartum hemorrhage in patients with disseminated intravascular coagulation (DIC) despite emergency hysterectomy. MATERIALS AND METHODS: We retrospectively assessed TAE performed after emergency hysterectomy in 15 patients between July 2008 and January 2022. Underlying condition, technical success, clinical success, angiographic findings, laboratory findings, pregnancy-modified DIC score (The International Society on Thrombosis and Haemostasis), blood transfusion, ICU (Intensive care unit) admission day, hospital day, in-hospital mortality, and long-term sequelae were evaluated. RESULTS: All patients were diagnosed with DIC before embolization, with a 43.9 mean DIC score. All patients showed positive angiographic findings for active bleeding. Thirty-eight bleeding arteries were confirmed. The remnant uterine artery (n=25) was the most common focus of persistent bleeding, followed by the cervicovaginal artery (n=6), pudendal artery (n=3), obturator artery (n=2), vesical artery (n=1), and unspecified artery from the internal iliac artery (n=1). Technical and clinical success rates were 100% (15/15) and 93.3% (14/15), respectively. Mean nadir hemoglobin (Hb) level before embolization was 4.9 g/dL. All patients underwent massive transfusion before embolization (mean 33.2 packs of RBC). Postoperatively, a smaller amount of blood was transfused than before the procedure (mean 10.6 packs of RBC). Mean nadir Hb level after embolization was 8.2 g/dL. There was one instance each of in-hospital death, hypoxic brain damage, and ischemic acute kidney injury. CONCLUSION: Despite hysterectomy for postpartum bleeding, there could be multiple residual or uncontrolled bleeding foci, especially in case of DIC, for which TAE could be an effective treatment.

Characterization of rhodanine derivatives as potential disease-modifying drugs for experimental mouse osteoarthritis.

OBJECTIVE: This study was performed to characterize selected rhodanine derivatives as potential preclinical disease-modifying drugs for experimental osteoarthritis (OA) in mice. METHODS: Three rhodanine derivatives, designated rhodanine (R)-501, R-502, and R-503, were selected as candidate OA disease-modifying drugs. Their effects were evaluated by intra-articular (IA) injection in OA mouse models induced by DMM (destabilization of the medial meniscus) or adenoviral overexpression in joint tissues of hypoxia-inducible factor (HIF)-2α or zinc importer ZIP8. The regulatory mechanisms impacted by the rhodanine derivatives were examined in primary-culture chondrocytes and fibroblast-like synoviocytes (FLS). RESULTS: All three rhodanine derivatives inhibited OA development caused by DMM or overexpression of HIF-2α or ZIP8. Compared to vehicle-treated group, for example, IA injection of R-501 in DMM-operated mice reduced median OARSI grade from 3.78 (IQR 3.00-5.00) to 1.89 (IQR 0.94-2.00, P = 0.0001). R-502 and R-503 also reduced from 3.67 (IQR 2.11-4.56) to 2.00 (IQR 1.00-2.00, P = 0.0030) and 2.00 (IQR 1.83-2.67, P = 0.0378), respectively. Mechanistically, the rhodanine derivatives inhibited the nuclear localization and transcriptional activity of HIF-2α in chondrocytes and FLS. They did not bind to Zn2+ or modulate Zn2+ homeostasis in chondrocytes or FLS; instead, they inhibited the nuclear localization and transcriptional activity of the Zn2+-dependent transcription factor, MTF1. HIF-2α, ZIP8, and interleukin-1ß could upregulate matrix-degrading enzymes in chondrocytes and FLS, and the rhodanine derivatives inhibited these effects. CONCLUSION: IA administration of rhodanine derivatives significantly reduced OA pathogenesis in various mouse models, demonstrating that these derivatives have disease-modifying therapeutic potential against OA pathogenesis.

Da Vinci SP robotic approach to colorectal surgery: two specific indications and short-term results.

BACKGROUND: Da Vinci® Single Port (dvSP) was recently developed. Its application in colorectal surgery is under investigation. The aim of this study was to explore the safety and feasibility of dvSP for intersphincteric (dvSP-ISR), right colectomy (dvSP-RC), and transverse colectomy (dvSP-TC). Surgical indication and short-term results were analyzed. METHODS: All consecutive patients from a prospective database of patients who underwent dvSP-ISR, dvSP-RC, and dvSP-TC at Korea University Anam Hospital from November 2020 to December 2021, were analyzed. Perioperative, pathological, and oncological short-term outcomes were analyzed. RESULTS: A total of 7 dvSP-ISR, 5 dvSP-RC, and 1 dvSP-TC were performed. Median age was 56.0 (55.0-61.0) years for the dvSP-ISR and 54.0 (44.7-63.5) years for the dvSP-RC/TC. Median body mass index was 22.8 (17.1-24.8) kg/m2 for the dvSP-ISR and 23.6 (20.8-26.9) kg/m2 for the dvSP-RC/TC. All dvSP-ISR patients received neoadjuvant long-course chemoradiotherapy, including one patient with squamocellular carcinoma who was treated with 5-fluorouracil (5-FU)/mitomycin. All other patients, excluding one dvSP-RC patient with Crohn's disease, had an adenocarcinoma. Median operation time was 280 (240-370) minutes for the dvSP-ISR and 220 (201-270) minutes for the dvSP-RC/TC. Estimated blood loss was insignificant. No intraoperative complications or conversions to multiport/open surgery was reported. Median post-operative stay was 7.0 (6.0-10.0) days for the dvSP-ISR and 5.0 (4.0-6.7) days for the dvSP-RC/TC. Quality of mesorectum was complete for six patients, and nearly complete for one. Median number of retrieved lymph nodes were 21 (17-25) for the dvSP-ISR and 28 (24-49) for the dvSP-RC/TC. Proximal and distal resection margins were tumor free. Four patients experienced post-operative complications not related to the platform which were: ileus, voiding dysfunction, infected pelvic hematoma, and wound infection. Median follow-up was 9 (6-11) months and 11 (7-17) months for the dvSP-ISR and dvSP-RC/TC, respectively. Two patients had systemic recurrence; all others were tumor free. CONCLUSIONS: The dvSP platform is safe and feasible for intersphincteric resection with right lower quadrant access, and right/transverse colectomy with suprapubic access. Further studies are needed to evaluate benefit differences compared to multiport robotic platform.

Convolutional Neural Network to Stratify the Malignancy Risk of Thyroid Nodules: Diagnostic Performance Compared with the American College of Radiology Thyroid Imaging Reporting and Data System Implemented by Experienced Radiologists.

BACKGROUND AND PURPOSE: Comparison of the diagnostic performance for thyroid cancer on ultrasound between a convolutional neural network and visual assessment by radiologists has been inconsistent. Thus, we aimed to evaluate the diagnostic performance of the convolutional neural network compared with the American College of Radiology Thyroid Imaging Reporting and Data System (TI-RADS) for the diagnosis of thyroid cancer using ultrasound images. MATERIALS AND METHODS: From March 2019 to September 2019, seven hundred sixty thyroid nodules (≥10 mm) in 757 patients were diagnosed as benign or malignant through fine-needle aspiration, core needle biopsy, or an operation. Experienced radiologists assessed the sonographic descriptors of the nodules, and 1 of 5 American College of Radiology TI-RADS categories was assigned. The convolutional neural network provided malignancy risk percentages for nodules based on sonographic images. Sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were calculated with cutoff values using the Youden index and compared between the convolutional neural network and the American College of Radiology TI-RADS. Areas under the receiver operating characteristic curve were also compared. RESULTS: Of 760 nodules, 176 (23.2%) were malignant. At an optimal threshold derived from the Youden index, sensitivity and negative predictive values were higher with the convolutional neural network than with the American College of Radiology TI-RADS (81.8% versus 73.9%, P = .009; 94.0% versus 92.2%, P = .046). Specificity, accuracy, and positive predictive values were lower with the convolutional neural network than with the American College of Radiology TI-RADS (86.1% versus 93.7%, P < .001; 85.1% versus 89.1%, P = .003; and 64.0% versus 77.8%, P < .001). The area under the curve of the convolutional neural network was higher than that of the American College of Radiology TI-RADS (0.917 versus 0.891, P = .017). CONCLUSIONS: The convolutional neural network provided diagnostic performance comparable with that of the American College of Radiology TI-RADS categories assigned by experienced radiologists.

Risk factors for local recurrence and long term survival after minimally invasive intersphincteric resection for very low rectal cancer: Multivariate analysis in 161 patients.

INTRODUCTION: Intersphincteric resection (ISR) is the ultimate anal-sparing technique as an alternative to abdominoperineal resection in selected patients. Oncological safety is still debated. This study analyses long-term oncological results and evaluates risk factors for local recurrence (LR) and overall survival (OS) after minimally-invasive ISR. MATERIALS AND METHODS: Retrospective single-center data were collected from a prospectively maintained colorectal database. A total of 161 patients underwent ISR between 2008 and 2018. OS and local recurrence-free survival (LRFS) were assessed using Kaplan-Meier analysis (log-rank test). Risk factors for OS and LRFS were assessed with Cox-regression analysis. RESULTS: Median follow-up was 55 months. LR occurred in 18 patients. OS and LRFS rates at 1, 3, and 5 years were 96%, 91%, and 80% and 96%, 89%, and 87%, respectively. Tumor size (p = 0.035) and clinical T-stage (p = 0.029) were risk factors for LRFS on univariate analysis. On multivariate analysis, tumor size (HR 2.546 (95% CI: 0.976-6.637); p = 0.056) and clinical T-stage (HR 3.296 (95% CI: 0.941-11.549); p = 0.062) were not significant. Preoperative CEA (p < 0.001), pathological T-stage (p = 0.033), pathological N-stage (p = 0.016) and adjuvant treatment (p = 0.008) were prognostic factors for OS on univariate analysis. Preoperative CEA (HR 4.453 (95% CI: 2.015-9.838); p < 0.001) was a prognostic factor on multivariate analysis. CONCLUSIONS: This study confirms the oncological safety of minimally-invasive ISR for locally advanced low-lying rectal tumors when performed in experienced centers. Despite not a risk factor for LR, tumor size and, locally advanced T-stage with anterior involvement should be carefully evaluated for optimal surgical strategy. Preoperative CEA is a prognostic factor for OS.

Robotic-assisted resection for beyond TME rectal cancer: a novel classification and analysis from a specialized center.

Locally advanced rectal cancer often requires an extended resection beyond the total mesorectal excision plane (bTME) to obtain clear resection margins. We classified three types of bTME rectal cancer following local disease diffusion: radial (adjacent pelvic organs), lateral (pelvic lateral lymph nodes) and longitudinal (below 3.5 cm from the anal verge, submitted to intersphincteric resection). The primary aim of this study was to evaluate the application of robotic surgery to the three types of bTME regarding the short and long-term oncological outcomes. Secondary aim was to identify survival prognostic factors for bTME rectal cancers. A total of 137 patients who underwent robotic-assisted bTME procedures between 2008 and 2018 were extracted from a prospectively collected database. Patient-related, operative and pathological factors were assessed. Morbidity was moderately high with 66% of patients reporting postoperative complications. Median follow up was 47 months (IQR, 31.5-66.5). Local recurrence rate was 15.3% with a statistical difference between the three types of bTME (p = 0.041). Disease progression/distant metastasis rate was 33.6%. Overall survival was significantly different (p = 0.023) with 1- and 3-years rates of: 77.8% and 55.0% (radial; n = 19); 96.6% and 84.8% (lateral; n = 30); 97.7% and 86.9% (longitudinal; n = 88). No statistical difference was observed for disease-free survival (p = 0.897). Local recurrence-free survival was significantly different between the groups (p = 0.031). Multivariate analysis showed that (y)pT (p = 0.028; HR (95% CI) 5.133 (1.192-22.097)), (y)pN (p = 0.014; HR (95% CI) 2.835 (1.240-6.482)) and type of bTME were associated to OS whilst (y)pT (p = 0.072) and type of bTME were not associated to LRFS.

A multicentre comparative study between laparoscopic and open surgery for intussusception in adults.

AIM: Intussusception in adults is rare and requires surgery in most cases. While abdominal laparoscopic surgery (LS) is becoming more popular, there are few reports on the outcomes of adult intussusception treated with LS. This study compared the feasibility of LS vs open surgery (OS) for adult intussusception. METHOD: We reviewed retrospectively the medical records of adult patients with intussusception from three tertiary hospitals between 2000 and 2016. The patients were divided into LS and OS groups, and their surgical outcomes were compared. RESULTS: Surgery was indicated in 71 patients with intussusception (41 LS and 30 OS). The median age of the patients was 49.0 and 51.5 years in the LS and OS groups, respectively (P = 0.930). Overall, nine (12.7%) patients had a negative laparotomy or laparoscopy with spontaneous reduction of the intussusception. Conversion to OS from LS was necessary in one patient (2.4%). The operative time and intra-operative and postoperative complication rates were not significantly different. However, there were more serious complications such as bowel perforation and major vessel injury in the LS group. The patients in the LS group had a shorter time to first food intake and hospital stay vs patients in the OS group (4.0 vs 6.0 days, P < 0.001, and 7.0 vs 10.5 days, P < 0.001, respectively). CONCLUSION: LS may be feasible for adult intussusception; there may be more severe intra-operative complications than in OS.

Author Correction: Regulation of volatile and non-volatile pheromone attractants depends upon male social status.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Intraobserver and interobserver reliability of the computed tomography-based radiographic classification of primary elbow osteoarthritis: comparison with plain radiograph-based classification and clinical assessment.

OBJECTIVES: To develop a staging system that could better reflect symptoms by the spurs quantification in the fossa and joint space narrowing using computed tomography (CT) for elbow arthritis and to evaluate its reproducibility with multiple readers. METHODS: This retrospective study evaluated 81 cases of primary elbow osteoarthritis using both plain radiography and CT. Qualitative and quantitative analyses were independently performed by four orthopedic surgeons using previous and newly proposed staging systems. The reproducibility of the new system was analyzed with intraclass correlation coefficients (ICC). Correlations between symptoms and radiologic classification were assessed using Pearson's correlation coefficient (PCC). RESULTS: The interobserver agreement (1) and intraobserver agreement (2) among the four evaluators was present by ICC. (1) The system of Hastings and Rettig [first observation, 0.544 (95% confidence interval (CI), 0.436-0.649); second observation, 0.582 (95% CI, 0.478-0.682)] and Broberg and Morrey's staging system [first observation, 0.620 (95% CI, 0.521-0.714); second observation, 0.656 (95% CI, 0.562-0.743)] showed substantial and moderate retrospective agreement, whereas the CT-based staging system showed almost perfect agreement [first observation, 0.867 (95% CI, 0.820-0.906); second observation, 0.909 (95% CI, 0.875-0.936)]. (2) The intraobserver agreement was almost perfect in the Brogerg and Morrey's and CT-based staging systems. CT-based staging showed high correlation with visual analogue scale (PCC 0.754, P < 0.001) and Mayo elbow performance score (PCC -0.614, P < 0.001) and moderate correlation with range of motion (PCC -0.458, P < 0.001). CONCLUSIONS: CT-based staging system was highly reproducible and clinically feasible than previous plain radiograph-based staging systems.

Regulation of volatile and non-volatile pheromone attractants depends upon male social status.

We investigated the regulation of chemical signals of house mice living in seminatural social conditions. We found that male mice more than doubled the excretion of major urinary proteins (MUPs) after they acquired a territory and become socially dominant. MUPs bind and stabilize the release of volatile pheromone ligands, and some MUPs exhibit pheromonal properties themselves. We conducted olfactory assays and found that female mice were more attracted to the scent of dominant than subordinate males when they were in estrus. Yet, when male status was controlled, females were not attracted to urine with high MUP concentration, despite being comparable to levels of dominant males. To determine which compounds influence female attraction, we conducted additional analyses and found that dominant males differentially upregulated the excretion of particular MUPs, including the pheromone MUP20 (darcin), and a volatile pheromone that influences female reproductive physiology and behavior. Our findings show that once male house mice become territorial and socially dominant, they upregulate the amount and types of excreted MUPs, which increases the intensities of volatiles and the attractiveness of their urinary scent to sexually receptive females.

Hybrid transgastric approach for the treatment of gastroesophageal junction pathologies.

Flexible endoscopy has evolved to the point that it includes many endoluminal procedures that once required open or laparoscopic surgery, for instance, antireflux surgery, pyloromyotomy, mucosal and submucosal tumor resections, and even full-thickness resection. However, these procedures remain technically demanding due to flexible technology issues: difficult imaging, limited energy devices, lack of staplers, unsatisfactory suturing abilities, and so on. Transgastric laparoscopy or hybrid laparoscopy/flex endoscopy has been described for almost two decades as an alternative to a pure endoluminal approach, mainly for pancreatic pseudocyst drainage and full-thickness and mucosal resection of various lesions. The approach has never been widely adopted mostly due to cumbersome and difficult to maintain methods of gastric access. We propose to expand the indications of transgastric laparoscopy by using novel endoscopically placed ports to replicate endoscopic procedures particularly in the difficult to access proximal stomach such as endoluminal antireflux surgery. Under general anesthesia, five female pigs (mean weight: 27.6 kg) had endoscopic placement of 3, 5 mm intragastric ports (Endo-TAGSS, Leakwood KS, USA) using a technique similar to percutaneous endoscopic gastrostomy. A 5-mm laparoscope was used for visualization. Laparoendoscopic-assisted plication of the gastroesophageal junction (GEJ) was performed using 3-0 interrupted sutures (Polysorb®, Covidien, Mansfield, MA, USA). A functional lumen imagine probe (EndoFLIP®, Crospon, Inc., Galway, Ireland) was used to measure diameter, cross sectional area (CSA), distensibility, and compliance of GEJ before and after intervention. Once the TAGSS ports were removed, the gastrotomies were closed by using endoscopic over-the-scope clips. At the end of the procedure, animals were euthanized. Five laparoendoscopic-assisted endoluminal plications were performed. The mean operative time was 65.6 min (Endoscopic evaluation: 3.2 min, TAGSS Insertion: 11 min, EndoFLIP evaluation + GEJ Plication: 43.25 min, gastric wall closure: 15 minutes). In all cases, this technique was effective and allowed to achieve an adequate GEJ plication by endoscopic grading and EndoFLIP measurements. Median pre-plication GEJ diameter (D) and median pre-plication GEJ cross-sectional area (CSA) were 11.42 mm (8.6-13.6 mm) and 104.8 mm2 (58-146 mm2). After the procedure, these values were decreased to 6.14 mm (5.7-6.6 mm) and 29.8 mm2 (25-34 mm2) respectively (p = 0.0079). Median pre-plication distensibility (d) and compliance (C) were 7.87 mm2/mmHg (2.4-22.69 mm2/mmHg) and 190.56 mm3/mmHg (70.9-502.8 mm3/mmHg). After the procedure, these values decreased to 1.5 mm2/mmHg (0.7-2.2 mm2/mmHg) and 52.17 mm3/mmHg (21.9-98.7 mm3/mmHg) respectively (p = 0.0317). No intraoperative events were observed. Endoscopically, all valves were felt to be transitioned from a Hill grade 3 (normal state for the animal model) to a Hill grade 1 at the procedure completion. A hybrid laparoendoscopic approach is a feasible alternative for performing intragastric procedures with the assistance of conventional laparoscopic instruments; especially in cases where the intervention location limits the access to standard endoscopy or where endoscopic technology is inadequate. Further evaluation is planned in survival models and clinical trials.

Dosimetric analysis of stereotactic rotational versus static intensity-modulated radiation therapy for pancreatic cancer.

PURPOSE: Stereotactic body radiation therapy is a promising treatment modality for locally advanced pancreatic cancer. To determine the optimal radiation treatment, we compared the plan characteristics of volumetric-modulated arc therapy and intensity-modulated radiation therapy when administered with stereotactic body radiation therapy to treat pancreatic cancer. PATIENTS AND METHODS: Fifteen patients with locally advanced pancreatic cancer were treated by stereotactic body radiation therapy at a dose of 24-32Gy in four fractions with marker-guided gated volumetric-modulated arc therapy. Four dimensional-computed tomography scans were used to assess the target and surrounding normal organs. The same images, contours, and dose constraints were used for dual-arc volumetric-modulated arc therapy and 9-field intensity-modulated radiation therapy planning. Plans were compared using dosimetric parameters and treatment performance. RESULTS: Volumetric-modulated arc therapy required significantly lower monitor units (1726 vs. 4188; P<0.001) and shorter treatment delivery time in comparison with intensity-modulated radiation therapy (22.5min vs. 52.4min; P<0.001). Regarding target volume coverage, both modalities demonstrated comparable results (V95%, 99.3% vs. 99.4%; P=0.796). Both modalities satisfied the dosimetric determinants for duodenal toxicity and the maximum and mean doses administered to normal organ were also statistically similar. CONCLUSION: In comparison with 9-field intensity-modulated radiation therapy, volumetric-modulated arc therapy significantly reduces the number of monitoring units and treatment delivery times while administering similar dosimetric quality. Based on these results, volumetric-modulated arc therapy might be an appropriate treatment for locally advanced pancreatic cancer when combined with stereotactic body radiation therapy.

Histogram analysis of greyscale sonograms to differentiate between the subtypes of follicular variant of papillary thyroid cancer.

AIM: To evaluate the diagnostic value of histogram analysis using ultrasound (US) to differentiate between the subtypes of follicular variant of papillary thyroid carcinoma (FVPTC). MATERIALS AND METHODS: The present study included 151 patients with surgically confirmed FVPTC diagnosed between January 2014 and May 2016. Their preoperative US features were reviewed retrospectively. Histogram parameters (mean, maximum, minimum, range, root mean square, skewness, kurtosis, energy, entropy, and correlation) were obtained for each nodule. RESULTS: The 152 nodules in 151 patients comprised 48 non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTPs; 31.6%), 60 invasive encapsulated FVPTCs (EFVPTCs; 39.5%), and 44 infiltrative FVPTCs (28.9%). The US features differed significantly between the subtypes of FVPTC. Discrimination was achieved between NIFTPs and infiltrative FVPTC, and between invasive EFVPTC and infiltrative FVPTC using histogram parameters; however, the parameters were not significantly different between NIFTP and invasive EFVPTC. CONCLUSION: It is feasible to use greyscale histogram analysis to differentiate between NIFTP and infiltrative FVPTC, but not between NIFTP and invasive EFVPTC. Histograms can be used as a supplementary tool to differentiate the subtypes of FVPTC.

Sequential chemotherapy/radiotherapy was comparable with concurrent chemoradiotherapy for stage I/II NK/T-cell lymphoma.

Background: In stage I/II natural killer (NK)/T-cell lymphoma, concurrent chemoradiotherapy (CCRT) had previously been shown to result in superior outcome compared with anthracycline-containing regimens, which have since been considered ineffective. The role of CCRT in comparison with approaches employing nonanthracycline-containing chemotherapy (CT) and sequential radiotherapy (RT) in such patients remains to be defined. Patients and methods: Three hundred and three untreated patients (207 men, 96 women; median age: 51, 18-86 years) with stage I/II NK/T-cell lymphoma who had received nonanthracycline-containing regimens were collected from an international consortium and retrospectively analyzed. Treatment included single modality (CT and RT), sequential modalities (CT + RT; RT + CT) and concurrent modalities (CCRT; CCRT + CT). The impact of clinicopathologic parameters and types of treatment on complete response (CR) rate, progression-free-survival (PFS) and overall-survival (OS) was evaluated. Results: For CR, stage (P = 0.027), prognostic index for NK/T-cell lymphoma (PINK) (P = 0.026) and types of initial treatment (P = 0.011) were significant prognostic factors on multivariate analysis. On Cox regression analysis, ECOG performance score (P = 0.021) and PINK-EBV DNA (PINK-E) (P = 0.002) significantly impacted on PFS; whereas ECOG performance score (P = 0.008) and stage (P < 0.001) significantly impacted on OS. For comparing CCRT ± CT and sequential CT + RT, CCRT ± CT patients (n = 190) were similar to sequential CT + RT patients (n = 54) in all evaluated clinicopathologic parameters except two significantly superior features (higher proportion of undetectable circulating EBV DNA on diagnosis and lower PINK-E scores). Despite more favorable pre-treatment characteristics, CCRT ± CT patients had CR rate, PFS and OS comparable with sequential CT + RT patients on multivariate and Cox regression analyses. Conclusions: In stage I/II NK/T-cell lymphomas, when effective chemotherapeutic regimens were used, CCRT and sequential CT + RT gave similar outcome.

Can probiotics enhance vaccine-specific immunity in children and adults?

The growing use of probiotics by the general public has heightened the interest in understanding the role of probiotics in promoting health and preventing disease. General practitioners and specialists often receive inquiries from their patients regarding probiotic products and their use to ward off systemic infection or intestinal maladies. Enhanced immune function is among the touted health benefits conferred by probiotics but has not yet been fully established. Results from recent clinical trials in adults suggest a potential role for probiotics in enhancing vaccine-specific immunity. Although almost all vaccinations are given during infancy and childhood, the numbers of and results from studies using probiotics in pediatric subjects are limited. This review evaluates recent clinical trials of probiotics used to enhance vaccine-specific immune responses in adults and infants. We highlight meaningful results and the implications of these findings for designing translational and clinical studies that will evaluate the potential clinical role for probiotics. We conclude that the touted health claims of probiotics for use in children to augment immunity warrant further investigation. In order to achieve this goal, a consensus should be reached on common study designs that apply similar treatment timelines, compare well-characterised probiotic strains and monitor effective responses against different classes of vaccines.

Association of Condylar Bone Quality with TMJ Osteoarthritis.

The etiology and treatment of temporomandibular joint (TMJ) osteoarthritis (TMJOA) remain complex and unclear. Based on clinical observations, we hypothesized that low condylar bone quality is significantly correlated with TMJOA and explored this association in a cross-sectional study with human patients. A total of 254 postmenopausal female participants were included in this study. Radiographic findings from cone beam computed tomography (CBCT) and clinical symptoms were used to classify each TMJ data sample as healthy control ( n = 124) or TMJOA ( n = 130). Condylar bone mineral density (BMD) (computed tomography Hounsfield unit [CT HU]) and bone volume fraction (BV/TV) were measured and modeled as predictors of healthy control versus TMJOA status in multilevel logistic regression analyses. Both CT HU (adjusted odds ratio [AOR] = 0.9989, interquartile odds ratio [IOR] = 0.4206) and BV/TV (AOR= 0.8096, IOR = 0.1769) were negatively associated with TMJOA ( P = 0.049, 0.011, respectively). To assess the diagnostic performance of CT HU and BV/TV for identification of TMJOA, receiver operating characteristic (ROC) curves were plotted. The estimated areas under the curve (AUC) were 0.6622 for BV/TV alone, 0.6074 for CT HU alone, and 0.7136 for CT HU and BV/TV together. The model incorporating CT HU and BV/TV together had a significantly higher AUC than the models using BV/TV alone ( P = 0.038) or HU alone ( P = 0.021). In conclusion, we found that low condylar bone quality was significantly correlated with TMJOA development and that condylar CT HU and BV/TV can be used together as a potential diagnostic tool for TMJOA. Careful clinical evaluation of the condyle coupled with appropriate radiographic interpretation would thus be critical for the early detection of TMJOA.

Improved design for a low temperature scanning tunneling microscope with an in situ tip treatment stage.

The Low Temperature Scanning Tunneling Microscope (LT-STM) is an extremely valuable tool not only in surface science but also in condensed matter physics. For years, numerous new ideas have been adopted to perfect LT-STM performances-Ultra-Low Vibration (ULV) laboratory and the rigid STM head design are among them. Here, we present three improvements for the design of the ULV laboratory and the LT-STM: tip treatment stage, sample cleaving stage, and vibration isolation system. The improved tip treatment stage enables us to perform field emission for the purpose of tip treatment in situ without exchanging samples, while our enhanced sample cleaving stage allows us to cleave samples at low temperature in a vacuum without optical access by a simple pressing motion. Our newly designed vibration isolation system provides efficient space usage while maintaining vibration isolation capability. These improvements enhance the quality of spectroscopic imaging experiments that can last for many days and provide increased data yield, which we expect can be indispensable elements in future LT-STM designs.

Positive Rates of Preliminary Crossmatches Among Transplantation Candidates Waitlisted for Different Organs in the Korean Network for Organ Sharing.

OBJECTIVE: For deceased-donor organ transplantations, negative T cell crossmatches (XMs) are mandatory for kidney and pancreas allocation in the Korean Network for Organ Sharing (KONOS) organ allocation system. Submission and periodic renewal of serum to the KONOS is required for all transplantation candidates of kidney or pancreas and these sera are distributed to 23 laboratories for preliminary XMs. We have investigated how sensitization status varies among transplantation candidates waitlisted for different organs. METHODS: Positive rates of T cell XMs performed during recent 1-year period (from March 2014 to February 2015) in the Korea Organ Donation Agency laboratory have been analyzed according to different organs. For 163 cases of deceased donors, 3605 recipients (22.1 recipients per one donor) were crossmatched using both of National Institutes of Health and antihuman globulin complement-dependent cytotoxicity (CDC) methods and flow cytometry method. RESULTS: T cell XM positive rates varied among transplantation candidates for different organs. The positive rate was high for kidney (485/3,145, 15.4%), and low for pancreas or kidney/pancreas (7/200, 3.5%), lung (0/41, 0%), and heart (11/221, 5.0%). Among XM-positive individuals, nearly two-thirds of the kidney transplantation candidates showed strong sensitization status with CDC+/flow+ results (64.5%), whereas pancreas or kidney/pancreas transplantation candidates more commonly showed weaker sensitization status with CDC-/flow+ results (85.7%). CONCLUSION: Kidney transplantation candidates show a much higher positive rate and stronger sensitization status than candidates for other organs. The results of this study would be useful for determining the number of candidates to be crossmatched for different organs.