ACL Mucoid Degeneration-Anterior and Posterior Arthroscopic Decompression for Combined Knee Flexion-Extension Deficit.

Mucoid degeneration of the ACL (MDACL, ACL ganglion cysts) is a disease involving ACL thickening due to accumulation of mucoid substance and fiber degeneration with possible formation of "ganglions". Clinically, it leads to anteroposterior impingement and painful limitation of knee range of motion due to impingement of the anterior portion of the thickened ACL with the intercondylar notch during knee extension and the thickened posterior part of the ligament with posterior structures of the knee in flexion. Different treatment methods have been described, including total or partial resection of the ACL degenerative fibers. However, these techniques do not allow for ACL preservation and are associated with a risk of postoperative instability. Also, most procedures treat anterior impingement only. Therefore, the aim of this technical note is to present an arthroscopic technique allowing for minimally invasive anteroposterior ACL decompression. The technique is focused on evacuation of the interfibrous mucoid substance, ganglions, and bony decompression, as well as maintenance of ligament integrity. Its greatest advantage is that it is safe and ACL-preserving yet allows for comprehensive treatment of all intra- and extra-ligamentous possible reasons of MDACL origin and promoting good healing conditions.

Imaging Biomarkers to Predict Outcomes in Patients With Large B-Cell Lymphoma With a Day 28 Partial Response by 18F-FDG PET/CT Imaging Following CAR-T Therapy.

BACKGROUND: CD19 directed CAR-T therapy for Large B-cell lymphoma (LBCL) has shown great therapeutic response in patients with relapsed/refractory disease with response rates of 60-80%. However, in patients with a partial response (PR) on initial day 28 post CAR-T therapy imaging, clinical uncertainty remains as half of these patients will ultimately have relapsed disease.   PATIENTS: In 24 patients receiving CD19 directed CAR-T therapy for relapsed/refractory LBCL achieving a PR on day 28, we utilize imaging biomarkers by 18F-FDG PET/CT imaging at pre CAR-T therapy baseline and day 28 to determine factors that may predict best overall response (B-OR), progression free survival (PFS), and overall survival (OS).   METHODS: Out of 75 patients receiving CAR-T therapy at a single institution, we retrospectively identified and reviewed 25 (33%) as achieving a PR on day 28. PR was defined using the 2014 Lugano classification system. All patients received standard of care CD19 directed CAR-T therapy with axicabtagene ciloleucel. Two independent nuclear medicine physicians measured baseline (pre-CAR-T therapy) and day 28 PET/CT SUVmax, SUVmean and TMV (cm3) of each lesion (node, organ or marrow uptake, if any) using ROVER software. All statistical tests were two-sided and conducted at the 0.05 level of significance. R version 1.3.1099 (R-studio) was used for statistical modeling.   CONCLUSION: We demonstrate that a higher day 28 SUVmax was significantly higher in those with a B-OR of PR and in our modeling, a lower day 28 SUVmax may predict favorable PFS and OS. Additionally, lower TMV, both at baseline and day 28, may also be predictive of longer PFS and OS, while lower TLG at baseline, but not day 28 is significantly associated with a B-OR of CR. While further study is warranted, these imaging biomarkers may allow for early identification of those with a day 28 PR at highest risk for relapse leading to early intervention to improve long term outcomes.

Safety and Effectiveness of SB2 (Infliximab Biosimilar) in Adult Patients with Immune-Mediated Inflammatory Diseases: A Post-Marketing Surveillance in Korea.

INTRODUCTION: SB2 is a biosimilar of infliximab (IFX), which is approved for rheumatoid arthritis (RA), ankylosing spondylitis (AS), adult and pediatric Crohn's disease (CD), adult and pediatric ulcerative colitis (UC), psoriatic arthritis (PsA), and plaque psoriasis (PsO). The drug approval process in Korea includes post-marketing surveillance (PMS) studies to re-examine the safety and effectiveness of approved new medications. METHODS: This was a prospective, multi-center, open-label, observational, phase 4 PMS study of IFX-naïve patients or patients switched from reference IFX or another IFX-biosimilar to SB2 in all approved indications. The primary endpoint was to evaluate the safety of SB2 reported as adverse events (AEs) and adverse drug reactions (ADRs). The secondary endpoint was to evaluate the effectiveness measured as investigators' overall effectiveness assessment, categorized as improved, stable, or worsened. Furthermore, disease-specific activity scores were collected for each indication [28-joint Modified Disease Activity Score (DAS28) for RA, Korean Bath Ankylosing Spondylitis Disease Activity Index (KBASDAI), Crohn's Disease Activity Index (CDAI), and Full Mayo Score for UC]. RESULTS: In the safety and effectiveness analysis, 180 and 128 patients were included, respectively. Most patients (83.9%) were IFX-naïve patients and 16.1% were switched patients. RA (48.9%) and AS (31.1%) were the most frequent indications. Overall, 23 (12.8%) patients reported AEs and 14 (7.8%) patients reported ADRs. Serious adverse events (SAEs) were reported by 3 (1.7%) patients. As per investigators' overall effectiveness assessments, SB2 was effective in 94.6% (105/111) of IFX-naïve patients and 82.4% (14/17) of switched patients. In IFX-naïve patients, disease activity scores decreased significantly from baseline to week 30 (week 24 for AS); mean (SD) changes of disease scores for each indication were DAS28 - 1.9 (0.79) for RA, KBASDAI - 3.8 (1.68) for AS, CDAI - 200.4 (112.47) for CD, and Full Mayo Score - 6.6 (2.92) for UC. The persistence rate of SB2 treatments was 88.3% with median treatment duration of 30.1 weeks. CONCLUSION: This PMS study of the IFX-biosimilar SB2 in Korea confirmed the safety and effectiveness of SB2 in major indications.

SABR for High-Risk Prostate Cancer: A Prospective Multilevel MRI-Based Dose Escalation Trial.

PURPOSE: Radiation dose intensification improves outcome in men with high-risk prostate cancer (HR-PCa). A prospective trial was conducted to determine safety, feasibility, and maximal tolerated dose of multilevel magnetic resonance imaging (MRI)-based 5-fraction SABR in patients with HR-PCa. METHODS AND MATERIALS: This phase I clinical trial enrolled patients with HR-PCa with grade group ≥4, prostate-specific antigen (PSA) ≥20 ng/mL, or radiographic ≥T3, and well-defined prostatic lesions on multiparametric MRI (mpMRI) into 4 dose-escalation cohorts. The initial cohort received 47.5 Gy to the prostate, 50 Gy to mpMRI-defined intraprostatic lesion(s), and 22.5 Gy to pelvic lymph nodes in 5 fractions. Radiation doses were escalated for pelvic nodes to 25 Gy and mpMRI lesion(s) to 52.5 Gy and then 55 Gy. Escalation was performed sequentially according to rule-based trial design with 7 to 15 patients per cohort and a 90-day observation period. All men received peri-rectal hydrogel spacer, intraprostatic fiducial placement, and 2 years of androgen deprivation. The primary endpoint was maximal tolerated dose according to a 90-day acute dose-limiting toxicity (DLT) rate <33%. DLT was defined as National Cancer Institute Common Toxicity Criteria for Adverse Events ≥grade 3 treatment-related toxicity. Secondary outcomes included acute and delayed gastrointestinal (GI)/genitourinary (GU) toxicity graded with Common Toxicity Criteria for Adverse Events. RESULTS: Fifty-five of the 62 enrolled patients were included in the analysis. Dose was escalated through all 4 cohorts without observing any DLTs. Median overall follow-up was 18 months, with a median follow-up of 42, 24, 12, and 7.5 months for cohorts 1 to 4 respectively. Acute and late grade 2 GU toxicities were 25% and 20%, while GI were 13% and 7%, respectively. Late grade 3 GU and GI toxicities were 2% and 0%, respectively. CONCLUSIONS: SABR dose for HR-PCa was safely escalated with multilevel dose painting of 47.5 Gy to prostate, 55 Gy to mpMRI-defined intraprostatic lesions, and 25 Gy to pelvic nodal region in 5 fractions. Longer and ongoing follow-up will be required to assess late toxicity.

The impact of bridging therapy prior to CD19-directed chimeric antigen receptor T-cell therapy in patients with large B-cell lymphoma.

In the relapsed/refractory setting for treatment of large B-cell lymphoma (LBCL), chimeric antigen receptor T-cell (CAR-T) therapy has emerged as an effective treatment modality. Patients often have aggressive disease that requires prompt treatment in the form of bridging therapy (BT) for disease stabilisation while CAR-T cells are manufactured. Patients (n = 75) undergoing CAR-T therapy infusion for LBCL at our institution were identified. A total of 52 (69·3%) received BT and 23 (30·7%) received no BT (NBT). BT modalities included systemic BT (SBT) in 28 patients, radiation BT (RBT) in 14, and high-dose steroid BT (HDS) in 10. There was no difference in incidence of cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome between BT and NBT (P = 0·18 and P = 0·53 respectively). Prolonged cytopenias at Day 180 were more common in BT than NBT (50% vs. 13·3%, P = 0·04). The SBT and RBT subgroups had more cytopenias at Day 180 compared to the HDS and NBT subgroups (58·3% and 57·1% vs. 20% and 13·3% respectively, P = 0·04). Disease response at last follow-up, progression-free survival and overall survival were similar between BT, NBT, and BT subgroups. In summary, BT can be safely considered in patients undergoing CAR-T therapy. However, those undergoing BT with SBT or RBT are at higher risk of prolonged cytopenias after CAR-T therapy.

Cosmetic Outcomes of a Phase 1 Dose Escalation Study of 5-Fraction Stereotactic Partial Breast Irradiation for Early Stage Breast Cancer.

PURPOSE: Our purpose was to evaluate cosmetic changes after 5-fraction adjuvant stereotactic partial breast irradiation (S-PBI). METHODS AND MATERIALS: Seventy-five women with in situ or invasive breast cancer stage 0, I, or II, with tumor size ≤3 cm, were enrolled after lumpectomy in a phase 1 dose escalation trial of S-PBI into cohorts receiving 30, 32.5, 35, 37.5, or 40 Gy in 5 fractions. Before S-PBI, 3 to 4 gold fiducial markers were placed in the lumpectomy cavity for tracking with the Synchrony respiratory tracking system. S-PBI was delivered with a CyberKnife robotic radiosurgery system. Patients and physicians evaluated global cosmesis using the Harvard Breast Cosmesis Scale. Eight independent panelists evaluated digital photography for global cosmesis and 10 subdomains at baseline and follow-up. McNemar tests were used to evaluate change in cosmesis, graded as excellent/good or fair/poor, from baseline to year 3. Wilcoxon signed rank tests were used to evaluate change in subdomains. Cohen's kappa (κ) statistic was used to estimate interobserver agreement (IOA) between raters, and Fleiss' κ was used to estimate IOA between panelists. RESULTS: Median cosmetic follow-up was 5, 5, 5, 4, and 3 years for the 30, 32.5, 35, 37.5, and 40 Gy cohorts. Most patients reported excellent/good cosmesis at both baseline (86.3%) and year 3 (89.8%). No dose cohort had significantly worsened cosmesis by year 3 on McNemar analysis. No cosmetic subdomain had significant worsening by year 3. IOA was fair for patient-physician (κ = 0.300, P < .001), patient-panel (κ = 0.295, P < .001), physician-panel (κ = 0.256, P < .001), and individual panelists (Fleiss κ = 0.327, P < .001). CONCLUSIONS: Dose escalation of S-PBI from 30 to 40 Gy in 5 fractions for early stage breast cancer was not associated with a detectable change in cosmesis by year 3. S-PBI is a promising modality for treatment of early stage breast cancer.

Risk Factors for Fat Necrosis After Stereotactic Partial Breast Irradiation for Early-Stage Breast Cancer in a Phase 1 Clinical Trial.

PURPOSE: This study reports predictive dosimetric and physiologic factors for fat necrosis after stereotactic-partial breast irradiation (S-PBI). METHODS AND MATERIALS: Seventy-five patients with ductal carcinoma-in situ or invasive nonlobular epithelial histologies stage 0, I, or II, with tumor size <3 cm were enrolled in a dose-escalation, phase I S-PBI trial between January 2011 and July 2015. Fat necrosis was evaluated clinically at each follow-up. Treatment data were extracted from the Multiplan Treatment Planning System (Cyberknife, Accuray). Univariate and stepwise logistic regression analyses were conducted to identify factors associated with palpable fat necrosis. RESULTS: With a median follow-up of 61 months (range: 4.3-99.5 months), 11 patients experienced palpable fat necrosis, 5 cases of which were painful. The median time to development of fat necrosis was 12.7 months (range, 3-42 months). On univariate analyses, higher V32.5-47.5 Gy (P < .05) and larger breast volume (P < .01) were predictive of any fat necrosis; higher V35-50 Gy (P < .05), receiving 2 treatments on consecutive days (P = .02), and higher Dmax (P = .01) were predictive of painful fat necrosis. On multivariate analyses, breast volume larger than 1063 cm3 remained a predictive factor for any fat necrosis; receiving 2 treatments on consecutive days and higher V45 Gy were predictive of painful fat necrosis. Breast laterality, planning target volume (PTV), race, body mass index, diabetic status, and tobacco or drug use were not significantly associated with fat necrosis on univariate analysis. CONCLUSIONS: Early-stage breast cancer patients treated with breast conserving surgery and S-PBI in our study had a fat necrosis rate comparable to other accelerated partial breast irradiation modalities, but S-PBI is less invasive. To reduce risk of painful fat necrosis, we recommend not delivering fractions on consecutive days; limiting V42.5 < 50 cm3, V45 < 20 cm3, V47.5 < 1 cm3, Dmax ≤ 48 Gy and PTV < 100 cm3 when feasible; and counseling patients about the increased risk for fat necrosis when constraints are not met and for those with breast volume >1000 cm3.

Tramadol use is associated with enhanced postoperative outcomes in breast cancer patients: a retrospective clinical study with in vitro confirmation.

BACKGROUND: There is growing interest in the effect of postoperative analgesics on oncological outcomes after cancer surgery. We investigated the impact of tramadol after breast cancer surgery on recurrence and mortality and explored the mechanism by which tramadol affects cultured breast cancer cells in vitro. METHODS: Electronic medical records of patients who underwent breast cancer surgery between November 2005 and December 2010 at Severance Hospital in Korea were reviewed. Cox regression analyses were used to identify factors related to postoperative recurrence and mortality. We performed the sensitivity test with propensity score matching to adjust for selection bias. In addition, we investigated the effects of tramadol on human breast adenocarcinoma (Michigan Cancer Foundation-7 [MCF-7]) cells via assessment of cell viability, clonogenic assay, and cell cycle analysis in vitro. RESULTS: Of 2588 breast cancer patients, 36.4% had received tramadol. Those who received tramadol had a 0.71-fold decreased risk of recurrence and a 0.56-fold decrease in mortality. The MCF-7 cell viability assays showed that tramadol had an anti-proliferative effect by cell cycle arrest, suppressing colony formation, and regulation of oestrogen and progesterone receptors. Tramadol induced apoptosis of MCF-7 cells via extracellular signal-regulated kinases by decreasing of 5-hydroxytryptamine (HT)2B receptor and transient receptor potential vanilloid-1 expression. CONCLUSIONS: After breast cancer surgery, patients who received tramadol had a decreased risk of postoperative recurrence and mortality. The anti-tumour effect of tramadol appears to involve inhibition of proliferation, induction of apoptosis, and effects on 5-HT2B receptor and TRPV-1.

Propofol intravenous anaesthesia with desflurane compared with desflurane alone on postoperative liver function after living-donor liver transplantation: A randomised controlled trial.

BACKGROUND: Propofol is an anaesthetic that resembles α-tocopherol and it has been suggested that it protects against ischaemia-reperfusion injury in liver transplantation. Living-donor liver transplantation (LDLT) presents an opportunity to test this hypothesis in both donors and recipients. OBJECTIVES: We compared clinical outcomes after LDLT following anaesthesia with propofol and desflurane against desflurane alone. DESIGN: A randomised, parallel study. SETTING: Single-centre trial, study period June 2014 and May 2017. PATIENTS: Sixty-two pairs of adult donors and recipients who underwent LDLT. INTERVENTION: Patients were randomised to receive either desflurane balanced anaesthesia or propofol total intravenous anaesthesia combined with desflurane anaesthesia. MAIN OUTCOME MEASURES: The primary outcome was peak liver transaminase levels during the first 7 days after surgery. Liver function was assessed at 10 different time-points (before surgery, 1 h after reperfusion, upon arrival in the ICU, and daily until postoperative day 7). Creatinine was measured to evaluate the incidence of acute kidney injury. TNF-α, IL-1ß, IL-6 and TGF-ß1 were assessed in 31 donors after induction, at hepatectomy and at the end of surgery and in 52 recipients after induction, and 1, 3 and 24 h after reperfusion. RESULTS: Peak liver transaminase levels were not significantly different between the two groups. Liver function tests and creatinine were also similar between groups at all time-points. There was no difference in the incidence of postoperative complications, including acute kidney injury. With the exception of higher TNF-α in donors of the Propofol group at hepatectomy (0.60 ±â€Š0.29 vs. 1.03 ±â€Š0.53, P = 0.01) cytokine results were comparable between the two groups. CONCLUSION: Despite the simultaneous administration of propofol infusion in both donors and recipients, no improvement in laboratory or surgical outcome was observed after LDLT compared with patients who received desflurane anaesthesia alone. TRIAL REGISTRATION: NCT02504138 at clinicaltrials.gov.

Design and Construction of Vibrio cholerae Strains That Harbor Various CTX Prophage Arrays.

Toxigenic Vibrio cholerae strains arise upon infection and integration of the lysogenic cholera toxin phage, the CTX phage, into bacterial chromosomes. The V. cholerae serogroup O1 strains identified to date can be broadly categorized into three main groups: the classical biotype strains, which harbor CTX-cla; the prototype El Tor strains (Wave 1 strains), which harbor CTX-1; and the atypical El Tor strains, which harbor CTX-2 (Wave 2 strains) or CTX-3~6 (Wave 3 strains). The efficiencies of replication and transmission of CTX phages are similar, suggesting the possibility of existence of more diverse bacterial strains harboring various CTX phages and their arrays in nature. In this study, a set of V. cholerae strains was constructed by the chromosomal integration of CTX phages into strains that already harbored CTX phages or those that did not harbor any CTX phage or RS1 element. Strains containing repeats of the same kind of CTX phage, strains containing the same kind of CTX phage in each chromosome, strains containing alternative CTX phages in one chromosome, or containing different CTX phages in each chromosome have been constructed. Thus, strains with any CTX array can be designed and constructed. Moreover, the strains described in this study contained the toxT-139F allele, which enhances the expression of TcpA and cholera toxin. These characteristics are considered to be important for cholera vaccine development. Once their capacity to provoke immunity in human against V. cholerae infection is evaluated, some of the generated strains could be developed further to yield cholera vaccine strains.

Treatment of Unstable Distal Clavicle Fractures With Multiple Steinmann Pins-A Modification of Neer's Method: A Series of 56 Consecutive Cases.

OBJECTIVES: To introduce an alternative fixation technique for Neer type II fractures using Steinmann pins (S-pins). DESIGN: Retrospective case series study. SETTING: Operating room followed by clinic in tertiary hospital. PATIENTS/PARTICIPANTS: Between 2001 and 2013, among 66 consecutive patients diagnosed with Neer type II distal clavicle fractures, 11 patients were excluded and 56 clavicles of 55 patients who underwent surgical treatment with multiple transacromial S-pins were selected for analysis. INTERVENTION: Multiple transacromial S-pin (2.0-mm diameter) fixation was performed. Interfragmentary fixation was performed with 2.7-mm screws in case of oblique fractures. MAIN OUTCOME MEASURES: Radiographic results, complications, and clinical outcomes including the Constant-Murley score, the University of California at Los Angeles Shoulder score, and the disabilities of the arm, shoulder, and hand score were evaluated. RESULTS: Radiologic union was achieved in all patients. Coracoclavicular distance was increased by 6.4% compared with that of the uninjured side (P < 0.001). Fourteen patients had lateral migrations of 1 pin (mean migration distance, 11.6 mm). The mean Constant-Murley score was 94.3 (range, 85-100), mean University of California at Los Angeles score was 33.1 (range, 29-35), and mean disabilities of the arm, shoulder, and hand score was 2.7 (range, 0-8.3). The average follow-up period was 30.5 months (range, 24-81 months). CONCLUSIONS: Good functional and radiologic results were achieved by the insertion of multiple transacromial S-pins with interfragmentary screw fixation. With its wide indication and relatively simple procedure, this technique may be a possible surgical option for the treatment of Neer type II distal clavicle fractures. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Advanced Interval Type-2 Fuzzy Sliding Mode Control for Robot Manipulator.

In this paper, advanced interval type-2 fuzzy sliding mode control (AIT2FSMC) for robot manipulator is proposed. The proposed AIT2FSMC is a combination of interval type-2 fuzzy system and sliding mode control. For resembling a feedback linearization (FL) control law, interval type-2 fuzzy system is designed. For compensating the approximation error between the FL control law and interval type-2 fuzzy system, sliding mode controller is designed, respectively. The tuning algorithms are derived in the sense of Lyapunov stability theorem. Two-link rigid robot manipulator with nonlinearity is used to test and the simulation results are presented to show the effectiveness of the proposed method that can control unknown system well.

Advanced Fuzzy Potential Field Method for Mobile Robot Obstacle Avoidance.

An advanced fuzzy potential field method for mobile robot obstacle avoidance is proposed. The potential field method primarily deals with the repulsive forces surrounding obstacles, while fuzzy control logic focuses on fuzzy rules that handle linguistic variables and describe the knowledge of experts. The design of a fuzzy controller--advanced fuzzy potential field method (AFPFM)--that models and enhances the conventional potential field method is proposed and discussed. This study also examines the rule-explosion problem of conventional fuzzy logic and assesses the performance of our proposed AFPFM through simulations carried out using a mobile robot.

Solitary recurrence of castration-resistant prostate cancer with low or undetectable levels of prostate specific antigen salvaged with local ablative radiation therapy: A case report.

Prostate cancer recurrences are usually first detected by increased levels of prostate specific antigen (PSA), and systemic therapy is often initiated if distant metastasis is confirmed. However, low or nearly undetectable levels of PSA in the modern era of ultrasensitive PSA assay may be difficult to interpret in patients with a history of prostate cancer. Deciding whether to initiate additional systemic therapy in limited indolent metastatic disease while balancing the quality of life of the patient and ensuring the oncologic control of the disease may be challenging. In the present study, the case of a biopsy-confirmed solitary spine recurrence of prostate cancer with nearly undetectable but persistent levels of PSA (0.05 ng/ml) is reported. Treatment of the recurrence with local ablative radiotherapy improved the pain experienced by the patient, and reduced his levels of PSA to undetectable limits (<0.05 ng/ml). Repeated imaging analysis, PSA assay and clinical assessment demonstrated durable control of the disease without the requirement for additional systemic treatments. The present case highlighted the importance of initiating appropriate work-up according to the clinical scenario. Local treatment for solitary or oligometastatic recurrence of prostate cancer may enhance the effectiveness of current therapeutic strategies and benefit certain patients.

The effect of botulinum neurotoxin type A on capsule formation around silicone implants: the in vivo and in vitro study.

This study confirms that botulinum neurotoxin type A (BoNT-A) decreases capsular contracture and elucidates a possible mechanism. Silicone blocks were implanted subcutaneously in 20 mice. The experimental groups received BoNT-A (1, 2·5 or 5 U) instilled into the subcutaneous pocket. After 30 days, periprosthetic capsules were harvested and evaluated. The effect of BoNT-A on the differentiation of human dermal fibroblasts to myofibroblasts in culture was examined by Western blot analysis. Changes in transforming growth factor-beta1 (TGF-ß1) expression in cultured fibroblasts were determined by enzyme-linked immunosorbent assay (ELISA). In in vivo study, the thickness of capsules (P < 0·05) and the number of alpha-smooth muscle actin (α-SMA)(+) cells in capsules (P < 0·05) were significantly decreased in the experimental groups. TGF-ß1 was significantly underexpressed in the experimental groups (P < 0·05). In in vitro study, BoNT-A did not significantly affect fibroblast viability. Western blot analysis showed that α-SMA protein levels were significantly decreased in the experimental groups (P < 0·05). Based on ELISA, the amount of TGF-ß1 was significantly decreased in the experimental groups (P < 0·05), especially cells treated with a high dose of BoNT-A (P < 0·001). This study confirms that BoNT-A prevents capsular formation around silicone implants, possibly by blocking TGF-ß1 signalling and interrupting the differentiation of fibroblasts to myofibroblasts.

The polyamine spermine induces the unfolded protein response via the MAPK cascade in Arabidopsis.

In Arabidopsis three basic region leucine zipper (bZIP) transcription factor genes, bZIP17, bZIP28, and bZIP60, play crucial roles in the unfolded protein response (UPR). Previously we found that bZIP60 is one of the spermine-induced genes. Consequently we further investigated the response of all the three bZIP genes to spermine. Expression of bZIP17, bZIP28, and bZIP60, and also their target genes was activated by spermine application as well as in plants with elevated endogenous spermine levels. Furthermore, spermine activated the splicing of the bZIP60 transcript mediated by the ribonuclease activity of inositol-requiring enzyme 1 and also recruited bZIP17 and bZIP60 proteins from endoplasmic reticulum to nucleus. We therefore propose that spermine is a novel UPR inducer. Moreover, induction of UPR by spermine required calcium-influx to the cytoplasm and the genes for mitogen-activated protein kinase kinase 9 (MKK9), mitogen-activated protein kinase 3 (MPK3) and MPK6. The result indicates that spermine-induced UPR is mediated by the MKK9-MPK3/MPK6 cascade in Arabidopsis.

Non-Hodgkin Lymphoma of the Stomach in a Patient Treated with Natalizumab.

A 61-year-old man with relapsing-remitting multiple sclerosis developed extranodal large B-cell lymphoma of the stomach following monthly natalizumab infusions for 6 years. Development of lymphoproliferative disorders increases with chronic use of immunosuppression. Cases of primary central nervous system lymphoma as well as one case of peripheral T-cell lymphoma have previously been reported with natalizumab use. Given the absence of a known association between multiple sclerosis and extranodal presentations of diffuse large B-cell lymphoma, a causal association with natalizumab administration cannot be excluded.

Ultrasound-based diagnosis for the cervical lymph nodes in a tuberculosis-endemic area.

OBJECTIVES/HYPOTHESIS: No previous ultrasound (US) studies have investigated the diagnostic accuracy of specific US-based diagnostic protocol for cervical lymph node (LN) lesions in a tuberculosis-endemic area. This study aimed to assess the accuracy of US-based diagnosis of cervical LNs in a tuberculosis-endemic area. STUDY DESIGN: This was a retrospective cohort study. METHODS: We enrolled 495 consecutive patients who underwent US examination of the LNs in the neck. A single radiologist carried out the US examination, and established a US-based diagnosis at the time of the examination in each of the patients. We calculated the diagnostic accuracy of US for LNs in the neck by using the final results as a reference standard. RESULTS: Of 476 study cases, the number of tuberculous, nontuberculous benign, malignant, and indeterminate US category cases was 74, 224, 152, and 26, respectively. Confirmed diagnoses in these cases were as follow: tuberculous LN (n = 69), nontuberculous benign LN (n = 249), and malignant LN (n = 158). The sensitivity, specificity, positive and negative predictive values, and accuracy of tuberculous, malignant, and nontuberculous benign US categories were 90.9%, 96.4%, 81.1%, 98.4%, and 95.6%; 92.8%, 96.6%, 93.4%, 96.3%, and 95.3%; and 92.2%, 95.0%, 95.1%, 92.0%, and 93.6%, respectively. All US categories showed a high sensitivity and specificity. CONCLUSIONS: The present US-based diagnostic protocol for cervical LNs in a tuberculosis-endemic area may be useful. LEVEL OF EVIDENCE: 4.

Pediatric tracheostomy revisited: a nine-year experience using horizontal intercartilaginous incision.

OBJECTIVES/HYPOTHESIS: To describe our tracheostomy procedure using a vertical skin incision and a horizontal intercartilaginous incision and to compare our postoperative results with those in the recent literature. STUDY DESIGN: Retrospective chart review and literature review. METHODS: One hundred eleven children underwent tracheostomy using a vertical skin incision and a horizontal intercartilaginous incision over a 9-year period. A retrospective chart review was undertaken with respect to the following variables: demographics, weight, primary diagnosis, surgical indication, follow-up duration, decannulation, interval between tracheostomy and decannulation, and complications experienced. In addition, the outcomes were compared to results from a literature review. RESULTS: Of the 111 patients, 56 had a history of prolonged intubation, 52 had upper airway obstruction, and three underwent tracheostomy for tracheobronchial toileting. Three (2.7%) patients experienced early major complications without major sequelae, and 14 (12.6%) experienced late major complications. Twenty-one (18.9%) patients were decannulated during the follow-up period, whereas 17 (17.8%) died of their primary disease or tracheostomy-related complications (15 died of their primary disease and two died of tracheostomy-related complications). The complication rates showed overall no differences, but our patient series showed significantly less stomal granulation tissue formation and non-significant trend for less suprastomal collapse as compared with previous literature. CONCLUSIONS: Pediatric tracheostomy using a vertical skin incision and horizontal intercartilaginous incision is comparable with the conventional procedure in terms of complication and mortality rates. Future randomized controlled studies are mandatory to directly compare conventional tracheotomy using a vertical skin incision and a horizontal intercartilaginous incision with our procedure. LEVEL OF EVIDENCE: 4.