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Ankylosing spondylitis (AS) is rarely accompanied by other autoimmune diseases and/or hematologic disorders. We herein report a 46-year-old man with AS coexisting with relapsing polychondritis (RP), antiphospholipid syndrome (APS) and myelodysplastic syndrome (MDS). While receiving anti-TNF therapy for AS, the patient developed anemia and was diagnosed with MDS. After six months, he developed swelling and redness of the nose and both auricles. RP was diagnosed by an ear biopsy. Afterward, during the evaluation of a repeated fever, APS was diagnosed. This case of AS with multiple autoimmune diseases and hematologic malignancy successfully responded to a Janus kinase inhibitor (baricitinib).

Anaphylaxis is a potentially life-threatening condition that occurs in the emergency department (ED). Although anaphylaxis is rapidly recognized and treated in the hospital compared with that in the community, in some cases, it does not respond to proper management.The aim of this study is to describe our experience of cases of refractory anaphylaxis leading to cardiac arrest in hospital, to review their characteristics compared with those seen in the community, and to discuss the best management practices for anaphylaxis-induced cardiac arrest with a literature review.We reviewed the medical records of patients referred to the ED with possible in-hospital anaphylaxis between January 2017 and May 2021. According to the anaphylaxis protocol, epinephrine, corticosteroid, and antihistamine were administered immediately on-site at our institution before the study period. Refractory anaphylaxis was defined as the development of anaphylaxis-induced cardiac arrest even after following the anaphylaxis protocol.A total of 246 cases were evaluated for possible anaphylaxis, with 236 cases meeting the criteria for a diagnosis of anaphylaxis. Among them, 178 patients showed the signs and symptoms of shock, and cardiac arrest occurred in 6 patients (2.5%). Of the six patients, three had a return of spontaneous circulation before admission to the ED, while two died due to refractory cardiac arrest despite resuscitation in the ED. Following post-cardiac arrest care, including temperature management, one patient who received extracorporeal cardiopulmonary resuscitation survived neurologically intact.We present our case series to highlight the risk of developing refractory anaphylaxis with subsequent in-hospital cardiac arrest. Patients may progress to cardiac arrest within minutes despite prompt recognition and management. If patients present with potentially fatal symptoms, a more aggressive approach, including intravenous adrenaline infusion, should be taken.

A novel injectable methylcellulose (MC) hydrogel containing calcium phosphate nanoparticles (CaP NPs) was prepared by an in situ formation process, in which the precursor salts induced a salt-out effect in the MC solution. The thermo-sensitive properties of MC-CaP NPs composite hydrogels with different crystalline phases were characterized by rheometry, infrared spectroscopy and injectability test. The as-prepared MC hydrogels with bioactive CaP NPs had a suitable injectability at the body temperature, irrespective of the crystalline phases of CaP NPs. At the physiological pH condition, the structure of the MC hydrogel containing CaP NPs was analyzed by scanning electron microscopy, X-ray diffraction (XRD). The XRD results indicate that the in situ synthesized CaP NPs had a crystalline phase of hydroxyapatite (HAP). The in vitro study using mesenchymal stem cells showed that MC-HAP NPs composite hydrogel was biocompatible. The in vivo study indicated that the regeneration rate of new mature bone was also higher in the MC-HAP NPs composite hydrogel than in the pure MC hydrogel. The results of this study indicate that injectable MC-HAP NPs composite hydrogel has a great potential for bone tissue regeneration.

In addition to trauma center levels and types, trauma volume may be an important factor impacting outcomes in severe pediatric trauma.All severely injured pediatric patients treated at adult trauma centers were identified from the National Trauma Data Bank. All qualifying centers were stratified into four groups based on the cumulative pediatric trauma case volumes with ISS15: lowest (group 1), lower (group 2), higher (group 3), and highest (group 4) volume centers. Mortality rates among the groups were compared.A total of 3747 patients were stratified into group 1 (n=2122, median annual pediatric trauma volume 3 cases/year), group 2 (n=842, 15 cases/year), group 3 (n=494, 24 cases/year), and group 4 (n=289, 43 cases/year). In the hierarchical logistic regression analysis, the highest volume centers (group 4) were shown to have improved mortality (odds ratio 0.474, 95% confidence interval [CI] 0.301-0.747) compared to the lowest volume centers (group 1). Odds ratios of group 4 against group 1 for subgroups were 0.634 (age10, 95% CI 0.335-1.198), 0.491 (blunt injury, 95% CI 0.310-0.777), and 0.495 (level 1 center, 95% CI 0.312-0.785).In severe pediatric trauma treated at adult trauma centers, higher volume centers were associated with improved mortality in comparison to the lower volume centers.Level III, therapeutic/care management, retrospective comparative study without negative criteria.

Contribution of autophagy and regulation of related proteins to the degeneration of retinal pigment epithelium (RPE) in age-related macular degeneration (AMD) remain unknown. We report that upregulation of KRT8 (keratin 8) as well as its phosphorylation are accompanied with autophagy and attenuated with the inhibition of autophagy in RPE cells under oxidative stress. KRT8 appears to have a dual role in RPE pathophysiology. While increased expression of KRT8 following autophagy provides a cytoprotective role in RPE, phosphorylation of KRT8 induces pathologic epithelial-mesenchymal transition (EMT) of RPE cells under oxidative stress, which is mediated by MAPK1/ERK2 (mitogen-activated protein kinase 1) and MAPK3/ERK1. Inhibition of autophagy further promotes EMT, which can be reversed by inhibition of MAPK. Thus, regulated enhancement of autophagy with concurrent increased expression of KRT8 and the inhibition of KRT8 phosphorylation serve to inhibit oxidative stress-induced EMT of RPE cells as well as to prevent cell death, suggesting that pharmacological manipulation of KRT8 upregulation through autophagy with combined inhibition of the MAPK1/3 pathway may be attractive therapeutic strategies for the treatment of AMD.

Robotic colorectal surgery was first performed at our institution in January 2014. The objective of this study is to present our initial experience with robotic colorectal surgery. This is a retrospective review of the prospectively collected data of all patients who underwent robotic colorectal surgery from January 2014 to April 2015. Baseline, perioperative, and postoperative data were obtained for analysis. A total of 101 patients with a mean age of 56 and a body mass index of 31 underwent robotic colorectal surgery between January 2014 and April 2015. The indication for surgery was malignancy in approximately 40 per cent, diverticulitis in 40 per cent, and benign diseases in 20 per cent of the patients. The most common operation was sigmoidectomy (40%) followed by low anterior resection (36%), abdominoperineal resection (7%), right hemicolectomy (6%), rectopexy (6%), total colectomy (4%), and left hemicolectomy (1%). The mean operative and docking time was 226 (range, 104–496) minutes and 3 (range, 1–18) minutes, respectively. The median number of lymph nodes harvested was 19 (range, 0–34). The median length of stay was 3 (range, 1–18) days. Anastomotic leak occurred in one patient and surgical site infection in two patients. Robotic colorectal surgery is safe and technically feasible.

BACKGROUND Congenital muscular torticollis is a common childhood musculoskeletal anomaly that might result in permanent craniofacial deformity, facial asymmetry, and changes in the cervical vertebrae, if not treated during early childhood. Although there have been many studies on cervical vertebral changes, their onset in children has not been previously studied. METHODS Fifteen patients (aged

Non-small-cell lung cancer (NSCLC) is commonly caused by a mutation in the epidermal growth factor receptor (EGFR) and subsequent aberrant EGFR signaling with uncontrolled kinase activity. A deletion mutation in EGFR exon 19 is frequently observed in EGFR gene mutations. We designed a DNAzyme to suppress the expression of mutant EGFR by cleaving the mutant EGFR mRNA. The DNAzyme (named Ex19del Dz) specifically cleaved target RNA and decreased cancer cell viability when transfected into gefitinib-resistant lung cancer cells harboring EGFR exon 19 deletions. The DNAzyme decreased EGFR expression and inhibited its downstream signaling pathway. In addition to EGFR downregulation, Ex19del Dz containing CpG sites activated Toll-like receptor 9 (TLR9) and its downstream signaling pathway via p38 kinase, causing an immunostimulatory effect on EGFR-mutated NSCLC cells. Thus, dual effects of this DNAzyme harboring the CpG site, such as TLR9 activation and EGFR downregulation, leads to apoptosis of EGFR-mutated NSCLC cells. [BMB Reports 2018; 51(1): 27-32].

Background Congenital muscular torticollis (CMT) is a benign condition. With early diagnosis and appropriate management, it can be cured completely, leaving no residual deformity. However, long-standing, untreated CMT can lead to permanent craniofacial deformities and asymmetry. Methods Four adult patients presented to the author with long-standing, untreated CMT. Initial clinical assessment demonstrated tightness of the sternocleidomastoid muscle on the affected side. Investigation of cervical spine using 3-dimensional computed tomography scans with cervical segmentation allowed a 3-dimensional module to be separately created for each vertebra to detect any anatomical changes. Results A change in the axis of the vertebral column was noted when compared to that of the skull. Also, there were apparent anatomical changes affecting the vertebrae, which were most noticeable at the level of the atlas and axis vertebrae. These changes decreased gradually till reaching the seventh cervical vertebra, which appeared to be normal in all patients. The changes in the atlas vertebra were mostly due to its intimate relation with the skull base. The changes of the axis were the most significant, affecting mainly the superior articular facet, the lamina, and the body. Conclusions There were seemingly permanent changes along the cervical spine region in the adult patients with long-standing, untreated CMT in the form of bending and rotation deformities that might result in residual torticollis postoperatively.

Deformational plagiocephaly (DP) refers to cranial asymmetry resulting from uneven external forces. A strong association exists between DP and developmental delay. We investigated the effect of DP severity on developmental delay.Between 2010 and 2016, data from 155 patients with DP were reviewed retrospectively. Two indices were used to evaluate the deformation quantitatively: cranial index (CI) and cranial vault asymmetry index (CVAI). The Bayley Scales of Infant Development-II was used to evaluate the neurodevelopment of patients.According to the CI of the study population, 2 patients showed scaphocephaly, 12 showed mesocephaly, and 141 showed brachycephaly. For CVAI, 10 patients showed values of3.5, 10 patients showed mild deformity (3.5-6.25), 27 patients showed moderate deformity (6.25-8.75), and 108 patients showed severe deformity. The means of the mental development index (MDI) and psychomotor development index (PDI) were 91.69 ± 16.8 and 92.28 ± 17.59, respectively; after the exclusion of patients with confounding factors, the values were 96.26 and 92.9, respectively. The Spearman correlation coefficients between MDI and CI and CVAI were -0.019662 and 0.118916, respectively, whereas for PDI, the values were -0.195428 and -0.012386, respectively.There was a statistically significant neurodevelopmental delay in patients with DP. However, accelerated neurodevelopment was also encountered in many patients. MDI was found to be more affected by multiple confounding factors than PDI, whereas PDI was only affected by congenital anomalies. There was no definitive relationship between the severity of DP and the degree of developmental delay in our study group.

Background/purpose While pediatric trauma centers are shown to have lower splenectomy rate as compared to adult trauma centers, it remains unknown whether other institutional factors such as case volumes would have an impact on the splenectomy rate in pediatric blunt splenic injury (BSI). Methods Pediatric patients who sustained BSI were identified from the National Trauma Data Bank 2007–2014. A hierarchical logistic regression model was built to evaluate differences in risk-adjusted splenectomy rate and in-hospital mortality in between trauma centers with different pediatric BSI case volumes. Results A total of 7621 children who met criteria were treated at trauma centers with different pediatric BSI case volumes (0–60, 61–120, 121–180, 181–240 cases during 2007–2014 for Group 1, 2, 3, and 4, respectively). High volume centers were shown to have decreased splenectomy rates (odds ratios [OR] 0.50 and 0.64, 95% confidence intervals [CI] 0.30–0.83, 0.44–0.95 for Groups 3 and 4, respectively) with an additional survival benefit in Group 4 (OR 0.452, 95%CI 0.257–0.793) when compared to the lowest volume centers (Group 1). Conclusions Higher pediatric BSI case volume was associated with lower splenectomy rate with an additional survival benefit. Trauma centers' volume in pediatric BSI may be an important factor for the improved splenic preservation. Level of evidence Retrospective comparative study, Level III.

Incidental appendectomy (IA) could potentially increase the risk of morbidity after abdominal procedures; however, such effect is not clearly established. The aim of our study is to test the association of IA with morbidity after abdominal procedures. We identified 743 (0.37%) IA among 199,233 abdominal procedures in the National Surgical Quality Improvement Program database (2005-2009). Cases with and without IA were matched on the index current procedural terminology code. Patient characteristics were compared using chi-squared test for categorical variables and Student t test for continuous variables. Multivariate logistic regression analysis was performed. Emergency and open surgeries were associated with performing IA. Multivariate analysis showed no association of IA with mortality [odds ratio (OR) = 0.51, 95% confidence interval (CI) = 0.26-1.02], overall morbidity (OR = 1.16, 95% CI = 0.92-1.47), or major morbidity (OR = 1.20, 95% CI = 0.99-1.48). However, IA increased overall morbidity among patients undergoing elective surgery (OR = 1.31, 95% CI = 1.03-1.68) or those ≥30 years old (OR = 1.23, 95% CI = 1.00-1.51). IA was also associated with higher wound complications (OR = 1.46, 95% CI = 1.05-2.03). In conclusion, IA is an uncommonly performed procedure that is associated with increased risk of postoperative wound complications and increased risk of overall morbidity in a selected patient population.

Purpose Safety profile of different gastrostomy procedures in small children has not been well studied. This study was conducted to investigate whether complication and mortality rates differ between surgical gastrostomy (G-tube) and percutaneous endoscopic gastrostomy (PEG) in infants and neonates. Methods In this retrospective study utilizing the Kids' Inpatient Database, all infants who underwent either G-tube or PEG as a sole procedure were identified. Variables included age, gender, race, presence of neurological impairment, prematurity, complex chronic condition, and severity of illness/risk of mortality subclasses. Postoperative complication, reoperation, and mortality rates were compared between G-tube and PEG. A subgroup of neonates was also analyzed. Results A total of 1456 infants were identified (G-tube n=874, PEG n=582). In univariate analysis, the rates of adverse outcomes were not significantly different (G-tube vs PEG complication rate was 7.3% and 6.7%, p =0.65; mortality rate 1.3% and 0.7%, p =0.29, respectively). Adjusted odds ratios (ORs) for complication were 1.07 (G-tube vs PEG, 95% confidence interval [CI] 0.700–1.620) for overall infants and 1.19 (95% CI 0.601–2.350) for the neonatal subgroup. Similarly, adjusted ORs for mortality did not differ significantly both in infants (OR 1.749, 95% CI 0.532–5.755) and in the neonatal subgroup (OR 2.153, 95% CI 0.566–8.165). Conclusions When G-tube and PEG were performed as the only procedure throughout a hospitalization in infants and neonates, the two techniques had comparable risks of postoperative complications and mortalities. Level of evidence Retrospective comparative study, Level III.

Histone deacetylase 2 (HDAC2) is crucial for embryonic development, affects cytokine signaling relevant for immune responses, and is often significantly overexpressed in solid tumors, but little is known of its role in human lung cancer. In this study, we demonstrated the aberrant expression of HDAC2 in lung cancer tissues and investigated oncogenic properties of HDAC2 in human lung cancer cell lines. HDAC2 inactivation resulted in regression of tumor cell growth and activation of cellular apoptosis via p53 and Bax activation and Bcl2 suppression. In cell cycle regulation, HDAC2 inactivation caused induction of p21WAF1/CIP1 expression, and simultaneously suppressed the expressions of cyclin E2, cyclin D1, and CDK2, respectively. Consequently, this led to the hypophosphorylation of pRb protein in G1/S transition and thereby inactivated E2F/DP1 target gene transcriptions of A549 cells. In addition, we demonstrated that HDAC2 directly regulated p21WAF1/CIP1 expression in a p53-independent manner. However, HDAC1 was not related to p21WAF1/CIP1 expression and tumorigenesis of lung cancer. Lastly, we observed that sustained-suppression of HDAC2 in A549 lung cancer cells attenuated in vitro tumorigenic properties and in vivo tumor growth of the mouse xenograft model. Taken together, we suggest that the aberrant regulation of HDAC2 and its epigenetic regulation of gene transcription in apoptosis and cell cycle components play an important role in the development of lung cancer.

Human immunodeficiency virus type 1 (HIV-1) transmembrane glycoprotein gp41 is targeted by broadly-reactive neutralizing antibodies 2F5 and 4E10, making it an attractive target for vaccine development. To better assess immunogenic properties of gp41, we generated five soluble glutathione S-transferase fusion proteins encompassing C-terminal 30, 64, 100, 142, or 172 (full-length) amino acids of gp41 ectodomain from M group consensus envelope sequence. Antibody responses in HIV-1-infected patients were evaluated using these proteins and overlapping peptides. We found (i) antibody responses against different regions of gp41 varied tremendously among individual patients, (ii) patients with stronger antibody responses against membrane-proximal external region exhibit broader and more potent neutralizing activity, and (iii) several patients mounted antibodies against epitopes that are near, or overlap with, those targeted by 2F5 or 4E10. These soluble gp41 fusion proteins could be an important source of antigens for future vaccine development efforts.

Histone deacetylases (HDACs) are known to play a central role in the regulation of several cellular properties interlinked with the development and progression of cancer. Recently, HDAC1 has been reported to be overexpressed in hepatocellular carcinoma (HCC), but its biological roles in hepatocarcinogenesis remain to be elucidated. In this study, we demonstrated overexpression of HDAC1 in a subset of human HCCs and liver cancer cell lines. HDAC1 inactivation resulted in regression of tumor cell growth and activation of caspase-independent autophagic cell death, via LC3B-II activation pathway in Hep3B cells. In cell cycle regulation, HDAC1 inactivation selectively induced both p21(WAF1/Cip1) and p27(Kip1) expressions, and simultaneously suppressed the expression of cyclin D1 and CDK2. Consequently, HDAC1 inactivation led to the hypophosphorylation of pRb in G1/S transition, and thereby inactivated E2F/DP1 transcription activity. In addition, we demonstrated that HDAC1 suppresses p21(WAF1/Cip1) transcriptional activity through Sp1-binding sites in the p21(WAF1/Cip1) promoter. Furthermore, sustained suppression of HDAC1 attenuated in vitro colony formation and in vivo tumor growth in a mouse xenograft model. Taken together, we suggest the aberrant regulation of HDAC1 in HCC and its epigenetic regulation of gene transcription of autophagy and cell cycle components. Overexpression of HDAC1 may play a pivotal role through the systemic regulation of mitotic effectors in the development of HCC, providing a particularly relevant potential target in cancer therapy.