Background/Aims: Current society guidelines recommend antibiotic prophylaxis for 3 to 5 days after endoscopic ultrasound–guided fine-needle aspiration (EUS-FNA) of pancreatic cystic lesions (PCLs). The overall quality of the evidence supporting this recommendation is low. In this study, we aimed to assess cyst infection and adverse event rates after EUS-FNA of PCLs among patients treated with or without postprocedural prophylactic antibiotics. Methods: We retrospectively reviewed all patients who underwent EUS-FNA of PCLs between 2015 and 2019 at two large-volume academic medical centers with different practice patterns of postprocedural antibiotic prophylaxis. Data on patient demographics, cyst characteristics, fine-needle aspiration technique, periprocedural and postprocedural antibiotic prophylaxis, and adverse events were retrospectively extracted. Results: A total of 470 EUS-FNA procedures were performed by experienced endosonographers for the evaluation of PCLs in 448 patients, 58.7% of whom were women. The mean age was 66.3±12.8 years. The mean cyst size was 25.7±16.9 mm. Postprocedural antibiotics were administered in 274 cases (POSTAB+ group, 58.3%) but not in 196 cases (POSTAB– group, 41.7%). None of the patients in either group developed systemic or localized infection within the 30-day follow-up period. Procedure-related adverse events included mild abdominal pain (8 patients), intra-abdominal hematoma (1 patient), mild pancreatitis (1 patient), and perforation (1 patient). One additional case of pancreatitis was recorded; however, the patient also underwent endoscopic retrograde cholangiopancreatography. Conclusions The incidence of infection after EUS-FNA of PCLs is negligible. Routine use of postprocedural antibiotics does not add a significant benefit.

Background: and Purpose To explore the causal relationships of elements of the exposome with ischemic stroke and its subtypes at the omics level and to provide evidence for stroke prevention. Methods We conducted a Mendelian randomization study between exposure and any ischemic stroke (AIS) and its subtypes (large-artery atherosclerotic disease [LAD], cardioembolic stroke [CE], and small vessel disease [SVD]). The exposure dataset was the UK Biobank involving 361,194 subjects, and the outcome dataset was the MEGASTROKE consortium including 52,000 participants. Results: We found that higher blood pressure (BP) (systolic BP: odds ratio [OR], 1.02; 95% confidence interval [CI], 1.01 to 1.04; diastolic BP: OR, 1.03; 95% CI, 1.01 to 1.05; pulse pressure: OR, 1.03; 95% CI, 1.00 to 1.06), atrial fibrillation (OR, 1.18; 95% CI, 1.13 to 1.25), and diabetes (OR, 1.13; 95% CI, 1.07 to 1.18) were significantly associated with ischemic stroke. Importantly, higher education (OR, 0.69; 95% CI, 0.60 to 0.79) decreased the risk of ischemic stroke. Higher systolic BP (OR, 1.06; 95% CI, 1.02 to 1.10), pulse pressure (OR, 1.08; 95% CI, 1.02 to 1.14), diabetes (OR, 1.28; 95% CI, 1.13 to 1.45), and coronary artery disease (OR, 1.58; 95% CI, 1.25 to 2.00) could cause LAD. Atrial fibrillation could cause CE (OR, 1.90; 95% CI, 1.71 to 2.11). For SVD, higher systolic BP (OR, 1.04; 95% CI, 1.00 to 1.07), diastolic BP (OR, 1.06; 95% CI, 1.01 to 1.12), and diabetes (OR, 1.22; 95% CI, 1.10 to 1.36) were causal factors. Conclusions The study revealed elements of the exposome causally linked to ischemic stroke and its subtypes, including conventional causal risk factors and novel protective factors such as higher education.

Adipose tissue is a promising target for treating obesity and metabolic diseases. However, pharmacological agents usually fail to effectively engage adipocytes due to their extraordinarily large size and insufficient vascularization, especially in obese subjects. We have previously shown that during cold exposure, connexin43 (Cx43) gap junctions are induced and activated to connect neighboring adipocytes to share limited sympathetic neuronal input amongst multiple cells. We reason the same mechanism may be leveraged to improve the efficacy of various pharmacological agents that target adipose tissue. Using an adipose tissue-specific Cx43 overexpression mouse model, we demonstrate effectiveness in connecting adipocytes to augment metabolic efficacy of the β ₃-adrenergic receptor agonist Mirabegron and FGF21. Additionally, combing those molecules with the Cx43 gap junction channel activator danegaptide shows a similar enhanced efficacy. In light of these findings, we propose a model in which connecting adipocytes via Cx43 gap junction channels primes adipose tissue to pharmacological agents designed to engage it. Thus, Cx43 gap junction activators hold great potential for combination with additional agents targeting adipose tissue.

Background/Aims: Data on treatment efficacy and safety of glecaprevir/pibrentasvir (GLE/PIB) for chronic hepatitis C virus (HCV) infection in Asian patients with severe renal impairment are limited. This study aimed to study the treatment and side effects of GLE/PIB in these patients infected with non-1 genotype (GT) HCV. Methods: We prospectively recruited patients with Child’s A cirrhosis and eGFR <30 mL/min/1.73 m2 in Hong Kong and Taiwan during 2017–2018 to receive GLE/PIB treatment. Results: Twenty-one patients (GT2, n=7; GT3, n=6; and GT6, n=8) received GLE/PIB for 11.2±1.8 weeks. All except one were treatment-naïve. GLE/PIB was initiated in 16 patients while on dialysis (seven on peritoneal dialysis [PD] and nine on hemodialysis) and in five patients before dialysis. One patient died of PD-related peritonitis during treatment and two were lost to follow up. The SVR12 rate in the remaining 18 patients was 100%. All patients achieved undetectable levels at 4-, 12-, 24- and 48-week after treatment. Patients with deranged alanine aminotransferase showed normalization after 4 weeks and the response was sustained for 48 weeks. No significant adverse event was observed. Conclusions GLE/PIB treatment was associated with high efficacy and tolerability in HCV-infected patients with severe renal impairment.

Objective To establish a liquid biopsy technique of KRAS gene G12D mutation and to assess its diagnostic value. Methods KRAS G12D mutation was analyzed by ddPCR in plasma DNA from 52 colorectal cancer patients and compared that of to 80 healthy subjects. KRAS gene sequencing in cancerous tissue of colorectal cancer patient being set as a golden standard, we evaluated the accuracy of ddPCR and analyzed the correlation between G12D mutation rate, plasma concentration;and their clinical manifestations in CRC. Results ddPCR indicated that KRAS G12D mutation rate and concentration(26.92％, 81.5 copies/mL) in the plasma samples of colorectal cancer patients were significantly higher than that of healthy subjects (8.75％, 16 copies/mL). Colorectal cancer patients with highly differentiated adenocarcinoma showed a significantly higher number of mutant copies than medium and low differentiated adenocarcinoma(P＜0.05);M2 patients had a significantly higher number of mutant copies than N1 and NO patients (P＜0.05);The concordance rate of KRAS gene mutation between cancerous tissue and plasma ctDNA was 87.50％ in CRC.Conclusions ddPCR is a fast, noninvasive and accurate method for plasma testing of ctDNA, and the test results could be used to monitor the course of the disease and as clinical guidelines.

Antirheumatic Agents ; adverse effects ; Dermatitis, Exfoliative ; Humans ; Hydroxychloroquine ; adverse effects ; Lupus Erythematosus, Systemic ; drug therapy ; Psoriasis ; chemically induced

BACKGROUND: Traumatic brain injury (TBI) is associated with most trauma-related deaths. Secondary brain injury is the leading cause of in-hospital deaths after traumatic brain injury. By early prevention and slowing of the initial pathophysiological mechanism of secondary brain injury, pre-hospital service can significantly reduce case-fatality rates of TBI. In China, the incidence of TBI is increasing and the proportion of severe TBI is much higher than that in other countries. The objective of this paper is to review the pre-hospital management of TBI in China. DATA SOURCES: A literature search was conducted in January 2014 using the China National Knowledge Infrastructure (CNKI). Articles on the assessment and treatment of TBI in pre-hospital settings practiced by Chinese doctors were identified. The information on the assessment and treatment of hypoxemia, hypotension, and brain herniation was extracted from the identified articles. RESULTS: Of the 471 articles identified, 65 met the selection criteria. The existing literature indicated that current practices of pre-hospital TBI management in China were sub-optimal and varied considerably across different regions. CONCLUSION: Since pre-hospital care is the weakest part of Chinese emergency care, appropriate training programs on pre-hospital TBI management are urgently needed in China.

BACKGROUND: A long length of stay (LOS) in the emergency department (ED) associated with overcrowding has been found to adversely affect the quality of ED care. The objective of this study is to determine whether patients who speak a language other than English at home have a longer LOS in EDs compared to those whose speak only English at home.METHODS: A secondary data analysis of a Queensland state-wide hospital EDs dataset (Emergency Department Information System) was conducted for the period, 1 January 2008 to 31 December 2010.RESULTS: The interpreter requirement was the highest among Vietnamese speakers (23.1%) followed by Chinese (19.8%) and Arabic speakers (18.7%). There were significant differences in the distributions of the departure statuses among the language groups (Chi-squared=3236.88,P<0.001). Compared with English speakers, the Beta coeffi cient for the LOS in the EDs measured in minutes was among Vietnamese, 26.3 (95%CI: 22.1-30.5); Arabic, 10.3 (95%CI: 7.3-13.2); Spanish, 9.4 (95%CI: 7.1-11.7); Chinese, 8.6 (95%CI: 2.6-14.6); Hindi, 4.0 (95%CI: 2.2-5.7); Italian, 3.5 (95%CI: 1.6-5.4); and German, 2.7 (95%CI: 1.0-4.4). The fi nal regression model explained 17% of the variability in LOS.CONCLUSION: There is a close relationship between the language spoken at home and the LOS at EDs, indicating that language could be an important predictor of prolonged LOS in EDs and improving language services might reduce LOS and ease overcrowding in EDs in Queensland's public hospitals.

BACKGROUNDSeveral reports have shown the progression of articular cartilage degeneration after anterior cruciate ligament (ACL) reconstruction. No report has been published about the cartilage comparing changes after single-bundle (SB) and double-bundle (DB) ACL reconstructions. The purpose of this study was to evaluate the articular cartilage changes after SB and DB ACL reconstructions by second-look arthroscopy.

METHODSNinety-nine patients who received arthroscopic ACL reconstruction were retrospectively reviewed at an average of 14 months after reconstruction, 58 patients underwent SB ACL reconstruction and 41 patients underwent DB ACL reconstruction. Hamstring tendon autografts were used in all patients. Second-look arthroscopy was done in conjunction with the tibial staple fixation removal at least one year after the initial ACL reconstruction. Arthroscopic evaluation and grading of the articular cartilage degeneration for all patients were performed at the initial ACL reconstruction, and at the second-look arthroscopy.

RESULTSThe average cartilage degeneration at the patellofemoral joint (PFJ) was found significantly worsened after both SB and DB ACL reconstructions. This worsening were not seen at medial tibiofemoral joint (TFJ) and lateral TFJ. Grade II cartilage damage was the most common. At second-look arthroscopy, the average patellar cartilage degeneration was 1.14 ± 0.14 (at first look 0.52 ± 0.11) for the SB group, and 1.22 ± 0.15 (at first look 0.56 ± 0.12) for the DB group. The average trochlear cartilage degeneration was 1.05 ± 0.16 (at fist look 0.10 ± 0.06) and 0.66 ± 0.17 (at fist look 0.17 ± 0.09), respectively. The average patellar cartilage degeneration showed no significant difference in both groups. However, the average trochlea cartilage degeneration in DB group was significantly less than in SB group.

CONCLUSIONSPatellofemoral cartilage degeneration continued to aggravate after ACL reconstruction. DB ACL reconstruction could significantly decrease the trochlea cartilage degeneration compared with SB ACL reconstruction.

Adolescent ; Adult ; Anterior Cruciate Ligament ; surgery ; Anterior Cruciate Ligament Reconstruction ; methods ; Arthroscopy ; methods ; Cartilage, Articular ; surgery ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Second-Look Surgery ; methods ; Treatment Outcome ; Young Adult

BACKGROUNDThe proliferation and apoptosis property of mesenchymal stem cells derived from peripheral blood (PB-MSCs) were investigated under hypoxia and serum deprivation conditions in vitro so as to evaluate the feasibility for autologous PB-MSCs applications in cartilage repair.

METHODSMSCs were mobilized into peripheral blood by granulocyte colony stimulating factor (G-CSF) and AMD3100. The blood samples were collected from central ear artery of rabbits. Adhered cells were obtained by erythrocyte lysis buffer and identified as MSCs by adherence to plastic, spindle shaped morphology, specific surface markers, differentiation abilities into osteoblasts, adipocytes and chondroblasts in vitro under appropriate conditions. MSCs were cultured in four groups at different oxygen tension (20% O2 and 2% O2), with or without 10% fetal bovine serum (FBS) conditions: 20% O2 and 10% FBS complete medium (normal medium, N), 20% O2 and serum deprivation medium (D), 2% O2 and 10% FBS complete medium (hypoxia, H), 2% O2 and serum deprivation (HD). Cell proliferation was determined by CCK-8 assay. Apoptosis was detected by Annexin V/PI and terminal deoxynucleotide transferase dUTP nick end labeling (TUNEL) staining.

RESULTSSpindle-shaped adherent cells were effectively mobilized from peripheral blood by a combined administration of G-CSF plus AMD3100. These cells showed typical fibroblast-like phenotype similar to MSCs from bone marrow (BM-MSCs), and expressed a high level of typical MSCs markers CD29 and CD44, but lacked in the expression of hematopoietic markers CD45 and major histocompatibility complex Class II (MHC II). They could also differentiate into osteoblasts, adipocytes and chondroblasts in vitro under appropriate conditions. No significant morphological differences were found among the four groups. It was found that hypoxia could enhance proliferation of PB-MSCs regardless of serum concentration, but serum deprivation inhibited proliferation at the later stage of culture. Apart from that, hypoxia or serum deprivation could promote the apoptosis of PB-MSCs after 48 hours; the effect was stronger when these two conditions combined together. Furthermore, the effect of serum deprivation on apoptosis was stronger compared with that of hypoxia.

CONCLUSIONSPB-MSCs possess similar phenotypes as BM-MSCs. Their differentiation and proliferation abilities make them a new source of seed cells for ischemia-related cell therapy and tissue engineering in the field of the articular cartilage repair.

Animals ; Apoptosis ; physiology ; Cell Hypoxia ; physiology ; Cell Proliferation ; Cells, Cultured ; In Situ Nick-End Labeling ; Mesenchymal Stromal Cells ; cytology ; Rabbits