Renal relapse in children and adolescents with childhood-onset lupus nephritis: a 20-year study.

OBJECTIVES: There is little data on renal relapse in childhood-onset LN (cLN). We investigate the incidence, predictive factors and outcomes related to renal relapse. METHODS: We conducted a retrospective cohort study of all cLN diagnosed at ≤18 years between 2001-2021 to investigate the incidence and outcomes related to renal relapse. RESULTS: Ninety-five Chinese cLN patients (91% proliferative LN) were included. Induction immunosuppression was prednisolone and CYC [n = 36 (38%)] or MMF [n = 33 (35%)]. Maintenance immunosuppression was prednisolone and MMF [n = 53 (54%)] or AZA [n = 29 (31%)]. The rates of complete remission/partial remission (CR/PR) at 12 months were 78.9%/7.4%. Seventy renal relapses occurred in 39 patients over a follow-up of 10.2 years (s.d. 5.9) (0.07 episode/patient-year). Relapse-free survival was 94.7, 86.0, 80.1, 71.2, 68.3, 50.3 and 44.5% at 1, 2, 3, 4, 5, 10 and 20 years, respectively. Multivariate analysis showed that LN diagnosis <13.1 years [adjusted hazard ratio (HRadj) 2.59 995% CI 1.27, 5.29), P = 0.01], AZA maintenance [HRadj 2.20 (95% CI 1.01, 4.79), P = 0.05], PR [HRadj 3.9 (95% CI 1.03, 9.19), P = 0.01] and non-remission [HRadj 3.08 (95% CI 1.35, 11.3), P = 0.04] at 12 months were predictive of renal relapse. Renal relapse was significantly associated with advanced chronic kidney disease (stages 3-5) and end-stage kidney disease (17.9% vs 1.8%, P < 0.01). Furthermore, patients with renal relapse showed an increased incidence of infections (30.8% vs 10.7%, P = 0.02), osteopenia (38.5% vs 17.9%, P = 0.04) and hypertension (30.8% vs 7.1%, P < 0.01). CONCLUSION: Renal relapse is common among cLN, especially among young patients, and is associated with an increased incidence of morbidity and mortality. Attaining CR and the use of MMF appear to decrease the incidence of renal relapse.

The impact of hydrocodone rescheduling on utilization, abuse, misuse, and overdose deaths.

PURPOSE: To evaluate the impact of increased federal restrictions on hydrocodone combination product (HCP) utilization, misuse, abuse, and overdose death. METHODS: We assessed utilization, misuse, abuse, and overdose death trends involving hydrocodone versus select opioid analgesics (OAs) and heroin using descriptive and interrupted time-series (ITS) analyses during the nine quarters before and after the October 2014 rescheduling of HCPs from a less restrictive (CIII) to more restrictive (CII) category. RESULTS: Hydrocodone dispensing declined >30% over the study period, and declines accelerated after rescheduling. ITS analyses showed that immediately postrescheduling, quarterly hydrocodone dispensing decreased by 177M dosage units while codeine, oxycodone, and morphine dispensing increased by 49M, 62M, and 4M dosage units, respectively. Postrescheduling, hydrocodone-involved misuse/abuse poison center (PC) case rates had a statistically significant immediate drop but a deceleration of preperiod declines. There were small level increases in codeine-involved PC misuse/abuse and overdose death rates immediately after HCP's rescheduling, but these were smaller than level decreases in rates for hydrocodone. Heroin-involved PC case rates and overdose death rates increased across the study period, with exponential increases in PC case rates beginning 2015. CONCLUSIONS: HCP rescheduling was associated with accelerated declines in hydrocodone dispensing, only partially offset by smaller increases in codeine, oxycodone, and morphine dispensing. The net impact on hydrocodone and other OA-involved misuse/abuse and fatal overdose was unclear. We did not detect an immediate impact on heroin abuse or overdose death rates; however, the dynamic nature of the crisis and data limitations present challenges to causal inference.

Training in endoscopic ultrasonography: An Asian perspective.

Training of endoscopic ultrasonography (EUS) in Asia faces two major challenges: (i) the ever-increasing demand for skills to handle a growing range of interventional EUS procedures; and (ii) a continual shortage of EUS training programs. As the therapeutic application of EUS continues to expand, the need to train more new endosonographers and upgrade skills of existing ones has become more critical than ever before. A formal fellowship to acquire EUS knowledge and skills in an advanced endoscopy center has always been perceived as the best way of training novices, but such opportunities remain limited in most Asian countries. To keep up with the pace of development in EUS, more short-term EUS programs have been conducted across Asia in recent years. Such programs are generally intensive and may combine didactic lectures, live-case demonstrations, and hands-on training on phantoms, or live animal models for teaching. Although not as rigorous as conventional full-time EUS fellowships, such short-term programs are not necessarily inferior in quality. With courses offered from basic to advanced levels, and at regular intervals, busy practising endoscopists have the flexibility to attend the course that best matches their individual levels of experience, learn at their own pace and acquire EUS knowledge and skills over as many courses as desired. This open-ended progressive learning model is more agile than established fixed-term learning models and is expected to adapt better to future needs.

Effects of exercise and manual therapy on pain associated with hip osteoarthritis: a systematic review and meta-analysis.

AIM: To explore the effects of exercise (water-based or land-based) and/or manual therapies on pain in adults with clinically and/or radiographically diagnosed hip osteoarthritis (OA). METHODS: A systematic review and meta-analysis was performed, with patient reported pain assessed using a visual analogue scale (VAS) or the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain subscale. Data were grouped by follow-up time (0-3 months=short term; 4-12 months=medium term and; >12 months=long term), and standardised mean differences (SMD) with 95% CIs were used to establish intervention effect sizes. Study quality was assessed using modified PEDro scores. RESULTS: 19 trials were included. Four studies showed short-term benefits favouring water-based exercise over minimal control using the WOMAC pain subscale (SMD -0.53, 95% CI -0.96 to -0.10). Six studies supported a short-term benefit of land-based exercise compared to minimal control on VAS assessed pain (SMD -0.49, 95% CI -0.70 to -0.29). There were no medium (SMD -0.23, 95% CI -0.48 to 0.03) or long (SMD -0.22, 95% CI -0.51 to 0.06) term benefits of exercise therapy, or benefit of combining exercise therapy with manual therapy (SMD -0.38, 95% CI -0.88 to 0.13) when compared to minimal control. CONCLUSIONS: Best available evidence indicates that exercise therapy (whether land-based or water-based) is more effective than minimal control in managing pain associated with hip OA in the short term. Larger high-quality RCTs are needed to establish the effectiveness of exercise and manual therapies in the medium and long term.

BOB CAT: A Large-Scale Review and Delphi Consensus for Management of Barrett's Esophagus With No Dysplasia, Indefinite for, or Low-Grade Dysplasia.

OBJECTIVES: Barrett's esophagus (BE) is a common premalignant lesion for which surveillance is recommended. This strategy is limited by considerable variations in clinical practice. We conducted an international, multidisciplinary, systematic search and evidence-based review of BE and provided consensus recommendations for clinical use in patients with nondysplastic, indefinite, and low-grade dysplasia (LGD). METHODS: We defined the scope, proposed statements, and searched electronic databases, yielding 20,558 publications that were screened, selected online, and formed the evidence base. We used a Delphi consensus process, with an 80% agreement threshold, using GRADE (Grading of Recommendations Assessment, Development and Evaluation) to categorize the quality of evidence and strength of recommendations. RESULTS: In total, 80% of respondents agreed with 55 of 127 statements in the final voting rounds. Population endoscopic screening is not recommended and screening should target only very high-risk cases of males aged over 60 years with chronic uncontrolled reflux. A new international definition of BE was agreed upon. For any degree of dysplasia, at least two specialist gastrointestinal (GI) pathologists are required. Risk factors for cancer include male gender, length of BE, and central obesity. Endoscopic resection should be used for visible, nodular areas. Surveillance is not recommended for <5 years of life expectancy. Management strategies for indefinite dysplasia (IND) and LGD were identified, including a de-escalation strategy for lower-risk patients and escalation to intervention with follow-up for higher-risk patients. CONCLUSIONS: In this uniquely large consensus process in gastroenterology, we made key clinical recommendations for the escalation/de-escalation of BE in clinical practice. We made strong recommendations for the prioritization of future research.

Melatonin regulation as a possible mechanism for probiotic (VSL#3) in irritable bowel syndrome: a randomized double-blinded placebo study.

BACKGROUND: Probiotics have treatment efficacy in irritable bowel syndrome (IBS), but the exact mechanism remains obscure. One hypothesis is the mediation of melatonin levels, leading to changes in IBS symptoms. AIM: The purpose of this study was to evaluate the effects of a probiotic, VSL#3, on symptoms, psychological and sleep parameters, and pain sensitivity in IBS, and relate these parameters to in vivo melatonin levels. METHODS: Forty-two IBS patients were randomly assigned to receive VSL#3 or placebo for 6 weeks. Subjects completed bowel and psychological questionnaires, underwent rectal sensitivity testing and saliva melatonin assays. RESULTS: Abdominal pain duration and distension intensity decreased significantly in the probiotic group, along with an increase in rectal distension pain thresholds. A correlation between increase in pain tolerance and improvement in abdominal pain scores (r = 0.51, p = 0.02) was seen with probiotic. There was an increase in salivary morning melatonin levels in males treated with VSL#3, which correlated (r = 0.61) with improved satisfaction in bowel habits. When grouped based on baseline diurnal melatonin levels, patients with normal diurnal fluctuations showed an increase in morning melatonin levels with VSL#3 treatment, which significantly correlated with improved satisfaction in bowel habits (r = 0.68). They also had reduced symptom severity scores and abdominal pain duration when treated with VSL#3, as well as satisfaction with bowel movements and quality-of-life. CONCLUSIONS: VSL#3 improved symptoms and increased rectal pain thresholds. Symptom improvement correlated with a rise in morning melatonin, significant in males and subjects with normal circadian rhythm. This suggests that probiotics may act by influencing melatonin production, hence modulating IBS symptoms, in individuals with a normal circadian rhythm.

Feasibility of full-thickness gastric resection using master and slave transluminal endoscopic robot and closure by Overstitch: a preclinical study.

BACKGROUND: Gastric submucosal tumors are often treated by laparoscopic wedge resection. This study aimed to examine the feasibility of gastric full-thickness resection through a totally endoscopic approach using the master and slave transluminal endoscopic robot (MASTER), and closure of the luminal defect with an endoscopic suturing device. METHODS: The operation was performed in two live porcine models under general anesthesia. First, the anterior wall of the stomach was slung to the abdominal wall using a percutaneous suturing device. An imaginary 5-cm lesion was marked using a needle knife. After the initial mucosal incision was made using an IT knife, the MASTER was introduced through a long overtube. A circumferential mucosal incision was completed with the MASTER to expose the muscularis propria which was grasped and incised to the serosal layer by electrocautery applied through the hook of the MASTER. The full-thickness resection of the gastric wall was completed with retraction using the grasper and dissection using the hook. While the defect was being created, the luminal space was maintained with traction of the percutaneous sutures. The defect was closed with suture plication using an Apollo Overstitch device. RESULTS: Two full-thickness gastric resections were performed in two nonsurvival porcine models (body weight = 30 and 35 kg, respectively) using the MASTER. The total procedure time was 56 min for the first model and 70 min for the second model. The luminal view was maintained during the whole procedure, and there was no damage to surrounding organs throughout the whole procedure. The gastric defects were closed successfully using Overstitch, with satisfactory gastric distension and no gas leakage afterward. CONCLUSION: The current experiment demonstrated the feasibility and safety of a totally endoscopic approach for the treatment of gastric submucosal tumors: full-thickness resection with the MASTER and successful closure of the defect using Overstitch.

Current status on the diagnosis and evaluation of pancreatic tumor in Asia with particular emphasis on the role of endoscopic ultrasound.

In Asia, the incidence of pancreatic cancer in some countries has been increasing. Owing to most cases being diagnosed late, prognosis for pancreatic cancer remains dismal. It is clear that the future for pancreatic cancer lies in early detection. While the possible presence of pancreatic masses is often first raised by non-invasive abdominal imaging, such as computerized tomography and magnetic resonance imaging, smaller lesions and locoregional lymph node metastases are often not detectable by these means. Endoscopic ultrasonography (EUS) offers a higher sensitivity (93-100%) for detection of small potentially curable pancreatic masses than other existing imaging modalities. It is also recommended for the evaluation of portal vein confluence, portal vein, celiac axis, and superior mesentric artery origin, and exclusion of resectability. Due to the closer proximity of EUS to the target structure, and lower rate of needle tract seeding, EUS-guided fine-needle aspiration of pancreatic mass is considered the most suitable tissue acquisition technique. Lastly, EUS also enables the performance of endoscopic interventions. Its performance can be further enhanced with newer techniques, including contrast-enhanced ultrasound and elastrography. It is anticipated that in the near future, molecular technologies may make it possible to detect microscopic amounts of cancer in tissue or blood, predict relapse and survival after therapy, as well as determine optimal therapy.

Factors determining diagnostic yield of endoscopic ultrasound guided fine-needle aspiration for pancreatic cystic lesions: a multicentre Asian study.

BACKGROUND AND AIM: The purpose of this study was to determine (1) the diagnostic yield for endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in patients with pancreatic cystic lesions, (2) additional value of EUS-FNA over EUS alone in the diagnosis of pancreatic cysts, and (3) diagnostic sensitivity and specificity of EUS and EUS-FNA in the subset of patients where histopathology of surgical specimens were available. METHODS: All patients who underwent EUS examination for the evaluation of pancreatic cystic lesions in six Asian centres were included in the study. RESULTS: Of 298 patients with pancreatic cysts who underwent EUS, 132 (44.3 %) underwent FNA. In the entire cohort, pseudocysts and intraductal papillary mucinous neoplasm (IPMN) were the predominant cystic lesions. The cytologic yield of EUS-FNA was 47 %. On univariate analysis, factors associated with higher cytologic yield included vascular involvement on EUS, presence of solid cystic component, and increased number of needle passes during EUS-FNA. On multivariate analysis, presence of solid cystic components and increased number of needle passes during EUS-FNA were associated with higher diagnostic yield of EUS-FNA. For pancreatic cysts with a solid component, the diagnostic yield of EUS-FNA increased significantly from 44 % with one pass to 78 % with more than one pass (p = 0.016). In the absence of a solid component, the diagnostic yield was 29 % with one pass and was not significantly different from the diagnostic yield of 50 % with more than one pass, p = 0.081. CONCLUSION: The cytologic yield of EUS-FNA was 47 %. When a solid component was present in the cyst, doing more than one pass during EUS-FNA increased its diagnostic yield.

Assistive Technology to Promote Participation in Sport for People with Disabilities.

Participation in sports is identified in the UN Convention on the Rights of Persons with Disabilities as a fundamental right and is facilitated by the use of specialized Assistive Products (AP). However, little is known about the role everyday AP plays in promoting sport participation. PURPOSE: This study explores how the 50 priority APs on the World Health Organization's Assistive Products List can promote participation in sports. MATERIALS AND METHODS: We used an online survey with AP-users, caregivers, and coaches (n=96). Subsequently, we performed a thematic analysis for qualitative responses describing the use of APs in facilitating sport participation. RESULTS: Our results suggest everyday APs are required for sport participation for persons with disabilities. We present a conceptual model of AP use for sport participation. We found people with disability participate in a range of sports, contributing to community engagement. CONCLUSIONS: Access to everyday APs is integral to achieving the rights of persons with disabilities for participation in sport.

Long-Term Outcomes of Children and Adolescents With Biopsy-Proven Childhood-Onset Lupus Nephritis.

Introduction: Long-term data pertaining to childhood-onset lupus nephritis (cLN) remain extremely scarce. Methods: We conducted a retrospective cohort study of biopsy-proven cLN with onset age <18 years diagnosed from 2001 to 2020 to ascertain the long-term patient and kidney survival rates, and the incidence of advanced chronic kidney disease (CKD) (estimated glomerular filtration rate [eGFR] <60 ml/min per 1.73 m2). Results: A total of 92 subjects (78 female; age 13.7 ± 3.3 years; all Chinese) were included, with follow-up duration of 10.3 years (interquartile range, 5.8-15.9). Of these, 83 children (90%) had proliferative lupus nephritis (LN) (Class III/IV ± V). Mycophenolate was used for induction in 36%, whereas 34% received cyclophosphamide (CYC); 55% received mycophenolate as maintenance immunosuppression. The rates of complete remission (CR) and partial remission (PR) at 6 months and 12 months, respectively, were 65% and 20% and 78% and 8%. Two patients died (mortality rate 2.1/1000 patient-years), with a standardized mortality ratio of 22.3. Three patients (3.2%) developed end-stage kidney disease (ESKD), and advanced CKD occurred in 5 patients (5.4%). Survival rates without advanced CKD, ESKD, or death were 96.7%, 94.2%, 92.7%, 83.2% and 83.2% at 1 year, 5 years, 10 years, 15 years, and 20 years, respectively. Multivariate analysis revealed that severe kidney failure necessitating dialysis at presentation (adjusted hazard ratio 37.7, 95% confidence interval [CI] 4.0-355.6, P = 0.002), nonresponse (NR) after 12 months of treatment (adjusted hazard ratio 11.2, 95% CI 2.3-54.9, P = 0.003), and multiple nephritis flares (adjusted hazard ratio 2.6, 95% CI 1.1-6.2, P = 0.03) were predictive of advanced CKD, ESKD, or death. Other adverse outcomes included infections (2.9 episodes/100 patient-years), osteopenia (32%), hypertension (17%), short stature (14%), and avascular necrosis (7%). Conclusion: The long-term outcomes of cLN appeared to have improved in the present era with effective immunosuppression, cautious drug tapering, and assurance of medication adherence. There is still an unacceptably high prevalence of adverse outcomes.

Robot-assisted endoscopic submucosal dissection is effective in treating patients with early-stage gastric neoplasia.

BACKGROUND & AIMS: Endoscopic submucosal dissection (ESD) is a new technique for endoscopic resection of early-stage gastrointestinal cancers. Though ESD achieves high rate of en bloc resection, it is technically difficult to master. The development of a novel robotic endoscopic system that has 2 arms attached to an ordinary endoscope-Master and Slave Transluminal Endoscopic Robot (MASTER)-has improved the performance of complex endoluminal procedures. We evaluated the efficacy of MASTER-assisted ESD in treatment of patients with early-stage gastric neoplasia. METHODS: We performed a multicenter prospective study of 5 patients with early-stage gastric neoplasia, limited to the mucosa. After markings and circumferential mucosal incision, all submucosal dissections were performed using the MASTER system. We measured baseline demographics, tumor characteristics, and perioperative and clinical outcomes. RESULTS: All patients underwent successful MASTER-assisted ESD. The mean submucosal dissection time was 18.6 minutes (median, 16 minutes; range, 3-50 minutes). No perioperative complications were encountered. Three patients were discharged from the hospital within 12 hours and 2 on the third day after the procedures. Two patients were found to have intramucosal adenocarcinoma, 1 had high-grade dysplasia, 1 had low-grade dysplasia, and 1 had a hyperplastic polyp. The resection margins were clear of tumors in all 5 patients. No complications were observed at the 30-day follow-up examination. Follow-up endoscopic examinations revealed that none of the patients had residual or recurrent tumors. CONCLUSIONS: A flexible endoscopy robotic system can be used to perform ESD and effectively treat patients with early gastric neoplasia.

Current status on the diagnosis and management of pancreatic cysts in the Asia-Pacific region: role of endoscopic ultrasound.

Endoscopic ultrasound (EUS) and EUS-guided fine-needle aspiration (EUS-FNA) play increasingly prominent roles in the diagnosis and management of pancreatic cysts. The Asian Consortium of Endoscopic Ultrasound was recently formed to conduct collaborative research in this area. This is a review of literature on true pancreatic cysts. Due to the lack of systematic studies, there are no robust data on the true incidence of pancreatic cystic lesions in Asia and any change in over the recent decades. Certain EUS morphological features have been used to predict particular types of pancreatic cysts. Pancreatic cyst fluid viscosity, cytology, pancreatic enzymes, and tumor markers, in particular carcinoembryonic antigen, can aid in the diagnosis of pancreatic cysts. Hemorrhage and infection are the most common complications of EUS-FNA of pancreatic cysts. Pancreatic cysts can either be observed or resected depending on the benign or malignant nature, or malignant potential of the lesions. Guidelines from an international consensus did not require positive cytological findings to be present in their recommendation for resection, which included all mucinous cystic neoplasms, all main-duct intraductal papillary mucinous neoplasms (IPMN), all mixed IPMN, symptomatic side-branch IPMN, and side-branch IPMN larger than 3 cm. In patients with poor surgical risks, EUS-guided cyst ablation of mucinous pancreatic cysts is an alternative. As long-term prospective data on pancreatic cysts are still not available in Asia, management strategies are largely based on risk stratification by surgical risk and malignant potential. Gene expression profiling of pancreatic cyst fluid and confocal laser endomicroscopic examination of pancreatic cysts are novel techniques currently being studied.

Current status of Barrett's esophagus research in Asia.

In Western countries, the epidemiology of esophageal cancer has changed considerably over the past decades with a rise in the ratio of adenocarcinoma to squamous cell carcinoma. Although the prevalence of gastroesophageal reflux is increasing in Asia, the prevalences of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) have remained low in most Asian countries. The Asian Barrett's Consortium recently conducted a review of published studies on BE from Asia to assess the current status of BE research in Asia, and to recommend potential areas for future BE research in the region. Differences in study design, enrolled population, and endoscopic biopsy protocols used have led to substantial variability in the reported BE prevalence (0.06% to 19.9%) across Asia. In particular, some Japanese studies used diagnostic criteria that differed considerably from what was used in most Asian studies. As in Western countries, increased age, male sex, tobacco smoking, reflux symptoms, and erosive esophagitis have been found to be risk factors for BE in several case-control studies from Asia. The Prague C and M criteria, developed to provide better interobserver reliability in diagnosis and grading of BE, are currently under extensive evaluation in the Asian population. There is a need for standardized protocols for endoscopic and histopathologic diagnosis before initiating collaborative projects to identify etiologic determinants of BE and its ensuing malignant transformation. At present, data regarding the management and long-term outcome of BE are extremely limited in Asia. More studies of BE in this geographic area are warranted.

Repeated or Continuous Medically Supervised Ketamine Administration Associated with Hepatobiliary Adverse Events: A Retrospective Case Series.

INTRODUCTION: Emerging off-label medical uses of ketamine for the treatment of persistent conditions such as depression and chronic pain often require repeated administration. Cases reported by other countries suggest that long-term and repeated exposure to ketamine may be associated with several risks, including but not limited to hepatobiliary damage. OBJECTIVE: We aimed (1) to characterize the association between repeated administration of ketamine for off-label medical use and hepatobiliary events and (2) to describe recent trends in the use of ketamine across different clinical settings. METHODS: We conducted a retrospective case series analysis, utilizing reports identified from the US Food and Drug Administration Adverse Event Reporting System database as well as the medical literature. We included all cases reported through July 2018 describing both repeated exposure to ketamine in a hospital or ambulatory setting and a hepatobiliary adverse event. We excluded cases describing ketamine abuse. We identified adverse hepatobiliary events using the Medical Dictionary for Regulatory Activities (MedDRA®) and summarized various case characteristics including: patient demographics, route of ketamine administration, dose, time to onset of event, type of event, and pre-existing risk factors for hepatobiliary disease. To assess trends in the demand for ketamine, we used IQVIA, National Sales Perspectives™ to provide the nationally estimated number of vials sold for ketamine from the manufacturer to all US channels of distribution from 2013 through 2017. RESULTS: We identified 14 unique cases that met selection criteria with 21 hepatobiliary adverse events including liver enzyme elevation in all cases, biliary dilation with liver cirrhosis (n = 1), biliary dilation with cholangitis (n = 1), and pericholeductal fibrosis (n = 1). Most cases received ketamine for the treatment of complex regional pain syndrome or chronic pain. In cases with a reported time to onset, the majority of events occurred within 4 days. The nationally estimated number of ketamine vials sold in the USA from manufacturers to various channels of distribution increased from 1.2 million in 2013 to 2.1 million in 2017. CONCLUSIONS: We report an association between repeated or continuous administration of ketamine and hepatobiliary adverse events. Increased awareness among clinicians may mitigate these adverse outcomes, especially in the context of growing ketamine sales.

Plasma and CSF miRNA dysregulations in subarachnoid hemorrhage reveal clinical courses and underlying pathways.

BACKGROUND: Subarachnoid hemorrhage (SAH) is fatal and detrimental to quality of life. Clinically, options for monitoring are often limited, potentially missing subtle neurological changes especially in low-grade patients. This article reviewed miRNA dysregulation in SAH and analyzed their functional and clinical relevance. METHODS: With adherence to PRISMA guideline, PubMed, EMBASE, GEO and ArrayExpress were searched comprehensively for relevant clinical and animal models. Datasets were analyzed and enriched by experimentally validated targets and multiple databases using R v3.4.2, Ingenuity Pathway Analysis, and miRPath v3.0. RESULTS: Among 1926 search results, 18 studies were screened for full-text assessment. The 8 included studies revealed a marked miRNA dysregulation after SAH. 2 datasets were retrieved. In both serum and CSF, different miRNA profiles were associated with Early Brain Injury, Delayed Cerebral Infarction, vasospasm and prognosis. In CSF, a dramatic restructure of inter-miRNA correlation matrix was observed. Enrichment analysis revealed strong association (1) BBB instability, with adherens, extra-cellular matrix, actin cytoskeleton, integrin, TGF-ß, Wnt/ß-catenin etc; (2) autophagy, with MTORC1, HIF-1, ULK2, and FoxO etc; (3) apoptosis, with PI3K-Akt, p53, and AMPK. We analyzed common miRNAs across SAH and cerebral ischemia. They were related to neuronal differentiation, oxidation stress, apoptosis, angiogenesis, Alzheimer's disease, NMDA-induced calcium influx, excitotoxicity and NO production. CONCLUSIONS: Clinical progression of SAH is associated with different miRNA fingerprints. They carry neuro-pathological relevance and can be a potential biomarker which compliments SAH management.

Robotics for Advanced Therapeutic Colonoscopy.

Although colonoscopy was originally a diagnostic imaging procedure, it has now expanded to include an increasing range of therapeutic interventions. These procedures require precise maneuvers of instruments, execution of force, efficient transmission of force from the operator to the point of application, and sufficient dexterity in the mobilization of endoscopic surgical instruments. The conventional endoscope is not designed to support technically demanding endoscopic procedures. In case of colonoscopy, the tortuous anatomy of the colon makes inserting, moving, and orientating the endoscope difficult. Exerting excessive pressure can cause looping of the endoscope, pain to the patient, and even perforation of the colon. To mitigate the technical constraints, numerous technically enhanced systems have been developed to enable better control of instruments and precise delivery of force in the execution of surgical tasks such as apposing, grasping, traction, counter-traction, and cutting of tissues. Among the recent developments are highly dexterous robotic master and slave systems, computer-assisted or robotically enhanced conventional endoscopes, and autonomously driven locomotion devices that can effortlessly traverse the colon. Developments in endoscopic instrumentations have overcome technical barriers and opened new horizons for further advancements in therapeutic interventions. This review describes examples of some of these systems in the context of their applications to advanced therapeutic colonoscopy.