[Relationship between serum 1, 5-anhydroglucitol level and insulin resistance, microvascular complications in type 2 diabetes mellitus].

Objective: To explore the relationship between serum 1, 5-dehydratoglucitol (1, 5-AG) level and insulin resistance, microvascular complications in patients with type 2 diabetes mellitus (T2DM). Methods: The clinical data of 836 patients with T2DM admitted to the Changsha Central Hospital Affiliated to University of South China from May to December 2023 were retrospectively and cross-sectionally analyzed. Serum 1, 5-AG levels were detected by pyranose oxidase method. According to the microvascular complications (diabetic peripheral neuropathy, diabetic nephropathy, diabetic retinopathy), the patients were divided into simple group (no microvascular complications, n=490), complication group 1 (1 microvascular complications, n=217), and complication group 2 (2 or more microvascular complications, n=129). The relationship between serum 1, 5-AG level and the related indicators of insulin resistance in T2DM patients were explored by Spearman correlation analysis, and the influencing factors of microvascular complications in T2DM patients were explored by multiple ordered logistic regression analysis. Results: The levels of FBG(fasting blood glucose) [(7.37±0.56) mmol/L], FINS(fasting insulin) [(11.34±1.86) mU/L] and HOMA-IR(homeostatic model assessment of insulin resistance) (0.96±0.31) in simple group were lower than those in complication group 1 [(8.37±1.02) mmol/L, (16.26±2.32) mU/L, (1.32±0.41)], complication group 2 [(10.25±2.13) mmol/L, (18.53±2.67) mU/L, (1.54±0.44)], and FBG, FINS and HOMA-IR in complication group 1 were lower than those in complication group 2, and the differences were statistically significant (F=537.470, 791.690, 136.340, P<0.001). Serum 1, 5-AG level in simple group [77.16 (16.30, 128.07) µg/ml] was higher than that in complication group 1 [51.05 (14.67, 63.18) µg/ml] and complication group 2 [30.42 (12.53, 47.26) µg/ml], and the serum level of 1, 5-AG in complication group 1 was higher than that in complication group 2, and the difference was statistically significant (H=210.020, P<0.001). The results of Spearman correlation analysis showed that serum 1, 5-AG level was negatively correlated with FBG, FINS and HOMA-IR in T2DM patients (r=-0.431, -0.372, -0.546, P<0.001). The results of multiple ordered logistic regression analysis showed that Longer duration of diabetes (OR=2.261, 95%CI: 1.564-3.269), increased HbA1c (OR=2.040, 95%CI: 1.456-2.858), and increased HOMA-IR (OR=2.158, 95%CI: 1.484-3.137) and decreased 1, 5-AG (OR=2.512, 95%CI: 1.691-3.732) were independent risk factors for microvascular complications in T2DM patients (P<0.05). The results of ROC curve analysis showed that the area under the curve of serum 1, 5-AG in the identification of one microvascular complication was 0.763 (95%CI: 0.731-0.795), and the area under the curve of serum 1, 5-AG in the identification of two or more microvascular complications was 0.730 (95%CI: 0.692-0.767). Conclusion: Serum 1, 5-AG level is negatively correlated with insulin resistance in T2DM patients. Low serum 1, 5-AG level may be an independent risk factor for microvascular complications in T2DM patients.

FDG-PET to predict long-term outcome from anti-PD-1 therapy in metastatic melanoma.

BACKGROUND: We have previously shown that 75% of patients treated with programmed cell death protein 1 (PD-1) with or without CTLA4 who have not progressed by 1 year have complete metabolic response (CMR), including two-thirds of patients with partial response (PR). We now report 5-year outcomes. PATIENTS AND METHODS: Retrospective analysis of 104 patients with baseline and 1-year positron emission tomography (PET) and computed tomography (CT). The 1-year response was determined using RECIST for CT and European Organisation for Research and Treatment of Cancer (EORTC) criteria for PET. Progression-free survival (PFS) and overall survival (OS) were determined from the 1-year landmark. RESULTS: At the median follow-up of 61 months (range 58-64 months) from 1-year PET, 94% remained alive and all but one had discontinued treatment after a median treatment duration of 23 months (range 1-59 months). Disease progression occurred in 19 patients (18%): 10 (53%) while on treatment and 12 (63%) in solitary sites for which 8 (67%) received local treatment. RECIST PFS rate at 5 years after PET was higher in complete response (CR) compared with PR/stable disease (SD) (93% versus 76%, respectively) and CMR compared with non-CMR (90% versus 54%, respectively). In patients with PR, 5-year PFS rate was superior in CMR (88% and 59%). A total of 35 (34%) patients (14/29 in CR, 31/78 in CMR) discontinued treatment within 12 months, largely due to toxicity, with no impact on PFS rate compared with those that continued (84% versus 78%). Despite progression events, OS rate at 5 years was excellent and similar in patients with CR and PR/SD (100% versus 91%, respectively) as well as in those with CMR and non-CMR (96% versus 87%, respectively). CONCLUSIONS: Five years after the 1-year PET, sustained responses are observed in the majority of patients, particularly in those with CMR. PET continues to predict progression better than CT, particularly in those with residual disease on CT. In the minority that progress, often in solitary sites and managed locally, OS rate remains excellent. PET is effective in evaluating residual lesions on CT and can predict long-term benefit.

Case series: Vaginal pessary for pelvic organ prolapse and its association with vaginal cancer.

Vaginal pessaries have long been used in the management of pelvic organ prolapse as an alternative option for surgery. Vaginal cancer is a very rare form of gynaecological malignancy, and its association with vaginal ring pessaries has yet to be clearly established. We examined the cases of vaginal cancers in a tertiary state hospital for the last three years and found four cases of vaginal cancers, in which three of these cases were associated with a long history of using vaginal ring pessary for pelvic organ prolapse. Two of them had defaulted follow- up and presented with a vaginal mass and vaginal bleeding. These two cases did not have evidence of distant metastases, one of them underwent surgical removal of the tumour and radiotherapy, whilst the other case was initially given neoadjuvant chemotherapy, but the patient died prior to her planned surgery. The third patient declined further investigation and treatment after she was diagnosed with vaginal cancer. In conclusion, such potential serious long term complication from vaginal pessary should be informed prior to its insertion, it is also imperative to ensure compliance to regular follow- up for patients on vaginal pessaries, and to biopsy any suspicious chronic vaginal ulcers.

Is lower dose of intramuscular dexamethasone injection beneficial in reducing neonatal respiratory morbidity for elective caesarean section deliveries at 37 to 38 weeks? An observational study.

INTRODUCTION: The use of intramuscular (IM) dexamethasone injections before an elective caesarean delivery at term has been shown in multiple randomized controlled trials to reduce the rates of transient tachypnoea of the newborn, and admission to neonatal care. Recent studies have suggested that a complete course of IM steroids can be associated with long term harmful consequences to the infants born, and there have been studies suggesting that a lower dose of IM corticosteroids can be beneficial. Therefore, we aim to establish if halving the dose of dexamethasone to 12mg can demonstrate any benefit for term elective caesarean section deliveries whilst minimizing foetal exposure. METHODS: An observational controlled study comparing neonatal respiratory morbidities before and after the single dose 12mg dexamethasone was implemented in our obstetrics and gynaecology centre for term elective caesarean section deliveries. We included singleton pregnancies from 37+0 to 38+6 weeks undergoing elective caesarean section into our study. A total of 674 patients fulfilled the inclusion criteria and were recruited. We compared the rates and duration of admission to neonatal intensive care unit, the need for mechanical ventilation and the rate of transient tachypnoea of the newborn in the first half of 2019 without IM dexamethasone injections against the second half of the year when a single dose IM dexamethasone was given. RESULTS: IM dexamethasone injection did not show any significant benefit with regards to reducing the admission to neonatal care (OR 0.97, p- value 0.69), admission to neonatal intensive care unit (OR 0.91, p- value 0.80), the need for mechanical ventilation (OR 0.98, p- value 0.95), and the incidence of transient tachypnoea of the newborn (OR1.01, p- value 0.96). There was also no significant difference for the duration of admission in the neonatal intensive care unit for both groups (p- value 0.17). CONCLUSIONS: This study showed that there was no significant benefit gained from the lower dose antenatal corticosteroids for term elective caesarean section deliveries and considering that there have been long term harmful consequences demonstrated from the higher dose of antenatal corticosteroids at term, this practice should therefore be discontinued until a larger study is done to refute these findings. The use of such dexamethasone should only be a viable option in a research setting.

Mechanisms of resistance to selective RET tyrosine kinase inhibitors in RET fusion-positive non-small-cell lung cancer.

BACKGROUND: Rearranged during transfection (RET) gene fusions are a validated target in non-small-cell lung cancer (NSCLC). RET-selective inhibitors selpercatinib (LOXO-292) and pralsetinib (BLU-667) recently demonstrated favorable antitumor activity and safety profiles in advanced RET fusion-positive NSCLC, and both have received approval by the US Food and Drug Administration for this indication. Insights into mechanisms of resistance to selective RET inhibitors remain limited. PATIENTS AND METHODS: This study was performed at five institutions. Tissue and/or cell-free DNA was obtained from patients with RET fusion-positive NSCLC after treatment with selpercatinib or pralsetinib and assessed by next-generation sequencing (NGS) or MET FISH. RESULTS: We analyzed a total of 23 post-treatment tissue and/or plasma biopsies from 18 RET fusion-positive patients who received an RET-selective inhibitor (selpercatinib, n = 10; pralsetinib, n = 7; pralsetinib followed by selpercatinib, n = 1, with biopsy after each inhibitor). Three cases had paired tissue and plasma samples, of which one also had two serial resistant tissue specimens. The median progression-free survival on RET inhibitors was 6.3 months [95% confidence interval 3.6-10.8 months]. Acquired RET mutations were identified in two cases (10%), both affecting the RET G810 residue in the kinase solvent front. Three resistant cases (15%) harbored acquired MET amplification without concurrent RET resistance mutations, and one specimen had acquired KRAS amplification. No other canonical driver alterations were identified by NGS. Among 16 resistant tumor specimens, none had evidence of squamous or small-cell histologic transformation. CONCLUSIONS: RET solvent front mutations are a recurrent mechanism of RET inhibitor resistance, although they occurred at a relatively low frequency. The majority of resistance to selective RET inhibition may be driven by RET-independent resistance such as acquired MET or KRAS amplification. Next-generation RET inhibitors with potency against RET resistance mutations and combination strategies are needed to effectively overcome resistance in these patients.

FDG-PET response and outcome from anti-PD-1 therapy in metastatic melanoma.

Background: Immune checkpoint inhibitor therapy has resulted in impressive and durable clinical activity for many cancers including melanoma; however, there remain few reliable predictors for long-term response. This study investigated whether [18F]2-fluoro-2-deoxy-D-glucose (FDG-PET) imaging may better predict long-term outcomes compared with standard computed tomography (CT) response criteria. Patients and methods: Retrospective analysis of metastatic melanoma patients treated with anti-PD-1-based immunotherapy with baseline and 1-year FDG-PET and CT imaging at Melanoma Institute Australia. One-year response was determined using RECIST for CT and EORTC criteria for PET, coded as complete response (CR or CMR), partial response (PR or PMR), stable disease (SD or SMD) or progressive disease (PD or PMD). Progression-free survival (PFS) was determined from the 1-year landmark. Results: Patients (n = 104) were evaluated with median follow-up 30.1 months and 98% remain alive. Most received anti-PD-1 as monotherapy (67%) or combined with ipilimumab (31%). At 1 year, 28% had CR, 66% had PR and 6% had SD on CT, while 75% had CMR, 16% PMR and 9% SMD/PMD on PET. CMR was observed in 68% of patients with PR on CT. RECIST PFS post 1-year landmark was similar in patients with CR versus PR/SD, but improved in patients with CMR versus non-CMR {median not reached [NR] versus 12.8 month; hazard ratio [HR] 0.06 [95% confidence interval (CI) 0.02-0.23]; P < 0.01}. In patients with PR on CT, PFS was improved in patients with PR + CMR versus PR + non-CMR (median NR versus 12.8 months; HR 0.07 [95% CI 0.02-0.27]; P < 0.01). In the 78 CMR patients, 78% had discontinued treatment and 96% had ongoing response. Conclusions: Whilst only a small proportion of patients have a CR at 1 year, most patients with a PR have CMR on PET. Almost all patients with CMR at 1 year have ongoing response to therapy thereafter. PET may have utility in predicting long-term benefit and help guide discontinuation of therapy.

Design and development of low cost polyurethane biopolymer based on castor oil and glycerol for biomedical applications.

In the current study, we present the synthesis of novel low cost bio-polyurethane compositions with variable mechanical properties based on castor oil and glycerol for biomedical applications. A detailed investigation of the physicochemical properties of the polymer was carried out by using mechanical testing, ATR-FTIR, and X-ray photoelectron spectroscopy (XPS). Polymers were also tested in short term in-vitro cell culture with human mesenchymal stem cells to evaluate their biocompatibility for potential applications as biomaterial. FTIR analysis confirmed the synthesis of castor oil and glycerol based PU polymers. FTIR also showed that the addition of glycerol as co-polyol increases crosslinking within the polymer backbone hence enhancing the bulk mechanical properties of the polymer. XPS data showed that glycerol incorporation leads to an enrichment of oxidized organic species on the surface of the polymers. Preliminary investigation into in vitro biocompatibility showed that serum protein adsorption can be controlled by varying the glycerol content with polymer backbone. An alamar blue assay looking at the metabolic activity of the cells indicated that castor oil based PU and its variants containing glycerol are non-toxic to the cells. This study opens an avenue for using low cost bio-polyurethane based on castor oil and glycerol for biomedical applications.

Dutch Chronic Pancreatitis Registry (CARE): design and rationale of a nationwide prospective evaluation and follow-up.

BACKGROUND: Chronic pancreatitis is a complex disease with many unanswered questions regarding the natural history and therapy. Prospective longitudinal studies with long-term follow-up are warranted. METHODS: The Dutch Chronic Pancreatitis Registry (CARE) is a nationwide registry aimed at prospective evaluation and follow-up of patients with chronic pancreatitis. All patients with (suspected) chronic or recurrent pancreatitis are eligible for CARE. Patients are followed-up by yearly questionnaires and review of medical records. Study outcomes are pain, disease complications, quality of life, and pancreatic function. The target sample size was set at 500 for the first year and 1000 patients within 3 years. RESULTS: A total of 1218 patients were included from February 2010 until June 2013 by 76 participating surgeons and gastroenterologist from 33 hospitals. Participation rate was 90% of eligible patients. Eight academic centers included 761 (62%) patients, while 25 community hospitals included 457 (38%). Patient centered outcomes were assessed by yearly questionnaires, which had a response rate of 85 and 82% for year 1 and 2, respectively. The median age of patients was 58 years, 814 (67%) were male, and 38% had symptoms for less than 5 years. DISCUSSION: The CARE registry has successfully recruited over 1200 patients with chronic and recurrent pancreatitis in about 3 years. The defined inclusion criteria ensure patients are included at an early disease stage. Participation and compliance rates are high. CARE offers a unique opportunity with sufficient power to investigate many clinical questions regarding natural course, complications, and efficacy and timing of treatment strategies.

Subacute delayed ascending myelopathy: not just a post-traumatic disorder.

STUDY DESIGN: Case report. OBJECTIVES: Subacute delayed ascending myelopathy (SDAM), also known as subacute post-traumatic ascending myelopathy, is a rare early neurological complication of spinal cord injury (SCI), and the aetiology, pathogenesis and optimal management of this condition are poorly understood. The radiological features together with the clinical picture appear to be the most useful. We aim to increase awareness and further characterise SDAM. SETTING: Spinal Cord Injuries Unit, Royal North Shore Hospital, Sydney, Australia. METHODS AND RESULTS: We report two cases with radiological findings consistent with SDAM, and review the literature. Only a small number of cases have been reported and importantly, we report the first case occurring following a non-traumatic SCI. There are several hypotheses regarding pathogenesis, with several factors in our cases implicating a vascular mechanism. CONCLUSION: There is a lack of data characterising SDAM, and ascending myelopathy in a stable SCI should alert the clinician. Importantly, we propose that SDAM is the appropriate terminology.

[The Ogilvie syndrome in elderly patients with multimorbidity]. / Het Ogilvie-syndroom bij oudere patiënten met multiproblematiek.

Two patients presented with the Ogilvie syndrome which is an acute colonic pseudo-obstruction without any mechanical obstruction. Both patients suffered from multiple medical conditions such as infections, electrolyte disturbances and functional decline.The Ogilvie syndrome is particularly seen in patients with multimorbidity who stay in the hospital or nursing home. The incidence of the Ogilvie syndrome will probably increase because of ageing of our population and will be most prevalent in the frail elderly. The precise mechanism of this disease is still unclear, but there is evidence in the literature that the aetiology is multifactorial and runs via autonomic dysregulation of the colon.Early recognition and appropriate treatment may reduce the risk of complications and limit mortality, also depending on the related comorbidity.

Tumours with elevated levels of the Notch and Wnt pathways exhibit efficacy to PF-03084014, a γ-secretase inhibitor, in a preclinical colorectal explant model.

BACKGROUND: Dysregulation of the Notch pathway has been identified to play an important role in the development and progression of colorectal cancer (CRC). In this study, we used a patient-derived CRC explant model to investigate the efficacy of the clinical γ-secretase inhibitor (GSI) PF-03084014. METHODS: A total of 16 CRC explants were treated with PF-03084014. Knockdown of RBPjκ gene was used to determine the specificity of PF-03084014. Evaluation of the Notch and Wnt pathways in CRC explant tumours was performed by gene array and immunoblotting. RESULTS: We identified a subset of CRC tumours that exhibited elevations of the Notch and Wnt pathways sensitive to PF-03084014. Treatment with the GSI resulted in a significant reduction in cleaved Notch, Axin2 (Wnt-dependent gene) and active ß-catenin. In addition, knockdown of the RBPjκ gene showed that PF-03084014 has specificity for the Notch pathway in an HCT116 cell line xenograft model. Finally, an increase in apoptosis was observed in CRC001- and CRC021-sensitive tumours. CONCLUSION: This study provides evidence that inhibition of γ-secretase may be beneficial in a subset of patients with elevated levels of the Wnt and Notch pathways.

Recommendations for the use of next-generation sequencing in patients with metastatic cancer in the Asia-Pacific region: a report from the APODDC working group.

INTRODUCTION: Next-generation sequencing (NGS) diagnostics have shown clinical utility in predicting survival benefits in patients with certain cancer types who are undergoing targeted drug therapies. Currently, there are no guidelines or recommendations for the use of NGS in patients with metastatic cancer from an Asian perspective. In this article, we present the Asia-Pacific Oncology Drug Development Consortium (APODDC) recommendations for the clinical use of NGS in metastatic cancers. METHODS: The APODDC set up a group of experts in the field of clinical cancer genomics to (i) understand the current NGS landscape for metastatic cancers in the Asia-Pacific (APAC) region; (ii) discuss key challenges in the adoption of NGS testing in clinical practice; and (iii) adapt/modify the European Society for Medical Oncology guidelines for local use. Nine cancer types [breast cancer (BC), gastric cancer (GC), nasopharyngeal cancer (NPC), ovarian cancer (OC), prostate cancer, lung cancer, and colorectal cancer (CRC) as well as cholangiocarcinoma and hepatocellular carcinoma (HCC)] were identified, and the applicability of NGS was evaluated in daily practice and/or clinical research. Asian ethnicity, accessibility of NGS testing, reimbursement, and socioeconomic and local practice characteristics were taken into consideration. RESULTS: The APODDC recommends NGS testing in metastatic non-small-cell lung cancer (NSCLC). Routine NGS testing is not recommended in metastatic BC, GC, and NPC as well as cholangiocarcinoma and HCC. The group suggested that patients with epithelial OC may be offered germline and/or somatic genetic testing for BReast CAncer gene 1 (BRCA1), BRCA2, and other OC susceptibility genes. Access to poly (ADP-ribose) polymerase inhibitors is required for NGS to be of clinical utility in prostate cancer. Allele-specific PCR or a small-panel multiplex-gene NGS was suggested to identify key alterations in CRC. CONCLUSION: This document offers practical guidance on the clinical utility of NGS in specific cancer indications from an Asian perspective.

Are intravitreal injections essential during the COVID-19 pandemic? Global preferred practice patterns and practical recommendations.

Tertiary outpatient ophthalmology clinics are high-risk environments for COVID-19 transmission, especially retina clinics, where regular follow-up is needed for elderly patients with multiple comorbidities. Intravitreal injection therapy (IVT) for chronic macular diseases, is one of the most common procedures performed, associated with a significant burden of care because of the vigorous treatment regimen associated with multiple investigations. While minimizing the risk of COVID-19 infection transmission is a priority, this must be balanced against the continued provision of sight-saving ophthalmic care to patients at risk of permanent vision loss. This review aims to give evidence-based guidelines on managing IVT during the COVID-19 pandemic in common macular diseases such as age-related macular degeneration, diabetic macula edema and retinal vascular disease and to report on how the COVID-19 pandemic has affected IVT practices worldwide.To illustrate some real-world examples, 18 participants in the International Retina Collaborative, from 15 countries and across four continents, were surveyed regarding pre- and during- COVID-19 pandemic IVT practices in tertiary ophthalmic centers. The majority of centers reported a reduction in the number of appointments to reduce the risk of the spread of COVID-19 with varying changes to their IVT regimen to treat various macula diseases. Due to the constantly evolving nature of the COVID-19 pandemic, and the uncertainty about the normal resumption of health services, we suggest that new solutions for eye healthcare provision, like telemedicine, may be adopted in the future when we consider new long-term adaptations required to cope with the COVID-19 pandemic.

Integrated preclinical and clinical development of mTOR inhibitors in pancreatic cancer.

BACKGROUND: The purpose of this work was to determine the efficacy of inhibiting mammalian target of rapamycin (mTOR) in pancreatic cancer preclinical models and translate preclinical observations to the clinic. METHODS: Temsirolimus (20 mg Kg(-1) daily) was administered to freshly generated pancreatic cancer xenografts. Tumour growth inhibition was determined after 28 days. Xenografts were characterised at baseline by gene expression and comparative genomic hybridisation. Patients with advanced, gemcitabine-resistant pancreatic cancer were treated with sirolimus (5 mg daily). The primary end point was 6-month survival rate (6mSR). Correlative studies included immunohistochemistry assessment of pathway expression in baseline tumours, drug pharmacokinetics (PKs), response assessment by FDG-PET and pharmacodynamic effects in peripheral-blood mononuclear cells (PBMCs). RESULTS: In all, 4 of 17 xenografts (23%) responded to treatment. Sensitive tumours were characterised by gene copy number variations and overexpression of genes leading to activation of the PI3K/Akt/mTOR pathway. Activation of p70S6K correlated with drug activity in the preclinical studies. Sirolimus was well tolerated in the clinic, showed predictable PKs, exerted pathway inhibition in post-treatment PBMCs and resulted in a 6mSR of 26%. No correlation, however, was found between activated p70S6K in tumour tissues and anti-tumour effects. CONCLUSION: Sirolimus activity in pancreatic cancer was marginal and not predicted by the selected biomarker.

Direct patterning in sub-surface of stainless steel using laser pulses.

This paper reports for the first time on the direct creating microcavities in sub-surface of stainless steel using a single Nd:YAG laser pulse. The low peak power density is used in the process, which is in the order of 1 MW/cm(2). The formation of the microcavities in the sub-surface of stainless steel is an evidence of volume expulsion during laser-metal interaction. Direct patterning in the sub-surface of stainless steel is demonstrated by realizing a series of microcavities to form a pre-designed pattern. Potential applications of sub-surface patterning in metal, such as security marking, micro-heater, micro-insulator and micro-sensor, are discussed.

[A man with vomiting and retrosternal pain and dysphagia]. / Een brakende man met retrosternale pijn en dysfagie.

A 67-year-old male presents with complaints of severe retrosternal pain, frequent vomiting and dysphagia. Endoscopy revealed a very large intramural oesophageal hematoma, obliterating the lumen. Additional CT-imaging showed peri-oesophageal air collections, indicative for oesophageal perforation (compatible with Boerhaave's syndrome). Patient was treated successfully with intravenous antibiotics and fluid. Follow-up endoscopy after one year showed full recovery of the oesophageal wall.

An overview of the clinical applications of optical coherence tomography angiography.

Optical coherence tomography angiography (OCTA) has emerged as a novel, non-invasive imaging modality that allows the detailed study of flow within the vascular structures of the eye. Compared to conventional dye angiography, OCTA can produce more detailed, higher resolution images of the vasculature without the added risk of dye injection. In our review, we discuss the advantages and disadvantages of this new technology in comparison to conventional dye angiography. We provide an overview of the current OCTA technology available, compare the various commercial OCTA machines technical specifications and discuss some future software improvements. An approach to the interpretation of OCTA images by correlating images to other multimodal imaging with attention to identifying potential artefacts will be outlined and may be useful to ophthalmologists, particularly those who are currently still unfamiliar with this new technology. This review is based on a search of peer-reviewed published papers relevant to OCTA according to our current knowledge, up to January 2017, available on the PubMed database. Currently, many of the published studies have focused on OCTA imaging of the retina, in particular, the use of OCTA in the diagnosis and management of common retinal diseases such as age-related macular degeneration and retinal vascular diseases. In addition, we describe clinical applications for OCTA imaging in inflammatory diseases, optic nerve diseases and anterior segment diseases. This review is based on both the current literature and the clinical experience of our individual authors, with an emphasis on the clinical applications of this imaging technology.

GENIPAC: A Genomic Information Portal for Head and Neck Cancer Cell Systems.

Head and neck cancer (HNC)-derived cell lines represent fundamental models for studying the biological mechanisms underlying cancer development and precision therapies. However, mining the genomic information of HNC cells from available databases requires knowledge on bioinformatics and computational skill sets. Here, we developed a user-friendly web resource for exploring, visualizing, and analyzing genomics information of commonly used HNC cell lines. We populated the current version of GENIPAC with 44 HNC cell lines from 3 studies: ORL Series, OPC-22, and H Series. Specifically, the mRNA expressions for all the 3 studies were derived with RNA-seq. The copy number alterations analysis of ORL Series was performed on the Genome Wide Human Cytoscan HD array, while copy number alterations for OPC-22 were derived from whole exome sequencing. Mutations from ORL Series and H Series were derived from RNA-seq information, while OPC-22 was based on whole exome sequencing. All genomic information was preprocessed with customized scripts and underwent data validation and correction through data set validator tools provided by cBioPortal. The clinical and genomic information of 44 HNC cell lines are easily assessable in GENIPAC. The functional utility of GENIPAC was demonstrated with some of the genomic alterations that are commonly reported in HNC, such as TP53, EGFR, CCND1, and PIK3CA. We showed that these genomic alterations as reported in The Cancer Genome Atlas database were recapitulated in the HNC cell lines in GENIPAC. Importantly, genomic alterations within pathways could be simultaneously visualized. We developed GENIPAC to create access to genomic information on HNC cell lines. This cancer omics initiative will help the research community to accelerate better understanding of HNC and the development of new precision therapeutic options for HNC treatment. GENIPAC is freely available at http://genipac.cancerresearch.my/ .

Is there any association between referral indications for open-access upper gastrointestinal endoscopy and endoscopic findings?

BACKGROUND AND STUDY AIM: The total number of upper gastrointestinal endoscopies is increasing, and despite guidelines for endoscopy referral for general practitioners, the proportion of patients found to have no endoscopic abnormalities is still up to 60% (and increasing). The aim of this study was to assess the association between general practitioners' referral indications and endoscopic findings. PATIENTS AND METHODS: General practitioners of patients referred for an open-access endoscopy between January 2002 and December 2004 were asked to specify the reason for referral on a specially designed form. The relative frequency of patients actually having an endoscopic abnormality was assessed for each referral indication. RESULTS: A total of 1298 people were included in the study. A relevant endoscopic abnormality was found in 48% of patients. Patients with an endoscopic abnormality were not more often referred with "alarm" symptoms or failure of empirical treatment than patients without an abnormal endoscopic finding (31% with an endoscopic abnormality vs. 30% without an endoscopic abnormality had alarm symptoms; 57% of people in both groups experienced failure of empirical treatment). Referral with alarm symptoms had a positive predictive value of 4% for cancer (prevalence 2%; P < 0.01), and referral with reflux-like symptoms had a positive predictive value of 33% for finding reflux esophagitis (prevalence 22%; P < 0.01). CONCLUSIONS: General practitioners' referral indications for open-access endoscopy did not add any relevant predictive value for endoscopic findings in comparison with what might have been expected from overall prevalence. Only alarm symptoms slightly increased the probability of finding cancer and only reflux-like symptoms slightly increased the probability of finding reflux esophagitis.

Colonoscopic perforations: a review of 30,366 patients.

BACKGROUND: Although the incidence of perforation after endoscopic procedures of the colon is low, the rising number of procedures could pose relevant health problems. Recognizing risk factors and optimizing treatment may reduce perforation incidence and the probability of (severe) complications. This study aimed to determine perforation frequency and the management of endoscopic colonoscopic perforation. METHODS: A retrospective review of patient records was performed for all patients with iatrogenic colonic perforations after sigmoido/colonoscopy between 1990 and 2005. The patients' demographic data, endoscopic procedural information, perforation location, therapy, and outcome were recorded. RESULTS: In the 16-year period, 30,366 endoscopic colonic procedures were performed. In total, 35 colonic perforations occured (0.12%). All the patients underwent a laparotomy: for primary repair in 18 cases (56%), for resection with anastomosis in 8 cases (25%), and for resection without anastomosis in 6 cases (19%). In three patients (8.6%), no perforation was found. The postoperative course was uncomplicated in 21 cases (60%) and complicated in 14 cases (40%), including mortality for 3 patients (8.6% resulting from perforations and 0.01% resulting from total endoscopic colon procedures). The relative risk ratio of colonoscopic and sigmoidoscopic procedures for perforations was 4. Therapeutic procedures show a delay in presentation and diagnosis compared with diagnostic procedures. Of the 35 perforations, 26 (74%) occurred in the sigmoid colon. CONCLUSION: Iatrogenic colonic perforation is a serious but rare complication of colonoscopy. A perforation risk of 0.12% was found. The perforation risk was higher for colonoscopic procedures than for sigmoidoscopic procedures. The sigmoid colon is the area at greatest risk for perforation. Immediate operative management, preferably primary repair and sometimes resection, appears to be a good strategy for most patients.