Dental Protraction Versus Surgery for Cleft Lip and Palate: A Budget Impact Analysis.

Class III malocclusion for individuals with cleft lip and palate has historically been managed with surgery. Orthodontic protraction is a noninvasive alternative that may be associated with lower costs. This analysis investigated the budget impact of protraction versus surgery from an institutional perspective. Using a decision tree, analysis was conducted using costs derived from Medicaid reimbursement codes and using actual institutional reimbursement. Probabilities of success, failure, and complications were based on a clinical trial comparing the 2 treatment modalities. One-way and probabilistic sensitivity analyses tested the robustness of results to model parameters. Based on Medicaid fee schedules and failure rates requiring additional surgery, the total cost of protraction was $79,506 versus $172,807 for surgery, resulting in $93,302 cost-savings per patient. The cost and probability of surgery success, as well as the cost of surgery failure and repeat surgery, had the largest impact on these cost-savings. Probabilistic sensitivity analysis showed cost-savings of nearly $92,000 or higher in >50% of simulations. This study showed that protraction is associated with lower costs than surgery and may present a cost-effective alternative to surgery in eligible, appropriate patients.

microRNA-145-5p inhibits prostate cancer bone metastatic by modulating the epithelial-mesenchymal transition.

Objective: To investigate the effects of miRNA-145-5p on the tumor development and progression of prostate cancer (Pca) bone metastasis. Methods: Levels of miRNA-145-5p were assessed by real-time quantitative PCR in PC3 (bone metastatic Pca cells), 22RV1 (non-metastatic Pca cells), RWPE-1 (non-cancerous prostate epithelial cells) and Pca tissues collected from patients with and without bone metastases. The impact of miRNA-145-5p on cell proliferation was tested by CCK8 assay, colony formation assay and flow cytometric cell cycle analysis. Effects on invasion and migration of PC3 cells were determined by Transwell and wound healing assays. Western blotting, enzyme-linked immunosorbent assay, and flow cytometry apoptosis analyses were also performed to assess roles in metastasis. Results: Levels of miRNA-145-5p were decreased in Pca bone metastases and miRNA-145-5p inhibited cell proliferation, migration and invasion. miRNA-145-5p inhibited the expression of basic fibroblast growth factor (bFGF), insulin-like growth factor (IGF) and transforming growth factor-ß (TGF-ß) in PC3 cells. miR-145-5p increased the expression of the epithelial marker E-cadherin and reduced the expression of matrix metalloproteinase 2 and 9 (MMP-2 and MMP-9). It was found that miRNA-145-5p mediated the epithelial-mesenchymal transition (EMT) and induced apoptosis. Conclusions: miRNA-145-5p negatively regulated the EMT, inhibited Pca bone metastasis and promoted apoptosis in Pca bone metastasis. Mimicry of miRNA-145-5p action raises the possibility of a novel target for treating Pca with bone metastases.

Exosome-Derived miRNAs as Potential Biomarkers for Prostate Bone Metastasis.

Purpose: The purpose of this study was to identify the potential exosome-derived microRNAs (miRNAs) related to prostate cancer (Pca) bone metastasis. Methods: Two datasets were collected. One dataset was from the authors' institute, for which two groups of 10 patients each were designed: in the first one, the patients had early-stage localised Pca without bone metastasis, and in the other, the patients presented with Pca with bone metastasis. Then, the miRNA expression profiles of the blood exosomes were obtained and analysed. The other dataset was a public dataset of the miRNA expression transcriptome (GSE26964), which was downloaded from Gene Expression Omnibus (GEO). The results of both datasets were jointly analysed and the most bone-metastatic-related differentially expressed miRNAs (diff-miRNAs) were identified and further validated. Finally, a series of bioinformatics analyses were performed and the relationship between target genes of the diff-miRNAs and the pathogenesis and progression of bone metastasis of Pca were studied. Results: From the authors' dataset, in all, 313 diff-miRNAs were identified, of which 205 were up-regulated while 108 were down-regulated. From the GSE26964 dataset, 107 diff-miRNAs were found, of which 44 were up-regulated and 63 were down-regulated. Taking the intersection of the results of both datasets, four diff-miRNAs were identified: hsa-miR-125a-3p, hsa-miR-330-3p, hsa-miR-339-5p and hsa-miR-613. In all, 94 target genes of the four diff-miRNAs were predicted. After considering the intersection of the results from the GSE32269 dataset, we obtained 25 target genes. Although either positive or negative correlations were found among the diff-miRNAs with some of the target genes, there is a lack of evidence on how such correlations regulate the development and promotion of Pca bone metastasis. Conclusion: Hsa-miR-125a-3p, hsa-miR-330-3p, hsa-miR-339-5p and hsa-miR-613 are potential biomarkers for Pca bone metastasis.

Recurrent Stenoses in Arteriovenous Fistula (AVF) for Dialysis Access: cuttIng ballooN angioplaSTy combined wITh paclitaxel drUg-coaTed balloon angioplasty, an observatIONal study (INSTITUTION Study).

PURPOSE: To study the safety and efficacy of cutting balloon angioplasty (CBA) followed by paclitaxel drug-coated balloon (PCB) angioplasty for recurrent venous lesions in arteriovenous fistulas (AVFs). MATERIALS AND METHODS: We conducted a prospective single-arm cohort study of CBA followed by PCB angioplasty for recurrent AVF stenoses between September 2017 and April 2019. In total, 44 participants were recruited. Target lesions were included if they had recurred within 12 months post-angioplasty, were > = 0.5 cm upstream from the arteriovenous anastomosis, and did not involve the central veins. Up to two non-target lesions per circuit/participant with the same definition were allowed. Lesions were considered separate when there was an intervening 2-cm segment of normal vessel. Technical success was defined as complete lesion effacement on angioplasty. End-points of target and circuit patency were evaluated clinically at 3, 6, and 12 months post-procedure. RESULT: Technical success was 96% (42/44): Two participants were excluded from analysis due to the need for high-pressure balloon angioplasty as the target lesions did not efface with CBA. The median follow-up duration was 337.5 days. Mean stenosis pre- and post-angioplasty was 69.0% (51.6-84.8) and 20.8% (0-44.8), respectively. The target lesion primary, primary assisted and circuit patency for the entire study population (n = 42) were 61.6 ± 7.8%, 92.7 ± 4.0%, and 54.7 ± 7.9%, respectively, at 12 months. For participants without non-target lesions (n = 22), the rates were 77.3 ± 8.9%, 90.9 ± 6.1%, and 60.7 ± 11.0%, respectively, at 12 months. CONCLUSION: CBA followed by PCB angioplasty appears safe and feasible for treatment of recurrent venous lesions in dysfunctional AVFs.

SIroliMus coated angioPlasty versus plain balloon angioplasty in the tREatment of dialySis acceSs dysfunctION (IMPRESSION): study protocol for a randomized controlled trial.

BACKGROUND: Percutaneous transluminal angioplasty is the current standard treatment for arteriovenous fistula (AVF) stenosis. The mid- and long-term patency with plain balloon angioplasty (PBA) is however far from satisfactory. While paclitaxel-coated balloon angioplasty has been shown to be superior to PBA, concern over its safety profile has recently arisen after a reported possible increased mortality risk with a meta-analysis of large lower limb studies. An angioplasty balloon with a new type of drug coating, the sirolimus-coated balloon (SCB), has been proven to improve patency in the coronary arteries. However, its effect on AV access has yet to be studied. METHODS/DESIGN: This is an investigator-initiated, prospective, multicenter, double-blinded, randomized controlled clinical trial to assess the effectiveness of SCB compared to PBA in improving the patency of AVF after angioplasty. A total of 170 patients with mature AVF that requires PTA due to AVF dysfunction will be randomly assigned to treatment with a SCB or PBA at a 1:1 ratio, stratified by location of AVF and followed up for up to 1 year. The inclusion criteria include [1] adult patient aged 21 to 85 years who requires balloon angioplasty for dysfunctional arteriovenous fistula [2]; matured AVF, defined as being in use for at least 1 month prior to the angioplasty; and [3] successful angioplasty of the underlying stenosis with PBA, defined as less than 30% residual stenosis on digital subtraction angiography (DSA) and restoration of thrill in the AVF on clinical examination. The exclusion criteria include thrombosed or partially thrombosed access circuit at the time of treatment, presence of symptomatic or angiographically significant central vein stenosis that requires treatment with more than 30% residual stenosis post angioplasty, and existing stent placement within the AVF circuit. The primary endpoint of the study is access circuit primary patency at 6 months. The secondary endpoints are target lesion primary patency; access circuit-assisted primary patency; access circuit secondary patency at 3, 6, and 12 months; target lesion restenosis rate at 6 months; total number of interventions; complication rate; and cost-effectiveness. The trial is supported by Concept Medical. DISCUSSION: This study will evaluate the clinical efficacy and safety of SCB compared to PBA in the treatment of AVF stenosis in hemodialysis patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT04409912 . Registered on 1 June 2020.

Radioembolisation with Y90-resin microspheres followed by nivolumab for advanced hepatocellular carcinoma (CA 209-678): a single arm, single centre, phase 2 trial.

BACKGROUND: Therapeutic synergism between radiotherapy and immune checkpoint blockade has been observed in preclinical models of hepatocellular carcinoma. We aimed to study the safety and efficacy of sequential radioembolisation with yttrium-90-resin microspheres (Y90-radioembolisation) followed by nivolumab in patients with advanced hepatocellular carcinoma. METHODS: Patients with Child-Pugh A cirrhosis and advanced hepatocellular carcinoma not suitable for curative surgery were treated with Y90-radioembolisation followed by intravenous nivolumab 240 mg 21 days after Y90-radioembolisation and every 2 weeks thereafter. The primary endpoint, assessed in the per-protocol population, was the objective response rate, determined by RECIST version 1.1, defined as the proportion of patients with a confirmed complete or partial response observed for lesions both within and outside the Y90-radioembolisation field. This study is registered with ClinicalTrials.gov, NCT03033446 and has been completed. FINDINGS: 40 patients were enrolled, of whom 36 received Y90-radioembolisation followed by nivolumab. One (3%) patient had a complete response and ten (28%) had a partial response; the objective response rate was 30·6% (95% CI 16·4-48·1). The most common treatment-related adverse events of any grade were pruritus (18 [50%] of 36 patients) and maculopapular rash (13 [36%]). Two (6%) patients experienced grade 3-4 treatment-related adverse events: one patient had a grade 3 increase in alanine aminotransferase levels, grade 3 bilirubin increase, and grade 4 increase in aspartate aminotransferase levels, while the other had a grade 3 maculopapular rash. Five (14%) patients had a treatment-related serious adverse event (Steven-Johnson syndrome, hepatitis E infection, fever, liver abscesses, and ascites). INTERPRETATION: Y90-radioembolisation followed by nivolumab resulted in an encouraging objective response rate in patients with advanced hepatocellular carcinoma, although the activity observed was not as high as the study was powered for. This strategy should be further evaluated in patients with Barcelona Clinic Liver Clinic (BCLC) stage B hepatocellular carcinoma that is ineligible or refractory to transarterial chemoembolisation and patients with BCLC C disease without extrahepatic spread. FUNDING: National Medical Research Council Singapore, Bristol-Myers Squibb, Sirtex.

Real-World Data on Clinical Outcomes of Patients with Liver Cancer: A Prospective Validation of the National Cancer Centre Singapore Consensus Guidelines for the Management of Hepatocellular Carcinoma.

INTRODUCTION: Real-world management of patients with hepatocellular carcinoma (HCC) is crucially challenging in the current rapidly evolving clinical environment which includes the need for respecting patient preferences and autonomy. In this context, regional/national treatment guidelines nuanced to local demographics have increasing importance in guiding disease management. We report here real-world data on clinical outcomes in HCC from a validation of the Consensus Guidelines for HCC at the National Cancer Centre Singapore (NCCS). METHOD: We evaluated the NCCS guidelines using prospectively collected real-world data, comparing the efficacy of treatment received using overall survival (OS) and progression-free survival (PFS). Treatment outcomes were also independently evaluated against 2 external sets of guidelines, the Barcelona Clinic Liver Cancer (BCLC) and Hong Kong Liver Cancer (HKLC). RESULTS: Overall treatment compliance to the NCCS guidelines was 79.2%. Superior median OS was observed in patients receiving treatment compliant with NCCS guidelines for early (nonestimable vs. 23.5 months p < 0.0001), locally advanced (28.1 vs. 22.2 months p = 0.0216) and locally advanced with macrovascular invasion (10.3 vs. 3.3 months p = 0.0013) but not for metastatic HCC (8.1 vs. 6.8 months p = 0.6300), but PFS was similar. Better clinical outcomes were seen in BCLC C patients who received treatment compliant with NCCS guidelines than in patients with treatment only allowed by BCLC guidelines (median OS 14.2 vs. 7.4 months p = 0.0002; median PFS 6.1 vs. 4.0 months p = 0.0286). Clinical outcomes were, however, similar for patients across all HKLC stages receiving NCCS-recommended treatment regardless of whether their treatment was allowed by HKLC. CONCLUSION: The high overall compliance rate and satisfactory clinical outcomes of patients managed according to the NCCS guidelines confirm its validity. This validation using real-world data considers patient and treating clinician preferences, thus providing a realistic analysis of the usefulness of the NCCS guidelines when applied in the clinics.

Hepatic venous-portal gradient (HVPG) measurement: pearls and pitfalls.

Hepatic venous pressure gradient (HVPG) is the gold-standard for measurement of portal hypertension, a common cause for life-threatening conditions such as variceal bleeding and hepatic encephalopathy. HVPG also plays a crucial role in risk stratification, treatment selection and assessment of treatment response. Thus recognition of common pitfalls and unusual hepatic venous conditions is crucial. This article aims to provide a radiographical and clinical guide to HVPG with representative clinical cases.

Successful endoscopic surgery for emphysematous pyelonephritis in a non-diabetic patient with autosomal dominant polycystic kidney disease: A case report.

BACKGROUND: Emphysema pyelonephritis (EPN) is a very dangerous type of urinary tract infection. It is a lethal disease that develops rapidly and causes the patient to deteriorate rapidly, and it can easily lead to systemic infections and even sepsis. The incidence is extremely low, and it is prevalent in patients with diabetes. We here report a case of EPN in a non-diabetic patient with autosomal dominant polycystic kidney disease (ADPKD). We share the diagnosis and treatment procedure for this extremely rare condition to make this disease easier to identify and address early. CASE SUMMARY: A 47-year-old woman presented to the emergency department of our hospital with a high fever and left back pain lasting 4 d. She had a history of autosomal dominant polycystic kidney and polycystic liver. She was diagnosed with left type I EPN and her vital signs deteriorated so quickly that she underwent an emergency operation in which a D-J tube was inserted into her left ureter on the second day after admission. Two months later, she underwent a second-stage flexible ureteroscopy and lithotripsy. Despite postoperative sepsis, she finally recovered after active symptomatic support treatment and effective anti-infective treatment. CONCLUSION: Although EPN is more likely to occur in diabetic patients, for non-diabetic patients with ADPKD and upper urinary tract obstruction, the disease also causes rapid deterioration. Early and accurate diagnosis and timely removal of the obstruction by invasive means may be able to save the damaged kidney and the patient's life.

CD52-targeted depletion by Alemtuzumab ameliorates allergic airway hyperreactivity and lung inflammation.

Allergic asthma is a chronic inflammatory disorder associated with airway hyperreactivity (AHR) whose global prevalence is increasing at an alarming rate. Group 2 innate lymphoid cells (ILC2s) and T helper 2 (TH2) cells are producers of type 2 cytokines, which may contribute to development of AHR. In this study, we explore the potential of CD52-targeted depletion of type 2 immune cells for treating allergic AHR. Here we show that anti-CD52 therapy can prevent and remarkably reverse established IL-33-induced AHR by reducing airway resistance and alleviating lung inflammation. We further show that CD52 depletion prevents and treats allergic AHR induced by clinically relevant allergens such as Alternaria alternata and house dust mite. Importantly, we leverage various humanized mice models of AHR to show new therapeutic applications for Alemtuzumab, an anti-CD52 depleting antibody that is currently FDA approved for treatment of multiple sclerosis. Our results demonstrate that CD52 depletion is a viable therapeutic option for reduction of pulmonary inflammation, abrogation of eosinophilia, improvement of lung function, and thus treatment of allergic AHR. Taken together, our data suggest that anti-CD52 depleting monoclonal antibodies, such as Alemtuzumab, can serve as viable therapeutic drugs for amelioration of TH2- and ILC2-dependent AHR.

Perfluorobutane contrast-enhanced ultrasonography: a new standard for ultrasonography-guided thermal ablation of sonographically occult liver tumours?

INTRODUCTION: Image-guided thermal ablation, preferably with ultrasonography (US), is increasingly used for treatment of small liver tumours. Perfluorobutane-contrast-enhanced US (pCEUS) is a promising tool that may allow for targeting of tumours that are otherwise imperceptible on greyscale US. Although pCEUS has been reported to be effective, the literature has been limited outside of Japan and South Korea. We aimed to provide data that supports the use of pCEUS in the thermal ablation of sonographically occult liver tumours. METHODS: We conducted a retrospective single-centre study of 35 consecutive patients who underwent pCEUS-guided ablation of 48 liver tumours with a median size of 1.2 cm. Periprocedural, one-month post-treatment and relevant follow-up imaging studies were reviewed. Electronic records were also obtained, with long-term follow-up data of 12-28 months being available for 32 patients. RESULTS: 36 (75%) tumours that were imperceptible on greyscale US became visible with pCEUS. Overall, complete tumour ablation at one month was 89%. 1 (3%) patient developed a major complication following treatment, while 6 (17%) had minor post-treatment complaints. The local tumour progression rate was 17%, with a median time of 14 months. CONCLUSION: pCEUS has a role in US-guided thermal ablation of liver tumours, offering a high technical success rate that is comparable to reported data. Additional benefits may include improved procedural time and freedom from ionising radiation.

Management of arterial dissections in 12 patients during transarterial chemoembolization and yttrium-90 selective internal radiotherapy for primary and secondary liver tumours.

OBJECTIVE: To describe rates and management strategies of arterial dissections in transarterial chemoembolization (TACE) and Yttrium-90 selective internal radiotherapy (90Y SIRT) for primary and secondary liver tumours. MATERIALS AND METHODS: This retrospective review included 1377 hepatic angiographies between May 2010 and June 2015 in a single centre for TACE and 90Y SIRT of liver tumours. The angiogram results, management, treatment outcomes and follow-up angiography/imaging findings were recorded. RESULTS AND DISCUSSION: Twelve cases of arterial dissections (12/1377, 0.87%) were documented. Three dissections (3/633, 0.47%) occurred during TACE, seven (7/449, 1.56%) during pre-treatment planning angiographies (PTPA) for 90Y SIRT, and two (2/249, 0.80%) during the treatment procedure of 90Y SIRT. The preferred management strategy was to manoeuvre past the dissection and complete the procedure, which was achieved in six patients (50%). Angioplasty with stenting was performed in one patient. In three patients, the procedure was held off for up to 3 months to allow the dissection to heal before repeating the procedure. A dissection that occurred during PTPA was detected only when the patient returned for 90Y SIRT. PTPA was immediately repeated for this patient. The last patient opted for sorafenib. Residual 50% stenosis was seen in one patient on follow-up hepatic angiography, but he was otherwise asymptomatic. In the remaining patients, no residual dissection or clinical sequelae was observed on follow-up. CONCLUSION: Arterial dissection is a rare but important complication of transarterial locoregional therapy. Where possible, attempts should be made at completing the therapy. Deferring treatment can be considered as dissections usually heal within 3 months. LEVEL OF EVIDENCE: Level 4, case series.

Repurposing the power injectable peripherally inserted central catheter as a tunnelled, non-cuffed, centrally inserted central venous catheter in oncological patients for short- to mid-term vascular access: A pilot study.

OBJECTIVES: Usual short- to mid-term vascular accesses for oncologic patients include the peripherally inserted central catheter and non-tunnelled centrally inserted central catheters, inserted in the supraclavicular or infraclavicular area. Peripherally inserted central catheters can be restrictive in active patients; supraclavicular non-tunnelled centrally inserted central catheters are not ideal in terms of exit site location and cosmesis, while infraclavicular non-tunnelled centrally inserted central catheters may be associated with puncture-related complications. In this pilot study, we have evaluated the off-label use of peripherally inserted central catheters as a tunnelled supraclavicular centrally inserted central catheter. METHODS: Ten patients were recruited for this prospective study. A non-cuffed, power injectable peripherally inserted central catheter was inserted via a short subcutaneous tunnel into the internal jugular vein using the peel-away sheath and introducer as a tunneller. Puncture wounds were closed with tissue glue. Patients were followed up for comfort scores, dwell time and complications. RESULTS: The median dwell time was 94 days (mean of 113 days). One catheter was removed due to systemic fungemia, resulting in an acceptable complication rate of 0.97 per 1000 catheter days.Mean patient-reported comfort scores was 16 (out of 20). Pressurised injections for computer tomography imaging were performed in five patients without complications. CONCLUSION: Despite limited numbers, this method appears to be safe and well accepted with low complication rates. This modified vascular access is low profile, easily concealed, readily removable and compatible with pressure injector and uses a commonly found catheter in a modified fashion. Larger prospective trials will be needed to ascertain if it can be a standard of care for oncological patients.

DR3 stimulation of adipose resident ILC2s ameliorates type 2 diabetes mellitus.

Disturbances in glucose homeostasis and low-grade chronic inflammation culminate into metabolic syndrome that increase the risk for the development of type 2 diabetes mellitus (T2DM). The recently discovered group 2 innate lymphoid cells (ILC2s) are capable of secreting copious amounts of type 2 cytokines to modulate metabolic homeostasis in adipose tissue. In this study, we have established that expression of Death Receptor 3 (DR3), a member of the TNF superfamily, on visceral adipose tissue (VAT)-derived murine and peripheral blood human ILC2s is inducible by IL-33. We demonstrate that DR3 engages the canonical and/or non-canonical NF-κB pathways, and thus stimulates naïve and co-stimulates IL-33-activated ILC2s. Importantly, DR3 engagement on ILC2s significantly ameliorates glucose tolerance, protects against insulin-resistance onset and remarkably reverses already established insulin-resistance. Taken together, these results convey the potent role of DR3 as an ILC2 regulator and introduce DR3 agonistic treatment as a novel therapeutic avenue for treating T2DM.

PD-1 pathway regulates ILC2 metabolism and PD-1 agonist treatment ameliorates airway hyperreactivity.

Allergic asthma is a leading chronic disease associated with airway hyperreactivity (AHR). Type-2 innate lymphoid cells (ILC2s) are a potent source of T-helper 2 (Th2) cytokines that promote AHR and lung inflammation. As the programmed cell death protein-1 (PD-1) inhibitory axis regulates a variety of immune responses, here we investigate PD-1 function in pulmonary ILC2s during IL-33-induced airway inflammation. PD-1 limits the viability of ILC2s and downregulates their effector functions. Additionally, PD-1 deficiency shifts ILC2 metabolism toward glycolysis, glutaminolysis and methionine catabolism. PD-1 thus acts as a metabolic checkpoint in ILC2s, affecting cellular activation and proliferation. As the blockade of PD-1 exacerbates AHR, we also develop a human PD-1 agonist and show that it can ameliorate AHR and suppresses lung inflammation in a humanized mouse model. Together, these results highlight the importance of PD-1 agonistic treatment in allergic asthma and underscore its therapeutic potential.

The endoplasmic reticulum protein SEC22B interacts with NBEAL2 and is required for megakaryocyte α-granule biogenesis.

Studies of inherited platelet disorders have provided many insights into platelet development and function. Loss of function of neurobeachin-like 2 (NBEAL2) causes gray platelet syndrome (GPS), where the absence of platelet α-granules indicates NBEAL2 is required for their production by precursor megakaryocytes. The endoplasmic reticulum is a dynamic network that interacts with numerous intracellular vesicles and organelles and plays key roles in their development. The megakaryocyte endoplasmic reticulum is extensive, and in this study we investigated its role in the biogenesis of α-granules by focusing on the membrane-resident trafficking protein SEC22B. Coimmunoprecipitation (co-IP) experiments using tagged proteins expressed in human HEK293 and megakaryocytic immortalized megakaryocyte progenitor (imMKCL) cells established binding of NBEAL2 with SEC22B, and demonstrated that NBEAL2 can simultaneously bind SEC22B and P-selectin. NBEAL2-SEC22B binding was also observed for endogenous proteins in human megakaryocytes using co-IP, and immunofluorescence microscopy detected substantial overlap. SEC22B binding was localized to a region of NBEAL2 spanning amino acids 1798 to 1903, where 2 GPS-associated missense variants have been reported: E1833K and R1839C. NBEAL2 containing either variant did not bind SEC22B coexpressed in HEK293 cells. CRISPR/Cas9-mediated knockout of SEC22B in imMKCL cells resulted in decreased NBEAL2, but not vice versa. Loss of either SEC22B or NBEAL2 expression resulted in failure of α-granule production and reduced granule proteins in imMKCL cells. We conclude that SEC22B is required for α-granule biogenesis in megakaryocytes, and that interactions with SEC22B and P-selectin facilitate the essential role of NBEAL2 in granule development and cargo stability.

Interventional Radiology Procedures for COVID-19 Patients: How we Do it.

With astonishing speed, COVID-19 has become a global pandemic. As it is uncertain when the pandemic will be controlled, it is crucial for procedurists of all stripes to be familiar and confident in performing procedures for COVID-19 patients to prevent intra-hospital infection. In this article, we will detail our approach on how to perform interventional procedures for COVID-19 patients at the bedside in the isolation room and with the patient transferred to the interventional radiology centre. These workflows have been developed in conjunction with multiple other stakeholders within our hospital, drawing from valuable lessons we have learnt from the SARS outbreak of 2003.