Antimicrobial proteins and polypeptides in pulmonary innate defence

Inspired air contains a myriad of potential pathogens, pollutants and inflammatory stimuli. In the normal lung, these pathogens are rarely problematic. This is because the epithelial lining fluid in the lung is rich in many innate immunity proteins and peptides that provide a powerful anti-microbial screen. These defensive proteins have anti-bacterial, anti- viral and in some cases, even anti-fungal properties. Their antimicrobial effects are as diverse as inhibition of biofilm formation and prevention of viral replication. The innate immunity proteins and peptides also play key immunomodulatory roles. They are involved in many key processes such as opsonisation facilitating phagocytosis of bacteria and viruses by macrophages and monocytes. They act as important mediators in inflammatory pathways and are capable of binding bacterial endotoxins and CPG motifs. They can also influence expression of adhesion molecules as well as acting as powerful anti-oxidants and anti-proteases. Exciting new antimicrobial and immunomodulatory functions are being elucidated for existing proteins that were previously thought to be of lesser importance. The potential therapeutic applications of these proteins and peptides in combating infection and preventing inflammation are the subject of ongoing research that holds much promise for the future

Arguments against the requirement of a biological license application for human pancreatic islets: The position statement of the islets for us collaborative presented during the fda advisory committee meeting

The Food and Drug Administration (FDA) has been regulating human islets for allo-transplantation as a biologic drug in the US. Consequently, the requirement of a biological license application (BLA) approval before clinical use of islet transplantation as a standard of care procedure has stalled the development of the field for the last 20 years. Herein, we provide our commentary to the multiple FDA’s position papers and guidance for industry arguing that BLA requirement has been inappropriately applied to allogeneic islets, which was delivered to the FDA Cellular, Tissue and Gene Therapies Advisory Committee on 15 April 2021. We provided evidence that BLA requirement and drug related regulations are inadequate in reassuring islet product quality and potency as well as patient safety and clinical outcomes. As leaders in the field of transplantation and endocrinology under the “Islets for US Collaborative” designation, we examined the current regulatory status of islet transplantation in the US and identified several anticipated negative consequences of the BLA approval. In our commentary we also offer an alternative pathway for islet transplantation under the regulatory framework for organ transplantation, which would address deficiencies of in current system

An evaluation of the suitability of selected waste products in feeds for three fish species

Five types of aquatic food industry waste products (carp offal, carp roe, fish frames, trout offal and surimi processing waste) together with fish meal were evaluated for their suitability as potential fish meal replacements, partially or wholly, in diets for three species (rainbow trout, Murray cod and shortfin eel) cultured in Australia, using a number of criteria.The proximate composition of the ingredients on a dry matter basis including protein content, lipid and ash, varied considerably. The essential amino acid (EAA) contents of the waste products and fish meal decreased in the order: carp roe &gt; fish meal &gt; carp offal &gt; \u27surimi\u27 processing waste &gt; fish frames &gt; trout offal. The results of cluster analysis of A/E ratios of waste products and fish whole body fell within three clusters. The EAAI of whole body tissue of Murray cod, rainbow trout and Australian shortfin eel however, were closest to fish meal, followed by fish frame waste and/or \u27surimi\u27 waste. The results on A/E ratios and EAAI did not conform to the raw data on TAA and EAA. Therefore, the study emphasizes the need to have a multi-prong approach to determine the suitability of ingredients for incorporation into fish feeds.<br /

Impact of hospital volume on local recurrence and distant metastasis in bladder cancer patients treated with radical cystectomy in Sweden

Objective. This study evaluated the impact of hospital volume on local recurrence and distant metastasis in a population-based series of radical cystectomy patients in Sweden. Material and methods. All patients who underwent cystectomy for bladder cancer in 1997-2002 in Sweden and were reported to the National Bladder Cancer Registry were included. A high-volume hospital (HVH) was defined as one with >= 10 cystectomies/year and a low-volume hospital (LVH) as one with pT2 and 69 (11%) were microscopic non-radical. Corresponding figures for the 516 (46%) LVH patients were 35 (7%), 68 (13%), 191 (37%), 222 (43%) and 96 (19%). Local recurrence was observed in 245 patients (22%): 113 (19%) at HVHs and 132 (26%) at LVHs. Distant metastasis was found in 363 (32%): 203 (33%) at HVHs and 160 (31%) at LVHs. Perioperative chemotherapy was given to 193 (17%). Multivariate Cox proportional hazards analysis showed that local recurrence was associated with LVHs and non-organ-confined disease, whereas distant metastasis was correlated with non-organ-confined disease and lymph-node metastases. Conclusions. In this retrospective analysis, local tumour recurrence after cystectomy was common, particularly in patients with non-organ-confined disease. Furthermore, local recurrence was more frequent at LVHs than HVHs, and overall survival was better at HVHs. These findings suggest that concentrating cystectomies in HVHs may improve outcomes such as local recurrence and overall survival

Anticoagulation practices in total pancreatectomy with autologous islet cell transplant patients: an international survey of clinical programs

Diabetes mellitus: pathophysiological changes and therap

836-P: Glucose-Dependent Insulin Production and Insulin-Independence in Type 1 Diabetes from Stem Cell–Derived, Fully Differentiated Islet Cells—Updated Data from the VX-880 Clinical Trial

VX-880 is an investigational allogeneic stem cell-derived, fully differentiated, pancreatic islet cell replacement therapy being evaluated in a phase 1/2 clinical trial in patients with T1D and impaired hypoglycemic awareness and severe hypoglycemia. The phase 1/2 trial has three parts: Part A in which 2 patients are enrolled sequentially and receive half the target dose (presented at ADA 2022), Part B in which 5 patients are enrolled sequentially and receive the target (full) dose, and Part C where 10 patients are enrolled concurrently and receive the target (full) dose. The first two patients infused with VX-880 at half the target dose (in Part A) had restored insulin production and glucose control. One of these patients achieved and has maintained insulin independence, defined as at least one week off exogenous insulin, HbA1C ≤7%, post-prandial serum glucose at 90 minutes ≤180 mg/dL, fasting serum glucose ≤126 mg/dL, and fasting or stimulated C-peptide ≥166 pmol/L (latter 3 measured during mixed-meal tolerance test). The safety profile was consistent with the immunosuppressive regimen used in the study and the perioperative period. Part B is now fully enrolled and multiple patients have been dosed with the full (target) dose. Longer-term data on both patients in Part A and new data on patients who received the full (target) dose in Part B will be provided in the presentation. These results are the first from a clinical trial of allogeneic, fully differentiated, insulin producing, stem cell-derived islets which has demonstrated the potential to restore insulin production and glycemic control and provide insulin independence in patients with T1D. Disclosure T.W.Reichman: Consultant; Sernova, Corp., Research Support; Vertex Pharmaceuticals Incorporated. J.L.Shih: Employee; Vertex Pharmaceuticals Incorporated. C.Wang: Employee; Vertex Pharmaceuticals Incorporated. D.Melton: None. F.Pagliuca: Employee; Vertex Pharmaceuticals Incorporated, Stock/Shareholder; Vertex Pharmaceuticals Incorporated. B.Sanna: Employee; Vertex Pharmaceuticals Incorporated. L.S.Kean: Advisory Panel; HiFiBio, Mammoth Biosciences, Consultant; Vertex Pharmaceuticals Incorporated, Other Relationship; Bristol-Myers Squibb Company, Research Support; Bristol-Myers Squibb Company, Adaptive Biotechnologies, Merck & Co., Inc., Tessera, Novartis. A.L.Peters: Advisory Panel; Abbott Diabetes, Medscape, Novo Nordisk, Vertex Pharmaceuticals Incorporated, Zealand Pharma A/S, Research Support; Abbott Diabetes, Dexcom, Inc., Insulet Corporation, Stock/Shareholder; Omada Health, Inc., Livongo. P.Witkowski: Advisory Panel; Vertex Pharmaceuticals Incorporated, Novartis. M.R.Rickels: Consultant; Sernova, Corp., Vertex Pharmaceuticals Incorporated, Zealand Pharma A/S, Research Support; Dompé. C.Ricordi: Advisory Panel; Vertex Pharmaceuticals Incorporated. A.Naji: None. J.F.Markmann: None. B.A.Perkins: Advisory Panel; Dexcom, Inc., Insulet Corporation, Novo Nordisk, Sanofi, Vertex Pharmaceuticals Incorporated, Other Relationship; Abbott, Medtronic, Sanofi, Research Support; Novo Nordisk, Bank of Montreal (BMO). M.Wijkstrom: None. S.Paraskevas: None. B.Bruinsma: Employee; Vertex Pharmaceuticals Incorporated. G.Marigowda: Employee; Vertex Pharmaceuticals Incorporated