Effects of cancer screening restart strategies after COVID-19 disruption

Background Many breast, cervical, and colorectal cancer screening programmes were disrupted due to the COVID-19 pandemic. This study aimed to estimate the effects of five restart strategies after the disruption on required screening capacity and cancer burden.Methods Microsimulation models simulated five restart strategies for breast, cervical, and colorectal cancer screening. The models estimated required screening capacity, cancer incidence, and cancer-specific mortality after a disruption of 6 months. The restart strategies varied in whether screens were caught up or not and, if so, immediately or delayed, and whether the upper age limit was increased.Results The disruption in screening programmes without catch-up of missed screens led to an increase of 2.0, 0.3, and 2.5 cancer deaths per 100 000 individuals in 10 years in breast, cervical, and colorectal cancer, respectively. Immediately catching-up missed screens minimised the impact of the disruption but required a surge in screening capacity. Delaying screening, but still offering all screening rounds gave the best balance between required capacity, incidence, and mortality.Conclusions Strategies with the smallest loss in health effects were also the most burdensome for the screening organisations. Which strategy is preferred depends on the organisation and available capacity in a country.Subject terms: Health policy, Population screening, Cancer screening, Cancer screening     

The Mineralization Regulator ANKH Mediates Cellular Efflux of ATP,Not Pyrophosphate

The plasma membrane protein ankylosis homologue (ANKH, mouse ortholog: Ank) prevents pathological mineralization of joints by controlling extracellular levels of the mineralization inhibitor pyrophosphate (PPi). It was long thought that ANKH acts by transporting PPi into the joints. We recently showed that when overproduced in HEK293 cells, ANKH mediates release of large amounts of nucleoside triphosphates (NTPs), predominantly ATP, into the culture medium. ATP is converted extracellularly into PPi and AMP by the ectoenzyme ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1). We could not rule out, however, that cells also release PPi directly via ANKH. We now addressed the question of whether PPi leaves cells via ANKH using HEK293 cells that completely lack ENPP1. Introduction of ANKH in these ENPP1-deficient HEK293 cells resulted in robust cellular ATP release without the concomitant increase in extracellular PPi found in ENPP1-proficient cells. Ank activity was previously shown to be responsible for about 75% of the PPi found in mouse bones. However, bones of Enpp1^−/− mice contained <2.5% of the PPi found in bones of wild-type mice, showing that Enpp1 activity is also a prerequisite for Ank-dependent PPi incorporation into the mineralized bone matrix in vivo. Hence, ATP release precedes ENPP1-mediated PPi formation. We find that ANKH also provides about 25% of plasma PPi, whereas we have previously shown that 60% to 70% of plasma PPi is derived from the NTPs extruded by the ABC transporter, ABCC6. Both transporters that keep plasma PPi at sufficient levels to prevent pathological calcification therefore do so by extruding NTPs rather than PPi itself. © 2022 American Society for Bone and Mineral Research (ASBMR).     

A broad spectrum HVT-H5 avian influenza vector vaccine which induces a rapid onset of immunity

Current methods to combat highly pathogenic avian influenza (HPAI) outbreaks in poultry rely on stamping out and preventive culling, which can lead to high economic losses and invoke ethical resistance. Emergency vaccination could be an alternative as vaccination is one of the most efficient and cost-effective measures to protect poultry from HPAI infection, preventing spreading to other poultry and greatly reducing the potential transmission to humans. Current conventional inactivated AI vaccines may be useful for combating AI outbreaks, but do not fulfil all targets of an ideal AI vaccine, including mass applicability and rapid onset of immunity. We aimed to further investigate the potential of Herpesvirus of Turkeys (HVT) as a vector containing a recombinant H5 hemagglutinin of HPAI H5N1. This HVT-H5 vector was analysed in vitro, tested for onset of immunity against AI challenge, breadth of protection, reduction of virus shedding, and induction of both antibody and cellular responses in SPF layers or broiler chicks containing maternal derived antibodies (MDA+). In SPF layers HVT-H5 provided full protection to lethal challenges with 4 antigenically diverse HPAI H5N1 strains from 2 weeks post vaccination (w.p.v.), while in MDA+ birds full protection was provided from 3 w.p.v. to homologous challenge. Also shedding of challenge virus was reduced in both SPF and MDA+ birds. HVT-H5 induced a protective HI titre (≥4) to 11 HPAI H5N1 strains at 3 w.p.v. in 3-week-old SPF layers and to HPAI H5N8 A/ch/Neth/14015531/2014. Besides inducing a protective antibody response HVT-H5 also induced an influenza-specific T cell response. This data demonstrates that HVT-H5 vaccine appears to fulfil many of the criteria for an ideal AI vaccine including early onset of immunity, a broad protection, reduced virus shedding, protection in presence of AI-MDA and could be a useful tool in the combat of AI outbreaks worldwide.     

One-Anastomosis Gastric Bypass Revision for Gastroesophageal Reflux Disease: Long Versus Short Biliopancreatic Limb Roux-en-Y Gastric Bypass

Purpose

One-anastomosis gastric bypass (OAGB) may be associated with refractory gastroesophageal reflux disease (GERD). The nature of this GERD remains unclear. This complication can be treated either with an additional enteroenterostomy without shortening of gastric pouch (long biliopancreatic limb Roux-en-Y gastric bypass (L-BPL-RYGB)) or revision to conventional short biliopancreatic limb Roux-en-Y gastric bypass (S-BPL-RYGB). The objective of this study is to compare the aforementioned procedures in terms of efficacy on GERD symptoms.

Materials and Methods

Retrospective analysis between October 2012 and June 2020.

Results

Fifty-two patients underwent OAGB revision to S-BPL-RYGB (n = 21) or L-BPL-RYGB (n = 31) secondary to GERD. Investigation with pH impedance prior to revision was performed in 15 patients showing biliary reflux (BR) in 7 (46.6%), acid reflux (AR) in 6 (40%), and no confirmation in 2. Patients with AR had a revision to S-BPL-RYGB, whereas patients with BR underwent L-BPL-RYGB. Among the patients without pH metry results (n = 37), S-BPL-RYGB was performed for associated disabling digestive disorders or nutritional deficiencies. GERD was treated in 68% of patients with L-BPL-RYGB versus 95% of patients after S-BPL-RYGB. Patients, whose decision for revisional procedure was based on the results of pH impedance testing, did not reveal refractory GERD.

Conclusion

L-BPL-RYGB seems appropriate in patients with BR, whereas conversion to S-BPL-RYGB should be preferred if AR is present.

Graphical Abstract