Improving Xenon-129 lung ventilation image SNR with deep-learning based image reconstruction.

PURPOSE: To evaluate the feasibility and utility of a deep learning (DL)-based reconstruction for improving the SNR of hyperpolarized 129Xe lung ventilation MRI. METHODS: 129Xe lung ventilation MRI data acquired from patients with asthma and/or chronic obstructive pulmonary disease (COPD) were retrospectively reconstructed with a commercial DL reconstruction pipeline at five different denoising levels. Quantitative imaging metrics of lung ventilation including ventilation defect percentage (VDP) and ventilation heterogeneity index (VHI) were compared between each set of DL-reconstructed images and alternative denoising strategies including: filtering, total variation denoising and higher-order singular value decomposition. Structural similarity between the denoised and original images was assessed. In a prospective study, the feasibility of using SNR gains from DL reconstruction to allow natural-abundance xenon MRI was evaluated in healthy volunteers. RESULTS: 129Xe ventilation image SNR was improved with DL reconstruction when compared with conventionally reconstructed images. In patients with asthma and/or COPD, DL-reconstructed images exhibited a slight positive bias in ventilation defect percentage (1.3% at 75% denoising) and ventilation heterogeneity index (˜1.4) when compared with conventionally reconstructed images. Additionally, DL-reconstructed images preserved structural similarity more effectively than data denoised using alternative approaches. DL reconstruction greatly improved image SNR (greater than threefold), to a level that 129Xe ventilation imaging using natural-abundance xenon appears feasible. CONCLUSION: DL-based image reconstruction significantly improves 129Xe ventilation image SNR, preserves structural similarity, and leads to a minor bias in ventilation metrics that can be attributed to differences in the image sharpness. This tool should help facilitate cost-effective 129Xe ventilation imaging with natural-abundance xenon in the future.

Glucosylceramide synthase modulation ameliorates murine renal pathologies and promotes macrophage effector function in vitro.

While significant advances have been made in understanding renal pathophysiology, less is known about the role of glycosphingolipid (GSL) metabolism in driving organ dysfunction. Here, we used a small molecule inhibitor of glucosylceramide synthase to modulate GSL levels in three mouse models of distinct renal pathologies: Alport syndrome (Col4a3 KO), polycystic kidney disease (Nek8jck), and steroid-resistant nephrotic syndrome (Nphs2 cKO). At the tissue level, we identified a core immune-enriched transcriptional signature that was shared across models and enriched in human polycystic kidney disease. Single nuclei analysis identified robust transcriptional changes across multiple kidney cell types, including epithelial and immune lineages. To further explore the role of GSL modulation in macrophage biology, we performed in vitro studies with homeostatic and inflammatory bone marrow-derived macrophages. Cumulatively, this study provides a comprehensive overview of renal dysfunction and the effect of GSL modulation on kidney-derived cells in the setting of renal dysfunction.

HPV Extended Genotyping to Triage Abnormal Cervical Cancer Screens-Balancing the Harms and Benefits of an Additional Triage Test before Direct Colposcopy Referral.

The Netherlands' cervical cancer screening program transitioned to primary human papillomavirus (HPV) screening in 2017. After the introduction of HPV-based screening, the country saw increases in colposcopy referral rates and detections of low-grade lesions. In July 2022, genotyping was introduced, and those with borderline or mild dyskaryotic (BMD) cytologic abnormalities were only referred to colposcopy if positive for HPV type 16 or 18, and repeat screening otherwise. In this article, various strategies using extended genotyping (HPV16/18/31/33/45/52/58) as a triage test after an abnormal screen were explored using data from HPV-positive participants with normal or BMD cytology in the Population-Based Screening Study Amsterdam (POBASCAM) trial. The authors assessed positive and negative predictive values and colposcopy referral rates for each strategy using extended genotyping to triage women to either direct referral to colposcopy or repeat screening. Direct referral did not meet positive and negative predictive value thresholds for efficiency for any strategies. However, the authors note that direct referral may nonetheless be useful among those with BMD due to minimal increases in colposcopy referrals and concerns of loss to follow-up at repeat screening. These findings demonstrate the potential utility of extended genotyping as a triage test in primary HPV screening programs. The results should be considered alongside the fact that referral to repeat screening may result in loss of engagement of women who need treatment to prevent invasive cancer. See related article by Kroon et al., p. 1037.

Strategies to accelerate the elimination of cervical cancer in British Columbia, Canada: a modelling study.

BACKGROUND: To eliminate cervical cancer in Canada by 2040, defined as an annual age-standardized incidence rate (ASIR) lower than 4.0 per 100 000 women, the Canadian Partnership Against Cancer (CPAC) identified 3 priorities for action: increasing human papillomavirus (HPV) vaccine coverage, implementing HPV-based screening and increasing screening participation, and improving follow-up after abnormal screen results. Our objective was to explore the impact of these priorities on the projected time to elimination of cervical cancer in British Columbia. METHODS: We used OncoSim-Cervical, a microsimulation model led and supported by CPAC and developed by Statistics Canada that simulates HPV transmission and the natural history of cervical cancer for the Canadian population. We updated model parameters to reflect BC's historical participation rates and program design. We simulated the transition to HPV-based screening and developed scenarios to explore the additional impact of achieving 90% vaccination coverage, 95% screening recruitment, 90% ontime screening, and 95% follow-up compliance. We projected cervical cancer incidence, ASIR, and year of elimination for the population of BC for 2023-2050. RESULTS: HPV-based screening at current vaccination, participation, and follow-up rates can eliminate cervical cancer by 2034. Increasing on-time screening and follow-up compliance could achieve this target by 2031. Increasing vaccination coverage has a small impact over this time horizon. INTERPRETATION: With the implementation of HPV-based screening, cervical cancer can be eliminated in BC before 2040. Efforts to increase screening participation and follow-up through this transition could potentially accelerate this timeline, but the transition from cytology- to HPV-based screening is fundamental to achieving this goal.

Investigating the healthcare-seeking behaviors of mobile phone users to improve cervical cancer screening in rural Uganda.

OBJECTIVE: Cervical cancer is the leading cause of cancer in low- and middle-income countries, despite being preventable. Uganda, which lacks an effective screening program, has one of the highest global cervical cancer incidence rates. Mobile health (mHealth) technology has the potential to improve healthcare-seeking behaviors and access. The present study describes the connection between mobile phone access and healthcare-seeking behaviors in rural Uganda. METHODS: Women were eligible for this cross-sectional study if they had no prior screening or treatment for cervical cancer in the past 5 years, were aged 30 to 49 years old, and were residents of the South Busoga Forest reserve. Survey data was analyzed using descriptive statistics and chi-square tests. RESULTS: Of the 1434 participants included in the analysis, 91.4% reported having access to a mobile phone. Most respondents were aged 30-40 years, had a partner, had ≤primary education, and were farmers. Participants with mobile phone access were significantly more likely to report attending a healthcare outreach visit (access = 87.3%, no access = 72.6%, P < 0.001) or visiting a health center (access = 96.9%, no access = 93.5%, P < 0.001). Participants in both groups had largely positive attitudes around and good knowledge of cervical cancer screening. CONCLUSION: While attendance to healthcare services was high amongst participants, those with mobile phone access were more likely to seek healthcare services. Further inquiry into this association between mobile phone access and healthcare-seeking behavior is needed to optimize the improvements to cervical cancer screening when implementing interventions such as mHealth technology.

Age, sex, and lung volume dependence of dissolved xenon-129 MRI gas exchange metrics.

PURPOSE: To characterize the dependence of Xe-MRI gas transfer metrics upon age, sex, and lung volume in a group of healthy volunteers. METHODS: Sixty-five subjects with no history of chronic lung disease were assessed with 129Xe-MRI using a four-echo 3D radial spectroscopic imaging sequence and a dose of xenon titrated according to subject height that was inhaled from a lung volume of functional residual capacity (FRC). Imaging was repeated in 34 subjects at total lung capacity (TLC). Regional maps of the fractions of dissolved xenon in red blood cells (RBC), membrane (M), and airspace (Gas) were acquired at an isotropic resolution of 2 cm, from which global averages of the ratios RBC:M, RBC:Gas, and M:Gas were computed. RESULTS: Data from 26 males and 36 females with a median age of 43 y (range: 20-69 y) were of sufficient quality to analyze. Age (p = 0.0006) and sex (p < 0.0001) were significant predictors for RBC:M, and a linear regression showed higher values and steeper decline in males: RBC:M(Males) = -0.00362 × Age + 0.60 (p = 0.01, R2 = 0.25); RBC:M(Females) = -0.00170 × Age + 0.44 (p = 0.02, R2 = 0.15). Similarly, age and sex were significant predictors for RBC:Gas but not for M:Gas. RBC:M, M:Gas and RBC:Gas were significantly lower at TLC than at FRC (plus inhaled volume), with an average 9%, 30% and 35% decrease, respectively. CONCLUSION: Expected age and sex dependence of pulmonary function concurs with 129Xe RBC:M imaging results, demonstrating that these variables must be considered when reporting Xe-MRI metrics. Xenon doses and breathing maneuvers should be controlled due to the strong dependence of Xe-MRI metrics upon lung volume.

Evidence of Decreased Long-term Risk of Cervical Precancer after Negative Primary HPV Screens Compared with Negative Cytology Screens in a Longitudinal Cohort Study.

BACKGROUND: The growing use of primary human papillomavirus (HPV) cervical cancer screening requires determining appropriate screening intervals to avoid overtreatment of transient disease. This study examined the long-term risk of cervical precancer after HPV screening to inform screening interval recommendations. METHODS: This longitudinal cohort study (British Columbia, Canada, 2008 to 2022) recruited women and individuals with a cervix who received 1 to 2 negative HPV screens (HPV1 cohort, N = 5,546; HPV2 cohort, N = 6,624) during a randomized trial and women and individuals with a cervix with 1 to 2 normal cytology results (BCS1 cohort, N = 782,297; BCS2 cohort, N = 673,778) extracted from the provincial screening registry. All participants were followed through the registry for 14 years. Long-term risk of cervical precancer or worse [cervical intraepithelial neoplasia grade 2 or worse (CIN2+)] was compared between HPV and cytology cohorts. RESULTS: Cumulative risks of CIN2+ were 3.2/1,000 [95% confidence interval (CI), 1.6-4.7] in HPV1 and 2.7/1,000 (95% CI, 1.2-4.2) in HPV2 after 8 years. This was comparable with the risk in the cytology cohorts after 3 years [BCS1: 3.3/1,000 (95% CI, 3.1-3.4); BCS2: 2.5/1,000 (95% CI, 2.4-2.6)]. The cumulative risk of CIN2+ after 10 years was low in the HPV cohorts [HPV1: 4.7/1,000 (95% CI, 2.6-6.7); HPV2: 3.9 (95% CI, 1.1-6.6)]. CONCLUSIONS: Risk of CIN2+ 8 years after a negative screen in the HPV cohorts was comparable with risk after 3 years in the cytology cohorts (the benchmark for acceptable risk). IMPACT: These findings suggest that primary HPV screening intervals could be extended beyond the current 5-year recommendation, potentially reducing barriers to screening.

Incidence, Healthcare Resource Use and Costs Associated With Incisional Hernia Repair.

Background: Incisional hernia (IH) is a common complication of abdominal surgery affecting between 12.8% and 30% of patients. In spite of this, rates of IH repair remain low, at around 5% in the literature. We aimed to assess the rate of IH repair in the UK across surgical specialties and the cost burden associated with IH repair. Methods: This is a retrospective observational study of patients undergoing abdominal surgery in England between 2012 and 2022 using the Hospital Episode Statistics (HES) database. Index abdominal surgery was identified between March 2014 and March 2017. Diagnostic and surgical procedure codes were used to identify pre-operative risk factors, index surgeries, IH repair and healthcare contact. Healthcare resource use (HCRU) costs were derived for index surgery and all post-index, non-elective inpatient admissions and outpatient visits using Healthcare Resource Group (HRG) codes within HES. Results: Of 297,134 patients undergoing abdominal surgery, 5.1% (n = 15,138) subsequently underwent incisional hernia repair. By specialty, rates were higher in Colorectal (10.0%), followed by Hepatobiliary (8.2%), Transplant (6.8%), Urological (4.0%), Bariatric (3.5%), Vascular (3.2%) and Gynaecological (2.6%) surgery. Patients undergoing IH repair had more healthcare contacts, longer length of inpatient stays and more A+E visits vs. those with no IH repair post index surgery (83% ≥ 1 A+E visit vs. 69%), as well as higher rates of referral to mental health services (19.8% vs. 11.5%). IH repair was associated with an average HCRU cost of £23,148 compared to £12,321 in patients with no IH repair. Conclusion: Patients undergoing IH repair have a greater morbidity than those not undergoing repair, shown by higher HCRU and more healthcare contacts. Despite this, rates of surgery for IH are low, suggesting that most patients with hernias are not undergoing repair. Emphasis must be placed squarely on primary prevention, rather than cure.

The economic burden of cervical cancer on women in Uganda: Findings from a cross-sectional study conducted at two public cervical cancer clinics.

There is limited research on how a cervical cancer diagnosis financially impacts women and their families in Uganda. This analysis aimed to describe the economic impact of cervical cancer treatment, including how it differs by socio-economic status (SES) in Uganda. We conducted a cross-sectional study from September 19, 2022 to January 17, 2023. Women were recruited from the Uganda Cancer Institute and Jinja Regional Referral Hospital, and were eligible if they were ≥ of 18 years and being treated for cervical cancer. Participants completed a survey that included questions about their out-of-pocket costs, unpaid labor, and family's economic situation. A wealth index was constructed to determine their SES. Descriptive statistics were reported. Of the 338 participants, 183 were from the lower SES. Women from the lower SES were significantly more likely to be older, have ≤ primary school education, and have a more advanced stage of cervical cancer. Over 90% of participants in both groups reported paying out-of-pocket for cervical cancer. Only 15 participants stopped treatment because they could not afford it. Women of a lower SES were significantly more likely to report borrowing money (higher SES n = 47, 30.5%; lower SES n = 84, 46.4%; p-value = 0.004) and selling possessions (higher SES n = 47, 30.5%; lower SES n = 90, 49.7%; p-value = 0.006) to pay for care. Both SES groups reported a decrease in the amount of time that they spent caring for their children since their cervical cancer diagnosis (higher SES n = 34, 31.2%; lower SES n = 36, 29.8%). Regardless of their SES, women in Uganda incur out-of-pocket costs related to their cervical cancer treatment. However, there are inequities as women from the lower SES groups were more likely to borrow funds to afford treatment. Alternative payment models and further economic support could help alleviate the financial burden of cervical cancer care in Uganda.

Genetic and biologic risk factors associated with hernia formation: A review.

BACKGROUND: This systematic review aims to identify genetic and biologic markers associated with abdominal hernia formation. METHODS: Following PRIMSA-guidelines, we searched PubMed, MEDLINE, Embase, Scopus, and COCHRANE databases. RESULTS: Of 5946 studies, 65 were selected, excluding parastomal hernias due to insufficient data. For inguinal hernias, five studies unveiled 92 susceptible loci across 66 genes, predominantly linked to immune responses. Eleven studies observed elevated MMP-2 levels, with seven highlighting greater MMP-2 in direct compared to indirect inguinal hernias. One incisional hernia study identified unique gene-expression profiles in 174 genes associated with inflammation and cell-adhesion. In hiatal hernias, several genetic risk loci were identified. For all hernia categories, type I/III collagen ratios diminished. CONCLUSIONS: Biological markers in inguinal hernias appears consistent. Yet, the genetic predisposition in incisional hernias remains elusive. Further research to elucidate these genetic and biological intricacies can pave the way for more individualized patient care.

Transferring laparoscopic skills to robotic-assisted surgery: a systematic review.

Robotic-Assisted Surgery (RAS) is experiencing rapid expansion, prompting the integration of robotic technical skills training into surgical education programs. As access to robotic training platforms remains limited, it is important to investigate the transferability of laparoscopic skills to RAS. This could potentially support the inclusion of early years laparoscopic training to mitigate the learning curve associated with robotic surgery. This study aims to assess the transferability of laparoscopic skills to robotic surgery. A systematic search was conducted using the PRISMA checklist to identify relevant articles. PubMed, MEDLINE, Embase, and Cochrane databases were searched, and inclusion and exclusion criteria were applied to collate eligible articles. Included were original articles comparing the performance of comparable tasks on both laparoscopic and robotic platforms written in English. Non-peer reviewed papers, conference abstracts, reviews, and case series were excluded. Seventeen articles met the inclusion criteria. Among these, 10 studies (59%) demonstrated skill transferability from laparoscopic surgery (LS) to robotic surgery (RS); while one study (5.8%) showed no significant transferability. Four studies highlighted the positive impact of prior laparoscopic training on robotic skill, whereas six papers suggested no significant difference between laparoscopic novices and experienced laparoscopists when utilizing a robotic simulator. Five studies evaluated advanced surgical skills such as intracorporeal knot tying and suturing, revealing superior robotic performance among experienced laparoscopists compared to novice learners. Laparoscopic skills appear to be transferrable to robotic surgery, particularly in complex surgical techniques. Robotic simulators demonstrate a significant reduction in the learning curve for surgical novices, albeit to a lesser extent for experienced laparoscopists.

The burden of travelling for cervical cancer treatment in Uganda: A mixed-method study.

BACKGROUND: Uganda has one of the highest rates of cervical cancer in the world. Many women are diagnosed and treated with advanced stages of the disease. With only one facility offering comprehensive cervical cancer care in Uganda, many women are required to travel significant distances and spend time away from their homes to receive cervical cancer care. It is important to understand the burden of time away from home while attending treatment because it can inform the expansion of cervical cancer treatment programmes. The aim of this mixed-methods paper is to describe how the distance to cervical cancer treatment locations impacts women in Uganda. METHODS: Women were recruited from 19 September, 2022, to 17 January, 2023, at the Uganda Cancer Institute (UCI) and the cancer clinic at Jinja Regional Referral Hospital (JRRF). Women were eligible for the study if they were (i) aged ≥18 years with a histopathologic diagnosis of cervical cancer; (ii) being treated at the UCI or JRRF for cervical cancer; and (iii) able to provide consent to participate in the study in English, Luganda, Lusoga, Luo, or Runyankole. All participants completed a quantitative survey and a selected group was sampled for semi-structured interviews. Data were analysed using the convergent parallel mixed-methods approach. Descriptive statistics were reported for the quantitative data and qualitative data using an inductive-deductive thematic analysis approach. RESULTS: In all, 351 women participated in the quantitative section of the study and 24 in the qualitative. The quantitative and qualitative findings largely aligned and supported one another. Women reported travelling up to 14 h to receive treatment and 20% noted that they would spend three or more nights away from home during their current visit. Major themes of the qualitative include means of transportation, spending the night away from home, and financial factors. CONCLUSION: Our findings show that travelling to obtain cervical cancer care can be a significant burden for women in Uganda. Approaches should be considered to reduce this burden such as additional satellite cervical cancer clinics or subsidised transportation options.

Colposcopy referral rates post-introduction of primary screening with human papillomavirus testing: evidence from a large British Columbia cohort study.

Background: Shifting from cytology to human papillomavirus (HPV)-based cervical cancer screening will initially increase colposcopy referrals. The anticipated impact on health systems has been raised as a concern for implementation. It is unclear if the higher rate of colposcopy referrals is sustained after initial HPV-based screens or reverts to new lower baselines due to earlier detection and treatment of precancer. This study aimed to investigate long-term rates of colposcopy referrals after participation in HPV-based screening. Methods: Participants of HPV for Cervical Cancer Screening trial (HPV FOCAL) received one (HPV1, N = 6204) or two (HPV2, N = 9540) HPV-based screens. After exit, they returned to British Columbia's (BC) cytology screening program. A comparison cohort from the BC screening population (BCS, N = 1,140,745) was identified, mirroring trial inclusion criteria. All participants were followed for 10-14 years through the provincial screening registry. Colposcopy referral rates per 1000 screens were calculated for each group. Trial colposcopy referrals for HPV1 and HPV2 were calculated under two referral scenarios: (1) all HPV positive referred to colposcopy; (2) cytology triage with ASCUS or greater referred to colposcopy. Colposcopy referrals from post-trial screens in HPV1 an HPV2 and all screens in BCS were based on actual recommendations from the screening program. A multivariable flexible survival regression model compared hazard ratios (HR) throughout follow-up. Findings: Scenario 2 referral rates were higher during initial HPV screen(s) vs cytology screen (HPV1: 28 per 1000 screens (95% CI: 24, 33), HPV2: 32 per 1000 screens (95% CI: 29, 36), BCS: 8 per 1000 screens (95% CI: 8.9)). However, post-trial rates in HPV1 and HPV2 were significantly lower than in BCS. Cumulative rates in HPV1 and HPV2 approached the cumulative rate in BCS 11-12 years after HPV-based screening (HPV1: 11 per 1000 screens (95% CI: 10, 12), HPV2: 16 per 1000 screens (95% CI: 15-17), BCS: 11 per 1000 screens (95% CI: 10, 11)). Adjusted models demonstrated reductions in referral rates in HPV1 (HR = 0.6, 95% CI: 0.5, 0.7) and HPV2 (HR = 0.7, 95% CI: 0.6, 0.8) relative to BCS by 54 and 72 months post-final HPV screen respectively. Interpretation: Reduced colposcopy referral rates were observed after initial rounds of HPV-based screening. After initial HPV screening, referral rates to colposcopy after cytology triage were below the current rates seen in a centralized cytology program after approximately four years. Any expected increase in referrals at initiation of HPV-based screening could be countered by staged program implementation. Funding: This work was supported by the National Institutes of Health (R01 CA221918), Michael Smith Health Research BC (RT-2021-1595), and the Canadian Institutes of Health Research (MCT82072).

Higher perceived stress during the COVID-19 pandemic increased menstrual dysregulation and menopause symptoms.

BACKGROUND: The increased stress the world experienced with the coronavirus disease (COVID-19) pandemic affected mental health, disproportionately affecting females. However, how perceived stress in the first year affected menstrual and menopausal symptoms has not yet been investigated. OBJECTIVES: This study evaluates the effect that the first year of the COVID-19 pandemic had on female reproductive and mental health. METHODS: Residents in British Columbia, Canada, were surveyed online as part of the COVID-19 Rapid Evidence Study of a Provincial Population-Based Cohort for Gender and Sex. A subgroup of participants (n = 4171), who were assigned female sex at birth (age 25-69 years) and were surveyed within the first 6-12 months of the pandemic (August 2020-February 2021), prior to the widespread rollout of vaccines, was retrospectively asked if they noticed changes in their menstrual or menopausal symptoms, and completing validated measures of stress, depression and anxiety. DESIGN: This is a population-based online retrospective survey. RESULTS: We found that 27.8% reported menstrual cycle disturbances and 6.7% reported increased menopause symptoms. Those who scored higher on perceived stress, depression and anxiety scales were more likely to report reproductive cycle disturbances. Free-text responses revealed that reasons for disturbances were perceived to be related to the pandemic. CONCLUSION: The COVID-19 pandemic has highlighted the need to research female-specific health issues, such as menstruation. Our data indicate that in the first year of the pandemic, almost one-third of the menstruating population reported disturbances in their cycle, which was related to percieved stress, depression and anxiety scores.

Understanding the cervical cancer self-collection preferences of women living in urban and rural Rwanda.

Cervical cancer is a leading cause of cancer among women in low- and middle-income countries. Women in Rwanda have high rates of cervical cancer due to limited access to effective screening methods. Research in other low-resource settings similar to Rwanda has shown that HPV-based self-collection is an effective cervical cancer screening method. This study aims to compare the preferences of Rwandan women in urban and rural settings toward self-collection and to report on factors related to self-collection amenability. A cross-sectional survey was conducted from June 1-9, 2022. Women were recruited from one urban and one rural clinic in Rwanda. Women were eligible for the study if they were ≥ 18 years and spoke Kinyarwanda or English. The survey consisted of 51 questions investigating demographics and attitudes towards self-collection for cervical cancer screening. We reported descriptive statistics stratified by urban and rural sites. In total, 169 urban and 205 rural women completed the survey. The majority of respondents at both sites had a primary school or lower education and were in a relationship. Both urban and rural respondents were open to self-collection; however, rates were higher in the rural site (79.9% urban and 95.6% rural; p-value<0.001). Similarly, women in rural areas were more likely to report feeling unembarrassed about self-collection (65.3% of urban, 76.8% of rural; p-value<0.001). Notably, almost all urban and rural respondents (97.6% urban and 98.5% rural) stated they would go for a cervical cancer pelvic examination to a nearby health center if their self-collected results indicated any concern (p-value = 0.731). Rwandan women in both urban and rural areas largely support self-collection for cervical cancer screening. Further research is needed to better understand how to implement self-collection screening services in Rwanda.

Age-Specific Trends of Invasive Cervical Cancer Incidence in British Columbia, Canada, 1971-2017.

This study examined invasive cervical cancer (ICC) incidence trends in British Columbia (BC) by age and stage-at-diagnosis relative to World Health Organization ICC elimination targets (4 per 100,000 persons). Incident ICC cases (1971-2017) were obtained from the BC Cancer Registry. Annual age-standardized incidence rates (ASIRs) per 100,000 persons were generated using the direct method. ASIRs were examined among all ages 15+ years and eight age groups using Joinpoint Regression with the Canadian 2011 standard population. Standardized rate ratios (SRRs) compared stage II-IV (late) versus stage I (early) ASIRs by age (2010-2017). ICC ASIRs did not reach the elimination target. ASIRs declined from 18.88 to 7.08 per 100,000 persons (1971-2017). Stronger declines were observed among ages 45+ years, with the largest decline among ages 70-79 years (AAPC = -3.2%, 95% CI = -3.9% to -2.6%). Among ages 25-69 years, varying levels of attenuation in declining trends and stabilization were observed since the 1980s. SRRs indicated higher rates of late-stage ICC among ages 55+ years (SRR-55-69 years = 1.34, 95% CI = 1.08-1.71). Overall, ICC incidence declined in BC since 1971 but did not reach the elimination target. The pace of decline varied across age groups and increased with age. Continued efforts are needed to progress cervical cancer elimination among all age groups.

Hyperpolarised xenon-129 diffusion-weighted magnetic resonance imaging for assessing lung microstructure in idiopathic pulmonary fibrosis.

Background: Hyperpolarised 129-xenon (129Xe) magnetic resonance imaging (MRI) shows promise in monitoring the progression of idiopathic pulmonary fibrosis (IPF) due to the lack of ionising radiation and the ability to quantify functional impairment. Diffusion-weighted (DW)-MRI with hyperpolarised gases can provide information about lung microstructure. The aims were to compare 129Xe DW-MRI measurements with pulmonary function tests (PFTs), and to assess whether they can detect early signs of disease progression in patients with newly diagnosed IPF. Methods: This is a prospective, single-centre, observational imaging study of patients presenting with IPF to Northern General Hospital (Sheffield, UK). Hyperpolarised 129Xe DW-MRI was performed at 1.5 T on a whole-body General Electric HDx scanner and PFTs were performed on the same day as the MRI scan. Results: There was an increase in global 129Xe apparent diffusion coefficient (ADC) between the baseline and 12-month visits (mean 0.043 cm2·s-1, 95% CI 0.040-0.047 cm2·s-1 versus mean 0.045 cm2·s-1, 95% CI 0.040-0.049 cm2·s-1; p=0.044; n=20), with no significant change in PFTs over the same time period. There was also an increase in 129Xe ADC in the lower zone (p=0.027), and an increase in 129Xe mean acinar dimension in the lower zone (p=0.033) between the baseline and 12-month visits. 129Xe DW-MRI measurements correlated strongly with diffusing capacity of the lung for carbon monoxide (% predicted), transfer coefficient of the lung for carbon monoxide (KCO) and KCO (% predicted). Conclusions: 129Xe DW-MRI measurements appear to be sensitive to early changes of microstructural disease that are consistent with progression in IPF at 12 months. As new drug treatments are developed, the ability to quantify subtle changes using 129Xe DW-MRI could be particularly valuable.

PhysVENeT: a physiologically-informed deep learning-based framework for the synthesis of 3D hyperpolarized gas MRI ventilation.

Functional lung imaging modalities such as hyperpolarized gas MRI ventilation enable visualization and quantification of regional lung ventilation; however, these techniques require specialized equipment and exogenous contrast, limiting clinical adoption. Physiologically-informed techniques to map proton (1H)-MRI ventilation have been proposed. These approaches have demonstrated moderate correlation with hyperpolarized gas MRI. Recently, deep learning (DL) has been used for image synthesis applications, including functional lung image synthesis. Here, we propose a 3D multi-channel convolutional neural network that employs physiologically-informed ventilation mapping and multi-inflation structural 1H-MRI to synthesize 3D ventilation surrogates (PhysVENeT). The dataset comprised paired inspiratory and expiratory 1H-MRI scans and corresponding hyperpolarized gas MRI scans from 170 participants with various pulmonary pathologies. We performed fivefold cross-validation on 150 of these participants and used 20 participants with a previously unseen pathology (post COVID-19) for external validation. Synthetic ventilation surrogates were evaluated using voxel-wise correlation and structural similarity metrics; the proposed PhysVENeT framework significantly outperformed conventional 1H-MRI ventilation mapping and other DL approaches which did not utilize structural imaging and ventilation mapping. PhysVENeT can accurately reflect ventilation defects and exhibits minimal overfitting on external validation data compared to DL approaches that do not integrate physiologically-informed mapping.

Functional imaging in asthma and COPD: design of the NOVELTY ADPro substudy.

The NOVEL observational longiTudinal studY (NOVELTY; ClinicalTrials.gov identifier NCT02760329) is a global, prospective, observational study of ∼12 000 patients with a diagnosis of asthma and/or COPD. Here, we describe the design of the Advanced Diagnostic Profiling (ADPro) substudy of NOVELTY being conducted in a subset of ∼180 patients recruited from two primary care sites in York, UK. ADPro is employing a combination of novel functional imaging and physiological and metabolic modalities to explore structural and functional changes in the lungs, and their association with different phenotypes and endotypes. Patients participating in the ADPro substudy will attend two visits at the University of Sheffield, UK, 12±2 months apart, at which they will undergo imaging and physiological lung function testing. The primary end-points are the distributions of whole lung functional and morphological measurements assessed with xenon-129 magnetic resonance imaging, including ventilation, gas transfer and airway microstructural indices. Physiological assessments of pulmonary function include spirometry, bronchodilator reversibility, static lung volumes via body plethysmography, transfer factor of the lung for carbon monoxide, multiple-breath nitrogen washout and airway oscillometry. Fractional exhaled nitric oxide will be measured as a marker of type-2 airways inflammation. Regional and global assessment of lung function using these techniques will enable more precise phenotyping of patients with physician-assigned asthma and/or COPD. These techniques will be assessed for their sensitivity to markers of early disease progression.