A Multimodal Generative AI Copilot for Human Pathology.

The field of computational pathology[1,2] has witnessed remarkable progress in the development of both task-specific predictive models and task-agnostic self-supervised vision encoders[3,4]. However, despite the explosive growth of generative artificial intelligence (AI), there has been limited study on building general purpose, multimodal AI assistants and copilots[5] tailored to pathology. Here we present PathChat, a vision-language generalist AI assistant for human pathology. We build PathChat by adapting a foundational vision encoder for pathology, combining it with a pretrained large language model and finetuning the whole system on over 456,000 diverse visual language instructions consisting of 999,202 question-answer turns. We compare PathChat against several multimodal vision language AI assistants and GPT4V, which powers the commercially available multimodal general purpose AI assistant ChatGPT-4[7]. PathChat achieved state-of-the-art performance on multiple-choice diagnostic questions from cases of diverse tissue origins and disease models. Furthermore, using open-ended questions and human expert evaluation, we found that overall PathChat produced more accurate and pathologist-preferable responses to diverse queries related to pathology. As an interactive and general vision-language AI Copilot that can flexibly handle both visual and natural language inputs, PathChat can potentially find impactful applications in pathology education, research, and human-in-the-loop clinical decision making.

Impact of the universal health insurance benefits on cervical cancer mortality in Colombia.

BACKGROUND: Cervical cancer patients in Colombia have a lower likelihood of survival compared to breast cancer patients. In 1993, Colombia enrolled citizens in one of two health insurance regimes (contributory-private insurance and subsidized- public insurance) with fewer benefits in the subsidized regime. In 2008, the Constitutional Court required the Colombian government to unify services of both regimes by 2012. This study evaluated the impact of this insurance change on cervical cancer mortality before and after 2012. METHODS: We accessed 24,491 cervical cancer mortality records for 2006-2020 from the vital statistics of Colombia's National Administrative Department of Statistics (DANE). We calculated crude mortality rates by health insurance type and departments (geopolitical division). Changes by department were analyzed by rate differences between 2006 and 2012 and 2013-2020, for each health insurance type. We analyzed trends using join-point regressions by health insurance and the two time-periods. RESULTS: The contributory regime (private insurance) exhibited a significant decline in cervical cancer mortality from 2006 to 2012, characterized by a noteworthy average annual percentage change (AAPC) of -3.27% (P = 0.02; 95% CI [-5.81, -0.65]), followed by a marginal non-significant increase from 2013 to 2020 (AAPC 0.08%; P = 0.92; 95% CI [-1.63, 1.82]). In the subsidized regime (public insurance), there is a non-significant decrease in mortality between 2006 and 2012 (AAPC - 0.29%; P = 0.76; 95% CI [-2.17, 1.62]), followed by a significant increase from 2013 to 2020 (AAPC of 2.28%; P < 0.001; 95% CI [1.21, 3.36]). Examining departments from 2013 to 2020 versus 2006 to 2012, the subsidized regime showed fewer cervical cancer-related deaths in 5 out of 32 departments, while 6 departments had higher mortality. In 21 departments, mortality rates remained similar between both regimes. CONCLUSION: Improvement of health benefits of the subsidized regime did not show a positive impact on cervical cancer mortality in women enrolled in this health insurance scheme, possibly due to unresolved administrative and socioeconomic barriers that hinder access to quality cancer screening and treatment.

Outcomes of surgical treatment of patellar instability in children with Down syndrome.

BACKGROUND: patellar instability is a relatively frequent musculoskeletal disorder in children with Down syndrome (DS). However, such a condition has seldom been studied in the literature, even less its surgical treatment. Different techniques have been offered for this condition; the evidence for surgical options is scarce and primarily based on case reports or case series with few patients and heterogeneous techniques. Given this background, we aimed to evaluate the outcomes of a uniform kind of surgical procedure for such a condition that combined lateral soft tissue release, medial patellofemoral ligament (MPFL) reconstruction (using a partial-thickness quadriceps tendon autograft), the Roux-Goldthwait procedure, and V-Y quadricepsplasty (if needed). MATERIALS AND METHODS: This retrospective study involved 11 skeletally immature patients (12 knees; 9 males and 2 females), 5.5 to 14.1 years of age, with DS who had patellofemoral instability (PFI) and were managed by this technique between October 2018 and March 2020. Preoperative radiography, CT scan, and MRI were performed to evaluate the physis status, lower limb alignment, patellar height, trochlear morphology, and any associated knee pathology. A functional knee assessment was done by using the Kujala score and the modified Lysholm score. RESULTS: The mean time of follow-up (± SD) was 47.7 ± 5.8 months (range: 39-56). Pre-operatively, the Kujala score (± SD) was 52.6 ± 14.3 (range: (31-74), and at final follow-up, it was 92.2 ± 4.4 (range: (88-98), showing a significant improvement (P < 0.001). The preoperative modified Lysholm score (± SD) was 54.3 ± 8.1 (range: 39-62), and at final follow-up it was 92.4 ± 5.3 (range: 82-96), showing a significant improvement (P < 0.001). All patients had a stable patella without a recurrence of instability and regained full ROM. There was no incidence of a patellar fracture or femoral physis injury. CONCLUSIONS: Our proposed technique of combined soft tissue procedures, including lateral soft tissue release, MPFL reconstruction (using a partial-thickness quadriceps tendon autograft), the Roux-Goldthwait procedure, and V-Y quadricepsplasty, was an effective method for treating patellar instability in children with DS while avoiding physeal injury and patellar fracture. Functional scores and radiological outcomes were improved. LEVEL OF EVIDENCE: IV; retrospective case series.

Artificial intelligence's impact on breast cancer pathology: a literature review.

This review discusses the profound impact of artificial intelligence (AI) on breast cancer (BC) diagnosis and management within the field of pathology. It examines the various applications of AI across diverse aspects of BC pathology, highlighting key findings from multiple studies. Integrating AI into routine pathology practice stands to improve diagnostic accuracy, thereby contributing to reducing avoidable errors. Additionally, AI has excelled in identifying invasive breast tumors and lymph node metastasis through its capacity to process large whole-slide images adeptly. Adaptive sampling techniques and powerful convolutional neural networks mark these achievements. The evaluation of hormonal status, which is imperative for BC treatment choices, has also been enhanced by AI quantitative analysis, aiding interobserver concordance and reliability. Breast cancer grading and mitotic count evaluation also benefit from AI intervention. AI-based frameworks effectively classify breast carcinomas, even for moderately graded cases that traditional methods struggle with. Moreover, AI-assisted mitotic figures quantification surpasses manual counting in precision and sensitivity, fostering improved prognosis. The assessment of tumor-infiltrating lymphocytes in triple-negative breast cancer using AI yields insights into patient survival prognosis. Furthermore, AI-powered predictions of neoadjuvant chemotherapy response demonstrate potential for streamlining treatment strategies. Addressing limitations, such as preanalytical variables, annotation demands, and differentiation challenges, is pivotal for realizing AI's full potential in BC pathology. Despite the existing hurdles, AI's multifaceted contributions to BC pathology hold great promise, providing enhanced accuracy, efficiency, and standardization. Continued research and innovation are crucial for overcoming obstacles and fully harnessing AI's transformative capabilities in breast cancer diagnosis and assessment.

Health-related quality of life of pediatric brain tumor survivors after treatment in Jordan.

Background: The number of cancer survivors and survivorship are increasing. Health-related quality of life (HRQOL) has not been widely studied in low-and-middle-income countries (LMICs). The aim of this study is to explore HRQOL of childhood brain tumor survivors and its determinants in Jordan. Methods: Health-related quality of life information was collected from 80 patients treated at the King Hussein Cancer Center and their parents using the Pediatric Quality of Life Inventory (PedsQL) Generic Core Scales questionnaire in Arabic. Multivariable linear OLS regression models were used to analyze correlates of HRQOL and compare differences between child- and parent-reported responses. Results: Health-related quality of life scores reported by survivors and by parents were positively correlated on all subscales and total PedsQL scores (r = 0.59, P = .001). Survivors reported better HRQOL in cognitive subscale (ß = 0.56, P = .03) and worse HRQOL in work subscale (ß = 0.43, P = .04), but no significant differences in the physical, emotional, and social subscales and total PedsQL scores. Significant predictors of HRQOL reported by parents and by children were different. Supratentorial tumor location was associated with a 10.97-unit lower physical HRQOL score, and recurrence of tumors predicted a 17.5-unit lower total HRQOL score, indicating worse quality of life. Male gender (ß = 14.9, P = .002) and diagnosis of hypopituitarism (ß = 16.1, P = .03) were associated with better HRQOL. Furthermore, patients that only had radiotherapy treatment had better emotional HRQOL (ß = 32.9, P = .006) compared to patients that had combined radiotherapy and chemotherapy. Conclusion: This study provides evidence on determinants of HRQOL of pediatric brain tumor patients in Jordan. Future studies need to capitalize on the findings of this study to institute a system for regular assessment of quality of life of pediatric cancer patients in Jordan and other countries with similar health care systems and sociocultural backgrounds.

The impact of in-house pathology services on downstaging cervical cancer in Tanzania over an 18-year period.

PURPOSE: Reducing time between cancer screening, diagnosis, and initiation of treatment is best achieved when services are available in the same hospital. Yet, comprehensive cancer centers are typically unavailable in low- and middle-income countries (LMICs), where resources are limited and services scattered. This study explored the impact of establishing an in-house pathology laboratory at the largest public cancer hospital in Tanzania on the downstaging of cervical cancer. METHODS: We examined clinical datasets of 8,322 cervical cancer patients treated at the Ocean Road Cancer Institute (ORCI). The first period included patients treated from 2002 to 2016, before establishment of the pathology laboratory at ORCI; the second period (post-pathology establishment) included data from 2017 to 2020. Logistic regression analysis evaluated the impact of the pathology laboratory on stage of cervical cancer diagnosis. RESULTS: Patients treated during the post-pathology period were more likely to be clinically diagnosed at earlier disease stages compared to patients in the pre-pathology period (pre-pathology population diagnosed at early disease stage: 44.08%; post-pathology population diagnosed at early disease stage: 59.38%, p < 0.001). After adjustment for age, region of residence, and place of biopsy, regression results showed patients diagnosed during the post-pathology period had higher odds of early stage cervical cancer diagnosis than patients in the pre-pathology period (OR 1.35, 95% CI (1.16, 1.57), p < 0.001). CONCLUSIONS: Integrated and comprehensive cancer centers can overcome challenges in delivering expedited cervical cancer diagnosis and treatment. In-house pathology laboratories play an important role in facilitating timely diagnosis and rapid treatment of cervical and possibly other cancers in LMICs.

Behaviors and Advocacy Related to COVID-19 among Cancer Patients: The Health Belief Model and Opportunities for Messaging and Education.

Cancer patients have an increased risk of severe COVID-19 outcomes and were recommended to be vaccinated, wear a mask, practice social distancing, and increase hand hygiene. We used the Health Belief Model (HBM) to identify constructs that were associated with the likelihood of adhering to and advocating for CDC COVID-19 prevention recommendations. We surveyed adult cancer patients who had an onsite appointment at the Penn State Cancer Institute or at the Hematology and Oncology Associates of Northeastern Pennsylvania. Survey measures included adherence to and informing others of COVID-19 recommendations as well as HBM constructs. Relationships between HBM constructs and outcomes were assessed with Spearman's correlation and multivariable ordinal logistic regression. Of the 106 participants who completed the survey for our objectives of interest, 76% always wore a mask, 29% always practiced social distancing, and 24% washed their hands at least 10 times a day. Limited advocacy behaviors were captured for the COVID-19 vaccine (30%), social distancing (36%), and wearing masks (27%). Perceived benefits, perceived barriers, and cues-to-action were positively associated with the likelihood of adherence or advocacy of COVID-19 recommendations among cancer patients, whereas perceived susceptibility and self-efficacy were negatively associated with the likelihood of adherence or advocacy of COVID-19 recommendations among cancer patients. Perceived benefits may be the strongest predictor for adherence and advocacy for specific COVID-19 guidelines. Future messaging and educational campaigns focused on improving adherence to or advocacy of specific health behaviors should be informed by the HBM and originate from multiple outlets.

Tobacco Use Among Dental Students in Morocco: Opportunities for Professional Cancer Education.

The study aimed to evaluate tobacco use, attitudes, knowledge, and perceptions about tobacco control policies and smoking cessation counseling among dental students in Morocco. This cross-sectional study was conducted at the Dentistry Faculty of the Mohammed VI University of Health Sciences of Casablanca, using the Global Health Professions Student Survey (GHPSS) tool. Participants completed a self-administered survey questionnaire, including information on socio-demographic characteristics, tobacco use, exposure to secondhand smoke, attitudes, behavior and cessation, curriculum, and training. A total of 426 dental students were included in the study. Over 15% of the participants were current smokers, and 31.2% had tried smoking at least once. About 29.3% reported having been exposed to secondhand smoke in family settings and 49.5% in other environments. The majority of the students had felt that health professionals were role models for their patients. However, only 20% had felt they had received formal training in smoking cessation approaches. More than 70% of smokers had tried to quit smoking in the past year; however, only 41.7% reported having received help or advice. It is crucial that education and public health officials join efforts to plan and carry out programs aimed at training dental students in evidence-based cessation counseling methods, in order to change their own smoking behavior and assist their future patients. Improving dental school curriculums with regard to tobacco use prevention and cessation is also a powerful means of alleviating the national burden of cancer.

The potential association between psychiatric symptoms and the use of levonorgestrel intrauterine devices (LNG-IUDs): A systematic review.

BACKGROUND: Levonorgestrel (LNG)-intrauterine devices (IUDs) are an effective method of contraception; however, there is growing evidence regarding potential psychiatric side effects such as depressive symptoms, anxiety, and suicidal thoughts. Therefore, we conducted this systematic review to summarise the psychiatric effects of using LNG-IUDs. METHODS: We searched six databases (MEDLINE, Web of Science, Scopus, Science Direct, Cochrane Library, and PsycInfo), and we included all study designs. The included studies were extracted, quality assessed, and qualitatively summarised. RESULTS: Out of the screened studies, only 22 were finally included. While ten studies showed increased depressive symptoms, two studies showed reduced symptoms. Moreover, one study showed increased anxiety, another one reported an increased risk of suicide, four studies concluded no association with depressive symptoms, and four other studies showed uncertainty about a potential association but mentioned other psychiatric symptoms. CONCLUSION: Despite unreliable data, many studies report psychiatric symptoms associated with LNG-IUDs, predominantly depression. Gynaecologists, general practitioners, and psychiatrists should therefore be aware of these potential risks, especially depressive symptoms and suicidality. Counselling patients about these risks should be mandatory. Further studies should investigate the absolute risk of mental disorders associated with LNG-IUDs and other hormonal contraceptives.KEY MESSAGESMany researchers are reporting adverse psychiatric events associated with levonorgestrel intrauterine devices (LNG-IUDs).Despite their effectiveness, a proper psychiatric assessment should be done before inserting LNG-IUDs.Proper counselling regarding the depressive symptoms and suicidality should be done by the treating obstetrician.Further studies should investigate the absolute risk of mental disorders associated with LNG-IUDs and other hormonal contraceptives.

To Laparoscopically Preserve Fertility in Intraabdominal Giant Myoma with Application of Contained In-Bag Morcellation: Mission Impossible?

A technical video was produced to demonstrate in step-by-step fashion a multiple contained myomectomy of a 20 × 30 cm giant myoma and seven additional fibroids found in the same patient, which required two different types of specimen retrieval bags for the electronic power morcellation. This complete surgical procedure included leiomyomata enucleation, contained in-bag electronic power morcellation, uterine reconstruction and the application of an adhesion prophylactic medical product.

Construction of ceRNA Networks Associated With CD8 T Cells in Breast Cancer.

Background: The infiltration of CD8 T cells is usually linked to a favorable prognosis and may predict the therapeutic response of breast cancer patients to immunotherapy. The purpose of this research is to investigate the competing endogenous RNA (ceRNA) network correlated with the infiltration of CD8 T cells. Methods: Based on expression profiles, CD8 T cell abundances for each breast cancer (BC) patient were inferred using the bioinformatic method by immune markers and expression profiles. We were able to extract the differentially expressed RNAs (DEmRNAs, DEmiRNAs, and DElncRNAs) between low and high CD8 T-cell samples. The ceRNA network was constructed using Cytoscape. Machine learning models were built by lncRNAs to predict CD8 T-cell abundances. The lncRNAs were used to develop a prognostic model that could predict the survival rates of BC patients. The expression of selected lncRNA (XIST) was validated by quantitative real-time PCR (qRT-PCR). Results: A total of 1,599 DElncRNAs, 89 DEmiRNAs, and 1,794 DEmRNAs between high and low CD8 T-cell groups were obtained. Two ceRNA networks that have positive or negative correlations with CD8 T cells were built. Among the two ceRNA networks, nine lncRNAs (MIR29B2CHG, NEAT1, MALAT1, LINC00943, LINC01146, AC092718.4, AC005332.4, NORAD, and XIST) were selected for model construction. Among six prevalent machine learning models, artificial neural networks performed best, with an area under the curve (AUC) of 0.855. Patients from the high-risk category with BC had a lower survival rate compared to those from the low-risk group. The qRT-PCR results revealed significantly reduced XIST expression in normal breast samples, which was consistent with our integrated analysis. Conclusion: These results potentially provide insights into the ceRNA networks linked with T-cell infiltration and provide accurate models for T-cell prediction.

Breast Cancer Screening in Low-Income Countries: A New Program for Downstaging Breast Cancer in Tanzania.

Background: Most breast cancer diagnoses in Tanzania are in advanced stages. The Ocean Road Cancer Institute (ORCI) established a new breast cancer screening program in 2014 to reduce advanced-stage diagnoses. This study is aimed at describing the screening program's referral process and at identifying patient and health system factors that contribute to patients completing diagnostic testing referrals. Methods: Six-hundred and forty patients were included in the study. Testing types, outcomes, and date of diagnostic results were abstracted from records at ORCI and Muhimbili National Hospital (MNH) to determine the proportion of testing completed and the duration between initial referrals and diagnostic tests. Prediction of completion of diagnostic testing was investigated in logistic regression. Results: Of the patients who received referrals for further testing, fifty-two percent completed the recommended ultrasound (USS), mammography (MMG), and fine-needle aspiration cytology (FNAC). Only 33.0% of patients completed the recommended MMG referrals compared to 55.0% for ultrasound and 68.7% for FNAC. The average number of days between initial screening and results was 42 days for MMG, 20 days for USS, and 18 days for FNAC. Significant predictors for completing referrals for USS, FNAC, and MMG included age < 44 and >55 years, presenting with symptoms at the initial appointment, and education. The odds of completing an USS was 3.03 (95% CI, 1.65-5.64) for patients 25-34, 2.27 (95% CI, 1.17-4.48) for patients 35-44, and 4.41 (95% CI, 1.66-10.11) for patients older than 55 years compared to the reference group (age 19-24). The presence of symptoms at the initial appointment was a significant predictor of FNAC. The odds of completing an FNAC was 1.55 (95% CI, 1.02-3.72) for symptomatic compared to nonsymptomatic patients. Education was a significant predictor of MMG. The odds of receiving MMG was 4.29 (95% CI, 1.05-21.00) for patients with tertiary education or higher compared to primary education or lower. Possession of health insurance for treatment and living in Dar es Salaam were not significant predictors. Discussion. Future research should focus on patients' understanding of recommended referrals and factors that influence decision-making. Investigating the cost effectiveness of scaling up screening programs and setting up a patient navigation program that follow patients as they complete the recommended treatment plan will be crucial for Tanzania and other developing countries as they seek to launch and strengthen screening programs.

Factors influencing cervical cancer screening among pregnant women in Nairobi, Kenya.

To characterize cervical cancer screening knowledge, beliefs, behaviors, and sociodemographic factors among women aged 25-45 years who access and utilize prenatal care services in Nairobi, Kenya. A descriptive cross-sectional design using a convenience sample of pregnant women receiving prenatal health services at a public and a private hospital in Nairobi, Kenya. Constructs from the Health Belief Model (HBM) guided the design, interpretation of the results, and recommendations. Data were analyzed using SPSS version 24. Bivariate analyses were conducted to examine associations between variables. There was a significant association (p=0.001) between knowledge and screening behaviors. There was no association (p=0.066) between cervical cancer beliefs (perceived susceptibility, perceived severity, perceived benefits, perceived barriers, and self-efficacy) and screening behaviors. Knowledge and beliefs influence cervical cancer screening behavior. Low cervical cancer screening uptake substantiates the need for tailoring culturally specific health behavior change communication to address misconceptions about cervical cancer screening in Kenya.

Return on Investment of a Breast Cancer Screening Program in Tanzania: Opportunity for Patient and Public Education.

Breast cancer is the second incident and second cause of cancer mortality among women in Tanzania due to late-stage presentation. The screening clinic at the Ocean Road Cancer Institute (ORCI) can help detect cases early and reduce cost of treatment. We calculated the return on investment (ROI) of the ORCI breast screening clinic. Screening and treatment data of all newly diagnosed breast cancer patients seen at ORCI during 2016-2018 were abstracted from the medical records. Also, data on time, resources, and cost of screening and treatment were obtained. The cost of treating screened patients was compared with cost of treating unscreened patients, and differences in cost of treatment were compared with cost of operating the screening program. Of the 730 total patients, 58 were screened prior to treatment, and 672 were not. There was no significant difference between stage at diagnosis and treatments received by screened and unscreened patients (79.3% late- stage vs 72.2% late-stage diagnosis, respectively (p = .531), or cost of treatment between the two groups (cost, in Tanzanian Shillings, for screened (2,167,155.14 or $954.27) vs unscreened (1,918,592.28 or $844.52), (p = .355). There was also no significant difference in cost of treatment between the screened and unscreened groups and a slightly negative ROI (- 0.05%) from implementing the program. The breast screening clinic in Tanzania has not yet proven its cost-effectiveness in reducing stage with screening. The likelihood that patients have utilized the clinic for treatment rather than early detection is a possible reason for the lack of cost-effectiveness. Future studies should focus on educational initiatives to encourage screening at early disease stage. Public education should increase awareness about the clinic for early detection. The experience of this program is ideal for dissemination to other low-income countries that are initiating cancer early detection and cancer education programs.

Argentina's National Program for Control of Breast Cancer: Time 1, Patient Navigation, and Patient Cancer Education Experience.

Argentina has the second highest mortality rate for breast cancer (BC) in South America. The age-standardized incidence of BC in Argentina is 73 per 100,000. Despite the availability of early detection services, 30% of BCs are diagnosed at advanced disease stages. The National Cancer Institute (NCI) of Argentina and the National Program for Control of Breast Cancer (NPCBC) focus on two main objectives: guaranteeing adequate and timely BC treatment and reducing BC mortality in Argentina. These objectives are addressed by maintaining three core concepts: quality control, disease monitoring, and wide coverage of available early detection and treatment services. The NPCBC is currently implementing the "Time 1 Survey Study." Time 1 is defined as the time from the first appearance of BC signs or symptoms to the first consult within the public healthcare system. This timeframe is important in Argentina because it is outside of the health timeframes and data parameters monitored by the national cancer data registry system. The Time 1 Survey study has the potential to serve as an informational tool for BC patient navigation efforts in Argentina because it can be used to identify and characterize the barriers and delays that women face during Time 1. Lessons and experiences included in this study could be translated to other Latin American and middle-income countries for developing cancer control programs that can lead to improving treatment and reducing mortality through patient navigation and cancer education efforts for the public, health professionals, and patients.

Age-specific burden of cervical cancer associated with HIV: A global analysis with a focus on sub-Saharan Africa.

HIV substantially worsens human papillomavirus (HPV) carcinogenicity and contributes to an important population excess of cervical cancer, particularly in sub-Saharan Africa (SSA). We estimated HIV- and age-stratified cervical cancer burden at a country, regional and global level in 2020. Proportions of cervical cancer (a) diagnosed in women living with HIV (WLHIV), and (b) attributable to HIV, were calculated using age-specific estimates of HIV prevalence (UNAIDS) and relative risk. These proportions were validated against empirical data and applied to age-specific cervical cancer incidence (GLOBOCAN 2020). HIV was most important in SSA, where 24.9% of cervical cancers were diagnosed in WLHIV, and 20.4% were attributable to HIV (vs 1.3% and 1.1%, respectively, in the rest of the world). In all world regions, contribution of HIV to cervical cancer was far higher in younger women (as seen also in empirical series). For example, in Southern Africa, where more than half of cervical cancers were diagnosed in WLHIV, the HIV-attributable fraction decreased from 86% in women ≤34 years to only 12% in women ≥55 years. The absolute burden of HIV-attributable cervical cancer (approximately 28 000 cases globally) also shifted toward younger women: in Southern Africa, 63% of 5341 HIV-attributable cervical cancer occurred in women <45 years old, compared to only 17% of 6901 non-HIV-attributable cervical cancer. Improved quantification of cervical cancer burden by age and HIV status can inform cervical cancer prevention efforts in SSA, including prediction of the impact of WLHIV-targeted vs general population approaches to cervical screening, and impact of HIV prevention.

Timing of Toenail Collection and Concentrations of Metals in Pancreatic Cancer. Evidence Against Disease Progression Bias.

Trace elements such as cadmium, arsenic, zinc or selenium increase or decrease risk of a wide range of human diseases. Their levels in toenails may provide a measure of mid-term intake of trace elements for studies in humans. However, in biologically and clinically aggressive diseases as pancreatic cancer, the progression of the disease could modify such concentrations and produce reverse causation bias. The aim was to analyze the influence of specific time intervals between several clinical events and the collection of toenails upon concentrations of trace elements in patients with pancreatic cancer. Subjects were 118 incident cases of pancreatic adenocarcinoma prospectively recruited in eastern Spain. Toenails were collected at cancer diagnosis, and soon thereafter interviews were conducted. Information on cancer signs and symptoms was obtained from medical records and patient interviews. Levels of 12 trace elements were determined in toenail samples by inductively coupled plasma mass spectrometry. General linear models adjusting for potential confounders were applied to analyze relations between log concentrations of trace elements and the time intervals, including the interval from first symptom of cancer to toenail collection (iST). Toenail concentrations of the 12 trace elements were weakly or not influenced by the progression of the disease or the diagnostic procedures. Concentrations of aluminum were slightly higher in subjects with a longer iST (age, sex and stage adjusted geometric means: 11.44 vs. 7.75 µg/g for iST > 120 days vs. ≤ 40 days). There was a weak inverse relation of iST with concentrations of zinc and selenium (maximum differences of about 20 and 0.08 µg/g, respectively). Conclusions: concentrations of the trace elements were weakly or not influenced by the development of the disease before toenail collection. Only concentrations of aluminum increased slightly with increasing iST, whereas levels of zinc and selenium decreased weakly. Even in an aggressive disease as pancreatic cancer, toenail concentrations of trace elements may provide a valid measure of mid-term intake of trace elements, unaffected by clinical events and disease progression. Supplementary Information: The online version contains supplementary material available at 10.1007/s12403-021-00436-2.

Effects of HIV infection on metastatic cervical cancer and age at diagnosis among patients in Lusaka, Zambia.

OBJECTIVE: To examine the association between the duration of HIV infection and the stage of cervical cancer in Lusaka, Zambia. METHODS: This retrospective case-case study included 1583 cervical cancer patients from the Cancer Diseases Hospital in Lusaka, Zambia. A sub-population of HIV-positive patients with additional clinical HIV information was identified following linkage of cancer and HIV databases. Logistic regression models examined the relationship between HIV status and early-onset cervical cancer diagnosis, and between HIV infection duration and initial diagnosis of metastatic cervical cancer. RESULTS: The study population had an average age of 49 years and 40.9% had an initial diagnosis of metastatic cancer. HIV-positive women were more than twice as likely to be diagnosed at early-onset cervical cancer compared with HIV-negative women. Among the sub-population of HIV-positive patients, a longer duration of HIV infection was associated with 20% lowered odds of initial metastatic cancer diagnosis. CONCLUSION: The availability, accessibility, and impact of the cervical screening program in this population should be further examined to elucidate the relationship between cervical screening, age, and duration of HIV infection and the the stage of diagnosis of cervical cancer.