Concurrent Langerhans cell histiocytosis and acute myeloid leukemia: A rare presentation of a rare case.

A 72-year-old woman with no significant past medical history was admitted to the hospital for new-onset of leukocytosis with neutropenia, anemia, and thrombocytopenia, as well as a pruritic skin eruption. She was found to have acute myeloid leukemia (AML) with myelomonocytic differentiation. Her skin eruption consisted of widespread hemorrhagic crusted papules on the scalp and trunk. A skin biopsy was performed, which revealed a proliferation of mononuclear cells in the dermis with prominent epidermotropism and positive expression of CD1a and langerin (CD207), supporting a diagnosis of Langerhans cell histiocytosis (LCH). LCH is an uncommon proliferative disorder of activated Langerhans cells, which generally presents in children. In adults, it is exceptionally infrequent. Associated malignancies and rare reports of AML developing in subsequent years after an initial presentation of LCH have been described. Here we present an unusual concurrent presentation of LCH and AML in an adult.

Defining the Longitudinal Risk of CIN 3+ for

OBJECTIVE: To determine the baseline and cumulative risk of cervical intraepithelial neoplasia (CIN)3 and invasive cervical cancer in participants referred to colposcopy with high-grade cytology and

Validation of a natural language processing algorithm to identify adenomas and measure adenoma detection rates across a health system: a population-level study.

BACKGROUND AND AIMS: Measuring adenoma detection rates (ADRs) at the population level is challenging because pathology reports are often reported in an unstructured format; further, there is significant variation in reporting methods across institutions. Natural language processing (NLP) can be used to extract relevant information from text-based records. We aimed to develop and validate an NLP algorithm to identify colorectal adenomas that could be used to report ADR at the population level in Ontario, Canada. METHODS: The sampling frame included pathology reports from all colonoscopies performed in Ontario in 2015 and 2016. Two random samples of 450 and 1000 reports were selected as the training and validation sets, respectively. Expert clinicians reviewed and classified reports as adenoma or other. The training set was used to develop an NLP algorithm (to identify adenomas) that was evaluated using the validation set. The NLP algorithm test characteristics were calculated using expert review as the reference. We used the algorithm to measure ADR for all endoscopists in Ontario in 2019. RESULTS: The 1450 pathology reports were derived from 62 laboratories, 266 pathologists, and 532 endoscopists. In the training set, the NLP algorithm for any adenoma had a sensitivity of 99.60% (95% confidence interval (CI), 97.77-99.99), specificity of 99.01% (95% CI, 96.49-99.88), positive predictive value of 99.19% (95% CI, 97.12-99.90), and F1 score of .99. Similar results were obtained for the validation set. The median ADR was 33% (interquartile range, 26%-40%). CONCLUSIONS: When we used a population-based sample from Ontario, our NLP algorithm was highly accurate and was used at the system level to measure ADR.

Androgenetic alopecia in transgender and gender diverse populations: A review of therapeutics.

Androgenetic alopecia (AGA) management is a significant clinical and therapeutic challenge for transgender and gender-diverse (TGD) patients. Although gender-affirming hormone therapies affect hair growth, there is little research about AGA in TGD populations. After reviewing the literature on approved treatments, off-label medication usages, and procedures for treating AGA, we present treatment options for AGA in TGD patients. The first-line treatments for any TGD patient include topical minoxidil 5% applied to the scalp once or twice daily, finasteride 1 mg oral daily, and/or low-level laser light therapy. Spironolactone 200 mg daily is also first-line for transfeminine patients. Second-line options include daily oral minoxidil dosed at 1.25 or 2.5 mg for transfeminine and transmasculine patients, respectively. Topical finasteride 0.25% monotherapy or in combination with minoxidil 2% solution are second-line options for transmasculine and transfeminine patients, respectively. Other second-line treatments for any TGD patient include oral dutasteride 0.5 mg daily, platelet-rich plasma, or hair restoration procedures. After 6-12 months of treatment, AGA severity and treatment progress should be assessed via scales not based on sex; eg, the Basic and Specific Classification or the Bouhanna scales. Dermatologists should coordinate care with the patient's primary gender-affirming clinician(s) so that shared knowledge of all medications exists across the care team.

Androgenetic alopecia incidence in transgender and gender diverse populations: A retrospective comparative cohort study.

BACKGROUND: Androgenetic alopecia (AGA) is a significant challenge for many transgender and gender diverse (TGD) patients, but the rate of AGA among TGD patients receiving gender-affirming hormone therapy (GAHT) compared to cisgender patients has not yet been studied on a large scale. OBJECTIVE: We examined the incidence of AGA among TGD patients receiving GAHT compared to cisgender patients. METHODS: Retrospective cohort study using electronic health records from 37,826 patients seen at Fenway Health between August 1, 2014, and August 1, 2020. Crude and adjusted incidence rate ratios (aIRR) for AGA were calculated using Poisson regression. RESULTS: TGD patients receiving masculinizing GAHT had aIRR 2.50, 95% CI 1.71-3.65 and 1.30, 95% CI 0.91-1.86 compared to cisgender women and cisgender men, respectively. The rate of AGA for TGD patients receiving feminizing GAHT was not significantly different compared to cisgender men but was significantly increased compared to cisgender women (aIRR 1.91, 95% CI 1.25-2.92). LIMITATIONS: Inability to determine causation and limited generalizability. CONCLUSION: TGD patients receiving masculinizing GAHT have 2.5 times the rate of AGA compared to cisgender women, whereas TGD patients on feminizing GAHT did not have a significantly increased rate of AGA compared to cisgender men.

Facial cleft presenting as a congenital facial papule.

Tessier number 3 craniofacial clefts are a rare congenital deformity of the oronasoocular region with variable severity, most often with serious impacts on appearance and function due to involvement of the bone and soft tissue. However, they can occasionally manifest mildly as a skin-colored congenital facial papule present with subtle anatomic anomalies and signs of deeper involvement, such as crusting and oozing. Recognizing that a congenital facial papule, including non-midline lesions, may be the presenting sign of an underlying developmental anomaly is important to avoid missing the diagnosis of a more extensive underlying congenital defect. We present a rare case of a forme fruste variant of a Tessier number 3 craniofacial cleft to raise awareness of its presentation and advise initial management in hopes of improving outcomes.

Measuring the impact of the COVID-19 pandemic on organized cancer screening and diagnostic follow-up care in Ontario, Canada: A provincial, population-based study.

It is essential to quantify the impacts of the COVID-19 pandemic on cancer screening, including for vulnerable sub-populations, to inform the development of evidence-based, targeted pandemic recovery strategies. We undertook a population-based retrospective observational study in Ontario, Canada to assess the impact of the pandemic on organized cancer screening and diagnostic services, and assess whether patterns of cancer screening service use and diagnostic delay differ across population sub-groups during the pandemic. Provincial health databases were used to identify age-eligible individuals who participated in one or more of Ontario's breast, cervical, colorectal, and lung cancer screening programs from January 1, 2019-December 31, 2020. Ontario's screening programs delivered 951,000 (-41%) fewer screening tests in 2020 than in 2019 and volumes for most programs remained more than 20% below historical levels by the end of 2020. A smaller percentage of cervical screening participants were older (50-59 and 60-69 years) during the pandemic when compared with 2019. Individuals in the oldest age groups and in lower-income neighborhoods were significantly more likely to experience diagnostic delay following an abnormal breast, cervical, or colorectal cancer screening test during the pandemic, and individuals with a high probability of living on a First Nation reserve were significantly more likely to experience diagnostic delay following an abnormal fecal test. Ongoing monitoring and management of backlogs must continue. Further evaluation is required to identify populations for whom access to cancer screening and diagnostic care has been disproportionately impacted and quantify impacts of these service disruptions on cancer incidence, stage, and mortality. This information is critical to pandemic recovery efforts that are aimed at achieving equitable and timely access to cancer screening-related care.

Pap tests in the diagnosis of cervical cancer: Help or hinder?

OBJECTIVE: To evaluate the impact of pap tests on the time to diagnosis of cervical cancer. METHODS: In this population-based retrospective cohort study, Ontario women ≥21 years diagnosed with cervical cancer between 2011 and 2014 were identified and database data collected. The presence or absence of a pap test 0-2 years preceding cancer diagnosis was identified. Descriptive and modelling analyses were performed to determine the effect of pap results on cancer diagnosis. RESULTS: 2002 patients were identified, 75% received a pap test. 1250 patients had known cytology - 13% normal, 8% low-grade and 7.5% suspicious for cancer. Across all FIGO stages at diagnosis, 5-10% of cytology was low grade, 3-11.5% was positive for carcinoma and 4-41% was normal, which increased with advancing stage. For all cytology and FIGO stages (except stage 1A), OBGYNs had a significantly shorter time to diagnosis compared to family physicians. Factors increasing the odds of low-grade cytology were advanced stage (OR 4.5 (2.4-8.0), p < 0.01) and adenocarcinoma (OR 1.5 (1.1-2.1), p < 0.01). Low grade cytology resulted in the longest delay to diagnosis (p < 0.001). CONCLUSION: Pap tests are performed frequently in the 0-2 years prior to the diagnosis of cervical cancer which can result in false negative cytology and diagnostic delay in patients with advanced cancers.

Are Women Who Exit Colposcopy Without Treatment at Elevated Risk for Cervical Cancer?

OBJECTIVE: This study aims to estimate the risk of cervical cancer and impact of treatment and other factors in women referred for high-grade (HG) and low-grade (LG) cytologic changes and discharged from colposcopy. MATERIALS AND METHODS: A retrospective cohort study identified 14,787 and 41,916 women with a first-time HG and LG cytologic abnormality between 2007 and 2010 and underwent colposcopy within 1 year. Treatment status was determined within the episode of care. Incidence of cervical cancer postcolposcopy was determined up to March 2015. Logistic regression assessed impact of colposcopic care and patient factors on cancer risk. RESULTS: A total of 62% HG and 28.5% LG had treatment. A total of 28% and 37% with HG and LG abnormalities had only 1 colposcopic evaluation. Subsequent cancer incidence in the untreated HG group was 1.1% versus 0.3% in the treated group. For the LG group, cancer rates were 0.08% in both treatment groups. In the HG group, those with initial colposcopy only and no treatment had an elevated risk [adjusted odds ratio = 6.6 (95% CI = 3.9-11)] compared with treatment with multiple follow-ups. Other significant factors were advancing age and no screening postcolposcopy. For the LG group, those with initial colposcopy only were more at risk regardless of treatment [adjusted odds ratio = 3.8 (95% CI = 1.8-8.1)] compared with multiple colposcopies. CONCLUSIONS: Women who are untreated, with index HG cytology, remain at elevated risk for cervical cancer when the colposcopic episode is limited to 1 examination. Centralized programs are required to ensure that such women are not discharged prematurely or lost to follow up from colposcopy and subsequent screening.

Correlating bilayer tablet delamination tendencies to micro-environmental thermodynamic conditions during pan coating.

OBJECTIVE: The objective of this study was to determine the impact that the micro-environment, as measured by PyroButton data loggers, experienced by tablets during the pan coating unit operation had on the layer adhesion of bilayer tablets in open storage conditions. MATERIALS AND METHODS: A full factorial design of experiments (DOE) with three center points was conducted to study the impact of final tablet hardness, film coating spray rate and film coating exhaust temperature on the delamination tendencies of bilayer tablets. PyroButton data loggers were placed (fixed) at various locations in a pan coater and were also allowed to freely move with the tablet bed to measure the micro-environmental temperature and humidity conditions of the tablet bed. RESULTS: The variance in the measured micro-environment via PyroButton data loggers accounted for 75% of the variance in the delamination tendencies of bilayer tablets on storage (R(2 )= 0.75). A survival analysis suggested that tablet hardness and coating spray rate significantly impacted the delamination tendencies of the bilayer tablets under open storage conditions. The coating exhaust temperature did not show good correlation with the tablets' propensity to crack indicating that it was not representative of the coating micro-environment. Models created using data obtained from the PyroButton data loggers outperformed models created using primary DOE factors in the prediction of bilayer tablet strength, especially upon equipment or scale transfers. CONCLUSION: The coating micro-environment experienced by tablets during the pan coating unit operation significantly impacts the strength of the bilayer interface of tablets on storage.

Oral Psoriasis Therapies.

Oral psoriasis therapies include both older traditional immunosuppressants, such as methotrexate, cyclosporine, and acitretin, as well as newer, more targeted agents, such as apremilast, deucravacitinib, and oral interleukin-23 receptor antagonists. Patients may prefer oral therapies to injectable therapies based on the route of administration. Both older and newer oral psoriasis therapies can be utilized effectively in the treatment of psoriasis. Here, we will review oral agents used in the treatment of psoriasis as well as provide commentary on their role in our current, evolving psoriasis treatment paradigm.

Risk-based lung cancer screening performance in a universal healthcare setting.

Globally, lung cancer is the leading cause of cancer death. Previous trials demonstrated that low-dose computed tomography lung cancer screening of high-risk individuals can reduce lung cancer mortality by 20% or more. Lung cancer screening has been approved by major guidelines in the United States, and over 4,000 sites offer screening. Adoption of lung screening outside the United States has, until recently, been slow. Between June 2017 and May 2019, the Ontario Lung Cancer Screening Pilot successfully recruited 7,768 individuals at high risk identified by using the PLCOm2012noRace lung cancer risk prediction model. In total, 4,451 participants were successfully screened, retained and provided with high-quality follow-up, including appropriate treatment. In the Ontario Lung Cancer Screening Pilot, the lung cancer detection rate and the proportion of early-stage cancers were 2.4% and 79.2%, respectively; serious harms were infrequent; and sensitivity to detect lung cancers was 95.3% or more. With abnormal scans defined as ones leading to diagnostic investigation, specificity was 95.5% (positive predictive value, 35.1%), and adherence to annual recall and early surveillance scans and clinical investigations were high (>85%). The Ontario Lung Cancer Screening Pilot provides insights into how a risk-based organized lung screening program can be implemented in a large, diverse, populous geographic area within a universal healthcare system.

A combined experimental and modeling approach to study the effects of high-shear wet granulation process parameters on granule characteristics.

The purpose of the current work is to study the effects of high-shear wet granulation process parameters on granule characteristics using both experimental and modeling techniques. A full factorial design of experiments was conducted on three process parameters: water amount, impeller speed and wet massing time. Statistical analysis showed that the water amount has the largest impact on the granule characteristics, and that the effect of other process variables was more pronounced at higher water amount. At high water amounts, an increase in impeller speed and/or wet massing time showed a decrease in granule porosity and compactability. A strong correlation between granule porosity and compactability was observed. A three-dimensional population balance model which considers agglomeration and consolidation was employed to model the granulation process. The model was calibrated using the particle size distribution from an experimental batch to ensure a good match between the simulated and experimental particle size distribution. The particle size distribution of three other batches were predicted, each of which was manufactured under different process parameters (water amount, impeller speed and wet massing time). The model was able to capture and predict successfully the shifts in granule particle size distribution with changes in these process parameters.

Teledermatology for Enhancing Skin Cancer Diagnosis and Management: Retrospective Chart Review.

BACKGROUND: Skin cancer rates are at all-time highs, but the shortage of dermatologists compels patients to seek medical advice from general practitioners. A new referral pathway called the Suspected Skin Cancer (SSC) service was established to provide general practitioners in Waikato, New Zealand, with rapid diagnosis and treatment advice for lesions suspicious for skin cancer. OBJECTIVE: The aim of this study was to assess the quantity, quality, and characteristics of referrals to the SSC teledermatology service during its first 6 months. METHODS: A retrospective chart review of all referrals sent to the SSC teledermatology service during the first 6 months of its operation was conducted. Time to advice, diagnoses, diagnostic discordance, adherence to advice, and time to treatment were recorded. Diagnostic discordance between general practitioners, dermatologists, and pathologists was calculated. RESULTS: The SSC service received 340 referrals for 402 lesions. Dermatologists diagnosed 256 (63.7%) of these lesions as benign; 56 (13.9%) were histologically confirmed as malignant, including 19 (4.7%) melanomas. The overall discordance between referrer and dermatologist on specific and broad (ie, benign or malignant) diagnoses for 402 lesions was 47% and 26% (κ=0.58, SD 0.07), respectively; 44% and 26% (κ=0.61, SD 0.15) between referrer and pathologist; and 18% and 12% (κ=0.82, SD 0.12) between dermatologist and pathologist. The mean time between referral submission and receiving advice was 1.02 days. The average time to action (eg, excision) was 64.8 days. CONCLUSIONS: An electronic referral system can be an effective form of teledermatology for providing prompt diagnosis and management advice for benign and malignant skin lesions.

Equity for Sexual and Gender Diverse Persons in Medicine and Dermatology.

Dermatologists can play a key role in improving health equity for sexual and gender diverse (SGD) patients through cultivating awareness of how their patients' sexual and gender identity may affect their skin health, developing SGD-inclusive curricula and safe spaces in medical training, promoting workforce diversity, practicing with intersectionality in mind, and engaging in advocacy for their patients, whether it be through daily practice, legislative and public policy initiatives, or research.

Regulation of antigen-expressing dendritic cells by double negative regulatory T cells.

TCRαß(+) CD3(+) CD4(-) CD8(-) NK1.1(-) double negative (DN) Tregs comprise 1-3% of peripheral T lymphocytes in mice and humans. It has been demonstrated that DN Tregs can suppress allo-, xeno- and auto-immune responses in an Ag-specific fashion. However, the mechanisms by which DN Tregs regulate immune responses remain elusive. Whether DN Tregs can regulate DCs has not been investigated previously. In this study, we demonstrate that DN Tregs express a high level of CTLA4 and are able to down-regulate costimulatory molecules CD80 and CD86 expressed on Ag-expressing mature DCs (mDCs). DN Tregs from CTLA4 KO mice were not able to downregulate CD80 and CD86 expression, indicating that CTLA4 is critical for DN Treg-mediated downregulation of costimulatory molecule expression on Ag-expressing mature DCs. Furthermore, DN Tregs could kill both immature and mature allogeneic DCs, as well as Ag-loaded syngeneic DCs, in an Ag-specific manner in vitro and in vivo, mainly through the Fas-FasL pathway. These data demonstrate, for the first time, that DN Tregs are potent regulators of DCs and may have the potential to be developed as a novel immune suppression treatment.

Delivery of Cancer Care in Ontario, Canada, During the First Year of the COVID-19 Pandemic.

Importance: The COVID-19 pandemic has impacted cancer systems worldwide. Quantifying the changes is critical to informing the delivery of care while the pandemic continues, as well as for system recovery and future pandemic planning. Objective: To quantify change in the delivery of cancer services across the continuum of care during the COVID-19 pandemic. Design, Setting, and Participants: This population-based cohort study assessed cancer screening, imaging, diagnostic, treatment, and psychosocial oncological care services delivered in pediatric and adult populations in Ontario, Canada (population 14.7 million), from April 1, 2019, to March 1, 2021. Data were analyzed from May 1 to July 31, 2021. Exposures: COVID-19 pandemic. Main Outcomes and Measures: Cancer service volumes from the first year of the COVID-19 pandemic, defined as April 1, 2020, to March 31, 2021, were compared with volumes during a prepandemic period of April 1, 2019, to March 31, 2020. Results: During the first year of the pandemic, there were a total of 4 476 693 cancer care services, compared with 5 644 105 services in the year prior, a difference of 20.7% fewer services of cancer care, representing a potential backlog of 1 167 412 cancer services. While there were less pronounced changes in systemic treatments, emergency and urgent imaging examinations (eg, 1.9% more parenteral systemic treatments) and surgical procedures (eg, 65% more urgent surgical procedures), major reductions were observed for most services beginning in March 2020. Compared with the year prior, during the first pandemic year, cancer screenings were reduced by 42.4% (-1 016 181 screening tests), cancer treatment surgical procedures by 14.1% (-8020 procedures), and radiation treatment visits by 21.0% (-141 629 visits). Biopsies to confirm cancer decreased by up to 41.2% and surgical cancer resections by up to 27.8% during the first pandemic wave. New consultation volumes also decreased, such as for systemic treatment (-8.2%) and radiation treatment (-9.3%). The use of virtual cancer care increased for systemic treatment and radiation treatment and psychosocial oncological care visits, increasing from 0% to 20% of total new or follow-up visits prior to the pandemic up to 78% of total visits in the first pandemic year. Conclusions and Relevance: In this population-based cohort study in Ontario, Canada, large reductions in cancer service volumes were observed. While most services recovered to prepandemic levels at the end of the first pandemic year, a substantial care deficit likely accrued. The anticipated downstream morbidity and mortality associated with this deficit underscore the urgent need to address the backlog and recover cancer care and warrant further study.