Venom exaptation and adaptation during the trophic switch to blood-feeding by kissing bugs.

Kissing bugs are known to produce anticoagulant venom that facilitates blood-feeding. However, it is unknown how this saliva evolved and if the venom produced by the entomophagous ancestors of kissing bugs would have helped or hindered the trophic shift. In this study, we show that venoms produced by extant predatory assassin bugs have strong anticoagulant properties mediated chiefly by proteolytic degradation of fibrinogen, and additionally contain anticoagulant disulfide-rich peptides. However, venom produced by predatory species also has pain-inducing and membrane-permeabilizing activities that would be maladaptive for blood-feeding, and which venom of the blood-feeding species lack. This study demonstrates that venom produced by the predatory ancestors of kissing bugs was exapted for the trophic switch to blood-feeding by virtue of its anticoagulant properties. Further adaptation to blood-feeding occurred by downregulation of venom toxins with proteolytic, cytolytic, and pain-inducing activities, and upregulation and neofunctionalization of toxins with anticoagulant activity independent of proteolysis.

A venom peptide-induced NaV channel modulation mechanism involving the interplay between fixed channel charges and ionic gradients.

Venoms are used by arthropods either to immobilise prey or as defence against predators. Our study focuses on the venom peptide, Ta3a, from the African ant species, Tetramorium africanum and its effects on voltage-gated sodium (NaV) channels, which are ion channels responsible for the generation of electrical signals in electrically excitable cells, such as neurons. Using the NaV1.7 isoform as our model NaV channel we show that Ta3a prolongs single channel active periods with increased open probability and induces non-inactivating whole-cell currents. Ta3a-affected NaV1.7 channels exhibit a leftward (hyperpolarising) shift in activation threshold, constitutive activity even in the absence of an activating voltage stimulus, and at cell membrane voltages where channels are normally silent. Current-voltage experiments show that Ta3a shifts the voltage at which NaV current changes direction (reversal potential) by altering the local ionic concentration of permeant ions (Na+) rather than changing the channel's preference for ionic species. We propose a model where Ta3a maintains the positively charged voltage-sensing (S4) domains of the channel in the activated configuration where their electric field is exposed to the extracellular membrane surface to create an ionic bilayer comprising S4 domains and mobile anions (Cl-). This bilayer has a depolarising effect on the cell membrane, thus reducing the amount of externally applied voltage required for channel activation.

Simulation-based education in the Pacific Islands: educational experience, access, and perspectives of healthcare workers.

BACKGROUND: The World Health Organization (WHO) recommends simulation-based education (SBE) to acquire skills and accelerate learning. Literature focusing on SBE in the Pacific Islands is limited. The aim of this study was to determine Pacific Island healthcare workers' experiences, perspectives, and access to SBE. METHODS: This was a cross-sectional survey of Pacific Island healthcare workers. We designed an online questionnaire based on existing literature and expert consultation. The questionnaire included Likert scales, multiple-choice, multi-select and open-ended questions. Participants were healthcare workers recruited from professional networks across the region. Descriptive statistics and relative frequencies summarized data, and comparative testing included unpaired t-tests, Mann-Whitney U, Chi-squared and Fisher's exact tests. Free-text responses were presented to illustrate findings. RESULTS: Responses from 56 clinicians working in 11 Pacific Island countries were included. Fifty were medical doctors (89%), including 31 (55%) surgeons. Participants reported experience with scenario-based simulation (73%), mannequins (71%), and simulated patients (61%). Discrepancies were identified between previous simulation experience and current access for simulated patients (P = 0.002) and animal-based part-task trainers (P = 0.002). SBE was seen as beneficial for procedural skills, communication, decision-making and teamwork. Interest in further SBE was reported by most participants (96%). Barriers included equipment access (59%), clinical workload (45%) and COVID-19 restrictions (45%). CONCLUSION: Some Pacific Island healthcare workers have experience with SBE, but their ongoing access is predominantly limited to low-technology modalities. Despite challenges, there is interest in SBE initiatives. These findings may inform planning for SBE in the Pacific Islands and may be considered prior to programme implementation.

"I've yet to meet anyone who's not keen for simulation" - a qualitative study of simulation-based education in the Pacific Islands.

BACKGROUND: Simulation-based education (SBE) has been increasingly used to train healthcare workers in low-resource settings and has been endorsed by the World Health Organization (WHO). Consideration of the educational and cultural context is important to maximize the effectiveness of SBE. Despite its demonstrable benefits, there have been no studies of the general approach in the Pacific Islands. This study aimed to determine the factors that influence the uptake and success of SBE in the Pacific Islands. METHODS: In this qualitative study, participants were recruited via professional networks to contribute to focus groups. Questions focused on participants' previous experiences and perspectives on SBE. Data were manually transcribed before thematic analysis. The reporting of the research was guided by the Standards for Reporting Qualitative Research (SRQR). Human Research Ethics Committee approval was obtained. RESULTS: Two focus groups were conducted with 16 participants from six Pacific Island countries. Six themes and 15 subthemes were conceptualized from the data. Uptake of SBE is challenged by resource availability, clinical workloads and geographic remoteness. However, locally-driven solutions and positive attitudes towards SBE facilitate its success. CONCLUSION: This study reveals the complexity of factors affecting the uptake and success of SBE in the Pacific Islands. These findings can serve to optimize the impact of existing and future SBE programmes and may be considered by educators prior to programme implementation.

Safety and Immunogenicity of a DNA Vaccine With Subtype C gp120 Protein Adjuvanted With MF59 or AS01B: A Phase 1/2a HIV-1 Vaccine Trial.

BACKGROUND: An effective vaccine is required to end the HIV pandemic. We evaluated the safety and immunogenicity of a DNA (DNA-HIV-PT123) vaccine with low- or high-dose bivalent (TV1.C and 1086.C glycoprotein 120) subtype C envelope protein combinations, adjuvanted with MF59 or AS01B. METHODS: HIV Vaccine Trials Network (HVTN)108 was a randomized, placebo-controlled, double-blind, phase 1/2a trial conducted in the United States and South Africa. HIV-negative adults were randomly assigned to 1 of 7 intervention arms or placebo to assess DNA prime with DNA/protein/adjuvant boosts, DNA/protein/adjuvant co-administration, and low-dose protein/adjuvant regimens. HVTN111 trial participants who received an identical regimen were also included. Outcomes included safety and immunogenicity 2 weeks and 6 months after final vaccination. RESULTS: From June 2016 to July 2018, 400 participants were enrolled (N = 334 HVTN108, N = 66 HVTN111); 370 received vaccine and 30 received placebo. There were 48 grade 3 and 3 grade 4 reactogenicity events among 39/400 (9.8%) participants, and 32 mild/moderate-related adverse events in 23/400 (5.8%) participants. All intervention groups demonstrated high IgG response rates (>89%) and high magnitudes to HIV-1 Env gp120 and gp140 proteins; response rates for AS01B-adjuvanted groups approached 100%. V1V2 IgG magnitude, Fc-mediated functions, IgG3 Env response rates, and CD4+ T-cell response magnitudes and rates were higher in the AS01B-adjuvanted groups. The AS01B-adjuvanted low-dose protein elicited greater IgG responses than the higher protein dose. CONCLUSIONS: The vaccine regimens were generally well tolerated. Co-administration of DNA with AS01B-adjuvanted bivalent Env gp120 elicited the strongest humoral responses; AS01B-adjuvanted regimens elicited stronger CD4+ T-cell responses, justifying further evaluation.ClinicalTrials.gov registration: NCT02915016, registered 26 September 2016.

Prey Shifts Drive Venom Evolution in Cone Snails.

Venom systems are complex traits that have independently emerged multiple times in diverse plant and animal phyla. Within each venomous lineage there typically exists interspecific variation in venom composition where several factors have been proposed as drivers of variation, including phylogeny and diet. Understanding these factors is of broad biological interest and has implications for the development of antivenom therapies and venom-based drug discovery. Because of their high species richness and the presence of several major evolutionary prey shifts, venomous marine cone snails (genus Conus) provide an ideal system to investigate drivers of interspecific venom variation. Here, by analyzing the venom gland expression profiles of ∼3,000 toxin genes from 42 species of cone snail, we elucidate the role of prey-specific selection pressures in shaping venom variation. By analyzing overall venom composition and individual toxin structures, we demonstrate that the shifts from vermivory to piscivory in Conus are complemented by distinct changes in venom composition independent of phylogeny. In vivo injections of venom from piscivorous cone snails in fish further showed a higher potency compared with venom of nonpiscivores demonstrating a selective advantage. Together, our findings provide compelling evidence for the role of prey shifts in directing the venom composition of cone snails and expand our understanding of the mechanisms of venom variation and diversification.

Phylogeny, envenomation syndrome, and membrane permeabilising venom produced by Australia's electric caterpillar Comana monomorpha.

Zygaenoidea is a superfamily of lepidopterans containing many venomous species, including the Limacodidae (nettle caterpillars) and Megalopygidae (asp caterpillars). Venom proteomes have been recently documented for several species from each of these families, but further data are required to understand the evolution of venom in Zygaenoidea. In this study, we examined the 'electric' caterpillar from North-Eastern Australia, a limacodid caterpillar densely covered in venomous spines. We used DNA barcoding to identify this caterpillar as the larva of the moth Comana monomorpha (Turner, 1904). We report the clinical symptoms of C. monomorpha envenomation, which include acute pain, and erythema and oedema lasting for more than a week. Combining transcriptomics of venom spines with proteomics of venom harvested from the spine tips revealed a venom markedly different in composition from previously examined limacodid venoms that are rich in peptides. In contrast, the venom of C. monomorpha is rich in aerolysin-like proteins similar to those found in venoms of asp caterpillars (Megalopygidae). Consistent with this composition, the venom potently permeabilises sensory neurons and human neuroblastoma cells. This study highlights the diversity of venom composition in Limacodidae.

SARS-CoV-2 Viral Load in the Nasopharynx at Time of First Infection Among Unvaccinated Individuals: A Secondary Cross-Protocol Analysis of 4 Randomized Trials.

Importance: SARS-CoV-2 viral load (VL) in the nasopharynx is difficult to quantify and standardize across settings, but it may inform transmission potential and disease severity. Objective: To characterize VL at COVID-19 diagnosis among previously uninfected and unvaccinated individuals by evaluating the association of demographic and clinical characteristics, viral variant, and trial with VL, as well as the ability of VL to predict severe disease. Design, Setting, and Participants: This secondary cross-protocol analysis used individual-level data from placebo recipients from 4 harmonized, phase 3 COVID-19 vaccine efficacy trials sponsored by Moderna, AstraZeneca, Janssen, and Novavax. Participants were SARS-CoV-2 negative at baseline and acquired COVID-19 during the blinded phase of the trials. The setting included the US, Brazil, South Africa, Colombia, Argentina, Peru, Chile, and Mexico; start dates were July 27, 2020, to December 27, 2020; data cutoff dates were March 26, 2021, to July 30, 2021. Statistical analysis was performed from November 2022 to June 2023. Main Outcomes and Measures: Linear regression was used to assess the association of demographic and clinical characteristics, viral variant, and trial with polymerase chain reaction-measured log10 VL in nasal and/or nasopharyngeal swabs taken at the time of COVID-19 diagnosis. Results: Among 1667 participants studied (886 [53.1%] male; 995 [59.7%] enrolled in the US; mean [SD] age, 46.7 [14.7] years; 204 [12.2%] aged 65 years or older; 196 [11.8%] American Indian or Alaska Native, 150 [9%] Black or African American, 1112 [66.7%] White; 762 [45.7%] Hispanic or Latino), median (IQR) log10 VL at diagnosis was 6.18 (4.66-7.12) log10 copies/mL. Participant characteristics and viral variant explained only 5.9% of the variability in VL. The independent factor with the highest observed differences was trial: Janssen participants had 0.54 log10 copies/mL lower mean VL vs Moderna participants (95% CI, 0.20 to 0.87 log10 copies/mL lower). In the Janssen study, which captured the largest number of COVID-19 events and variants and used the most intensive post-COVID surveillance, neither VL at diagnosis nor averaged over days 1 to 28 post diagnosis was associated with COVID-19 severity. Conclusions and Relevance: In this study of placebo recipients from 4 randomized phase 3 trials, high variability was observed in SARS-CoV-2 VL at the time of COVID-19 diagnosis, and only a fraction was explained by individual participant characteristics or viral variant. These results suggest challenges for future studies of interventions seeking to influence VL and elevates the importance of standardized methods for specimen collection and viral load quantitation.

Safety and immunogenicity of a polyvalent DNA-protein HIV vaccine with matched Env immunogens delivered as a prime-boost regimen or coadministered in HIV-uninfected adults in the USA (HVTN 124): a phase 1, placebo-controlled, double-blind randomised controlled trial.

BACKGROUND: An effective HIV vaccine will most likely need to have potent immunogenicity and broad cross-subtype coverage. The aim of the HIV Vaccine Trials Network (HVTN) 124 was to evaluate safety and immunogenicity of a unique polyvalent DNA-protein HIV vaccine with matching envelope (Env) immunogens. METHODS: HVTN 124 was a randomised, phase 1, placebo-controlled, double-blind study, including participants who were HIV seronegative and aged 18-50 years at low risk for infection. The DNA vaccine comprised five plasmids: four copies expressing Env gp120 (clades A, B, C, and AE) and one gag p55 (clade C). The protein vaccine included four DNA vaccine-matched GLA-SE-adjuvanted recombinant gp120 proteins. Participants were enrolled across six clinical sites in the USA and were randomly assigned to placebo or one of two vaccine groups (ie, prime-boost or coadministration) in a 5:1 ratio in part A and a 7:1 ratio in part B. Vaccines were delivered via intramuscular needle injection. The primary outcomes were safety and tolerability, assessed via frequency, severity, and attributability of local and systemic reactogenicity and adverse events, laboratory safety measures, and early discontinuations. Part A evaluated safety. Part B evaluated safety and immunogenicity of two regimens: DNA prime (administered at months 0, 1, and 3) with protein boost (months 6 and 8), and DNA-protein coadministration (months 0, 1, 3, 6, and 8). All randomly assigned participants who received at least one dose were included in the safety analysis. The study is registered with ClinicalTrials.gov (NCT03409276) and is closed to new participants. FINDINGS: Between April 19, 2018 and Feb 13, 2019, 60 participants (12 in part A [five men and seven women] and 48 in part B [21 men and 27 women]) were enrolled. All 60 participants received at least one dose, and 14 did not complete follow-up (six of 21 in the prime-boost group and eight of 21 in the coadminstration group). 11 clinical adverse events deemed by investigators as study-related occurred in seven of 48 participants in part B (eight of 21 in the prime-boost group and three of 21 in the coadministration group). Local reactogenicity in the vaccine groups was common, but the frequency and severity of reactogenicity signs or symptoms did not differ between the prime-boost and coadministration groups (eg, 20 [95%] of 21 in the prime-boost group vs 21 [100%] of 21 in the coadministration group had either local pain or tenderness of any severity [p=1·00], and seven [33%] vs nine [43%] had either erythema or induration [p=0·97]), nor did laboratory safety measures. There were no delayed-type hypersensitivity reactions or vasculitis or any severe clinical adverse events related to vaccination. The most frequently reported systemic reactogenicity symptoms in the active vaccine groups were malaise or fatigue (five [50%] of ten in part A and 17 [81%] of 21 in the prime-boost group vs 15 [71%] of 21 in the coadministration group in part B), headache (five [50%] and 18 [86%] vs 12 [57%]), and myalgia (four [40%] and 13 [62%] vs ten [48%]), mostly of mild or moderate severity. INTERPRETATION: Both vaccine regimens were safe, warranting evaluation in larger trials. FUNDING: US National Institutes of Health and US National Institute of Allergy and Infectious Diseases.

Dyadic practice for the acquisition of laparoscopic skills (DALS)-A randomized controlled trial.

BACKGROUND: Laparoscopic simulation is integral to surgical education but requires significant resources. We aimed to compare the effectiveness of dyadic practice (DP), involving two individuals working together, to individual practice (IP) for novices acquiring laparoscopic skills and assess their learning experience. METHODS: We conducted a Randomized Controlled Trial comparing DP and IP for novice medical students who completed a laparoscopic simulation workshop. Participants were assessed individually pre-course (test 1), post-course (test 2), and 8-week retention (test 3) using a validated quantitative method. A post-course questionnaire and interview, analyzed with thematic analysis, assessed the learning experience. RESULTS: In total, 31 DP and 35 IP participants completed the study. There was no difference in mean scores between DP and IP groups in all three tests: test 1 (p = 0.55), test 2 (p = 0.26), test 3 (p = 0.35). In trend analysis, the DP group improved post-course (test 1 vs. 2: p = 0.02) and maintained this level at the retention test (2 vs. 3: p = 0.80, 1 vs. 3: p = 0.02). Whilst the IP group also improved post-course (test 1 vs. 2: p < 0.001), this improvement was not retained (2 vs. 3: p = 0.003, 1 vs. 3: p = 0.32). Thematic analysis revealed that DP participants valued peer support, peer feedback and observation time, but also acknowledged the limitations of reduced practical time and issues with teamwork. CONCLUSION: DP is non-inferior to IP for novices learning laparoscopic skills, is well received and may lead to superior long-term skill retention.

Challenges with non-descriptive compliance labeling of end-stage renal disease patients in accessibility for renal transplantation.

Non-descriptive and convenient labels are uninformative and unfairly project blame onto patients. The language clinicians use in the Electronic Medical Record, research, and clinical settings shapes biases and subsequent behaviors of all providers involved in the enterprise of transplantation. Terminology such as noncompliant and nonadherent serve as a reason for waitlist inactivation and limit access to life-saving transplantation. These labels fail to capture all the circumstances surrounding a patient's inability to follow their care regimen, trivialize social determinants of health variables, and bring unsubstantiated subjectivity into decisions regarding organ allocation. Furthermore, insufficient Medicare coverage has forced patients to ration or stop taking medication, leading to allograft failure and their subsequent diagnosis of noncompliant. We argue that perpetuating non-descriptive language adds little substantive information, increases subjectivity to the organ allocation process, and plays a major role in reduced access to transplantation. For patients with existing barriers to care, such as racial/ethnic minorities, these effects may be even more drastic. Transplant committees must ensure thorough documentation to correctly encapsulate the entirety of a patient's position and give voice to an already vulnerable population.

A guide to outcome evaluation of simulation-based education programmes in low and middle-income countries.

Evaluation is a vital part of any learning activity and is essential to optimize and improve educational programmes. It should be considered and prioritized prior to the implementation of any learning activity. However, comprehensive programme evaluation is rarely conducted, and there are numerous barriers to high-quality evaluation. This review provides a framework for conducting outcome evaluation of simulation-based education programmes in low and middle-income countries (LMICs). The basis of evaluation, including core ideas of theory, purpose and structure are outlined, followed by an examination of the levels and healthcare applications of the Kirkpatrick model of evaluation. Then, methods of conducting evaluation of simulation-based education in LMICs are discussed through the lens of a successful surgical simulation programme in Myanmar, a lower-middle-income country. The programme involved the evaluation of 11 courses over 4 years in Myanmar and demonstrated evaluation at the highest level of the Kirkpatrick model. Reviewing this programme provides a bridge between evaluation theory and practical implementation. A range of evaluation methods are outlined, including surveys, interviews, and clinical outcome measurement. The importance of a mixed-methods approach, enabling triangulation of quantitative and qualitative analysis, is highlighted, as are methods of analysing data, including statistical and thematic analysis. Finally, issues and challenges of conducting evaluation are considered, as well as strategies to overcome these barriers. Ultimately, this review informs readers about evaluation theory and methods, grounded in a practical application, to enable other educators in low-resource settings to evaluate their own activities.

Structural analysis of a U-superfamily conotoxin containing a mini-granulin fold: Insights into key features that distinguish between the ICK and granulin folds.

We are entering an exciting time in structural biology where artificial intelligence can be used to predict protein structures with greater accuracy than ever before. Extending this level of accuracy to the predictions of disulfide-rich peptide structures is likely to be more challenging, at least in the short term, given the tight packing of cysteine residues and the numerous ways that the disulfide bonds can potentially be linked. It has been previously shown in many cases that several disulfide bond connectivities can be accommodated by a single set of NMR-derived structural data without significant violations. Disulfide-rich peptides are prevalent throughout nature, and arguably the most well-known are those present in venoms from organisms such as cone snails. Here, we have determined the first three-dimensional structure and disulfide connectivity of a U-superfamily cone snail venom peptide, TxVIIB. TxVIIB has a VI/VII cysteine framework that is generally associated with an inhibitor cystine knot (ICK) fold; however, AlphaFold predicted that the peptide adopts a mini-granulin fold with a granulin disulfide connectivity. Our experimental studies using NMR spectroscopy and orthogonal protection of cysteine residues indicate that TxVIIB indeed adopts a mini-granulin fold but with the ICK disulfide connectivity. Our findings provide structural insight into the underlying features that govern formation of the mini-granulin fold rather than the ICK fold and will provide fundamental information for prediction algorithms, as the subtle complexity of disulfide isomers may be not adequately addressed by the current prediction algorithms.

Pretransplant malignancy in pediatrics is not a risk factor for renal graft failure.

BACKGROUND: In adults, pretransplant malignancy (PTM) negatively impacts patient survival due to immunosuppression regimens influencing post-transplantation tumor growth. Few reports investigate the outcomes of pediatric kidney transplantation with PTM. We compare transplant outcomes for pediatric patients with PTM to matched controls, including cancer types extending beyond Wilms tumor. METHODS: The United Network of Organ Sharing Database was queried to identify pediatric transplant recipients with histories of PTM. All PTM patients were matched to non-PTM patients, at a 1:1 ratio, with 0.001 match tolerance. Matching variables included transplant year, recipient age, recipient gender, recipient race, donor type, and prior transplant. Death-censored graft and patient survival were analyzed. All statistics were reported with 95% confidence intervals (CI). RESULTS: After propensity matching, 285 PTM and 285 non-PTM patients were identified, with transplant dates from 1990 to 2020. Median Kidney Donor Profile Index values were comparable between cohorts, 17% and 12%, respectively (p = .065). Kaplan-Meier analysis revealed that PTM patients did not have a significantly different rate of death-censored graft failure, compared to the non-PTM group [HR 0.76; 95% CI (0.54-1.1)]. There was also no difference in the overall survival between the two groups of patients [HR 1.1; 95% CI (0.66-2.0)]. CONCLUSION: A history of pediatric malignancy has minimal independent effect on their post-transplant survival. Additionally, pediatric patients with PTM demonstrated equivalent rates of graft survival. Thus, in contrast to adults, renal failure in children with history of pediatric malignancies should not be considered a complicating factor for renal transplantation.

Peptide toxins that target vertebrate voltage-gated sodium channels underly the painful stings of harvester ants.

Harvester ants (genus Pogonomyrmex) are renowned for their stings which cause intense, long-lasting pain, and other neurotoxic symptoms in vertebrates. Here, we show that harvester ant venoms are relatively simple and composed largely of peptide toxins. One class of peptides is primarily responsible for the long-lasting local pain of envenomation via activation of peripheral sensory neurons. These hydrophobic, cysteine-free peptides potently modulate mammalian voltage-gated sodium (NaV) channels, reducing the voltage threshold for activation and inhibiting channel inactivation. These toxins appear to have evolved specifically to deter vertebrates.

Identification of sodium channel toxins from marine cone snails of the subgenera Textilia and Afonsoconus.

Voltage-gated sodium (NaV) channels are transmembrane proteins that play a critical role in electrical signaling in the nervous system and other excitable tissues. µ-Conotoxins are peptide toxins from the venoms of marine cone snails (genus Conus) that block NaV channels with nanomolar potency. Most species of the subgenera Textilia and Afonsoconus are difficult to acquire; therefore, their venoms have yet to be comprehensively interrogated for µ-conotoxins. The goal of this study was to find new µ-conotoxins from species of the subgenera Textilia and Afonsoconus and investigate their selectivity at human NaV channels. Using RNA-seq of the venom gland of Conus (Textilia) bullatus, we identified 12 µ-conotoxin (or µ-conotoxin-like) sequences. Based on these sequences we designed primers which we used to identify additional µ-conotoxin sequences from DNA extracted from historical specimens of species from Textilia and Afonsoconus. We synthesized six of these µ-conotoxins and tested their activity on human NaV1.1-NaV1.8. Five of the six synthetic peptides were potent blockers of human NaV channels. Of these, two peptides (BuIIIB and BuIIIE) were potent blockers of hNaV1.3. Three of the peptides (BuIIIB, BuIIIE and AdIIIA) had submicromolar activity at hNaV1.7. This study serves as an example of the identification of new peptide toxins from historical DNA and provides new insights into structure-activity relationships of µ-conotoxins with activity at hNaV1.3 and hNaV1.7.

Cancer screening and management in the transgender population: Review of literature and special considerations for gender affirmation surgery.

BACKGROUND: Literature focused on cancer screening and management is lacking in the transgender population. AIM: To action to increase contributions to the scientific literature that drives the creation of cancer screening and management protocols for transgender and gender nonconforming (TGNC) patients. METHODS: We performed a systematic search of PubMed on January 5th, 2022, with the following terms: "TGNC", OR "transgender", OR "gender non-conforming", OR "gender nonbinary" AND "cancer screening", AND "breast cancer", AND "cervical cancer", AND "uterine cancer", AND "ovarian cancer", AND "prostate cancer", AND "testicular cancer", AND "surveillance", AND "follow-up", AND "management". 70 unique publications were used. The findings are discussed under "Screening" and "Management" categories. RESULTS: Screening: Current cancer screening recommendations default to cis-gender protocols. However, long-term gender-affirming hormone therapy and loss to follow-up from the gender-specific specialties contribute to a higher risk for cancer development and possible delayed detection. The only known screening guidelines made specifically for this population are from the American College of Radiology for breast cancer. Management: Prior to undergoing Gender Affirmation Surgery (GAS), discussion should address cancer screening and management in the organs remaining in situ. Cancer treatment in this population requires consideration for chemotherapy, radiation, surgery and/or reconstruction. Modification of hormone therapy is decided on a case-by-case basis. The use of prophylactic vs aesthetic techniques in surgery is still debated. CONCLUSION: When assessing transgender individuals for GAS, a discussion on the future oncologic risk of the sex-specific organs remaining in situ is essential. Cancer management in this population requires a multidisciplinary approach while the care should be highly individualized with considerations to social, medical, surgical and gender affirming surgery related specifications. Special considerations have to be made during planning for GAS as surgery will alter the anatomy and may render the organ difficult to sample for screening purposes. A discussion with the patient regarding the oncologic risk of remaining organs is imperative prior to GAS. Other special considerations to screening such as the conscious or unconscious will to unassociated with their remaining organs is also a key point to address. We currently lack high quality studies pertinent to the cancer topic in the gender affirmation literature. Further research is required to ensure more comprehensive and individualized care for this population.