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Bacterial flagella and type IV pili (TFP) are surface appendages that enable motility and mechanosensing through distinct mechanisms. These structures were previously thought to have no components in common. Here, we report that TFP and some flagella share proteins PilO, PilN, and PilM, which we identified as part of the Helicobacter pylori flagellar motor. H. pylori mutants lacking PilO or PilN migrated better than wild type in semisolid agar because they continued swimming rather than aggregated into microcolonies, mimicking the TFP-regulated surface response. Like their TFP homologs, flagellar PilO/PilN heterodimers formed a peripheral cage that encircled the flagellar motor. These results indicate that PilO and PilN act similarly in flagella and TFP by differentially regulating motility and microcolony formation when bacteria encounter surfaces.

Lentigo Maligna (LM) arises on chronically-sun damaged skin and can have extensive subclinical spread, often in functionally and cosmetically challenging areas. This two-part continuing medical education (CME) series reviews LM. Part I reviews epidemiology, risk factors, clinical presentation, diagnostic tools, biopsy technique, and histopathology of LM. Part II reviews both surgical and non-surgical treatment options. Surgical approaches - including conventional excision, Mohs micrographic surgery, and staged excision - remain first-line therapy to achieve cure. Some patients may be poor surgical candidates or elect for alternative treatments. Non-surgical modalities, such as topical and radiation therapy, are also reviewed. Finally, surveillance recommendations are discussed., (Copyright © 2024 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Lentigo maligna (LM) is an increasingly common subtype of melanoma, presenting as a slow-growing tan-brown macule or patch with irregular borders arising on chronically solar-damaged skin. This two-part continuing medical education (CME) series provides an overview of LM. Part I reviews LM's epidemiology, risk factors, and clinical presentation. Clinical tools to aid in diagnosis - such as dermoscopy and reflectance confocal microscopy - are discussed, as well as optimal biopsy strategies. Histopathology and current understanding of molecular underpinnings are also reviewed. Management of LM presents unique challenges given a predilection for subclinical spread on functionally and cosmetically sensitive areas such as the face. Part II reviews the two pillars of management including both surgical and non-surgical treatment options and surveillance., (Copyright © 2024. Published by Elsevier Inc.)

Vaccine science, nanotechnology, and immunotherapy are at the forefront of cancer treatment strategies, each offering significant potential for enhancing tumor-specific immunity and establishing long-lasting immune memory to prevent tumor recurrence. Despite the promise of these personalized and precision-based anti-cancer approaches, challenges such as immunosuppression, suboptimal immune activation, and T-cell exhaustion continue to hinder their effectiveness. The limited clinical success of cancer vaccines often stems from difficulties in identifying effective antigens, efficiently targeting immune cells, lymphoid organs, and the tumor microenvironment, overcoming immune evasion, enhancing immunogenicity, and avoiding lysosomal degradation. However, numerous studies have demonstrated that integrating nanotechnology with immunotherapeutic strategies in vaccine development can overcome these challenges, leading to potent antitumor immune responses and significant progress in the field. This review highlights the critical components of cancer vaccine and nanovaccine strategies for immunomodulatory antitumor therapy. It covers general vaccine strategies, types of vaccines, antigen forms, nanovaccine platforms, challenges faced, potential solutions, and key findings from preclinical and clinical studies, along with future perspectives. To fully unlock the potential of cancer vaccines and nanovaccines, precise immunological monitoring during early-phase trials is essential. This approach will help identify and address obstacles, ultimately expanding the available options for patients who are resistant to conventional cancer immunotherapies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: No standardized, evidence-based surveillance practices exist to guide and optimize recurrence detection in patients with cutaneous melanoma., Objective: To determine the most high-yield positive review of systems for signaling recurrence in patients with cutaneous melanoma., Methods: This retrospective cohort study assessed patients with a history of cutaneous melanoma and compared demographic and clinical characteristics, including a comprehensive review of systems, among those who experienced recurrence and those who did not., Results: A high-yield positive review of systems associated with cutaneous melanoma recurrence can be remembered using the mnemonic "ATLAS": Appetite change, Tiredness, Lymph node enlargement, Abdominal pain, and Shortness of breath LIMITATIONS: Retrospective design, limited sample size, and variability in follow-up time between recurrent and nonrecurrent cohorts., Conclusion: Any treating physician using this model may have a greater opportunity to detect recurrent cutaneous melanoma and improve outcomes while limiting cost and morbidity., Competing Interests: Conflicts of interest None disclosed., (Copyright © 2024 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Ultrasound-guided supraclavicular block (UGSCB) is an emerging technique gaining interest amongst emergency physicians that provides regional anaesthesia to the upper limb to tolerate painful procedures. It offers an alternative to the more traditional technique of a Bier block (BB). However, the effectiveness or safety of UGSCB when performed in the emergency department (ED) is unclear., Methods: SUPERB (SUPraclavicular block for Emergency Reduction versus Bier block) is a prospective open-label non-inferiority randomised controlled trial comparing the effectiveness of UGSCB versus BB for closed reduction of upper limb fractures and/or dislocations. Adult patients presenting with upper limb fracture and/or dislocation requiring closed reduction in ED were randomised to either UGSCB or BB. Once regional anaesthesia is obtained, closed reduction of the injured part was performed and immobilised. The primary outcome is maximal pain experienced during closed reduction measured via a visual analogue scale (VAS). Secondary outcomes include post-reduction pain, patient satisfaction, total opioid requirement in ED, ED length of stay, adverse events and regional anaesthesia failure., Results: Primary outcome analysis will be performed using both the intention-to-treat and per-protocol populations. The between-group difference in maximum pain intensity will be assessed using linear regression modelling with trial group allocation (UGSCB vs BB) included as a main affect. A pre-specified non-inferiority margin of 20 mm on the VAS scale will be used to establish non-inferiority of UGSCB compared to BB., Conclusion: SUPERB is the first randomised controlled trial to investigate the effectiveness and safety of UGSCB in the ED. The trial has the potential to demonstrate that UGSCB is an alternative safe and effective option for the management of upper extremity emergencies in the ED., (© 2024. The Author(s).)

Keloids are abnormal skin growths occurring in a significant portion of the global population. Despite their pervasiveness, the underlying pathophysiology of this scarring process is yet to be fully understood. In this review article, we delve into the current literature on the pathophysiological mechanisms of keloids. We take a top-down approach, first looking at host factors such as genetics and endocrine factors and then taking a more granular approach describing specific control factors such as germline keloid predisposition variants, epigenetics and transcriptomics, inflammatory and immune dysregulation, and the role of profibrotic and angiogenic cell signaling pathways. We then discuss current knowledge gaps, propose further research avenues, and explore potential future treatment options considering our increased understanding of keloid pathogenesis., (© 2024 The Authors.)

The extent to which the geographic diversity of the US plays a significant role in melanoma incidence and mortality over time has not been precisely characterized. We obtained age-adjusted melanoma data for the 50 states between 2001 and 2019 from the Surveillance, Epidemiology, and End Results registry and performed hierarchical clustering (complete linkage, Euclidean space) to uncover geo-temporal trend groups over 2 decades. While there was a global increase in incidence during this time (b 1  = +0.41, P < .0001), there were 6 distinct clusters (by absolute and Z-score) with significantly different temporal trends (analysis of covariance P < .0001). Cluster 2 states had the sharpest increase in incidence with b 1  = +0.66, P < .0001. For mortality, the global rate decreased (b 1  = -0.03, P = .0003) with 3 and 6 clusters by absolute and Z-scores, respectively (analysis of covariance P < .05). Cluster 1 states exhibited the smallest decline in mortality (b 1  = -0.017, P = .008). Mortality to incidence ratios declined (b 1  = -0.0037, P < .0001) and harbored 4 and 6 clusters by absolute and Z-score analysis, respectively (analysis of covariance P < .0001). Cluster 4 states had the lowest rate of mortality to incidence ratios decline (b 1  = -0.003, P < .0001). These results provide an unprecedented higher dimensional view of melanoma behavior over space and time. With more refined analyses, geospatial studies can uncover local trends which can inform public health agencies to more properly allocate resources., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Abdominal compartment syndrome (ACS) is typically attributed to critically unwell patients with trauma, burns, post surgery, and massive ascites. A rare but fatal cause of ACS is bulimia nervosa (BN), which is an eating disorder characterized by bingeing, followed by methods to avoid weight gain, including purging., Case Report: We present a case of a 20-year-old woman who presented with abdominal pain and distension after consuming a large quantity of food the previous night and was unable to purge. She was initially managed conservatively and discharged home, but returned subsequently on the same day with clinical features of ACS secondary to acute gastric distension. Decompression resulted in life-threatening reperfusion injury with critical electrolyte abnormalities and fatal cardiac arrest in the operating theatre. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: A systematic review of the literature found only 11 case reports of ACS secondary to BN, of which only 6 patients survived due to early diagnosis and decompression. Inability to purge and lower limb ischemia appeared to be associated with increased mortality. As BN is a common emergency presentation, the case and systematic review highlights the need to consider ACS as a potentially life-threatening complication of binge eating, particularly when there is unsuccessful purging., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The recent expansion of immunotherapy for stage IIB/IIC melanoma highlights a growing clinical need to identify patients at high risk of metastatic recurrence and, therefore, most likely to benefit from this therapeutic modality., Objective: To develop time-to-event risk prediction models for melanoma metastatic recurrence., Methods: Patients diagnosed with stage I/II primary cutaneous melanoma between 2000 and 2020 at Mass General Brigham and Dana-Farber Cancer Institute were included. Melanoma recurrence date and type were determined by chart review. Thirty clinicopathologic factors were extracted from electronic health records. Three types of time-to-event machine-learning models were evaluated internally and externally in the distant versus locoregional/nonrecurrence prediction., Results: This study included 954 melanomas (155 distant, 163 locoregional, and 636 1:2 matched nonrecurrences). Distant recurrences were associated with worse survival compared to locoregional/nonrecurrences (HR: 6.21, P < .001) and to locoregional recurrences only (HR: 5.79, P < .001). The Gradient Boosting Survival model achieved the best performance (concordance index: 0.816; time-dependent AUC: 0.842; Brier score: 0.103) in the external validation., Limitations: Retrospective nature and cohort from one geography., Conclusions: These results suggest that time-to-event machine-learning models can reliably predict the metastatic recurrence from localized melanoma and help identify high-risk patients who are most likely to benefit from immunotherapy., Competing Interests: Conflicts of interest YRS is an advisory board member/consultant and has received honoraria from Incyte Corporation, Castle Biosciences, Galderma, and Sanofi outside of the submitted work., (Copyright © 2023 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Acral and mucosal melanomas are often driven by sequence variants in the KIT receptor tyrosine kinase, with nearly 40% harboring alterations in the KIT locus. Despite advances in the knowledge of KIT -mutated melanomas, little is known about the molecular reprogramming that occurs during KIT-mediated melanoma progression owing to the rarity of acral and mucosal melanomas and the lack of comprehensive biological tools and models. To this end, we used a murine model that allows us to ascertain the molecular underpinnings of the stages of cancer progression-transformation, tumorigenesis, immune engagement, and tumor escalation. We found dramatic increases in biosynthetic demands associated with the transformation stage, including DNA and RNA metabolism, leading to replication stress. Tumorigenesis was closely linked to neuronal and axonal development, likely necessary for invasion into the host. Immune engagement highlighted early immune excitation and rejection pathways, possibly triggered by abrupt neoantigen exposure. Finally, tumor escalation pathways proved consistent with immune evasion, with immune-related pathways becoming significantly downregulated. To our knowledge, it is previously unreported that these critical milestones needed for KIT-driven melanoma tumor formation have been studied at the molecular level using isogenically matched and phenotypically defined cells., (© 2024 The Authors.)