A planetary health innovation for disease, food and water challenges in Africa.

Many communities in low- and middle-income countries globally lack sustainable, cost-effective and mutually beneficial solutions for infectious disease, food, water and poverty challenges, despite their inherent interdependence1-7. Here we provide support for the hypothesis that agricultural development and fertilizer use in West Africa increase the burden of the parasitic disease schistosomiasis by fuelling the growth of submerged aquatic vegetation that chokes out water access points and serves as habitat for freshwater snails that transmit Schistosoma parasites to more than 200 million people globally8-10. In a cluster randomized controlled trial (ClinicalTrials.gov: NCT03187366) in which we removed invasive submerged vegetation from water points at 8 of 16 villages (that is, clusters), control sites had 1.46 times higher intestinal Schistosoma infection rates in schoolchildren and lower open water access than removal sites. Vegetation removal did not have any detectable long-term adverse effects on local water quality or freshwater biodiversity. In feeding trials, the removed vegetation was as effective as traditional livestock feed but 41 to 179 times cheaper and converting the vegetation to compost provided private crop production and total (public health plus crop production benefits) benefit-to-cost ratios as high as 4.0 and 8.8, respectively. Thus, the approach yielded an economic incentive-with important public health co-benefits-to maintain cleared waterways and return nutrients captured in aquatic plants back to agriculture with promise of breaking poverty-disease traps. To facilitate targeting and scaling of the intervention, we lay the foundation for using remote sensing technology to detect snail habitats. By offering a rare, profitable, win-win approach to addressing food and water access, poverty alleviation, infectious disease control and environmental sustainability, we hope to inspire the interdisciplinary search for planetary health solutions11 to the many and formidable, co-dependent global grand challenges of the twenty-first century.

Establishing Consensus for Mohs Micrographic Surgical Techniques in the Treatment of Melanoma in Situ for Future Clinical Trials: A Modified Delphi Study.

BACKGROUND: Mohs micrographic surgery (MMS) is a promising treatment modality for melanoma in situ (MIS). However, variations in surgical technique limit the generalizability of existing data and may impede future study of MMS in clinical trials. METHODS: A modified Delphi method was selected to establish consensus on optimal MMS techniques for treating MIS in future clinical trials. The Delphi method was selected due to the limited current data, the wide range of techniques used in the field, and the intention to establish a standardized technique for future clinical trials. A literature review and interviews with experienced MMS surgeons were performed to identify dimensions of the MMS technique for MIS that (1) likely impacted costs or outcomes of the procedure, and (2) showed significant variability between surgeons. A total of 8 dimensions of technical variation were selected. The Delphi process consisted of 2 rounds of voting and commentary, during which 44 expert Mohs surgeons across the United States rated their agreement with specific recommendations using a Likert scale. RESULTS: Five of eight recommendations achieved consensus in Round 1. All 3 of the remaining recommendations achieved consensus in Round 2. Techniques achieving consensus in Round 1 included the use of a starting peripheral margin of ≤5 mm, application of immunohistochemistry, frozen tissue processing, and resecting to the depth of subcutaneous fat. Consensus on the use of Wood's lamp, dermatoscope, and negative tissue controls was established in Round 2. CONCLUSIONS: This study generated 8 consensus recommendations intended to offer guidance for Mohs surgeons treating MIS. The adoption of these recommendations will promote standardization to facilitate comparisons of aggregate data in multicenter clinical trials.

The Influence of Personality Traits on Driving Behaviors in Preclinical Alzheimer Disease.

INTRODUCTION: Alzheimer disease (AD) has a long preclinical phase in which AD pathology is accumulating without detectable clinical symptoms. It is critical to identify participants in this preclinical phase as early as possible since treatment plans may be more effective in this stage. Monitoring for changes in driving behavior, as measured with GPS sensors, has been explored as a low-burden, easy-to-administer method for detecting AD risk. However, driving is a complex, multifaceted process that is likely influenced by other factors, including personality traits, that may change in preclinical AD. METHODS: We examine the moderating influence of neuroticism and conscientiousness on longitudinal changes in driving behavior in a sample of 203 clinically normal older adults who are at varying risk of developing AD. RESULTS: Neuroticism moderated rates of change in the frequency of speeding as well as the number of trips taken at night. Conscientiousness moderated rates of change in typical driving space. CONCLUSIONS: Personality traits change in early AD and also influence driving behaviors. Studies that seek to utilize naturalistic driving behavior to establish AD risk need to accommodate interpersonal differences, of which personality traits are one of many possible factors. Future studies should explicitly establish how much benefit is provided by including personality traits in predictive models of AD progression.

Identifying critical quality metrics in Mohs Surgery: A national expert consensus process.

BACKGROUND: Amid a movement toward value-based healthcare, increasing emphasis has been placed on outcomes and cost of medical services. To define and demonstrate the quality of services provided by Mohs surgeons, it is important to identify and understand the key aspects of Mohs micrographic surgery (MMS) that contribute to excellence in patient care. OBJECTIVE: The purpose of this study is to develop and identify a comprehensive list of metrics in an initial effort to define excellence in MMS. METHODS: Mohs surgeons participated in a modified Delphi process to reach a consensus on a list of metrics. Patients were administered surveys to gather patient perspectives. RESULTS: Twenty-four of the original 66 metrics met final inclusion criteria. Broad support for the initiative was obtained through physician feedback. LIMITATIONS: Limitations of this study include attrition bias across survey rounds and participation at the consensus meeting. Furthermore, the list of metrics is based on expert consensus instead of quality evidence-based outcomes. CONCLUSION: With the goal of identifying metrics that demonstrate excellence in performance of MMS, this initial effort has shown that Mohs surgeons and patients have unique perspectives and can be engaged in a data-driven approach to help define excellence in the field of MMS.

Performance of Staging Systems for Non-Head and Neck Cutaneous Squamous Cell Carcinoma.

BACKGROUND: The performance of staging systems in non-head and neck cutaneous squamous cell carcinomas has not been well established. OBJECTIVE: To evaluate the performance of the American Joint Committee on Cancer 8th Edition and Brigham and Women's Hospital staging systems in non-head and neck squamous cell carcinomas. MATERIALS AND METHODS: Eligible tumors were identified and staged from an existing retrospective database. Cumulative incidence function curves of any poor outcome were generated. Distinctiveness, sensitivity, specificity, positive and negative predictive value, and concordance index were calculated. RESULTS: 1,042 primary tumors were included, with 38 resulting in any poor outcome and 16 in any major poor outcome. High-stage tumors represented 2.2% and 3.5% of tumors; these accounted for 10/38 of the poor outcomes (26.3%) and 8/16 of the major poor outcomes (50%). High-stage tumors predicted major poor outcomes with a sensitivity of 0.5 and specificity of 0.99 for the Brigham and Women's Hospital system, and a sensitivity of 0.5 and specificity of 0.97 for the American Joint Committee on Cancer 8th edition system. The concordance index for both was 0.74. CONCLUSION: Current staging systems can be used to predict poor outcomes in cutaneous squamous cell carcinomas off the head and neck.

Use of Imaging in Cutaneous Squamous Cell Carcinoma to Detect High-Risk Tumor Features, Nodal Metastasis, and Distant Metastasis: A Systematic Review.

BACKGROUND: Imaging has been shown to impact management and disease outcomes in cutaneous squamous cell carcinoma, but the literature on optimal modalities is lacking. OBJECTIVE: To perform a systematic review evaluating the performance of various imaging studies for the detection of perineural spread, bony invasion, nodal metastasis (NM), and distant metastasis in cutaneous squamous cell carcinoma. MATERIALS AND METHODS: Four databases were searched for relevant terms. Articles were included if they presented primary data on 5 or more subjects with cutaneous squamous cell carcinoma who underwent imaging to detect perineural spread, bony involvement, NM, or distant metastasis. RESULTS: Thirty studies and 1,027 subjects were included in the pooled analysis. Magnetic resonance imaging had a 94.9% sensitivity in detecting perineural spread. Computed tomography (CT) demonstrated a sensitivity of 75.7% and specificity of 98.6% in detecting bony invasion. While ultrasound, positron emission tomography-computed tomography, and CT all performed reasonably well in detecting NM, CT demonstrated the highest sensitivity (96.4%) and specificity (100%). Imaging changed management in up to 33% of cases. CONCLUSION: Imaging is useful in high-risk cutaneous squamous cell carcinoma. Magnetic resonance imaging performs best in the detection of perineural spread, and CT is the most accurate modality to detect bony invasion and NM.

Cutaneous Squamous Cell Carcinoma Outcomes in Solid Organ Transplant Recipients: A Matched Retrospective Cohort Study.

BACKGROUND: Solid organ transplant recipients with cutaneous squamous cell carcinoma (CSCC) have an increased risk of poor outcomes. However, a recent study demonstrated that immunosuppression is not an independent risk factor for these poor outcomes after controlling for primary tumor stage. OBJECTIVE: To evaluate whether transplant status is an independent risk factor for poor outcomes in CSCC. MATERIALS AND METHODS: A database of CSCCs treated at an academic center over 10 years was used to perform a retrospective cohort study comparing the risk of poor outcomes (local recurrence, regional and distant metastases, and disease-specific death) in solid organ transplant recipients and controls. Subjects were matched on age, tumor stage, sex, tumor site, and time to poor outcome. RESULTS: There were 316 tumors from 78 transplant patients and 316 tumors from 262 controls. On multivariate analysis, tumor stage and location on the head and neck were predictive of poor outcomes. There was no significant difference in the risk of poor outcomes in the transplant group versus the control group. CONCLUSION: Transplant status was not an independent risk factor for poor squamous cell carcinoma outcomes after controlling for stage, age, sex, site, and time to poor outcome.

Impact of Cutaneous Squamous Cell Carcinoma Histologic Features on Percent Interrater Agreement Regarding Tumor Differentiation.

BACKGROUND: Poor differentiation predicts adverse outcomes in cutaneous squamous cell carcinoma (CSCC), but there is no standardized, reliable grading system. OBJECTIVE: To explore which histologic features have the greatest impact on CSCC differentiation interrater agreement. MATERIALS AND METHODS: In a prior study, 40 raters graded differentiation for 45 squamous cell carcinomas, and percent interrater agreements were calculated. Cases graded as well/moderately differentiated with 100% agreement (10), those graded as poorly differentiated with ≥80% agreement (5), and those that received a variety of grades with ≤60% agreement (7) were pulled for the current study. Three raters graded individual histologic features for each case, and percent interrater agreements were calculated using both the well/moderately/poorly differentiated grading system and a dichotomized system. RESULTS: The percent interrater agreements were 34.8% for mitoses, 53% for pleomorphism, 59.1% for keratinization, 66.7% for cellular cohesion/intercellular bridges, and 78.8% for tumor edges. Percent agreements improved with dichotomous grading; the largest improvement was seen within the group of cases that had been graded as well/moderately differentiated with 100% agreement in the prior study. CONCLUSION: Future squamous cell carcinoma differentiation grading systems would benefit from eliminating mitotic rate, clearly defining how to grade other features, and dichotomous grading.

Evaluation of telehealth in delivering diagnostic developmental assessments for children in South Western Sydney during the COVID-19 pandemic: Clinician and family perspectives.

AIMS: Children with neuro-developmental disorders faced significant challenges in accessing services during the COVID-19 pandemic. Telehealth has been adopted by health services globally to facilitate access to clinical services. Our aims were to evaluate the utility of the telehealth modality for providing developmental assessment services and explore enablers and barriers to using telehealth, in a culturally diverse and socioeconomically disadvantaged population in Sydney. METHODS: We reviewed telehealth developmental assessments in South Western Sydney conducted between 1 April and 30 June 2020. Data were collated on demographics; telehealth modality; diagnostic formulation; recommendations; and requested follow up. We conducted retrospective semi-structured telephone interviews with 79 families and 11 clinicians about their telehealth experience. Thematic analysis was carried out on the open text responses. RESULTS: Of 205 children assessed across six sites, median age was 48 months; 45% were assessed with video and 55% with telephone only. Diagnostic formulation and therapeutic recommendations were provided for 203 (99%) children and 138 (67%) were asked to come for face-to-face follow-up. The majority of families (76%) were satisfied or extremely satisfied with telehealth. Median clinician satisfaction was 3.5 out of 5, whilst clinician confidence with diagnostic formulation was 4 out of 5. Qualitative data revealed a range of barriers and enablers. CONCLUSION: Telehealth was a successful modality for contributing to the assessment journey for children with neuro-developmental disorders in our culturally, linguistically and socioeconomically diverse clinical population in the context of a pandemic lockdown. We discuss the potential for telehealth modalities in child developmental assessments beyond the pandemic.

Nevus Spilus With Dermatoheliosis: A Histologic Mimicker of Melanoma in Situ at Melanoma Excision Margins.

ABSTRACT: Nevus spilus, or speckled lentiginous nevus, is a relatively common lesion that presents at birth or in early childhood. It consists of a background tan patch, which appears similar to a café au lait macule or lentigo simplex on histology, studded with various types of nevi. Rarely, these nevi can undergo malignant transformation to melanoma. When melanoma develops within a heavily photodamaged nevus spilus, evaluating excision margins may be challenging because the combined histologic features of nevus spilus and severe dermatoheliosis can mimic melanoma in situ. We report a case of an elderly man with extensive sun damage who developed malignant melanoma within an occult nevus spilus, resulting in multiple excisions with false-positive margins.

Improving rural health care reduces illegal logging and conserves carbon in a tropical forest.

Tropical forest loss currently exceeds forest gain, leading to a net greenhouse gas emission that exacerbates global climate change. This has sparked scientific debate on how to achieve natural climate solutions. Central to this debate is whether sustainably managing forests and protected areas will deliver global climate mitigation benefits, while ensuring local peoples' health and well-being. Here, we evaluate the 10-y impact of a human-centered solution to achieve natural climate mitigation through reductions in illegal logging in rural Borneo: an intervention aimed at expanding health care access and use for communities living near a national park, with clinic discounts offsetting costs historically met through illegal logging. Conservation, education, and alternative livelihood programs were also offered. We hypothesized that this would lead to improved health and well-being, while also alleviating illegal logging activity within the protected forest. We estimated that 27.4 km2 of deforestation was averted in the national park over a decade (∼70% reduction in deforestation compared to a synthetic control, permuted P = 0.038). Concurrently, the intervention provided health care access to more than 28,400 unique patients, with clinic usage and patient visitation frequency highest in communities participating in the intervention. Finally, we observed a dose-response in forest change rate to intervention engagement (person-contacts with intervention activities) across communities bordering the park: The greatest logging reductions were adjacent to the most highly engaged villages. Results suggest that this community-derived solution simultaneously improved health care access for local and indigenous communities and sustainably conserved carbon stocks in a protected tropical forest.

Impact of Iran's Forest Nationalization Law on Forest Cover Changes over Six Decades: A Case Study of a Zagros Sparse Coppice Oak Forest.

Forest nationalization policies in developing countries have often led to a reduction in local forest ownership rights and short- or long-term exploitative behaviors of stakeholders. The purpose of this research is to quantify the effect of Iran's Forest Nationalization Law (FNL) in a part of Zagros Forest over a 68-year time period (1955-2022) using 1955 historical aerial photos, 1968 Corona spy satellite photography, and classification of multi-temporal Landsat satellite images. A past classification change detection technique was used to identify the extent and the pattern of land use changes in time. For this purpose, six periods were defined, to cover the time before and after the implementation of FNL. A 0.27% deforestation trend was identified over the period after the FNL. Dense and open forested area has decreased from 7175.62 ha and 68,927.46 ha in 1955 to 5664.26 ha and 59,223.38 ha in 2022. The FNL brought decisive changes in the legal and forest management systems at the state level, mainly by giving their ownership to the state. Accordingly, the FNL and the related conservation plans have not fully succeeded in protecting, rehabilitating, recovering, and developing the sparse Zagros Forest ecosystems, as their most important goals.

Multiple roles for Bcl-3 in mammary gland branching, stromal collagen invasion, involution and tumor pathology.

BACKGROUND: The Bcl-3 protein is an atypical member of the inhibitor of -κB family that has dual roles as a transcriptional repressor and a coactivator for dimers of NF-κB p50 and p52. Bcl-3 is expressed in mammary adenocarcinomas and can promote tumorigenesis and survival signaling and has a key role in tumor metastasis. In this study, we have investigated the role of Bcl-3 in the normal mammary gland and impact on tumor pathology. METHODS: We utilized bcl-3-/- mice to study mammary gland structure in virgins and during gestation, lactation and early involution. Expression of involution-associated genes and proteins and putative Bcl-3 target genes was examined by qRT-PCR and immunoblot analysis. Cell autonomous branching morphogenesis and collagen I invasion properties of bcl-3-/- organoids were tested in 3D hydrogel cultures. The role of Bcl-3 in tumorigenesis and tumor pathology was also assessed using a stochastic carcinogen-induced mammary tumor model. RESULTS: Bcl-3-/- mammary glands demonstrated reduced branching complexity in virgin and pregnant mice. This defect was recapitulated in vitro where significant defects in bud formation were observed in bcl-3-/- mammary organoid cultures. Bcl-3-/- organoids showed a striking defect in protrusive collective fibrillary collagen I invasion associated with reduced expression of Fzd1 and Twist2. Virgin and pregnant bcl-3-/- glands showed increased apoptosis and rapid increases in lysosomal cell death and apoptosis after forced weaning compared to WT mice. Bcl-2 and Id3 are strongly induced in WT but not bcl-3-/- glands in early involution. Tumors in WT mice were predominately adenocarcinomas with NF-κB activation, while bcl-3-/- lesions were largely squamous lacking NF-κB and with low Bcl-2 expression. CONCLUSIONS: Collectively, our results demonstrate that Bcl-3 has a key function in mammary gland branching morphogenesis, in part by regulation of genes involved in extracellular matrix invasion. Markedly reduced levels of pro-survival proteins expression in bcl-3 null compared to WT glands 24 h post-weaning indicate that Bcl-3 has a role in moderating the rate of early phase involution. Lastly, a reduced incidence of bcl-3-/- mammary adenocarcinomas versus squamous lesions indicates that Bcl-3 supports the progression of epithelial but not metaplastic cancers.

Induction of alternative NF-κB within TAg-induced basal mammary tumors in activation-resistant inhibitor of κ-B kinase (IKKα) mutant mice.

BACKGROUND: The alternative NF-κB pathway is activated by the NF-κB-inducing kinase (NIK) mediated phosphorylation of the inhibitor of κ-B kinase α (IKKα). IKKα then phosphorylates p100/NFKB2 to result in its processing to the active p52 subunit. Evidence suggests that basal breast cancers originate within a subpopulation of luminal progenitor cells which is expanded by signaling to IKKα. OBJECTIVE: To determine the role of IKKα in the development of basal tumors. METHODS: Kinase dead IkkαAA/AA mice were crossed with the C3(1)-TAg mouse model of basal mammary cancer. Tumor growth and tumor numbers in WT and IkkαAA/AA mice were assessed and immunopathology, p52 expression and stem/progenitor 3D colony forming assays were performed. Nik-/- mammary glands were isolated and mammary colonies were characterized. RESULTS: While tumor growth was slower than in WT mice, IkkαAA/AA tumor numbers and pathology were indistinguishable from WT tumors. Both WT and IkkαAA/AA tumors expressed p52 except those IkkαAA/AA tumors where NIK, IKKαAA/AA and ErbB2 were undetectable. Colonies formed by WT and IkkαAA/AA mammary cells were nearly all luminal/acinar however, colony numbers and sizes derived from IkkαAA/AA cells were reduced. In contrast to IkkαAA/AA mice, virgin Nik-/- mammary glands were poorly developed and colonies were primarily derived from undifferentiated bipotent progenitor cells. CONCLUSIONS: C3(1)-TAg induced mammary tumors express p100/p52 even without functional IKKα. Therefore the development of basal-like mammary cancer does not strictly rely on IKKα activation. Signal-induced stabilization of NIK may be sufficient to mediate processing of p100NFKB2 which can then support basal-like mammary tumor formation. Lastly, in contrast to the pregnancy specific role of IKKα in lobuloalveogenesis, NIK is obligatory for normal mammary gland development.

Metastatic Spiradenocarcinoma Managed With PD-1 Inhibition.

Spiradenomas are rare skin adnexal tumors, usually benign, appearing in early adulthood. The etiology of this tumor is still debated. The tumor suppressor gene CYLD, responsible for the Brooke-Spiegler syndrome, causes spiradenomas, trichoepitheliomas, and cylindromas. With time, spiradenomas can degenerate into aggressive spiradenocarcinomas. With only 117 malignant cases reported, treatment recommendations are based on case reports and expert opinion. There is no standard of care beyond surgical resection for localized disease and no guidelines for management of metastatic disease. With the advent of immunotherapy and PD-1 inhibition, we present the first reported case of a metastatic spiradenocarcinoma managed with pembrolizumab.

Safety and Efficacy of Oral Benzodiazepines for Periprocedural Anxiolysis: A Systematic Review.

BACKGROUND: Oral benzodiazepines (BZDs) are useful tools for periprocedural anxiolysis. The United States Food and Drug Administration (FDA) recently issued a black-box warning of their risks of abuse and dependence. We performed a systematic review evaluating the safety and efficacy of oral BZDs for periprocedural anxiolysis in outpatient dermatologic, plastic surgery, dental, and ophthalmologic procedures performed under local anesthesia. METHODS: A systematic review of 5 databases was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Oral benzodiazepine safety and efficacy data were extracted from eligible articles. RESULTS: A total of 43 articles and 4,060 subjects were included. Oral BZDs consistently imparted a positive anxiolytic effect and demonstrated superior or equivalent scores in patient satisfaction, surgeon satisfaction, pain, and anxiety to comparator groups in most studies. Thirty-five subjects experienced transient hypoxia, and 2 experienced transient hypertension. A total of 195 mild, self-limited adverse effects were reported. None of the studies addressed the risks of abuse and dependence in this clinical setting. CONCLUSION: Short-term use of oral BZDs for periprocedural anxiolysis seems to be safe and effective. The 2020 FDA black-box warning should not deter their appropriate use in dermatologic surgery and other low-risk outpatient procedures.

A sensory bias overrides learned preferences of bumblebees for honest signals in Mimulus guttatus.

Insect pollinators readily learn olfactory cues, and this is expected to select for 'honest signals' that provide reliable information about floral rewards. However, plants might alternatively produce signals that exploit pollinators' sensory biases, thereby relaxing selection for signal honesty. We examined the innate and learned preferences of Bombus impatiens for Mimulus guttatus floral scent phenotypes corresponding to different levels of pollen rewards in the presence and absence of the innately attractive floral volatile compound ß-trans-bergamotene. Bees learned to prefer honest signals after foraging on live M. guttatus flowers, but only exhibited this preference when presented floral scent phenotypes that did not include ß-trans-bergamotene. Our results suggest that a sensory bias for ß-trans-bergamotene overrides the ability of B. impatiens to use honest signals when foraging on M. guttatus. This may represent a deceptive pollination strategy that allows plants to minimize investment in costly rewards without incurring reduced rates of pollinator visitation.

Postpartum headache: A broader differential.

A 40-year-old female presented to the ED with a history of intermittent headaches since a vaginal delivery 8 days prior. Her pregnancy was unremarkable and was not complicated by pre-eclampsia. She did not present with signs or symptoms consistent with postdural puncture headache or pre-eclampsia. Her delivery was not complicated by hypotension or post-partum hemorrhage. By chance, she was found to be hyponatremic and admitted to internal medicine for further work-up. She was diagnosed with postpartum lymphocytic adenohypophysitis and treated with steroids. She was discharged with a steroid taper and had complete resolution on follow up. Lymphocytic hypophysitis (LH), or commonly known as autoimmune hypophysitis, is a rare inflammatory condition affecting the pituitary gland. Acute LH can result in sudden death as demonstrated in some case reports. The most common symptom in >50% of cases is headache. First-line pharmacological treatment consists of high-dose corticosteroids and is effective in reducing pituitary size and improving endocrine insufficiency in 75% of cases. LH is a potential cause of postpartum headache that can be easily screened for with history and routine bloodwork and has good outcomes with early intervention. LH should be added to the differential for postpartum headaches presenting to the emergency department and routine blood work should be considered for all postpartum headaches.

A visually striking case of primary acrocyanosis: A rare cause of the blue digit.

Cold environments can trigger a variety of conditions, which, in their acute phase often present to the Emergency Department. Primary acrocyanosis is a distinct, rare condition which may be missed resulting in misdiagnosis and mismanagement. Primary acrocyanosis is a peripheral vascular disorder defined by painless, symmetrical discoloration of the distal appendages and uniquely characterized by persistence of the skin color changes after cold exposure. We present a case of a 24-year-old female who presented to the Emergency Department with peripheral cyanosis after cold exposure and was eventually diagnosed with primary acrocyanosis by Rheumatology. The prognosis for primary acrocyanosis is quite good in comparison to other acrosyndromes and once secondary causes of acrocyanosis have been ruled, out can be managed conservatively with lifestyle modifications and potential follow-up with Rheumatology.

Utility of Debulk Specimens During Mohs Micrographic Surgery for Cutaneous Squamous Cell Carcinoma.

BACKGROUND: Limited literature exists regarding whether intraoperative analysis of frozen debulk specimens during Mohs micrographic surgery (MMS) improves identification of high-risk features (HRF) of cutaneous squamous cell carcinoma (CSCC). OBJECTIVE: Primary: identification of new HRF on debulk specimens. Secondary: CSCC upstaged after considering debulk data. MATERIALS AND METHODS: A single-center, retrospective cohort study of patients with biopsy-proven CSCC treated by MMS with intraoperative frozen debulk analysis. Restricted (poor differentiation, new perineural invasion ≥0.1 mm, and Breslow depth >6 mm) and nonrestricted (any worsened tumor differentiation, any new perineural invasion, and Breslow depth >2 mm) analyses were performed. RESULTS: In restricted analysis, 3.94% of cases had 1 new HRF on debulk analysis. In nonrestricted analysis, 32.9% of cases had ≥1 new HRF; 7.6% increased by 2 HRF. Approximately 2.0% of cases were upstaged by American Joint Committee on Cancer system, eighth edition criteria, 1.4% by Brigham and Women's Hospital. Tumor size ≥2 cm, male sex, and moderate differentiation on biopsy were significantly associated with new HRF identified on debulk analysis. CONCLUSION: Intraoperative frozen debulk analysis can reveal HRF of CSCC not seen on biopsy or MMS stages, particularly among tumors ≥2 cm. American Joint Committee on Cancer system, eighth edition T2 tumors were most likely to be upstaged. Identification of new HRF on debulk analysis can improve CSCC staging and may impact patient treatment and follow-up.