Cerebral revascularization surgery reduces cerebrovascular events in children with sickle cell disease and moyamoya syndrome: Results of the stroke in sickle cell revascularization surgery retrospective study.

BACKGROUND: Recent studies suggest that cerebral revascularization surgery may be a safe and effective therapy to reduce stroke risk in patients with sickle cell disease and moyamoya syndrome (SCD-MMS). METHODS: We performed a multicenter, retrospective study of children with SCD-MMS treated with conservative management alone (conservative group)-chronic blood transfusion and/or hydroxyurea-versus conservative management plus surgical revascularization (surgery group). We monitored cerebrovascular event (CVE) rates-a composite of strokes and transient ischemic attacks. Multivariable logistic regression was used to compare CVE occurrence and multivariable Poisson regression was used to compare incidence rates between groups. Covariates in multivariable models included age at treatment start, age at moyamoya diagnosis, antiplatelet use, CVE history, and the risk period length. RESULTS: We identified 141 patients with SCD-MMS, 78 (55.3%) in the surgery group and 63 (44.7%) in the conservative group. Compared with the conservative group, preoperatively the surgery group had a younger age at moyamoya diagnosis, worse baseline modified Rankin scale scores, and increased prevalence of CVEs. Despite more severe pretreatment disease, the surgery group had reduced odds of new CVEs after surgery (odds ratio = 0.27, 95% confidence interval [CI] = 0.08-0.94, p = .040). Furthermore, comparing surgery group patients during presurgical versus postsurgical periods, CVEs odds were significantly reduced after surgery (odds ratio = 0.22, 95% CI = 0.08-0.58, p = .002). CONCLUSIONS: When added to conservative management, cerebral revascularization surgery appears to reduce the risk of CVEs in patients with SCD-MMS. A prospective study will be needed to validate these findings.

Diagnosis and Management of Acral Pigmented Lesions.

BACKGROUND: Survival outcomes in acral lentiginous melanoma (ALM) are worse than for cutaneous melanoma. Diagnostic delays are believed to contribute to worse outcomes in ALM, including advanced-stage disease at initial presentation. Acral lentiginous melanoma, especially in its early stages, may be difficult to discern from benign pigmented acral lesions. OBJECTIVE: The purpose of this article is to provide a comprehensive review of the diagnosis and management of acral pigmented lesions. MATERIALS AND METHODS: A literature review was performed. The outcomes included were the clinical and dermoscopic features and the management frameworks and considerations for acquired and congenital melanocytic nevi, acral melanosis, nonmelanocytic pigmented lesions, and ALM. RESULTS: Original research studies were primarily included. The use of dermoscopy, such as the 3-step algorithm and blotch (irregular), ridge pattern (parallel), asymmetry of structures, asymmetry of colors, furrow pattern (parallel), fibrillar pattern (BRAAFF) checklist, increases the diagnostic accuracy of acral pigmented lesions with high specificity and sensitivity. Short-term digital dermoscopic surveillance can be used to manage acral lesions, and histopathology should be collected when there is a concern for ALM. CONCLUSION: The use of dermoscopy and an understanding of how to manage acral lesions may limit the number of biopsies performed on the acral skin, decrease the time to diagnosis, and facilitate early detection of ALM.

Virtually Delivered Psychosocial Intervention for Prenatally Diagnosed Congenital Heart Disease: Feasibility and Acceptability of HEARTPrep.

Prenatal diagnosis of congenital heart disease (CHD) often leads to anxiety, depression, and traumatic stress in expectant mothers, with long-term implications for the child and family. However, psychosocial intervention is rarely incorporated into prenatal care. HEARTPrep is a virtually delivered psychosocial intervention aimed at reducing distress and social isolation and increasing parenting self-efficacy and hope for mothers expecting a baby with CHD to promote long-term child/family well-being. This study evaluated the feasibility and acceptability of HEARTPrep. Participants were mothers receiving cardiology care for a fetal CHD diagnosis. Partners could participate with the mother. HEARTPrep was delivered through a mobile app and telehealth. Feasibility was assessed through enrollment/retention rates. Acceptability was assessed through 20 Likert-scale and five open-ended questions. Of 39 recruited mothers, 35 (90%) enrolled. Half of partners (48%) also participated. Twenty-seven of 35 enrolled mothers (77%) completed HEARTPrep. On a scale from 0 (Not at All) to 4 (Very), mean item acceptability scores ranged from 3.5 to 3.9. Mothers reported HEARTPrep helped them feel less distressed (mean: 3.74), less alone (3.84), more prepared (3.89), and more hopeful (3.84). Opportunities to process emotions, develop coping skills, learn with their partner, navigate relationships, understand they are not alone, connect with peer support, access resources, and prepare for stressors were described as helpful. HEARTPrep is feasible and acceptable for mothers expecting a baby with CHD. Future research will evaluate its efficacy in preventing/reducing maternal mental health problems and improving postnatal clinical outcomes.

Acral Lentiginous Melanoma: A United States Multi-Center Substage Survival Analysis.

BACKGROUND: Acral lentiginous melanoma is associated with worse survival than other subtypes of melanoma. Understanding prognostic factors for survival and recurrence can help better inform follow-up care. OBJECTIVES: To analyze the clinicopathologic features, melanoma-specific survival, and recurrence-free survival by substage in a large, multi-institutional cohort of primary acral lentiginous melanoma patients. METHODS: Retrospective review of the United States Melanoma Consortium database, a multi-center prospectively collected database of acral lentiginous melanoma patients treated between January 2000 and December 2017. RESULTS: Of the 433 primary acral lentiginous melanoma patients identified (median [range] age: 66 [8-97] years; 53% female, 83% white), 66% presented with stage 0-2 disease and the median time of follow-up for the 392 patients included in the survival analysis was 32.5 months (range: 0-259). The 5-year melanoma-specific survivals by stage were 0 = 100%, I = 93.8%, II = 76.2%, III = 63.4%, IIIA = 80.8%, and IV = 0%. Thicker Breslow depth ((HR) = 1.13; 95% CI = 1.05-1.21; P < .001)) and positive nodal status ((HR) = 1.79; 95% CI = 1.00-3.22; P = .050)) were independent prognostic factors for melanoma-specific survival. Breslow depth ((HR = 1.13; 95% CI = 1.07-1.20; P < .001), and positive nodal status (HR = 2.12; 95% CI = 1.38-3.80; P = .001) were also prognostic factors for recurrence-free survival. CONCLUSION: In this cohort of patients, acral lentiginous melanoma was associated with poor outcomes even in early stage disease, consistent with prior reports. Stage IIB and IIC disease were associated with particularly low melanoma-specific and recurrence-free survival. This suggests that studies investigating adjuvant therapies in stage II patients may be especially valuable in acral lentiginous melanoma patients.

Real-world outcomes of melanoma surveillance using the MoleMap NZ telemedicine platform.

BACKGROUND: MoleMap NZ is a novel New Zealand-based store-and-forward telemedicine service to detect melanoma. It uses expert review of total body photography and close-up and dermoscopic images of skin lesions that are suspicious for malignancy. OBJECTIVE: The purpose of this study was to assess the effectiveness of MoleMap NZ as a melanoma early detection program. METHODS: We conducted a review of 2108 melanocytic lesions recommended for biopsy/excision by MoleMap NZ dermoscopists between January 2015 and December 2016. RESULTS: Pathologic diagnoses were available for 1571 lesions. Of these, 1303 (83%) lesions were benign and 260 (17%) lesions were diagnosed as melanoma, for a melanoma-specific benign:malignant ratio of 5.0:1. The number needed to biopsy to obtain 1 melanoma was 6. Among melanomas with available tumor thickness data (n = 137), 92% were <0.8 mm (range in situ to 3.1 mm), with in situ melanomas comprising 74%. LIMITATIONS: Only lesions recommended for excision were analyzed. Pathology results were available for 75% of these cases. Tumor thickness data were available for 53% of melanomas diagnosed. CONCLUSIONS: This real-world study of MoleMap NZ, a community-based teledermoscopy program, suggests that it has the potential to increase patients' access to specialist expertise via telemedicine. Additional studies are needed to more accurately define its efficacy.

Management of Melanoma during Pregnancy: A Case Series of 11 Women Treated at NYU Langone Health.

OBJECTIVES: Melanoma is one of the most common malignancies diagnosed during pregnancy. This study examined the impact of pregnancy on management decisions of melanoma patients treated at NYU Langone Health (NYULH). METHODS: We analyzed data for patients who were pregnant at initial or recurrent melanoma diagnosis at NYULH from 2012 to 2019 with prospective protocol-driven follow-up. RESULTS: Of the 900 female patients accrued during this period, 11 women in the childbearing range were pregnant at melanoma diagnosis. Six patients presented with early (stage 0 or I) disease and five with advanced (stage III or IV) melanoma. Women with early stage disease had normal deliveries and minimal changes to their treatment timeline and regimen. However, patients with more advanced stage disease opted for either termination of the pregnancy or early delivery and altered treatment timelines because of pregnancy. CONCLUSION: Both melanoma stage and gestational age at diagnosis contribute to the differences in the therapeutic management of melanoma in pregnant women. Given the complexity and variety of each case of melanoma during pregnancy, informed discussion between patients and physicians allows for individualized treatment plans that address each patient's unique situation.

New Systematic Therapies and Trends in Cutaneous Melanoma Deaths Among US Whites, 1986-2016.

Objectives. To determine the effect of new therapies and trends toward reduced mortality rates of melanoma.Methods. We reviewed melanoma incidence and mortality among Whites (the group most affected by melanoma) in 9 US Surveillance, Epidemiology, and End Results registry areas that recorded data between 1986 and 2016.Results. From 1986 to 2013, overall mortality rates increased by 7.5%. Beginning in 2011, the US Food and Drug Administration approved 10 new treatments for metastatic melanoma. From 2013 to 2016, overall mortality decreased by 17.9% (annual percent change [APC] = -6.2%; 95% confidence interval [CI] = -8.7%, -3.7%) with sharp declines among men aged 50 years or older (APC = -8.3%; 95% CI = -12.2%, -4.1%) starting in 2014. This recent, multiyear decline is the largest and most sustained improvement in melanoma mortality ever observed and is unprecedented in cancer medicine.Conclusions. The introduction of new therapies for metastatic melanoma was associated with a significant reduction in population-level mortality. Future research should focus on developing even more effective treatments, identifying biomarkers to select patients most likely to benefit, and renewing emphasis on public health approaches to reduce the number of patients with advanced disease.

Technological advances for the detection of melanoma: Advances in molecular techniques.

The growth of molecular technologies analyzing skin cells and inherited genetic variations has the potential to address current gaps in both diagnostic accuracy and prognostication in patients with melanoma or in individuals who are at risk for developing melanoma. In the second article in this continuing medical education series, novel molecular technologies are reviewed. These have been developed as adjunct tools for melanoma management and include the Pigmented Lesion Assay, myPath Melanoma, and DecisionDx-Melanoma tests, and genetic testing in patients with a strong familial melanoma history. These tests are commercially available and marketed as ancillary tools for clinical decision-making, diagnosis, and prognosis. We review fundamental principles behind each test, discuss peer-reviewed literature assessing their performance, and highlight the utility and limitations of each assay. The goal of this article is to provide a comprehensive, evidence-based foundation for clinicians regarding the management of patients with difficult pigmented lesions.

Technological advances for the detection of melanoma: Advances in diagnostic techniques.

Managing the balance between accurately identifying early stage melanomas while avoiding obtaining biopsy specimens of benign lesions (ie, overbiopsy) is the major challenge of melanoma detection. Decision making can be especially difficult in patients with extensive atypical nevi. Recognizing that the primary screening modality for melanoma is subjective examination, studies have shown a tendency toward overbiopsy. Even low-risk routine surgical procedures are associated with morbidity, mounting health care costs, and patient anxiety. Recent advancements in noninvasive diagnostic modalities have helped improve diagnostic accuracy, especially when managing melanocytic lesions of uncertain diagnosis. Breakthroughs in artificial intelligence have also shown exciting potential in changing the landscape of melanoma detection. In the first article in this continuing medical education series, we review novel diagnostic technologies, such as automated 2- and 3-dimensional total body imaging with sequential digital dermoscopic imaging, reflectance confocal microscopy, and electrical impedance spectroscopy, and we explore the logistics and implications of potentially integrating artificial intelligence into existing melanoma management paradigms.

Probing the Surface Structure of Semiconductor Nanoparticles by DNP SENS with Dielectric Support Materials.

Surface characterization is crucial for understanding how the atomic-level structure affects the chemical and photophysical properties of semiconducting nanoparticles (NPs). Solid-state nuclear magnetic resonance spectroscopy (NMR) is potentially a powerful technique for the characterization of the surface of NPs, but it is hindered by poor sensitivity. Dynamic nuclear polarization surface enhanced NMR spectroscopy (DNP SENS) has previously been demonstrated to enhance the sensitivity of surface-selective solid-state NMR experiments by 1-2 orders of magnitude. Established sample preparations for DNP SENS experiments on NPs require the dilution of the NPs on mesoporous silica. Using hexagonal boron nitride (h-BN) to disperse the NPs doubles DNP enhancements and absolute sensitivity in comparison to standard protocols with mesoporous silica. Alternatively, precipitating the NPs as powders, mixing them with h-BN, and then impregnating the powdered mixture with radical solution leads to further 4-fold sensitivity enhancements by increasing the concentration of NPs in the final sample. This modified procedure provides a factor of 9 improvement in NMR sensitivity in comparison to previously established DNP SENS procedures, enabling challenging homonuclear and heteronuclear 2D NMR experiments on CdS, Si, and Cd3P2 NPs. These experiments allow NMR signals from the surface, subsurface, and core sites to be observed and assigned. For example, we demonstrate the acquisition of DNP-enhanced 2D 113Cd-113Cd correlation NMR experiments on CdS NPs and natural isotropic abundance 2D 13C-29Si HETCOR of functionalized Si NPs. These experiments provide a critical understanding of NP surface structures.

Conversion Reactions of Atomically Precise Semiconductor Clusters.

Clusters are unique molecular species that can be viewed as a bridge between phases of matter and thus between disciplines of chemistry. The structural and compositional complexity observed in cluster chemistry serves as an inspiration to the material science community and motivates our search for new phases of matter. Moreover, the formation of kinetically persistent cluster molecules as intermediates in the nucleation of crystals makes these materials of great interest for determining and controlling mechanisms of crystal growth. Our lab developed a keen interest in clusters insofar as they relate to the nucleation of nanoscale semiconductors and the modeling of postsynthetic reaction chemistry of colloidal materials. In particular, our discovery of a structurally unique In37P20X51 (X = carboxylate) cluster en route to InP quantum dots has catalyzed our interest in all aspects of cluster conversion, including the use of clusters as precursors to larger nanoscale colloids and as platforms for examining postsynthetic reaction chemistry. This Account is presented in four parts. First, we introduce cluster chemistry in a historical context with a focus on main group, metallic, and semiconductor clusters. We put forward the concept of rational, mechanism-driven design of colloidal semiconductor nanocrystals as the primary motivation for the studies we have undertaken. Second, we describe the role of clusters as intermediates both in the synthesis of well-known material phases and in the discovery of unprecedented nanomaterial structures. The primary distinction between these two approaches is one of kinetics; in the case of well-known phases, we are often operating under high-temperature thermolysis conditions, whereas for materials discovery, we are discovering strategies to template the growth of kinetic phases as dictated by the starting cluster structure. Third, we describe reactions of clusters as model systems for their larger nanomaterial progeny with a primary focus on cation exchange. In the case of InP, cation exchange in larger nanostructures has been challenging due to the covalent nature of the crystal lattice. However, in the higher energy, strained cluster intermediates, cation exchange can be accomplished even at room temperature. This opens opportunities for accessing doped and alloyed nanomaterials using postsynthetically modified clusters as single-source precursors. Finally, we present surface chemistry of clusters as the gateway to subsequent chemistry and reactivity, and as an integral component of cluster structure and stability. Taken as a whole, we hope to make a compelling case for using clusters as a platform for mechanistic investigation and materials discovery.

Diagnosis and management of vulvar cancer: A review.

Vulvar malignancies represent a serious gynecologic health concern, especially given the increasing incidence over the past several decades. Squamous cell carcinoma and melanoma are common subtypes, although other neoplasms, such as basal cell carcinoma and Paget disease of the vulva, might be seen. Many vulvar cancers are initially misdiagnosed as inflammatory conditions, delaying diagnosis and worsening prognosis. It is essential that dermatologists are familiar with characteristic findings for each malignancy to ensure appropriate diagnosis and management. Herein, we review the unique epidemiologic and clinical characteristics of each major vulvar malignancy, as well as discuss their respective prognoses and current management recommendations.

Effects of Zn2+ and Ga3+ doping on the quantum yield of cluster-derived InP quantum dots.

As the commercial display market grows, the demand for low-toxicity, highly emissive, and size-tunable semiconducting nanoparticles has increased. Indium phosphide quantum dots represent a promising solution to these challenges; unfortunately, they typically suffer from low inherent emissivity resulting from charge carrier trapping. Strategies to improve the emissive characteristics of indium phosphide often involve zinc incorporation into or onto the core itself and the fabrication of core/shell heterostructures. InP clusters are high fidelity platforms for studying processes such as cation exchange and surface doping with exogenous ions since these clusters are used as single-source precursors for quantum dot synthesis. Here, we examined the incorporation of zinc and gallium ions in InP clusters and the use of the resultant doped clusters as single-source precursors to emissive heterostructured nanoparticles. Zinc ions were observed to readily react with InP clusters, resulting in partial cation exchange, whereas gallium resisted cluster incorporation. Zinc-doped clusters effectively converted to emissive nanoparticles, with quantum yields strongly correlated with zinc content. On the other hand, gallium-doped clusters failed to demonstrate improvements in quantum dot emission. These results indicate stark differences in the mechanisms associated with aliovalent and isovalent doping and provide insight into the use of doped clusters to make emissive quantum dots.

Melanoma risk after in vitro fertilization: A review of the literature.

BACKGROUND: The role of female sex hormones in the pathogenesis of malignant melanoma (MM) remains controversial. Although melanocytes appear to be hormonally responsive, the effect of estrogen on MM cells is less clear. Available clinical data does not consistently demonstrate that increased endogenous hormones from pregnancy or increased exogenous hormones from oral contraceptive pills and hormone replacement affect MM prevalence and outcome. OBJECTIVE: We sought to examine potential associations between in vitro fertilization (IVF) and melanoma. METHODS: A literature review was conducted. Primary outcomes were reported as associations between IVF and melanoma risk compared with the general population. Secondary outcomes included associations stratified by type of IVF regimen and subgroup, such as parous versus nulliparous patients. RESULTS: Eleven studies met our inclusion criteria. Five studies found no increased risk for MM among IVF users compared with the general population. Two studies found an increase in MM in clomiphene users, and 4 studies found an increase in MM among patients who were gravid or parous either before or after IVF. CONCLUSION: The reviewed studies do not reveal consistent patterns of association between IVF and MM among all infertile women. However, the data indicates a potential increased risk for MM in ever-parous patients treated with IVF. High-quality studies including a large number of MM cases that control for well-established MM risk factors are needed to adequately assess the relationship between IVF and MM, particularly among ever-parous women.

Main-Group-Semiconductor Cluster Molecules as Synthetic Intermediates to Nanostructures.

Main-group-semiconductor clusters are attractive atomically precise precursors for materials design. In particular, magic-sized clusters, those with elevated thermodynamic stability relative to other clusters of similar size, have been implicated as important intermediates in the synthesis of semiconductor nanostructures. A survey of the literature on the intermediacy of clusters in nanomaterial synthesis reveals two predominant mechanistic trends: monomer-driven growth and cluster assembly. In this Forum Article, we compare and contrast the systems in which these mechanisms are operative and attempt to extract the emerging design principles governing these transformations. Additionally, we highlight the gaps in our understanding of this emerging area of science and provide a roadmap for future reaction development.

A prospective study evaluating the utility of a 2-mm biopsy margin for complete removal of histologically atypical (dysplastic) nevi.

BACKGROUND: Complete removal of individual dysplastic nevi (DN) is often accomplished by a second surgical procedure after the initial biopsy. The choice to perform the second procedure is strongly influenced by histopathologic margin status of the initial biopsy specimen. OBJECTIVE: To evaluate the clinical and histopathologic outcomes of in toto biopsy of DN using a predetermined margin of normal skin. METHODS: We conducted a prospective study of a saucerization method using a defined 2-mm margin in patients undergoing biopsy of a pigmented skin lesion. RESULTS: We performed 151 biopsies in 138 patients. Overall, 137 of 151 lesions subjected to biopsy (90.7%) were melanocytic: 86 DN (57.0%), 40 nevi without atypia (26.5%), and 11 melanomas (7.3%). Of 78 DN, 68 (87.2%) were removed with clear histopathologic margins (8 DN were excluded because of inadequate processing). There was no clinical evidence of recurrence at any of the biopsy sites that were simply observed (i.e., not re-excised) over a median of 16.9 months. LIMITATIONS: There were few biopsies performed on the face. CONCLUSIONS: The complete histopathologic removal of nearly 9 of 10 DN using a peripheral margin of 2 mm of normal skin and a depth at the dermis and subcutaneous fat junction has the potential to decrease second procedures at DN biopsy sites, thereby decreasing patient morbidity and saving health care dollars.