Treatment Patterns, Outcomes, and Patient Satisfaction of Primary Epidermally Limited Nonmelanoma Skin Cancer.

BACKGROUND: Epidermally limited nonmelanoma skin cancer (ELNMSC) (superficial basal cell carcinoma [SBCC] and squamous cell carcinoma in situ [SCCIS]) is common. Data on outcomes and patient satisfaction are lacking. OBJECTIVE: To examine treatment efficacy and satisfaction in ELNMSC patients. PATIENTS AND METHODS: Retrospective cohort study of adults with primary SBCC or SCCIS. A 25% random subset completed a satisfaction questionnaire. RESULTS: Five hundred and fifty patients with 227 SBCC and 451 SCCIS were included; 329 tumors (49%) were treated with Mohs micrographic surgery (MMS) and 349 (51%) with non-MMS (imiquimod [n = 26], 5% 5-fluorouracil [n = 234], ingenol mebutate [n = 32], or cryotherapy [n = 57]). Five-year recurrence-free survival was high in both groups, with MMS having a small but statistically significant advantage (99% vs 95%, p = .004). More MMS patients were willing to undergo treatment again (97% vs 86%, p = .024). Dissatisfaction was mostly due to prolonged treatment course and pain associated with non-MMS treatments. CONCLUSION: Surgical and nonsurgical treatments for primary ELNMSC have low recurrence rates, though cure rate and patient satisfaction are higher with MMS. Treatment choice for epidermal NMSC may be guided through patient preferences regarding ability to comply with topical treatment, out-of-pocket costs, desire to treat surrounding field disease, and desire to avoid a surgical scar.

Sequential Curettage, 5-Fluorouracil, and Photodynamic Therapy for Field Cancerization of the Scalp and Face in Solid Organ Transplant Recipients.

BACKGROUND: Field cancerization with actinic keratoses and squamous cell carcinoma in situ (AK/SCCIS) represents a common therapeutic challenge in solid organ transplant recipients (SOTRs). These patients often show inadequate responses to methods traditionally used as monotherapy (e.g., topical chemotherapy). OBJECTIVE: To describe the clinical outcomes and feasibility of a sequential approach to treatment of field cancerization in SOTRs. METHODS: Four SOTRs with field cancerization of the scalp and/or face were treated using a sequential approach. Light curettage of hypertrophic lesions was followed by application of 5-fluorouracil 5% cream twice daily for 5 days and photodynamic therapy (PDT) with 1-hour incubation on day 6. Pain level during and after PDT was recorded. Photographs were obtained immediately before and after treatment and at follow-up appointments. RESULTS: All 4 patients tolerated this approach well and demonstrated excellent responses to treatment with complete or near-complete clinical resolution of AK/SCCIS lesions. Patients remained free of AK/SCCIS based on clinical examination 1 to 6 months after treatment. CONCLUSION: For SOTRs with field cancerization, sequential therapy represents a viable therapeutic regimen with good tolerability and durable clinical response. This approach warrants further investigation to determine which therapeutic combinations have optimal tolerability and efficacy.

Ablative Fractional Laser-Assisted Topical Fluorouracil for the Treatment of Superficial Basal Cell Carcinoma and Squamous Cell Carcinoma In Situ: A Follow-Up Study.

BACKGROUND: The authors previously reported the safety and short-term efficacy of ablative fractional laser (AFXL)-assisted delivery of topical fluorouracil in the treatment of superficial basal cell carcinoma (sBCC) and squamous cell carcinoma in situ (SCCis). OBJECTIVE: This follow-up study was conducted to assess whether tumor clearance was sustained in this cohort of patients at >9 months post-treatment. METHODS: Thirty primary sBCC or SCCis <2 cm on the trunk or extremities were treated with AFXL and a single application of topical 5-fluorouracil 5% under occlusion for 7 days. Among the 26 patients who achieved tumor clearance at 4 to 8 weeks post-treatment, 20 patients presented for this follow-up study and underwent shave biopsy to confirm histologic clearance. Mean follow-up time was 15 months. RESULTS: Considering those who had persistent tumor at 4 to 8 weeks post-treatment and those who presented for follow-up at >9 months post-treatment, overall treatment success was 79% (95% confidence interval: 67%-96%), with 92% (11/12) for SCCis and 67% (8/12) for sBCC. Neither the tumor location nor size significantly impacted treatment outcome (p = .96 and 0.87, respectively). CONCLUSION: Ablative fractional laser-assisted topical fluorouracil is a reasonable noninvasive treatment option for primary SCCis and sBCC, especially for lesions located in areas where self-application is not possible, or when clinician-administered therapy is preferred.

A systematic review of outcome data for dermatofibrosarcoma protuberans with and without fibrosarcomatous change.

BACKGROUND: To our knowledge, no systematic review of dermatofibrosarcoma protuberans (DFSP) outcomes based on the presence or absence of fibrosarcomatous (FS) change has been performed. OBJECTIVE: We sought to compare available outcome data for DFSP versus DFSP-FS. METHODS: The literature was searched for DFSP and DFSP-FS reports with outcome data (local recurrence, metastasis, or death from disease). Chi-square tests were calculated to determine whether DFSP and DFSP-FS significantly differed in risk of local recurrence, metastasis, and death from disease. RESULTS: In all, 24 reports containing 1422 patients with DFSP and 225 with DFSP-FS are summarized. Risk of local recurrence, metastasis, and death from disease in DFSP-FS was significantly higher as compared with DFSP (local recurrence 29.8% vs 13.7%, risk ratio 2.2 [95% confidence interval 1.7-2.9]; metastasis 14.4% vs 1.1%, risk ratio 5.5 [95% confidence interval 4.3-7.0]; and death from disease 14.7% vs 0.8%, risk ratio 6.2 [95% confidence interval 5.0-7.8]). There was no significant difference in DFSP-FS outcomes based on proportion of FS change within tumors. LIMITATIONS: This study is based on previously reported data from different hospitals with no uniform process for reporting FS change. The impact of confounders (age, immune status, tumor location, treatment) could not be evaluated because of limited data. CONCLUSION: Based on available retrospective data, risk of metastasis and death is elevated in DFSP-FS as compared with DFSP. Even a low degree of FS involvement portends worse outcomes.

The Z-advancement flap for reconstruction of lateral nasal tip and medial alar defects.

BACKGROUND: Reconstruction of lateral nasal tip and medial alar defects is challenging. Contour, symmetry, and skin texture of the nose, along with adequate nasal airway patency, should be preserved. The Z-advancement flap is a novel reconstruction technique designed for optimal cosmesis and function. OBJECTIVE: To evaluate the aesthetic and functional outcomes of Z-advancement flap nasal reconstruction. MATERIALS AND METHODS: Twenty-nine consecutive patients with defects 1 cm or less in diameter on the lateral nasal tip or medial ala underwent Z-advancement flap repair. Patients completed a survey assessing cosmesis and airway patency. Three physicians evaluated standardized photographs on visibility of scar lines, erythema and telangiectasia, and contour and symmetry of the ala and nostril opening. RESULTS: Twenty-eight (96%) patients completed survey questionnaires. All patients were satisfied with the look and feel of their reconstructed nose. Twenty-four (86%) saw no visible scar or abnormality. Postoperative photographs were available for review in 19 (66%) patients. In 95% to 96% of physician ratings, scars were invisible or visible only on close inspection, and alar symmetry was unchanged or only slightly altered. In 88%, nostril opening symmetry was unchanged or slightly altered. CONCLUSIONS: The Z-advancement flap preserves aesthetic subunits of the nose to produce excellent cosmesis and patient satisfaction for defects of the lateral nasal tip or medial ala 1 cm or less in diameter.

Assessing a Digital Scorecard on Global Immunization Progress: Stakeholder Views and Implications for Enhancing Performance and Accountability.

Global health agencies and regional and national stakeholders collaborated to develop the Immunization Agenda 2030 Scorecard, a digital data visualization platform displaying global, regional, and country-level immunization progress. The scorecard serves to focus attention and enable strategic actions around the measures visualized. To assess the scorecard's usability, appropriateness, and context for use, we interviewed 15 immunization officers working across five global regions. To further understand the implementation context, we also reviewed the characteristics of 15 public platforms visualizing population health data. We integrated thematic findings across both methods. Many platforms highlight service gaps and enable comparisons between geographies to foster political pressure for service improvements. We observed heterogeneity regarding the platforms' focus areas and participants' leading concerns, which were management capacity and resourcing. Furthermore, one-third of platforms were out of date. Results yielded recommendations for the scorecard, which participants felt was well suited to focus the attention of decision makers on key immunization data. A simpler design coupled with implementation strategies that more actively engage policymakers would better align the scorecard with other public platforms engaging intended users. For population health platforms to serve as effective accountability mechanisms, studying implementation determinants, including usability testing, is vital to meet stakeholder needs.

Luminance contrast of a visual stimulus modulates the BOLD response more than the cerebral blood flow response in the human brain.

The blood oxygenation level dependent (BOLD) response measured with functional magnetic resonance imaging (fMRI) depends on the evoked changes in cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO(2)) in response to changes in neural activity. This response is strongly modulated by the CBF/CMRO(2) coupling relationship with activation, defined as n, the ratio of the fractional changes. The reliability of the BOLD signal as a quantitative reflection of underlying physiological changes depends on the stability of n in response to different stimuli. The effect of visual stimulus contrast on this coupling ratio was tested in 9 healthy human subjects, measuring CBF and BOLD responses to a flickering checkerboard at four visual contrast levels. The theory of the BOLD effect makes a robust prediction-independent of details of the model-that if the CBF/CMRO(2) coupling ratio n remains constant, then the response ratio between the lowest and highest contrast levels should be higher for the BOLD response than the CBF response because of the ceiling effect on the BOLD response. Instead, this response ratio was significantly lower for the BOLD response (BOLD response: 0.23 ± 0.13, mean ± SD; CBF response: 0.42 ± 0.18; p=0.0054). This data is consistent with a reduced dynamic range (strongest/weakest response ratio) of the CMRO(2) response (~1.7-fold) compared to that of the CBF response (~2.4-fold) as luminance contrast increases, corresponding to an increase of n from 1.7 at the lowest contrast level to 2.3 at the highest contrast level. The implication of these results for fMRI studies is that the magnitude of the BOLD response does not accurately reflect the magnitude of underlying physiological processes.

Coupling of cerebral blood flow and oxygen metabolism is conserved for chromatic and luminance stimuli in human visual cortex.

The ratio of the changes in cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO(2)) during brain activation is a critical determinant of the magnitude of the blood oxygenation level dependent (BOLD) response measured with functional magnetic resonance imaging (fMRI). Cytochrome oxidase (CO), a key component of oxidative metabolism in the mitochondria, is non-uniformly distributed in visual area V1 in distinct blob and interblob regions, suggesting significant spatial variation in the capacity for oxygen metabolism. The goal of this study was to test whether CBF/CMRO(2) coupling differed when these subpopulations of neurons were preferentially stimulated, using chromatic and luminance stimuli to preferentially stimulate either the blob or interblob regions. A dual-echo spiral arterial spin labeling (ASL) technique was used to measure CBF and BOLD responses simultaneously in 7 healthy human subjects. When the stimulus contrast levels were adjusted to evoke similar CBF responses (mean 65.4% ± 19.0% and 64.6% ± 19.9%, respectively for chromatic and luminance contrast), the BOLD responses were remarkably similar (1.57% ± 0.39% and 1.59% ± 0.35%) for both types of stimuli. We conclude that CBF-CMRO(2) coupling is conserved for the chromatic and luminance stimuli used, suggesting a consistent coupling for blob and inter-blob neuronal populations despite the difference in CO concentration.

Perioperative antibiotic use of dermatologic surgeons in 2012.

BACKGROUND: Recommendations for antibiotic prophylaxis in dermatologic surgery have been established, but there is variability in perioperative antibiotic use of dermatologists. Authoritative guidelines have shifted away from routine use of antibiotic prophylaxis because there is no conclusive evidence that antibiotic use reduces risk of infective endocarditis or prosthetic joint infection. OBJECTIVE: To determine current practices of perioperative antibiotic use of Mohs-trained surgeons and to compare patterns of use with updated administration guidelines. METHODS AND MATERIALS: A survey was sent to American College of Mohs Surgery members in 2012. The main outcome measures were survey responses relating to demographic characteristics, experience with postoperative infection, familiarity with antibiotic guidelines, perioperative antibiotic practices, attitudes regarding antibiotic use, and antibiotic selection. RESULTS: Most survey respondents are familiar with the Antibiotic Prophylaxis in Dermatologic Surgery Advisory Statement 2008, but respondents give antibiotics for more indications than are recommended. Although not recommended, a high percentage reported giving antibiotics to patients at high risk of infective endocarditis or joint infection even when surgery does not breach oral mucosa or involve infected skin. CONCLUSION: Dermatologic surgeons overuse perioperative antibiotics for prevention of surgical site infection, infective endocarditis, and prosthetic joint infection based on current recommendations.

Indolent T-lymphoblastic proliferation involving hepatocellular carcinoma-presentation in novel settings and comprehensive review of literature.

Indolent T-lymphoblastic proliferation (iT-LBP) is a rare, non-clonal, extrathymic lymphoid proliferation with an immature T cell phenotype, indolent clinical course, and excellent prognosis. Although their pathogenesis is unclear, they are reported to be associated with Castleman disease, follicular dendritic cell tumors/sarcomas, angioimmunoblastic T cell lymphoma, hepatocellular carcinoma (HCC), myasthenia gravis, and acinic cell carcinoma. There are around 51 reported cases of iT-LBP in the literature. Recognition and accurate diagnosis of this entity is critical as it shares morphologic and immunophenotypic features with an aggressive malignancy-acute T cell leukemia/lymphoma (T-ALL). IT-LBP in HCC post-liver transplant and in metastatic sites has not been reported in the literature. Two case reports of patients presenting with recurrent and metastatic HCC in post-liver transplant settings are described. A 50-year-old man with an end-stage liver disease with HCC underwent liver transplant. A year later, he developed pulmonary metastasis with associated iT-LBP. A 69-year-old man underwent liver transplant for end-stage liver disease and HCC. Eighteen months later, he developed recurrent HCC in the transplanted liver and omental metastasis; both sites showed HCC with iT-LBP. iT-LBP in both patients expressed TdT, CD3, and CD4 and lacked CD34 and clonal T cell receptor gene rearrangements. On retrospective review, the pre-transplant HCC specimens lacked iT-LBP. We present two cases of iT-LBP associated with HCC in novel settings-in post-liver transplant patients and in recurrent/metastatic sites of HCC. In addition, a comprehensive literature review of clinical, histological, and immunophenotypic characteristics of reported cases of iT-LBP is presented.

Musculoskeletal disorders and ergonomics in dermatologic surgery: a survey of Mohs surgeons in 2010.

BACKGROUND: Dermatologic surgeons perform numerous procedures that put them at risk of developing work-related musculoskeletal disorders. OBJECTIVE: To study the prevalence of work-related musculoskeletal disorders and role of ergonomics in dermatologic surgery. METHODS AND MATERIALS: A survey study was sent to members of the American College of Mohs Surgery in 2010. The main outcome measures were survey responses relating to surgeon demographics, musculoskeletal symptoms, workstyle habits and attitudes, and ergonomic practices. RESULTS: Ninety percent of respondents reported some type of musculoskeletal symptoms or injuries. The most common complaints were neck, lower back, shoulder, and upper back pain. Most respondents were not using ergonomic modifications in their practice. CONCLUSION: Mohs surgeons have a high prevalence of musculoskeletal disorders. Symptoms present early and persist throughout the careers of Mohs surgeons. The nature of the occupation leaves the surgeon vulnerable to injury. Ergonomic modifications in behavior and workplace are recommended to reduce pain and injury to surgeons.

The appearance of pili annulati following alopecia areata.

Pili annulati is a rare autosomal-dominant hair shaft abnormality. It is characterized by alternating light and dark bands along the shaft due to air-filled cavities within the cortex of the hair shaft. Alopecia areata has been previously described as a common association with pili annulati, with improvement in alopecia areata coinciding with resolution of pili annulati. We report the case of a patient with a history of alopecia areata and alopecia universalis who developed the characteristic banded hair of pili annulati upon resolution of her alopecia areata. We provide direct microscopic examination of postregrowth hairs compared to normal and cross-polarized light microscopy.

HIV infection and aging independently affect brain function as measured by functional magnetic resonance imaging.

We investigated the interactions between human immunodeficiency virus (HIV) infection and aging and their effects on brain function demands by means of functional magnetic resonance imaging (fMRI). A multiple-regression model was used to study the association and interaction between fMRI measures, HIV serostatus, and age for 26 HIV-infected subjects and 25 seronegative subjects. Although HIV serostatus and age independently affected fMRI measures, no interaction occurred. Functional brain demands in HIV-positive subjects were equivalent to those of HIV-negative subjects who were 15-20 years older. Frailty parallels between HIV infection and aging could result from continued immunological challenges depleting resources and triggering increased metabolic demands. In the future, fMRI could be a noninvasive biomarker to assess HIV infection in the brain.

Cryptic Acute Promyelocytic Leukemia (APL) Presenting as Seizures in an Adolescent.

There are approximately 800 new cases of acute promyelocytic leukemia (APL) in the United States every year. APL is rarely observed in pediatric populations, and accounts for less than 5-10% of all pediatric cases of acute myeloid leukemia (AML). APL typically presents with symptoms related to the pancytopenia such as fatigue due to anemia, bleeding and bruising secondary to thrombocytopenia, and infections attributed to a lack of functioning leukocytes. The presentation of APL in the central nervous system (CNS) is a rare phenomenon. In addition, APL has a dismal prognosis when found in the CNS. In this case study, we describe a unique presentation of pediatric APL with cryptic insertion of the promyelocytic leukemia (PML)-retinoic acid receptor-alpha (RARA) fusion protein with a surprisingly excellent recovery.

Peripheral Blood Examination Findings in SARS-CoV-2 Infection.

OBJECTIVES: Peripheral blood abnormalities in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have not been fully elucidated. We report qualitative and quantitative peripheral blood findings in coronavirus disease 2019 (COVID-19) patients and compare them with a control group. METHODS: We reviewed electronic medical records, complete blood counts, peripheral blood smears, and flow cytometry data in 12 patients with SARS-CoV-2. These were compared with 10 control patients with symptoms suspicious for SARS-CoV-2 but who tested negative. RESULTS: No significant differences were noted in blood counts, except that absolute lymphopenia was present frequently in the control group (P < .05). Acquired Pelger-Huët anomaly (APHA) was noted in all COVID-19 cases, in most cases affecting over 5% of granulocytes. This contrasted with APHA in only 50% of control cases, affecting fewer than 5% of granulocytes in all cases (P < .05). Monolobate neutrophils were exclusive to COVID-19 cases. COVID-19 patients had greater frequency of plasmacytoid lymphocytes (P < .05). Flow cytometry data revealed absolute CD3+ T-cell count reduction in 6 of 7 patients; all of them required mechanical ventilation. CONCLUSIONS: Lymphopenia was infrequent in our COVID-19 cohort; however, flow cytometric analysis revealed absolute T-cell count reduction in most cases. COVID-19 cases had significant APHA with monolobate neutrophils and plasmacytoid lymphocytes as compared to controls.

Distortions but not Definitive Peaks by Capillary Serum Protein Electrophoresis Indicate Monoclonal Gammopathy of Undetermined Significance rather than Multiple Myeloma.

OBJECTIVE: Capillary electrophoresis of serum proteins demonstrates occasional distortions. Distortions or peaks in the gamma, beta, and alpha-2 zones may represent monoclonal gammopathy. In this study, we investigated if such distortions are associated with monoclonal gammopathy of undetermined significance (MGUS) or multiple myeloma. METHODS: Consecutive serum protein electrophoresis results were reviewed and immunofixation studies were recommended on specimens exhibiting distortions or distinct peaks in the gamma, beta or alpha-2 zones. RESULTS AND DISCUSSION: Of the 471 cases, we observed distortions in 101 cases. In the immunofixation studies, 17.8% of cases had a diagnosis of MGUS, but none contained multiple myeloma. CONCLUSIONS: We conclude that distortions in serum capillary electrophoresis may be associated with MGUS, but not multiple myeloma.

Effects of aging on cerebral blood flow, oxygen metabolism, and blood oxygenation level dependent responses to visual stimulation.

Calibrated functional magnetic resonance imaging (fMRI) provides a noninvasive technique to assess functional metabolic changes associated with normal aging. We simultaneously measured both the magnitude of the blood oxygenation level dependent (BOLD) and cerebral blood flow (CBF) responses in the visual cortex for separate conditions of mild hypercapnia (5% CO(2)) and a simple checkerboard stimulus in healthy younger (n = 10, mean: 28-years-old) and older (n = 10, mean: 53-years-old) adults. From these data we derived baseline CBF, the BOLD scaling parameter M, the fractional change in the cerebral metabolic rate of oxygen consumption (CMRO(2)) with activation, and the coupling ratio n of the fractional changes in CBF and CMRO(2). For the functional activation paradigm, the magnitude of the BOLD response was significantly lower for the older group (0.57 +/- 0.07%) compared to the younger group (0.95 +/- 0.14%), despite the finding that the fractional CBF and CMRO(2) changes were similar for both groups. The weaker BOLD response for the older group was due to a reduction in the parameter M, which was significantly lower for older (4.6 +/- 0.4%) than younger subjects (6.5 +/- 0.8%), most likely reflecting a reduction in baseline CBF for older (41.7 +/- 4.8 mL/100 mL/min) compared to younger (59.6 +/- 9.1 mL/100 mL/min) subjects. In addition to these primary responses, for both groups the BOLD response exhibited a post-stimulus undershoot with no significant difference in this magnitude. However, the post-undershoot period of the CBF response was significantly greater for older compared to younger subjects. We conclude that when comparing two populations, the BOLD response can provide misleading reflections of underlying physiological changes. A calibrated approach provides a more quantitative reflection of underlying metabolic changes than the BOLD response alone.