Therapies for cutaneous squamous cell carcinoma in recessive dystrophic epidermolysis bullosa: a systematic review of 157 cases.

BACKGROUND: Invasive cutaneous squamous cell carcinomas (cSCC) are a leading cause of death in recessive dystrophic epidermolysis bullosa (RDEB), a rare blistering genodermatosis. Outcomes of RDEB-cSCC therapies have primarily been described in case reports. Systematic studies are scarce. This systematic review aims to assess the pathophysiology, clinical characteristics, and outcomes of RDEB-cSCCs, with a focus on results and mechanisms of recent immunotherapies and anti-EGFR treatments. RESULTS: A systematic literature search of epidermolysis bullosa and cSCC was performed in February 2024, using PubMed, Embase, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and EudraCT databases. Cases with administration of systematic therapies and unpublished outcomes regarding death were tracked with corresponding authors. Data extraction and risk of bias assessment was performed by two independent reviewers. Of 1132 references in the original search, 163 relevant articles were identified, representing 59 case reports, 7 cohort studies, 49 abstracts, 47 in-vitro/in-vivo experiments, and 1 bioinformatic study. From these, 157 cases of RDEB-cSCCs were included. The majority of RDEB-cSCCs were well-differentiated (64.1%), ulcerated (59.6%), and at least 2 cm in size (77.6%), with a median age at diagnosis of 30 years old (range 6-68.4). Surgery was the primary form of treatment (n = 128), followed by chemotherapy and radiotherapy. Anti-EGFR therapy and immunotherapy was also reported beginning in 2009 and 2019, respectively. Survival time from first cSCC diagnosis to death was available in 50 cases. When stratified by their treatment regimen, median survival time was 1.85 years (surgery + chemotherapy, n = 6), 2 years (surgery only, n = 19), 4.0 years (+ anti-EFGR therapy, n = 10), 4 years (surgery + radiotherapy, n = 9), 4.6 years (+ immunotherapy, n = 4), and 9.5 years (surgery + chemotherapy + radiotherapy; n = 2). Treatment-related adverse events were primarily limited to impaired wound healing for immunotherapies and nausea and fatigue for anti-EGFR therapies. CONCLUSIONS: Despite the challenges of a limited sample size in a rare disease, this systematic review provides an overview of treatment options for cSCCs in RDEB. When surgical treatment options have been exhausted, the addition of immunotherapy and/or anti-EGFR therapies may extend patient survival. However, it is difficult to attribute extended survival to any single treatment, as multiple therapeutic modalities are often used to treat RDEB-cSCCs.

Social isolation and social connectedness among young adult cancer survivors: A systematic review.

BACKGROUND: Social isolation and connectedness are social determinants of health that have demonstrated effects on cancer-related outcomes. These constructs have been systematically evaluated among pediatric and older adult cancer populations. In this review, the authors evaluated the prevalence, correlates, and psychosocial implications of social isolation and connectedness among young adult (YA) cancer survivors aged 18-39 years. METHODS: Peer-reviewed articles published in English before June 2021 were identified from database searches and included articles' reference lists according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Included articles described studies that assessed social isolation and/or connectedness among YA cancer survivors. RESULTS: In total, 5094 unique records were identified; 4143 were excluded after title/abstract screening, and 907 were excluded after full-text review. Forty-four articles were included. Few studies used validated measures or directly assessed social isolation or connectedness. Social isolation was similarly prevalent among YAs and older cancer survivors and noncancer populations. Demographic, clinical, and behavioral risk and protective factors for social isolation were identified. Social isolation was related to worse psychological well-being, whereas social connectedness was often, but not always, related to better psychological well-being. CONCLUSIONS: This growing literature underscores the relevance of social isolation and connectedness as important health determinants among YA cancer survivors. The identified risk and protective factors can identify YAs who especially may benefit from screening for social isolation. Future studies are needed that directly, reliably, and validly evaluate social isolation and connectedness to inform the development of interventions to decrease isolation and increase connectedness.

Safety of topical medications in the management of paediatric atopic dermatitis: An updated systematic review.

AIM: New topical agents have been developed for the treatment of atopic dermatitis (AD) in recent years. This systematic review is intended to synthesize the clinical trial literature and concisely report the updated safety and adverse effects of topical medications used to treat atopic dermatitis in children. METHODS: A systematic search of Cochrane Library, Embase, PubMed and ClinicalTrials.gov from inception to March 2022 was conducted for trials of topical medications used to treat AD in patients <18 years (PROSPERO #CRD42022315355). Included records were limited to English-language publications and studies of ≥3 weeks duration. Phase 1 studies and those that lacked separate paediatric safety reporting were excluded. RESULTS: A total of 5005 records were screened; 75 records met inclusion criteria with 15 845 paediatric patients treated with tacrolimus, 12 851 treated with pimecrolimus, 3539 with topical corticosteroid (TCS), 700 with crisaborole and 202 with delgocitinib. Safety data was well reported in tacrolimus trials with the most frequently reported adverse events being burning sensation, pruritus and cutaneous infections. Two longitudinal cohort studies were included, one for tacrolimus and one for pimecrolimus, which found no significant increased risk of malignancy with topical calcineurin inhibitor (TCI) use in children. Skin atrophy was identified as an adverse event in TCS trials, which other medications did not. Systemic adverse events for the medications were largely common childhood ailments. CONCLUSION: Data discussed here support the use of steroid-sparing medications (tacrolimus, pimecrolimus, crisaborole, delgocitinib) as safe options with minimal adverse events for managing paediatric AD, although a larger number of TCI studies reported burning and pruritus compared to TCS studies. TCS was the only medication class associated with reports of skin atrophy in this review. The tolerability of these adverse events should be considered when treating young children. This review was limited to English-language publications and the variable safety reporting of trial investigators. Many newer medications were not included due to pooled adult and paediatric safety data that did not meet inclusion criteria.

Keloid treatments: an evidence-based systematic review of recent advances.

BACKGROUND: Keloids are pathologic scars that pose a significant functional and cosmetic burden. They are challenging to treat, despite the multitude of treatment modalities currently available. OBJECTIVE: The aim of this study was to conduct an evidence-based review of all prospective data regarding keloid treatments published between 2010 and 2020. METHODS: A systematic literature search of PubMed (National Library of Medicine), Embase (Elsevier), and Cochrane Library (Wiley) was performed in November of 2020. Search strategies with the keywords "keloid" and "treatment" were performed by a medical librarian. The search was limited to prospective studies that were peer-reviewed, reported on clinical outcomes of keloid therapies, and were published in the English language between January 1, 2010, and November 24, 2020. RESULTS: A total of 3462 unique citations were identified, of which 108 studies met inclusion criteria. Current literature supports silicone gel or sheeting with corticosteroid injections as first-line therapy for keloids. Adjuvant intralesional 5-fluorouracil (5-FU), bleomycin, or verapamil can be considered, although mixed results have been reported with each. Laser therapy can be used in combination with intralesional corticosteroids or topical steroids with occlusion to improve drug penetration. Excision of keloids with immediate post-excision radiation therapy is an effective option for recalcitrant lesions. Finally, silicone sheeting and pressure therapy have evidence for reducing keloid recurrence. CONCLUSIONS: This review was limited by heterogeneity of subject characteristics and study outcome measures, small sample sizes, and inconsistent study designs. Larger and more robust controlled studies are necessary to further understand the variety of existing and emerging keloid treatments, including corticosteroids, cryotherapy, intralesional injections, lasers, photodynamic therapy, excision and radiation, pressure dressings, and others.

Sex differences in initial treatment for genital extramammary Paget disease in the United States: A systematic review.

BACKGROUND: Surgery is the standard treatment for genital extramammary Paget disease (gEMPD). OBJECTIVE: To determine if gEMPD treatments and outcomes differ by sex and US region. METHODS: A systematic review was performed of all English-language studies on initial gEMPD treatment in Medline via PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov. At least 2 reviewers performed title and abstract review and data extraction. Surgical categories included total skinning procedures, partial skinning procedures, Mohs micrographic surgery (MMS), or unspecified surgery. Chi-squared tests of association were used for comparisons. RESULTS: A total of 60 studies comprising 302 (79.7%) female and 77 (20.3%) male patients met criteria. Women were most often initially recommended partial skinning procedures. In all, 74 (24.5%) women and 0 men underwent a total skinning procedure. Men were more likely to be offered MMS than women (40.3% vs 1.9%, P < .0001), despite men having a significantly greater extent of disease involving the perineum and perianal skin (21.1% vs 1.7%, P < .0001). Treatment recommendations varied by US region. LIMITATIONS: Only 20 states were represented. CONCLUSION: Women are more frequently offered total skinning procedures for gEMPD while men are more frequently offered MMS. MMS offers less recurrence and morbidity than total skinning procedures and should be recommended equally to both female and male patients with gEMPD.

Tools to Measure the Impact of Structural Racism and Discrimination on Gastrointestinal and Hepatology Disease Outcomes: A Scoping Review.

BACKGROUND & AIMS: Structural racism and discrimination (SRD) are important upstream determinants of health perpetuated by discriminatory laws and policies. Therefore, measuring SRD and its impact on health is critical to developing interventions that address resultant health disparities. We aimed to identify gastrointestinal (GI) or liver studies that report measures of SRD or interventions to achieve health equity in these domains by addressing upstream determinants of health. METHODS: We conducted a scoping review according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses scoping reviews guidelines. Studies that used an SRD measure or examined an upstream intervention in GI or liver disease were included. Studies that described health disparities in GI or liver conditions without mentioning SRD were excluded. Study characteristics, findings, and limitations were extracted. RESULTS: Forty-six articles (19 studies using SRD measures and 27 studies of upstream interventions) were identified. Measures of residential racial segregation were reported most frequently. SRD was associated with poorer health outcomes for racial and ethnic minority populations. Although upstream intervention studies focused primarily on policies related to colon cancer screening and organ graft allocation, racial and ethnic disparities often persisted post-intervention. CONCLUSIONS: To achieve health equity in GI and liver conditions, there is an urgent need for research that goes beyond describing health disparities to incorporating measures of SRD and implementing interventions that address this understudied determinant of health.

Uses of the NIH Toolbox® in Clinical Samples: A Scoping Review.

Background and Objectives: The NIH Toolbox® for the Assessment of Neurologic and Behavioral Function is a compilation of computerized measures designed to assess sensory, motor, emotional, and cognitive functioning of individuals across the life span. The NIH Toolbox was initially developed for use with the general population and was not originally validated in clinical populations. The objective of this scoping review was to assess the extent to which the NIH Toolbox has been used with clinical populations. Methods: Guided by the Joanna Briggs Methods Manual for Scoping Reviews, records were identified through searches of PubMed MEDLINE, PsycINFO, ClinicalTrials.gov, EMBASE, and ProQuest Dissertations and Theses Global (2008-2020). Database searches yielded 5,693 unique titles of original research that used at least one NIH Toolbox assessment in a sample characterized by any clinical diagnosis. Two reviewers screened titles, abstracts, and full texts for inclusion in duplicate. Conflicts at each stage of the review process were resolved by a group discussion. Results: Ultimately, 281 publication records were included in this scoping review (nJournal Articles = 104, nConference Abstracts = 84, nClinical Trial Registrations = 86, and nTheses/Dissertations = 7). The NIH Toolbox Cognition Battery was by far the most used of the 4 batteries in the measurement system (nCognition = 225, nEmotion = 49, nMotor = 29, and nSensation = 16). The most represented clinical category was neurologic disorders (n = 111), followed by psychological disorders (n = 39) and cancer (n = 31). Most (96.8%) of the journal articles and conference abstracts reporting the use of NIH Toolbox measures with clinical samples were published in 2015 or later. As of May 2021, these records had been cited a total of nearly 1,000 times. Discussion: The NIH Toolbox measures have been widely used among individuals with various clinical conditions across the life span. Our results lay the groundwork to support the feasibility and utility of administering the NIH Toolbox measures in research conducted with clinical populations and further suggest that these measures may be of value for implementation in fast-paced clinical settings as part of routine practice.

Evidence-Based Clinical Practice Guidelines for Laser-Assisted Drug Delivery.

Importance: Laser-assisted drug delivery (LADD) is used for various medical and cosmetic applications. However, there is insufficient evidence-based guidance to assist clinicians performing LADD. Objective: To develop recommendations for the safe and effective use of LADD. Evidence Review: A systematic literature review of Cochrane Central Register of Controlled Trials, Embase, and MEDLINE was conducted in December 2019 to identify publications reporting research on LADD. A multidisciplinary panel was convened to draft recommendations informed by the systematic review; they were refined through 2 rounds of Delphi survey, 2 consensus meetings, and iterative review by all panelists until unanimous consensus was achieved. Findings: Of the 48 published studies of ablative fractional LADD that met inclusion criteria, 4 were cosmetic studies; 21, oncologic; and 23, medical (not cosmetic/oncologic), and 6 publications of nonablative fractional LADD were included at the request of the expert panel, producing a total of 54 studies. Thirty-four studies (63.0%) were deemed to have low risk of bias, 17 studies (31.5%) had moderate risk, and 3 (5.5%) had serious risk. The key findings that informed the guidelines developed by the expert panel were as follows: LADD is safe in adults and adolescents (≥12 years) with all Fitzpatrick skin types and in patients with immunosuppression; it is an effective treatment for actinic keratosis, cutaneous squamous cell carcinoma in situ, actinic cheilitis, hypertrophic scars, and keloids; it is useful for epidermal and dermal analgesia; drug delivery may be increased through the application of heat, pressure, or occlusion, or by using an aqueous drug solution; laser settings should be selected to ensure that channel diameter is greater than the delivered molecule; antibiotic prophylaxis is not recommended, except with impaired wound healing; antiviral prophylaxis is recommended when treating the face and genitalia; and antifungal prophylaxis is not recommended. The guideline's 15 recommendations address 5 areas of LADD use: (I) indications and contraindications; (II) parameters to report; (III) optimization of drug delivery; (IV) safety considerations; and (V) prophylaxis for bacterial, viral, and fungal infections. Conclusions and Relevance: This systematic review and Delphi consensus approach culminated in an evidence-based clinical practice guideline for safe and effective use of LADD in a variety of applications. Future research will further improve our understanding of this novel treatment technique.

Development of a transient inline spiking system for evaluating virus clearance in continuous bioprocessing-Proof of concept for virus filtration.

The development of continuous/connected bioprocesses requires new approaches for viral clearance validation, both for specific unit operations and for the overall process. In this study, we have developed a transient inline spiking system that can be used to evaluate virus clearance at distinct time points during prolonged operation of continuous bioprocesses. The proof of concept for this system was demonstrated by evaluating the viral clearance for a virus filtration step, both with and without a prefilter upstream of the virus filter. The residence time distribution was evaluated using a previously identified noninteracting fluorescent tracer, while viral clearance was evaluated from measurements of the virus titer in samples obtained downstream of the virus filter. The measured log reduction values (LRV) for ϕX174, minute virus of mice, xenotropic murine leukemia virus, and a noninfectious mock virus particle were all within 0.5 log of those obtained using a traditional batch virus challenge for both model and real-world process streams (LRV between 2.2 and 3.4 for ϕX174 using a single layer of virus filter). The results demonstrate the effectiveness of transient inline spiking to validate the virus clearance capabilities in continuous bioprocessing, an essential element for the adoption of these processes for products made using mammalian cell lines.

Surgical excision margins for fibrohistiocytic tumors, including atypical fibroxanthoma and undifferentiated pleomorphic sarcoma: A probability model based on a systematic review.

BACKGROUND: Mohs micrographic surgery or wide local excision is the treatment of choice for fibrohistiocytic tumors with metastatic potential, including atypical fibroxanthoma (AFX) and cutaneous undifferentiated pleomorphic sarcoma (cUPS). Since margin clearance is the strongest predictor of clinical recurrence, improved recommendations for appropriate surgical margins help delineate uniform excision margins when intraoperative margin assessment is not available. OBJECTIVE: To determine appropriate surgical wide local excision margins for AFX and cUPS. METHODS: Literature search (Ovid MEDLINE, Embase, Web of Science, and Cochrane Library from inception to March 2020) to detect case-level data. Estimation of margins required using a mathematical model based on extracted cases without recurrences. RESULTS: Probabilistic modeling based on 100 cases extracted from 37 studies showed peripheral clearance margin (ie, wide local excision margin) calculated to clear 95% of all tumors was 2 cm for AFX and 3 cm for cUPS. AFX tumors 1 cm or less required a margin of 1 cm. LIMITATIONS: Data were extracted from published cases. CONCLUSIONS: Atypical fibroxanthoma removed with at least a 2-cm peripheral excision margin is less likely to recur. Smaller tumors 1 cm or less can be treated with a more conservative margin. Margin-control surgical techniques are recommended to ensure complete removal while minimizing surgical morbidity.

Risk Assessment and Considerations for Proper Management of Elderly Men with Advanced Prostate Cancer: A Systematic Review.

CONTEXT: Treatment decisions for elderly men with prostate cancer are complicated by the intersection of competing risks of cancer, potential complications of treatment, and individual patients' comorbidities. OBJECTIVE: To perform a systematic review of data guiding the assessment of elderly prostate cancer patients that addresses the risk from cancer and treatment, and to discuss a patient-centered approach to incorporating these factors into decision making. EVIDENCE ACQUISITION: Evidence was gathered via a systematic review of the current literature. The search strategy used the terms prostate cancer, elderly, geriatric, >75 yr of age, risk assessment, and treatment in several combinations, and was limited to phase ≥ II clinical trials published between January 2008 and November 2018. Additional supporting literature for the discussion was pulled by hand search. EVIDENCE SYNTHESIS: The benefits of treatment identified for systemic therapies commonly used to treat men with prostate in general extend to elderly patients. Evidence supports a multifaceted assessment of the risks of cancer and aging, and an understanding of the side effects of treatment to optimally guide therapeutic decision making for elderly patients. There is little evidence defining a geriatric risk stratification system specific to prostate cancer, and recommendations are predominantly based on adapted geriatric oncology approaches and expert consensus. CONCLUSIONS: The care of elderly men with prostate cancer should incorporate a review of cancer risk, an assessment of aging, and an understanding of the effects of treatment to provide the patient with thorough and personalized guidance for treatment decisions. Future studies of elderly men with prostate cancer can define and validate ideal risk stratification methods as well as management approaches that may be distinct from those for younger populations. PATIENT SUMMARY: Treatment decisions for elderly men with prostate cancer require consideration of the risk posed by the cancer coupled with an understanding of the patient's general health status.

Systematic review and meta-analysis of selected toxicities of approved ALK inhibitors in metastatic non-small cell lung cancer.

INTRODUCTION: Anaplastic lymphoma kinase (ALK) inhibitors are the mainstay treatment for patients with non-small cell lung carcinoma (NSCLC) harboring a rearrangement of the ALK gene or the ROS1 oncogenes. With the recent publication of pivotal trials leading to the approval of these compounds in different indications, their toxicity profile warrants an update. MATERIALS AND METHODS: A systematic literature search was performed in July 2017. Studies evaluating US FDA approved doses of one of the following ALK inhibitors: Crizotinib, Ceritinib, Alectinib or Brigatinib as monotherapy were included. Data were analyzed using random effects meta-analysis for absolute risks (AR), study heterogeneity, publication bias and differences among treatments. RESULTS: Fifteen trials with a total of 2,005 patients with evaluable toxicity data were included in this report. There was significant heterogeneity amongst different studies. The pooled AR of death and severe adverse events were 0.5% and 34.5%, respectively. Grade 3/4 nausea, vomiting, diarrhea, and constipation were uncommon: 2.6%, 2.5%, 2.7%, 1.2%, respectively. CONCLUSIONS: ALK inhibitors have an acceptable safety profile with a low risk of treatment-related deaths. Important differences in toxicity profile were detected amongst the different drugs.

Tuberculosis Among Temporary Visa Holders Working in the Tourism Industry - United States, 2012-2014.

Tuberculosis (TB) is a contagious bacterial disease of global concern. During 2013, an estimated nine million incident TB cases occurred worldwide (1). The majority (82%) were diagnosed in 22 countries, including South Africa and the Philippines, where annual incidence was 860 TB cases per 100,000 persons and 292 TB cases per 100,000 persons, respectively (1). The 2013 TB incidence in the United States was three cases per 100,000 persons (2). Under the Immigration and Nationality Act, TB screening is required for persons seeking permanent residence in the United States (i.e., immigrants and refugees), but it is not routinely required for nonimmigrants who are issued temporary visas for school or work (3). A portion of the U.S. tourism industry relies on temporary visa holders to accommodate seasonal and fluctuating demand for service personnel (4). This report describes three foreign-born persons holding temporary visas who had infectious TB while working at tourist destinations in the United States during 2012-2014. Multiple factors, including dormitory-style housing, transient work patterns, and diagnostic delays might have contributed to increased opportunity for TB transmission. Clinicians in seasonally driven tourist destinations should be aware of the potential for imported TB disease in foreign-born seasonal workers and promptly report suspected cases to health officials.

Racial Disparities in Asthma Hospitalizations Following Implementation of the Smoke-Free Air Law, Michigan, 2002-2012.

INTRODUCTION: Exposure to secondhand smoke has immediate adverse respiratory and cardiovascular effects. A growing body of literature examining health trends following the implementation of public smoking bans has demonstrated reductions in the rates of myocardial infarction and stroke, but there has been no extensive work examining asthma hospitalizations. The aim of this study was to determine the impact of the Michigan Smoke-Free Air Law (SFA law) on the rate of asthma hospitalizations among adults in Michigan and to determine any differential effects by race or sex. METHODS: Data on adult asthma hospitalizations were obtained from the Michigan Inpatient Database (MIDB). Poisson regression was used to model relative risks for asthma hospitalization following the SFA law with adjustments for sex, race, age, insurance type, and month of year. Race-based and sex-based analyses were performed. RESULTS: In the first year following implementation of the SFA law, adjusted adult asthma hospitalization rates decreased 8% (95% confidence interval [CI], 7%-10%; P < .001). While asthma hospitalization rates for both blacks and whites declined in the 12 months following implementation of the SFA law, blacks were 3% more likely to be hospitalized for asthma than whites (95% CI, 0%-7%; P = .04). The rate of decline in adult asthma hospitalizations did not differ by sex. CONCLUSION: The implementation of the SFA law was associated with a reduction in adult asthma hospitalization rates, with a greater decrease in hospitalization rates for whites compared with blacks. These results demonstrate that the SFA law is protecting the public's health and saving health care costs.

Consumption of Alcoholic Beverages and Liquor Consumption by Michigan High School Students, 2011.

INTRODUCTION: Excessive alcohol consumption was responsible for approximately 4,300 annual deaths in the United States among people younger than 21 from 2006 through 2010. Underage drinking cost the United States $24.6 billion in 2006. Previous studies have shown that liquor is the most common type of alcohol consumed by high school students. However, little is known about the types of liquor consumed by youth or about the mixing of alcohol with energy drinks. METHODS: The 2011 Michigan Youth Tobacco Survey was used to assess usual alcohol beverage consumption and liquor consumption and the mixing of alcohol with energy drinks by Michigan high school students. Beverage preferences were analyzed by demographic characteristics and drinking patterns. RESULTS: Overall, 34.2% of Michigan high school students consumed alcohol in the past month, and 20.8% reported binge drinking. Among current drinkers, liquor was the most common type of alcohol consumed (51.2%), and vodka was the most prevalent type of liquor consumed by those who drank liquor (53.0%). The prevalence of liquor consumption was similar among binge drinkers and nonbinge drinkers, but binge drinkers who drank liquor were significantly more likely than nonbinge drinkers to consume vodka and to mix alcohol with energy drinks (49.0% vs 18.2%, respectively). CONCLUSIONS: Liquor is the most common type of alcoholic beverage consumed by Michigan high school students; vodka is the most common type of liquor consumed. Mixing alcohol and energy drinks is common, particularly among binge drinkers. Community Guide strategies for reducing excessive drinking (eg, increasing alcohol taxes) can reduce underage drinking.

Botulism toxemia following laparoscopic appendectomy.

We describe a case of botulism infection in a patient who had undergone laparoscopic appendectomy, an occurrence not previously described in the literature. This case exemplifies the need for coordination between clinical and public health personnel to ensure the immediate recognition and treatment of suspected botulism cases.