Optimizing virus filtration for continuous processing using serial filtration at high area ratio.

Compared to batch operation, continuous bioprocessing can offer numerous advantages, including increased productivity, improved process control, reduced footprint, and increased flexibility. However, integration of traditional batch operations into a connected process can be challenging. In contrast to batch operations run at constant pressure or high flux, virus filtration in continuous processes may be operated at very low flux. This change in operating conditions may reduce the viral retention performance of the filter which has inhibited adoption of truly continuous virus filtration. To overcome this limitation, a novel approach is described that utilizes serial virus filtration, with a high area ratio between first to second stage filters, to achieve virus retention targets. In this study, virus filters were operated continuously (except for planned process interruptions) for 200 h in a serial configuration at a first to second stage filter area ratio of 13:1 and at a first stage flux of 5 L/m2/h. While the minute virus of mice (MVM) retention performance of the first stage filter was about 4 log reduction value (LRV), there was no virus detected in the second stage filtrate, translating to an MVM LRV across the filtration train of ≥6.7. The second stage filter was the dominant flow resistance at the start of the run but, as it was protected from foulants by the first stage filter, it suffered minimal fouling and the life of the filter train was controlled by the first stage. A theoretical case study projected that continuous virus filtration using serial configuration at high area ratio would have about 30% longer filter changeout time, 14% higher productivity, and virus retention nearly six LRV greater than single stage operation. The findings of this research are expected to provide valuable insights into optimizing virus filtration in continuous bioprocessing.

Mucocutaneous toxicities from MEK inhibitors: a scoping review of the literature.

BACKGROUND: MEK inhibitors cause a wide spectrum of mucocutaneous toxicities which can delay or interrupt life-saving therapy. PURPOSE: To summarize the morphology, incidence, and clinical presentation of mucocutaneous toxicities from MEK inhibitors via a scoping review of the literature. METHODS: We conducted a scoping review of the published literature, including clinical trials, retrospective and prospective studies, reviews, and case reports and series. All included literature was analyzed by a panel of pediatric and adult oncodermatologists. RESULTS: Of 1626 initial citations, 227 articles met final inclusion criteria. Our review identified follicular reactions, ocular toxicities, xerosis, eczematous dermatitis, edema, and paronychia as the most common mucocutaneous side effects from MEK inhibitor therapy. Grade 1 and 2 reactions were the most prevalent and were typically managed while continuing treatment; however, grade 3 toxicities requiring dose reductions or treatment interruptions were also reported. CONCLUSION: Mucocutaneous toxicities to MEK inhibitor therapy are common and most often mild in severity. Early recognition and treatment can mitigate disruptions in oncologic therapy.

Osteoporosis and bone health in pediatric patients with epidermolysis bullosa: A scoping review.

Nutritional compromise, low levels of vitamin D, chronic inflammation, abnormal growth, and physical inactivity affect bone metabolism and compromise long-term bone health in individuals with epidermolysis bullosa (EB). The result is a high risk for osteopenia, osteoporosis, and pathologic fractures, but this important consequence of EB has been the focus of few investigations. Our scoping review found 21 publications that assessed the current understanding and clinical practices for monitoring of osteoporosis and its treatment in EB. Recommendations summarized from 13 of these publications include early nutritional and weight assessments before 2 years of age; bloodwork every 6-12 months starting at birth; Tanner stage assessments every 6 months to detect any pubertal delay; DEXA scans starting at age 6 years with repeated scans every 1-2 years, except in mild cases; and vitamin D supplementation of 80-320 IU daily for children 0-7 years and 720 IU for patients >8 years.

Meeting a need: development and validation of PubMed search filters for immigrant populations.

Objective: There is a need for additional comprehensive and validated filters to find relevant references more efficiently in the growing body of research on immigrant populations. Our goal was to create reliable search filters that direct librarians and researchers to pertinent studies indexed in PubMed about health topics specific to immigrant populations. Methods: We applied a systematic and multi-step process that combined information from expert input, authoritative sources, automation, and manual review of sources. We established a focused scope and eligibility criteria, which we used to create the development and validation sets. We formed a term ranking system that resulted in the creation of two filters: an immigrant-specific and an immigrant-sensitive search filter. Results: When tested against the validation set, the specific filter sensitivity was 88.09%, specificity 97.26%, precision 97.88%, and the NNR 1.02. The sensitive filter sensitivity was 97.76%when tested against the development set. The sensitive filter had a sensitivity of 97.14%, specificity of 82.05%, precision of 88.59%, accuracy of 90.94%, and NNR [See Table 1] of 1.13 when tested against the validation set. Conclusion: We accomplished our goal of developing PubMed search filters to help researchers retrieve studies about immigrants. The specific and sensitive PubMed search filters give information professionals and researchers options to maximize the specificity and precision or increase the sensitivity of their search for relevant studies in PubMed. Both search filters generated strong performance measurements and can be used as-is, to capture a subset of immigrant-related literature, or adapted and revised to fit the unique research needs of specific project teams (e.g. remove US-centric language, add location-specific terminology, or expand the search strategy to include terms for the topic/s being investigated in the immigrant population identified by the filter). There is also a potential for teams to employ the search filter development process described here for their own topics and use.

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.

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.

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.

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.

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.

Health System Redesign of Cardiac Monitoring Oversight to Optimize Alarm Management, Safety, and Staff Engagement.

OBJECTIVE: The purpose of this quality improvement project was to improve health system patient safety by creating a cardiac monitoring structure aligned with national standards. BACKGROUND: Excessive alarms pose patient safety threats and are often false or clinically insignificant. The Joint Commission identified reduction of nonactionable alarms as a National Patient Safety Goal. METHODS: The conversion to structured monitoring occurred in 4 phases: 1) defining health system monitoring structure and processes; 2) co-create sessions; 3) implementation and impact analysis; and 4) ongoing evaluation and optimization. RESULTS: Twenty-two clinical units participated. At the conclusion of phase 4, total 30-day alarm rates decreased by 74% at the academic hospital and by 92% and 95% at the community hospitals and were sustained for 12 months. CONCLUSIONS: Decreasing alarm frequency can be safely achieved in academic and community hospitals by creating a system-wide monitoring infrastructure and standardized processes that engage interdisciplinary teams.

Postpartum NSAID Use and Adverse Outcomes among Women with Hypertensive Disorders of Pregnancy: A Systematic Review and Meta-analysis.

OBJECTIVE: This study was aimed to perform a systematic review and meta-analysis of the association between postpartum nonsteroidal anti-inflammatory drug (NSAID) use among women with hypertensive disorders of pregnancy (HDP) and risks of adverse postpartum outcomes. STUDY DESIGN: Studies were eligible if they included women who had been diagnosed with HDP and were postpartum, reported exposure to NSAIDs, were written in English, and were published between January 2000 and November 2019. Assessment of bias was performed using the Newcastle-Ottawa scale for observational studies or the Cochrane Collaborative tool for randomized trials. The primary outcome was maternal blood pressure ≥ 150 mm Hg systolic and/or 100 mm Hg diastolic. Secondary outcomes were persistent blood pressures ≥ 160 mm Hg systolic and/or 110 mm Hg diastolic, mean arterial pressure (MAP), initiation or up-titration of antihypertensive medication, length of hospital stay, rehospitalization for blood pressure control, and postpartum opioid use. A random-effect meta-analysis was performed using RevMan, with a p-value < 0.05 used to indicate statistical significance (PROSPERO CRD no.: 42019127043). RESULTS: Among 7,395 abstracts identified, seven studies (four randomized and three cohort studies, n = 777 patients) met inclusion criteria. All cohort analyses exhibited low levels of bias, while two randomized controlled trials exhibited a high risk of bias in blinding and inclusion criteria. There was no association between NSAID use and blood pressures ≥ 150 mm Hg systolic and/or 100 mm Hg diastolic (risk ratio [RR]: 1.21, 95% confidence interval [CI]: 0.89-1.64). Conversely, NSAID use was associated with a statistically significant, but clinically insignificant, increase in length of postpartum stay (0.21 days, 95% CI: 0.05-0.38). No other secondary outcomes were significantly different between groups. CONCLUSION: Postpartum NSAID use among women with HDP was not associated with maternal hypertension exacerbation. These findings support the recent American College of Obstetricians and Gynecologists' guideline change, wherein preeclampsia is no longer a contraindication to postpartum NSAID use. KEY POINTS: · Postpartum (PP) NSAID use does not worsen hypertension in preeclampsia.. · PP NSAID use is associated with a longer, though clinically insignificant, length of stay.. · Our findings support ACOG's recommendations for PP NSAID use..

Cardiopulmonary Resuscitation in Adults and Children With Mechanical Circulatory Support: A Scientific Statement From the American Heart Association.

Cardiac arrest in patients on mechanical support is a new phenomenon brought about by the increased use of this therapy in patients with end-stage heart failure. This American Heart Association scientific statement highlights the recognition and treatment of cardiovascular collapse or cardiopulmonary arrest in an adult or pediatric patient who has a ventricular assist device or total artificial heart. Specific, expert consensus recommendations are provided for the role of external chest compressions in such patients.

A meta-analysis of anatomy laboratory pedagogies.

The debate regarding anatomy laboratory teaching approaches is ongoing and controversial. To date, the literature has yielded only speculative conclusions because of general methodological weaknesses and a lack of summative empirical evidence. Through a meta-analysis, this study compared the effectiveness of instructional laboratory approaches used in anatomy education to objectively and more conclusively synthesize the existing literature. Studies published between January 1965 and December 2015 were searched through five databases. Titles and abstracts of the retrieved records were screened using eligibility criteria to determine their appropriateness for study inclusion. Only numerical data were extracted for analysis. A summary effect size was estimated to determine the effects of laboratory pedagogies on learner performance and perceptions data were compiled to provide additional context. Of the 3,035 records screened, 327 underwent full-text review. Twenty-seven studies, comprising a total of 7,731 participants, were included in the analysis. The meta-analysis detected no effect (standardized mean difference = -0.03; 95% CI = -0.16 to 0.10; P = 0.62) on learner performance. Additionally, a moderator analysis detected no effects (P ≥ 0.16) for study design, learner population, intervention length, or specimen type. Across studies, student performance on knowledge examinations was equivalent regardless of being exposed to either dissection or another laboratory instructional strategy. This was true of every comparison investigated (i.e., dissection vs. prosection, dissection vs. digital media, dissection vs. models/modeling, and dissection vs. hybrid). In the context of short-term knowledge gains alone, dissection is no better, and no worse, than alternative instructional modalities. Clin. Anat. 31:122-133, 2018. © 2017 Wiley Periodicals, Inc.

The Language of Data Program: Use of Gaming to Promote Critical Appraisal Skills.

This column shares the best evidence-based strategies and innovative ideas on how to facilitate the learning and implementation of EBP principles and processes by clinicians as well as nursing and interprofessional students. Guidelines for submission are available at http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1741-6787.

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.

Vaccination with tetanus, diphtheria, and acellular pertussis vaccine of pregnant women enrolled in Medicaid--Michigan, 2011-2013.

In October 2011, the Advisory Committee on Immunization Practices (ACIP) first recommended the routine administration of a tetanus, diphtheria, and acellular pertussis vaccine (Tdap) during pregnancy as a strategy to protect infants from pertussis (also known as whooping cough). This recommendation applied to women previously unvaccinated with Tdap and specified the optimal vaccination time as late second or third trimester (after 20 weeks' gestation). By vaccinating pregnant women, infants, who are at highest risk for mortality and morbidity from pertussis, gain passive immunity from maternal antibodies transferred to them in utero. Since this recommendation was made, little has been published on the percentage of women receiving Tdap during pregnancy. In Michigan, Medicaid pays for costs of pregnancy for approximately 40% of births. Infants enrolled in Medicaid are a particularly vulnerable population; in Michigan, their all-cause mortality is higher than that of privately insured infants. To assess vaccination coverage among pregnant women enrolled in a publicly funded insurance program in Michigan, Medicaid administrative claims data and statewide immunization information system data for mothers of infants born during November 2011-February 2013 were analyzed. This report describes the results of that analysis, which indicated that only 14.3% of these women received Tdap during pregnancy, with rates highest (17.6%) among non-Hispanic, non-Arab whites and lowest (6.8%) among Arab women. Vaccination was related to maternal age and gestational age at birth, but not to adequacy of prenatal care. In 2013, recognizing the importance of Tdap for every pregnancy, ACIP revised its guidelines to include a Tdap dose during every pregnancy. Ensuring that all infants receive the protection against pertussis afforded by maternal vaccination will require enhanced efforts to vaccinate pregnant women.

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.