bluuebunny/crossref_metadata_2025 huggingface dataset:
Examining Phenotypic Traits Contributing to the Spread in Northern European Potato Crops of EU_41_A2, a New Clonal Lineage of Phytophthora infestans
Authors: Puidet Britt , Mabon Romain , Guibert Michele , Kiiker Riinu , Soonvald Liina , Le Vinh Hong , Eikemo Håvard , Dewaegeneire Pauline , Saubeau Guillaume , Chatot Catherine , Aurousseau Frédérique , Cooke David E. L. , Lees Alison K. , Abuley Isaac K. , Hansen Jens G. , Corbière Roselyne , Leclerc Melen , Andrivon Didier
Published: June 2021

Until recently, genotypes of Phytophthora infestans were regionally distributed in Europe, with populations in western Europe being dominated by clonal lineages and those in northern Europe being genetically diverse because of frequent sexual reproduction. However, since 2013 a new clonal lineage (EU_41_A2) has successfully established itself and expanded in the sexually recombining P. infestans populations of northern Europe. The objective of this study was to study phenotypic traits of the new clonal lineage of P. infestans, which may explain its successful establishment and expansion within sexually recombining populations. Fungicide sensitivity, aggressiveness, and virulence profiles of isolates of EU_41_A2 were analyzed and compared with those of the local sexual populations from Denmark, Norway, and Estonia. None of the phenotypic data obtained from the isolates collected from Denmark, Estonia, and Norway independently explained the invasive success of EU_41_A2 within sexual Nordic populations. Therefore, we hypothesize that the expansion of this new genotype could result from a combination of fitness traits and more favorable environmental conditions that have emerged in response to climate change.
The End of Step 2 CS Should Be the Beginning of a New Approach to Clinical Skills Assessment
Authors: Baker Timothy K.
Published: June 2021

The discontinuation of the United States Medical Licensing Examination Step 2 Clinical Skills (CS) in 2020 in response to the COVID-19 pandemic marked the end of a decades-long debate about the utility and value of the exam. For all its controversy, the implementation of Step 2 CS in 2004 brought about profound changes to the landscape of medical education, altering the curriculum and assessment practices of medical schools to ensure students were prepared to take and pass this licensing exam. Its elimination, while celebrated by some, is not without potential negative consequences. As the responsibility for assessing students’ clinical skills shifts back to medical schools, educators must take care not to lose the ground they have gained in advancing clinical skills education. Instead, they need to innovate, collaborate, and share resources; hold themselves accountable; and ultimately rise to the challenge of ensuring that physicians have the necessary clinical skills to safely and effectively practice medicine.
Grounded in Justice: An Equity Framework for Chief Residents
Authors: Gilliam Courtney A. , Olszewski Aleksandra E. , McDade Jessica E. , Homer Paul , Grow H. Mollie , McPhillips Heather A. , Rooholamini Sahar N.
Published: June 2021

The 2019–2020 academic year was unprecedented, with navigating the COVID-19 pandemic and meaningfully engaging with the causes and consequences of long-standing racism and social injustice in the United States. In this article, the authors, all former chief residents, reflect on how they carried out their role during this last year using an approach that was grounded in equity and justice. They describe a framework based on their experiences, including setting the tone and culture of the residency program; providing medical education, teaching, and feedback; advocating for resident well-being and inclusion; participating in quality improvement and hospital policymaking; and partnering for institutional change. They end with a call to action to reconceptualize the role of the chief resident to include the genuine work of diversity, equity, and inclusion to ensure a more equitable future.
One-year follow-up ultrasonographic study of the subchondral bone surface of the distal femoral epiphysis in children aged 9–11 years
Authors: Iwame Toshiyuki , Matsuura Tetsuya , Suzue Naoto , Katsuura-Kamano Sakurako , Takao Shoichiro , Iwase Joji , Sairyo Koichi
Published: June 2021

The aim of this study was to investigate the subchondral bone surface of the distal femoral epiphysis and monitor the morphologic changes on ultrasonography (US) in growing children. A total of 160 football players aged 9–11 years underwent ultrasonographic examination of both knees. The regularity of the subchondral bone surface of the femoral condyles was classified as grade 0 (smooth), 1 (focal semilunar depression or indentation) or 2 (broad irregularity). The relationship between age and frequency of irregularity was analyzed. Children with a grade 2 were referred for radiography and MRI to check for osteochondritis dissecans (OCD). All players underwent repeat examination 1 year later. On initial examination, 82/320 knees (25.6%) were categorized as grade 0, 237/320 (74.1%) as grade 1 and 1 (0.3%) as grade 2. Logistic regression analysis revealed a significant association of increasing age with decreased irregularity of subchondral bone in the lateral and medial condyles (P = 0.019 and P < 0.001 for trend, respectively). One year later, logistic regression analysis showed that increasing age was significantly associated with decreased appearance of subchondral bone irregularity in the medial condyle (P = 0.005 for trend) and a greater likelihood of disappearance of irregularity in both condyles (P < 0.001 for trend). Of five knees classified as grade 2, four had evidence of OCD on radiography and MRI. Subchondral bone surface irregularity of the distal femoral epiphysis was more common on US in growing children aged 9–11 years, and transition from an irregular to a smooth outline accelerated after age 10 years. US is a reliable method for assessing the morphology of the distal femoral epiphysis and could be a useful screening tool for detecting OCD.
Patterns of femoral neck fracture and its treatment methods in patients with osteogenesis imperfecta
Authors: Hong Wan Kee , Lee Doo Jae , Chung HoeJoeng , Lim Chaemoon , Shin Chang Ho , Yoo Won Joon , Cho Tae-Joon
Published: June 2021

Femoral neck fracture (FNF) is not common in osteogenesis imperfecta patients but may result in serious complications if not properly treated in due time. We present three types of FNF in osteogenesis imperfecta and their characteristics, treatment methods and outcomes. Cases of FNF followed for more than 2 years were selected from the osteogenesis imperfecta database. Medical records and radiographs were reviewed to obtain demographic information and to determine ambulatory status, mode of injury, location of the fracture line, presence of preexisting implants, treatment methods and complications. Outcomes were evaluated according to the radiographic results and ambulatory function. The study investigated 15 FNFs in 10 patients including 1 Sillence type I, 1 type III and 8 type IV. They were either community or household ambulators. The mean age at fracture was 11.7 years. The fractures were followed for an average of 6.3 years. Six fractures were attributed to accidental injuries and nine without noticeable trauma. The fracture pattern was categorized into undisplaced (n = 3), angulated-stable (n = 7) or displaced-unstable (n = 5) types. Five fractures were fixed in-situ using screws or Kirschner wires. Other five fractures were treated by closed reduction and screw fixation and the remaining five fractures were managed by femoral valgus osteotomy. Bony union was achieved, and prefracture ambulatory status was restored in all cases. A high index of suspicion is required in the diagnosis of undisplaced or angulated-stable fractures. Treatment is usually challenging, but a judicious approach considering the fracture pattern and patient characteristics result in successful outcomes. The angulated-stable pattern of fracture is unique in osteogenesis imperfecta patients and requires special attention.
Evaluating Systemized Nomenclature of Medicine Clinical Terms Coverage of Complementary and Integrative Health Therapy Approaches Used Within Integrative Nursing, Health, and Medicine
Authors: Austin Robin R. , Lu Sheng-Chieh , Geiger-Simpson Elena , Ringdahl Deborah , Pruinelli Lisiane , Lindquist Ruth , Koithan Mary , Monsen Karen A. , Kreitzer Mary Jo , Delaney Connie W.
Published: June 2021

The use of complementary and integrative health therapy strategies for a wide variety of health conditions is increasing and is rapidly becoming mainstream. However, little is known about how or if complementary and integrative health therapies are represented in the EHR. Standardized terminologies provide an organizing structure for health information that enable EHR representation and support shareable and comparable data; which may contribute to increased understanding of which therapies are being used for whom and for what purposes. Use of standardized terminologies is recommended for interoperable clinical data to support sharable, comparable data to enable the use of complementary and integrative health therapies and to enable research on outcomes. In this study, complementary and integrative health therapy terms were extracted from multiple sources and organized using the National Center for Complementary and Integrative Health and former National Center for Complementary and Alternative Medicine classification structures. A total of 1209 complementary and integrative health therapy terms were extracted. After removing duplicates, the final term list was generated via expert consensus. The final list included 578 terms, and these terms were mapped to Systemized Nomenclature of Medicine Clinical Terms. Of the 578, approximately half (48.1%) were found within Systemized Nomenclature of Medicine Clinical Terms. Levels of specificity of terms differed between National Center for Complementary and Integrative Health and National Center for Complementary and Alternative Medicine classification structures and Systemized Nomenclature of Medicine Clinical Terms. Future studies should focus on the terms not mapped to Systemized Nomenclature of Medicine Clinical Terms (51.9%), to formally submit terms for inclusion in Systemized Nomenclature of Medicine Clinical Terms, toward leveraging the data generated by use of these terms to determine associations among treatments and outcomes.
Stimulating the Involvement of Family Members in the Medication Management Activities of Older Adults Through Ambient Displays
Authors: Rodríguez Marcela D. , García-Vázquez Juan-Pablo , Andrade Ángel G.
Published: June 2021

Little attention has been paid to how medication management technologies, designed for older adults, modify the participation of family caregivers. We developed a tablet-based ambient display that provides external cues to remind and motivate older adults to take their medications. This study aimed to understand the effect of ambient displays on the involvement of family members in the elderly's medication management. We conducted a 10-week study consisting of interviews administered weekly to nine elderly-caregivers. We identify that new involvement patterns of the family caregivers were provoked through external cues, which made them aware of older adults' medication adherence and encouraged younger relatives to help older adults.
Mobile Health Applications, Cancer Survivors, and Lifestyle Modification
Authors: Kelley Marjorie M. , Kue Jennifer , Brophy Lynne , Peabody Andrea L. , Foraker Randi E. , Yen Po-Yin , Tucker Sharon
Published: June 2021

Cancer survivors' well-being is threatened by the risk of cancer recurrence and the increased risk of chronic diseases resulting from cancer treatments. Improving lifestyle behaviors attenuates these risks. Traditional approaches to lifestyle modification (ie, counseling) are expensive, require significant human resources, and are difficult to scale. Mobile health interventions offer a novel alternative to traditional approaches. However, to date, systematic reviews have yet to examine the use of mobile health interventions for lifestyle behavior improvement among cancer survivors. The objectives of this integrative review were to synthesize research findings, critically appraise the scientific literature, examine the use of theory in intervention design, and identify survivors' preferences in using mobile health interventions for lifestyle improvement. Nineteen articles met eligibility requirements. Only two studies used quantitative methods. Study quality was low, and only one study reported the use of theory in app design. Unfortunately, the evidence has not yet sufficiently matured, in quality or in rigor, to make recommendations on how to improve health behaviors or outcomes. However, six themes emerged as important considerations for intervention development for cancer survivors (app features/functionality, social relationships/support, provider relationships/support, app content, app acceptability, and barriers to use). These findings underscored the need for rigorous, efficacy studies before the use of mobile health interventions can be safely recommended for cancer survivors.
Risk of Immune-related Adverse Events in Melanoma Patients With Preexisting Autoimmune Disease Treated With Immune Checkpoint Inhibitors
Authors: Tully Karl H. , Cone Eugene B. , Cole Alexander P. , Sun Maxine , Chen Xi , Marchese Maya , Roghmann Florian , Kilbridge Kerry L. , Trinh Quoc-Dien
Published: June 2021

Objective:

The objective of this study was to examine the risk of immune-related adverse events (irAEs) in patients with a preexisting autoimmune disease (pAID) presenting with a cutaneous melanoma receiving an immune checkpoint inhibitor (ICI) therapy.

Methods:

Data from the Surveillance, Epidemiology, and End Results cancer registries and linked Medicare claims between January 2010 and December 2015 was used to identify patients diagnosed with cutaneous melanoma who had pAID or received ICI or both. Patients were then stratified into 3 groups: ICI+pAID, non-ICI+pAID, and ICI+non-pAID. Inverse probability of treatment weighted Cox proportional hazards regression models were fitted to assess the risk of cardiac, pulmonary, endocrine, and neurological irAE.

Results:

In total, 3704 individuals were included in the analysis. The majority of patients consisted of non-ICI+pAID patients (N=2706/73.1%), while 106 (2.9%) patients and 892 (24.1%) were classified as ICI+pAID and ICI+non-pAID, respectively. The risk of irAE was higher in the ICI+pAID group compared with the non-ICI+pAID and ICI+non-pAID, respectively (non-ICI: cardiac: hazard ratio [HR]=3.59, 95% confidence interval [CI]: 2.83-4.55; pulmonary: HR=3.94, 95% CI: 3.23-4.81; endocrine: HR=1.72, 95% CI: 1.53-1.93; neurological: HR=3.88, 95% CI: 2.30-6.57/non-pAID: cardiac: HR=3.83, 95% CI: 3.39-4.32; pulmonary: HR=2.08, 95% CI: 1.87-2.32; endocrine: HR=1.23, 95% CI: 1.14-1.32; neurological: HR=3.77, 95% CI: 2.75-5.18).

Conclusions:

Patients with a pAID face a significantly higher risk of irAEs. Further research examining the clinical impact of these events on the patients’ oncological outcome and quality of life is urgently needed given our findings of significantly worse rates of adverse events.
Sluggish Cognitive Tempo and Daytime Sleepiness Mediate Relationships Between Sleep and Academic Performance
Authors: O'Hare Kirstie , White Naomi , Harding Rebecca , Galland Barbara , Sellbom Martin , Shine Ben , Schaughency Elizabeth
Published: June 2021

Objective:

Sleep difficulties, daytime sleepiness, and sluggish cognitive tempo (SCT) are associated with impairments in academic performance. SCT refers to symptoms of sluggishness, tiredness/lethargy, and slowed thinking/processing, but despite symptom overlap with sleepiness, research examining interrelations of SCT with sleep and daytime sleepiness is limited. The aims of this study were to evaluate the relationship between SCT and daytime sleepiness and to examine pathways between sleep, daytime sleepiness, SCT, and academic performance.

Method:

Participants were a community sample of 1628 parents/caregivers of children aged between 6 and 10 years who completed questionnaires about their child's behavior, sleep, and academic performance. Confirmatory factor analysis was used to examine whether SCT was distinct from daytime sleepiness. Then, structural equation modeling was used to examine direct and indirect pathways between sleep (sleep-disordered breathing [SDB] symptoms, sleep duration, and latency), daytime sleepiness, SCT, and academic performance in reading, writing, and math.

Results:

SCT and daytime sleepiness were distinct but moderately correlated (r = 0.33, p ≤ 0.001). Sleep, in particular SDB symptoms, predicted increased SCT and daytime sleepiness. SCT was directly and negatively associated with all domains of academic performance, daytime sleepiness was associated with poorer reading performance, and longer sleep duration was directly associated with poorer math performance. SCT and, to a lesser extent, daytime sleepiness mediated effects of sleep on academic performance.

Conclusion:

SCT symptoms are important for understanding how sleep difficulties affect academic performance in children. Sleep, daytime sleepiness, and SCT are interrelated but distinct factors that affect children's academic performance.
Allogeneic Stem Cell Transplantation Platforms With Ex Vivo and In Vivo Immune Manipulations: Count and Adjust
Authors: de Witte Moniek , Daenen Laura G. M. , van der Wagen Lotte , van Rhenen Anna , Raymakers Reiner , Westinga Kasper , Kuball Jürgen
Published: June 2021

Various allogeneic (allo) stem cell transplantation platforms have been developed over the last 2 decades. In this review we focus on the impact of in vivo and ex vivo graft manipulation on immune reconstitution and clinical outcome. Strategies include anti-thymocyte globulin- and post-transplantation cyclophosphamide-based regimens, as well as graft engineering, such as CD34 selection and CD19/αβT cell depletion. Differences in duration of immune suppression, reconstituting immune repertoires, and associated graft-versus-leukemia effects and toxicities mediated through viral reactivations are highlighted. In addition, we discuss the impact of different reconstituting repertoires on donor lymphocyte infusions and post allo pharmacological interventions to enhance tumor control. We advocate for precisely counting all graft ingredients and therapeutic drug monitoring during conditioning in the peripheral blood, and for adjusting dosing accordingly on an individual basis. In addition, we propose novel trial designs to better assess the impact of variations in transplantation platforms in order to better learn from our diversity of “counts” and potential “adjustments.” This will, in the future, allow daily clinical practice, strategic choices, and future trial designs to be based on data guided decisions, rather than relying on dogma and habits.
Novel Technique for 27-Gauge Forceps–Assisted Transscleral Refixation of the Dislocated CZ70BD Intraocular Lens
Authors: Yip Lai Ting , Fong Angie , Tsang Chi Wai
Published: June 2021

Purpose:

To report a novel technique for refixation of the dislocated CZ70BD intraocular lens.

Methods:

Posterior vitrectomy is performed with a 23-gauge or 25-gauge pars plana vitrectomy system with chandelier illumination. One needle of a double-arm 9-0 prolene needle is passed through the sclera 1.5 mm postlimbus. The needle is retrieved through the corneal paracentesis using a 27-G needle, and the suture is then cut. The suture end is passed through the eyelet of the dislocated CZ70BD intraocular lens inside the vitreous cavity. This is aided with a pair of 27-G MaxGrip forceps, which is inserted through a 27-G sclerostomy site at the intended scleral outlet. After passing the suture through the eyelet, the suture is pulled out at the 27-G sclerostomy site and a knot is tied and rotated. Similar procedure is performed for the second haptic if necessary.

Results:

Seven eyes were successfully operated on using this technique with a mean follow-up of 12.4 months. There was significant improvement in the best-corrected visual acuity after the operation (P = 0.016). Postoperative intraocular lens centration and alignment were satisfactory. One patient developed macula-on retinal detachment 1 month after the operation, which was successfully repaired without loss in the best-corrected visual acuity.

Conclusion:

The described novel technique is effective for refixation of dislocated CZ70BD intraocular lens.
LESSONS LEARNED FROM PACORES IN PROLIFERATIVE DIABETIC RETINOPATHY MANAGEMENT, DATA FROM LATIN AMERICA AND SPAIN
Authors: Arevalo J. Fernando , Beatson Bradley ,   for the Pan-American Collaborative Retina Study Group (PACORES)
Published: June 2021

Purpose:

To review the current literature on the management of proliferative diabetic retinopathy (PDR) and the challenges in the real-world setting.

Methods:

A review of the literature was performed on the therapeutic options for PDR, with a focus on the real-world data presented by the Pan-American Collaborative Retina Study Group.

Results:

Data from clinical trials and previous literature have reported that intravitreal antivascular endothelial growth factor (anti-VEGF) therapy is noninferior to the gold standard panretinal photocoagulation for treating PDR. However, PDR recurs rapidly after cessation of anti-VEGF therapy. This is especially important in the context of the diabetic population that is prone to loss to follow-up. In a real-world, prospective study, patients with prior panretinal photocoagulation followed by anti-VEGF therapy had higher rates of sustained PDR regression relative to anti-VEGF therapy alone.

Conclusion:

Owing to its transient therapeutic effect, anti-VEGF therapy in patients with diabetes can present a risk of recurrent retinal neovascularization and progression of PDR if follow-up cannot be guaranteed. A combined paradigm with less aggressive, immediate panretinal photocoagulation followed by anti-VEGF therapy should be considered in this population.
Microarray-based exploration of molecules associated with keloid pruritus
Authors: Asai Misachi , Kike Yuta , Kuwatsuka Yutaka , Kashiyama Kazuya , Tanaka Katsumi , Utani Atsushi , Murota Hiroyuki
Published: June 2021

Keloids are frequently accompanied with pruritus. Because traumatic stimuli such as scratching promotes keloid enlargement, alleviating pruritus is an important aspect of keloid management. To investigate the mechanism of keloid pruritus, we conducted a microarray-based comparison of keloid and nonkeloid skin. Relative expression levels of pruritus-associated ligands and receptors were determined, followed by construction of a heat map focused on serotonergic signaling, and finally pathway analysis. Results demonstrate relative up-regulation of various transcripts within keloid lesions, including those encoding a histamine receptor (H1R), a serotonin receptor (5-HT-2A), and an endothelin receptor (ET-A). Serotonergic signaling may be involved in keloid pruritus.
Association Between the Physical Work Environment and Work Functioning Impairment While Working From Home Under the COVID-19 Pandemic in Japanese Workers
Authors: Okawara Makoto , Ishimaru Tomohiro , Tateishi Seiichiro , Hino Ayako , Tsuji Mayumi , Ikegami Kazunori , Nagata Masako , Matsuda Shinya , Fujino Yoshihisa
Published: June 2021

Objective:

To examine the relationship between the physical work environment and work function while working from home (WFH).

Methods:

A cross-sectional study was conducted. Data from 5760 workers who worked from home at least 1 day a month were analyzed. The physical work environment while WFH was used as an exposure factor. The presence of work functioning impairment was measured using Work Functioning impairment Scale (WFun). Mixed-effects logistic regression was used with the prefecture of residence as a random effect.

Results:

Work functioning impairment was significantly associated with a “No” response to recommended environments. The highest odds ratio (OR) of work functioning impairment was associated with a “No” response to “There is enough light to do my work” (adjusted odds ratio [aOR]: 2.02, 95% confidence interval [CI]: 1.73 to 2.35, P < 0.01).

Conclusions:

Improving work environments may prevent negative health effects and improve productivity while WFH.
Factors Associated With Initiation of Extracorporeal Cardiopulmonary Resuscitation in the Pediatric Population: An International Survey
Authors: Nguyen Duy-Anh , De Mul Aurélie , Hoskote Aparna U. , Cogo Paola , da Cruz Eduardo M. , Erickson Simon , Lasa Javier J. , Thiagarajan Ravi R. , Bembea Melania M. , Karam Oliver ,   on behalf of PALISI, ESPNIC, ANZICS PSG
Published: June 2021

Although extracorporeal cardiopulmonary resuscitation (ECPR) is increasingly utilized in the pediatric critical care environment, our understanding regarding pediatric candidacy for ECPR remains unknown. Our objective is to explore current practice and indications for pediatric ECPR. Scenario-based, self-administered, online survey, evaluating clinical determinants that may impact pediatric ECPR initiation with respect to four scenarios: postoperative cardiac surgery, cardiac failure secondary to myocarditis, septic shock, and chronic respiratory failure in a former preterm child. Responders are pediatric critical care physicians from four societies. 249 physicians, mostly from North America, answered the survey. In cardiac scenarios, 40% of the responders would initiate ECPR, irrespective of CPR duration, compared with less than 20% in noncardiac scenarios. Nearly 33% of responders would consider ECPR if CPR duration was less than 60 minutes in noncardiac scenarios. Factors strongly decreasing the likelihood to initiate ECPR were out-of-hospital unwitnessed cardiac arrest and blood pH <6.60. Additional factors reducing this likelihood were multiple organ failure, pre-existing neurologic delay, >10 doses of adrenaline, poor CPR quality, and lactate >18 mmol/l. Pediatric intensive care unit location for cardiac arrest, good CPR quality, 24/7 in-house extracorporeal membrane oxygenation (ECMO) team moderately increase the likelihood of initiating ECPR. This international survey of pediatric ECPR initiation practices reveals significant differences regarding ECPR candidacy based on patient category, location of arrest, duration of CPR, witness status, and last blood pH. Further research identifying prognostic factors measurable before ECMO initiation should help define the optimal ECPR initiation strategy.
Extracorporeal Membrane Oxygenation Cannula–Related Infections: Epidemiology and Risk Factors
Authors: Winiszewski Hadrien , Boyadjian Charles , Besch Guillaume , Soumagne Thibaud , Jeanney Martin , Pili-Floury Sebastien , Fournier Damien , Belon François , Chocron Sidney , Capellier Gilles , Perrotti Andrea , Piton Gaël
Published: June 2021

Although being a potential major source of infection in extracorporeal membrane oxygenation (ECMO) patients, data regarding cannula-related infections (CRI) remain scarce. We therefore aimed at describing the epidemiology of CRI among critically ill patients supported by ECMO. Between October 2017 and November 2019, adult patients supported by either venoarterial (VA), venopulmonary arterial, or venovenous (VV) ECMO for more than 24 hours were prospectively enrolled. When CRI was suspected, cannula swab and subcutaneous needle aspirate samples were obtained for microbiological culture. Cannula tips were systematically sent for culture at the time of ECMO removal. Primary end-point was CRI, which was defined by sepsis or local sign of cannula infection and at least one positive culture among swab, subcutaneous needle aspirate or tip. Multivariate analysis was performed to identify risk factors of CRI. Hundred patients were included, including 77 VA, 12 venopulmonary arterial, and 11 VV ECMO. Cannula-related infections were diagnosed after a median duration of ECMO of 10 [7–13] days. Rate of CRI was 24%, including 10% with bacteremia. Most frequent involved pathogens were Enterobacteriaceae (n = 14), Enterococci (n = 8), and coagulase-negative Staphylococci (n = 7). By multivariate analysis, diabetes and ECMO duration were independently associated with CRI.
Burnout and Physician Gender
Authors: Hoff Timothy , Lee Do R.
Published: June 2021

Purpose:

Burnout (BO) is a serious phenomenon affecting US physicians. Female physicians, now accounting for a larger share of the workforce, are thought to experience higher levels of BO in some situations compared with their male counterparts. The current review aimed to systematically examine extant literature on physician BO as it relates especially to the female physician.

Methods:

Preferred Reporting Items for Systematic Reviews and Meta-Analyses guided search of 4 databases yielding empirical studies with relevant findings regarding female physician BO, published during the time period 2010−2019.

Results:

A total of 43 studies were included in the current review. Both male and female doctors have higher percentages of burned out doctors, with a third or more of each group indicating BO in each of the studies examined. These higher levels of BO remained regardless of where physicians worked, their clinical specialty, workloads, or age. However, the review supports the notion that for women doctors, there is generally a higher likelihood of experiencing BO compared with male doctors, particular with respect to the emotional exhaustion dimension of BO.

Conclusions:

BO is important for both female and male physicians; although women doctors may experience it to a greater degree. Women doctors will benefit from talent management approaches by health care organizations that recognize their greater tendency to BO compared with men. These approaches should be aimed at ameliorating the factors that give rise to feelings of emotional exhaustion in particular. Additional research is needed to better understand the full extent to which physician gender plays a role in BO.
Changes in Opioid Prescribing Following the Implementation of State Policies Limiting Morphine Equivalent Daily Dose in a Commercially Insured Population
Authors: Heins Sara E. , Castillo Renan C.
Published: June 2021

Background:

Prescription opioid mortality doubled 2002–2016 in the United States. Given the association between high-dose opioid prescribing and opioid mortality, several states have enacted morphine equivalent daily dose (MEDD) policies to limit high-dose prescribing. The study objective is to evaluate the impact of state-level MEDD policies on opioid prescribing among the privately insured.

Methods:

Claims data, 2010–2015 from 9 policy states and 2 control states and a comparative interrupted time series design were utilized. Primary outcomes were any monthly opioid use and average monthly MEDD. Stratified analyses evaluated theorized weaker policies (guidelines) and theorized stronger policies (passive alert systems, legislative acts, and rules/regulations) separately. Patient groups explicitly excluded from policies (eg, individuals with cancer diagnoses or receiving hospice care) were also examined separately. Analyses adjusted for covariates, state fixed effects, and time trends.

Results:

Both guideline and strong policy implementation were both associated with 15% lower odds of any opioid use, relative to control states. However, there was no statistically significant change in the use of high-dose opioids in policy states relative to control states. There was also no difference in direction and significance of the relationship among targeted patient groups.

Conclusions:

MEDD policies were associated with decreased use of any opioids relative to control states, but no change in high-dose prescribing was observed. While the overall policy environment in treatment states may have discouraged opioid prescribing, there was no evidence of MEDD policy impact, specifically. Further research is needed to understand the mechanisms through which MEDD policies may influence prescribing behavior.
The history of nasal reconstruction
Authors: Shaye David A.
Published: June 2021

Purpose of review

Total nasal reconstruction is a unique plastic surgery challenge of the highest order. The history of nasal reconstruction dates back to ancient times and it remains a fundamental challenge today. This article reviews the historical context of nasal reconstruction, and highlights how the essential tenets of this art have been conserved over millennia.

Recent findings

The disfiguring and brutal practice of nasal amputation created a demand for ‘nosemakers’ in India since 1500 BC. In 600 BC, Sushruta described the use of a leaf to make a template of the wound, and a cheek flap to supply tissue. In the 1400–1500s, the Italians relied on similar flap concepts, but employed a pedicled arm flap for soft tissue coverage. Eventually, the forehead flap, or ‘Indian method’ of nasal reconstruction, made its way to Europe in the 1800s. Its use has been a fundamental component of nasal reconstruction to this day.

Knowledge of the unique history of nasal reconstruction permits appreciation of this surgical integration of art and science. The story of nasal reconstruction has been one of global contribution and creativity that has stood the test of time.
Emergence of Hepatitis C Virus Genotype 2c Infection Among Human Immunodeficiency Virus–Infected Men Who Have Sex With Men in Tokyo, Japan
Authors: Okamoto Koh , Yamada Norie , Suzuki Tomohiko , Muramatsu Takashi , Uemura Haruka , Gatanaga Hiroyuki , Kato Takanobu , Hatakeyama Shuji
Published: June 2021

We report on hepatitis C virus genotype 2c infection in 12 human immunodeficiency virus–infected men who have sex with men in Tokyo, Japan. The uncommon strains from the 12 patients were genetically clustered; they suggested an emerging outbreak in this population at high risk of sexually transmitted infections.
Personalized Telerehabilitation for a Head-mounted Low Vision Aid: A Randomized Feasibility Study
Authors: Lorenzini Marie-Céline , Wittich Walter
Published: June 2021

SIGNIFICANCE

A recent trend in low vision rehabilitation has been the use of portable head-mounted displays to enhance residual vision. Our study confirms the feasibility of telerehabilitation and informs the development of evidence-based recommendations to improve telerehabilitation interventions to reduce device abandonment.

PURPOSE

To develop evidence-based recommendations for telerehabilitation, we conducted a feasibility study in preparation for a future randomized trial on the use of head-mounted displays.

METHODS

We recruited novice eSight Eyewear users, randomized 1:1: the experimental group received telerehabilitation by a low vision therapist using video conferencing; the control group completed at home self-training provided by the device manufacturer. The primary feasibility outcomes were whether the recruitment goal of 60 participants (30/group) was attainable within 1 year and how participants judged the accessibility and acceptability of the telerehabilitation. An exploratory outcome was the impact of telerehabilitation on eSight Eyewear use behavior.

RESULTS

Among 333 eSight users, 57 participants were enrolled, of which 35% withdrew from the study, whereas the remainder completed the 6-month follow-up. The withdrawal rate was higher in the control group but did not differ significantly from the experimental group. High accessibility (93% of participants accessed the platform) and global acceptability (100% overall satisfaction) were reported among those who completed the telerehabilitation protocol. The therapist had no difficulty judging the participants' reading performances qualitatively while participants used their device to read their eSkills and VisExc guides. Most participants improved their daily activities, based on qualitative reports of the attained goals. Seventy-nine percent of individuals declined to participate, whereas 16% of participants decided not to use eSight Eyewear anymore.

CONCLUSIONS

The data demonstrated the feasibility of a randomized controlled telerehabilitation study for people with low vision using a head-mounted display. Positive feedback from the participants and the therapist suggests the potential value of this modality for low vision services.
PAX-8 Expression in Salivary Duct Carcinoma
Authors: Serinelli Serenella , Mirchia Kanish , Gitto Lorenzo , Khurana Kamal K. , Zaccarini Daniel J.
Published: June 2021

Salivary duct carcinoma (SDC) is a high-grade adenocarcinoma resembling breast ductal carcinoma. It accounts for ~10% of malignant tumors of the salivary glands. Most cases show expression of CK7 and androgen receptor. PAX-8 is a transcription factor, with expression reported in renal, Müllerian, and thyroid carcinomas. Previous studies have described an absence of PAX-8 immunostaining in most primary salivary gland neoplasms, including SDCs. However, PAX-8 expression is frequently found in neoplasms that can metastasize to salivary glands, suggesting the possibility that this protein can be used to differentiate SDC from secondary neoplastic involvement of the salivary gland. We evaluated the expression of PAX-8 in 14 cases of SDC from our institution. One case showed diffuse moderate to strong PAX-8 positivity, while 2 tumors showed focal weak staining. Therefore, we conclude that although the majority of SDC are negative for PAX-8, rare diffuse positivity can be seen in these primary salivary gland tumors. This could potentially pose difficulty in ruling out metastatic disease from another PAX-8-positive primary neoplasm.
Prognostic and Clinicopathologic Associations of LAG-3 Expression in Triple-negative Breast Cancer
Authors: Stovgaard Elisabeth S. , Kümler Iben , List-jensen Kamille , Roslind Anne , Christensen Ib J. , Høgdall Estrid , Nielsen Dorte , Balslev Eva
Published: June 2021

The immune checkpoint molecule lymphocyte activation gene 3 (LAG-3) is currently being investigated as a possible target for immunotherapy in triple-negative breast cancer (TNBC), frequently as an addition to treatment with programmed cell death protein 1/programmed death ligand 1 (PD-L1) inhibition. However, expression of LAG-3, the frequency of coexpression with PD-L1, and the prognostic significance of this marker have not been studied extensively in TNBC. For this study, tissue microarrays (TMAs) were constructed from surgical specimens of 514 patients with TNBC. TMAs were stained immunohistochemically for LAG-3 and PD-L1 expression. Tumor-infiltrating lymphocytes (TILs) were evaluated on full glass slides. LAG-3 expression was significantly associated with improved overall survival and relapse-free survival. When adjusted for clinicopathologic factors, each increment of 10 LAG-3-positive intratumoral lymphocytes per TMA core was associated with improved overall survival (hazard ratio=0.93, 95% confidence interval: 0.89-0.97, P=0.002), and recurrence-free survival (hazard ratio=0.91, 95% confidence interval: 0.85-0.97, P=0.002). PD-L1 expression on immune cells and PD-L1 expression evaluated with the combined positive score and TILs were also associated with improved survival in both univariate and multivariate analyses. PD-L1 expression on tumor cells was only associated with improved survival in univariate analysis. LAG-3 expression was associated with both TILs and PD-L1 expression. Coexpression of LAG-3 and PD-L1 did not confer additional survival benefits. In conclusion, LAG-3 expression is associated with improved survival in TNBC. LAG-3 is often coexpressed with PD-L1, confirming that TNBC is likely a suitable candidate for cotreatment with LAG-3 and programmed cell death protein 1/PD-L1 inhibitors. However, coexpression does not confer additional survival benefits.
E-Cadherin Expression and Blunted Interferon Response in Blastic Plasmacytoid Dendritic Cell Neoplasm
Authors: Lorenzi Luisa , Lonardi Silvia , Vairo Donatella , Bernardelli Andrea , Tomaselli Michela , Bugatti Mattia , Licini Sara , Arisi Mariachiara , Cerroni Lorenzo , Tucci Alessandra , Vermi William , Giliani Silvia Clara , Facchetti Fabio
Published: June 2021

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive neoplasm derived from plasmacytoid dendritic cells (pDCs). In this study, we investigated by immunohistochemical analysis the expression of E-cadherin (EC) on pDCs in reactive lymph nodes and tonsils, bone marrow, and in BPDCN. We compared the expression of EC in BPDCN to that in leukemia cutis (LC) and cutaneous lupus erythematosus (CLE), the latter typically featuring pDC activation. In BPDCN, we also assessed the immunomodulatory activity of malignant pDCs through the expression of several type I interferon (IFN-I) signaling effectors and downstream targets, PD-L1/CD274, and determined the extent of tumor infiltration by CD8-expressing T cells. In reactive lymph nodes and tonsils, pDCs expressed EC, whereas no reactivity was observed in bone marrow pDCs. BPDCN showed EC expression in the malignant pDCs in the vast majority of cutaneous (31/33 cases, 94%), nodal, and spleen localizations (3/3 cases, 100%), whereas it was more variable in the bone marrow (5/13, 38,5%), where tumor cells expressed EC similarly to the skin counterpart in 4 cases and differently in other 4. Notably, EC was undetectable in LC (n=30) and in juxta-epidermal pDCs in CLE (n=31). Contrary to CLE showing robust expression of IFN-I-induced proteins MX1 and ISG5 in 20/23 cases (87%), and STAT1 phosphorylation, BPDCN biopsies showed inconsistent levels of these proteins in most cases (85%). Expression of IFN-I-induced genes, IFI27, IFIT1, ISG15, RSAD2, and SIGLEC1, was also significantly (P<0.05) lower in BPDCN as compared with CLE. In BPDCN, a significantly blunted IFN-I response correlated with a poor CD8+T-cell infiltration and the lack of PD-L1/CD274 expression by the tumor cells. This study identifies EC as a novel pDC marker of diagnostic relevance in BPDCN. The results propose a scenario whereby malignant pDCs through EC-driven signaling promote the blunting of IFN-I signaling and, thereby, the establishment of a poorly immunogenic tumor microenvironment.
Expanding the Spectrum of EWSR1-NFATC2-rearranged Benign Tumors
Authors: Ong Sheena L.M. , Lam Suk Wai , van den Akker Brendy E.W.M. , Kroon Herman M. , Briaire-de Bruijn Inge H. , Cleven Arjen H.G. , Savci-Heijink Dilara C. , Cleton-Jansen Anne-Marie , Baumhoer Daniel , Szuhai Karoly , Bovée Judith V.M.G.
Published: June 2021

A simple bone cyst (SBC) is a cystic bone lesion predominantly affecting young males. The cyst is lined by a fibrous membrane and filled with serosanguinous fluid. EWSR1/FUS-NFATC2 rearrangements were recently identified in SBC. We here report exactly the same rearrangement in 3 lesions diagnosed as vascular malformations of 2 elderly patients. In total, through Archer FusionPlex, fluorescence in situ hybridization and/or reverse transcriptase-polymerase chain reaction the EWSR1-NFATC2 rearrangement was identified in 6 of 9 SBC, 3 of 12 benign vascular tumors, and none of 5 aneurysmal bone cyst lacking USP6 fusion. Using fluorescence in situ hybridization, it was apparent that amplification of the fusion, as seen in EWSR1-NFATC2 round cell sarcomas, was absent, and that in the vascular tumors the fusion was present both in the lining cells as well as in the surrounding spindle cells. Of note, not all of the spaces in the vascular malformations were lined by endothelial cells. Aggrecan was positive in all cases but was not specific. NKX2-2 and NKX3-1 staining were negative in all cases. Thus, even though the overlap between the 2 entities is limited to the presence of few thick-walled cysts lacking endothelial lining in the benign vascular malformations, the spectrum of benign tumors containing NFATC2 fusions should be expanded and contains not only SBC in the young, but also vascular malformation/hemangioma in elderly patients.
Pseudoendocrine Sarcoma
Authors: Papke David J. , Dickson Brendan C. , Sholl Lynette , Fletcher Christopher D.M.
Published: June 2021

The number of recognized epithelioid soft tissue neoplasms continues to increase and includes epithelioid schwannoma, sclerosing epithelioid fibrosarcoma, and emerging entities such as sarcomas with GLI1 alterations. Here, we describe 23 cases of a previously unrecognized entity, provisionally termed “pseudoendocrine sarcoma.” Pseudoendocrine sarcoma is a rare, distinctive tumor of uncertain lineage with a predilection for paravertebral soft tissue in older adults. Fifteen patients (65%) were male and 8 were female. Age at presentation ranged from 29 to 78 years (median: 62 y). Nineteen tumors (83%) occurred in truncal locations, including 15 tumors (65%) in paravertebral soft tissue; other locations included the posterior head (2 tumors), thigh (1), and orbit (1). Tumor size ranged from 2 to 19 cm (median: 6.35 cm). Pseudoendocrine sarcoma is composed of sheets, trabeculae, and nests of epithelioid or ovoid cells with indistinct borders, palely eosinophilic cytoplasm, and highly monomorphic, round nuclei with speckled chromatin. Pseudoglandular architecture was at least focally present in 16 tumors (70%), large extracellular hyaline globules were identified in 12 tumors (52%), and psammomatous calcifications were present in 8 (35%). Metaplastic ossification was identified in 2 tumors, and myxoid stroma was present in 1. Lymphovascular invasion was present in 5 of 18 tumors (28%). Immunohistochemistry demonstrated that most tumors showed nuclear positivity for β-catenin (20/21 tumors; 95%), and some showed at least focal positivity for S-100 (9/22; 41%), desmin (3/8; 38%), or CD34 (2/8; 25%). All tumors were negative for neuroendocrine and epithelial markers, including synaptophysin (21 tumors), chromogranin (19), INSM1 (4), pan-K (16), CAM5.2 (13), AE1/AE3 (6), epithelial membrane antigen (20), and E-cadherin (13). DNA sequencing detected CTNNB1 point mutations in all 6 sequenced tumors: D32H, S33C, S33F, S37A, S37C, and S37F. RNA sequencing was negative for gene fusions in all 6 sequenced tumors. Clinical follow-up was available for 17 patients (74%; range: 4 mo to 20 y; median: 3.5 y), including 14 patients with >1 year of follow-up. Six of 14 patients with long-term follow-up experienced local recurrence (43%, at intervals of 3 to 6 y). One tumor showed a local lymph node metastasis within the primary excision specimen, and 3 patients developed distant lung metastases (21%). No patient died of the disease as yet. Despite its bland morphology and resemblance to the well-differentiated neuroendocrine tumor, pseudoendocrine sarcoma is best considered an intermediate-grade sarcoma, given its pathologic characteristics and clinical behavior.