bluuebunny/crossref_metadata_2025 huggingface dataset:
Fluid Balance and Ventilator-Associated Events Among Patients Admitted to ICUs in China: A Nested Case-Control Study*
Authors: Wang Wen , Zhu Shichao , He Qiao , Wang Mingqi , Kang Yan , Zhang Rui , Ji Peng , Zou Kang , Klompas Michael , Zong Zhiyong , Sun Xin
Published: August 2021

OBJECTIVES:

Fluid therapy is an important component of intensive care management, however, optimal fluid management is unknown. The relationship between fluid balance and ventilator-associated events has not been well established. This study investigated the dose-response relationship between fluid balance and ventilator-associated events.

DESIGN:

Nested case-control study.

SETTING:

The study was based on a well-established, research-oriented registry of healthcare-associated infections at ICUs of West China Hospital system (Chengdu, China).

PATIENTS:

A total of 1,528 ventilator-associated event cases with 3,038 matched controls, who consistently underwent mechanical ventilation for at least 4 days from April 1, 2015, to December 31, 2018, were included.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

We calculated cumulative fluid balance within 4 days prior to ventilator-associated event occurrence. A weighted Cox proportional hazards model with restricted cubic splines was used to evaluate the dose-response relationship. A nonlinear relationship between fluid balance and all three tiers of ventilator-associated events, patients with fluid balance between –1 and 0 L had the lowest risk (p < 0.05 for nonlinear test). The risk of ventilator-associated event was significantly higher in patients with positive fluid balance (4 d cumulative fluid balance: 1 L: 1.19; 3 L: 1.92; 5 L: 2.58; 7 L: 3.24), but not in those with negative fluid balance (–5 L: 1.34; –3 L: 1.14; –1 L: 0.98).

CONCLUSIONS:

There was nonlinear relationship between fluid balance and all three tiers of ventilator-associated event, with an fluid balance between –1 and 0 L corresponding to the lowest risk. Positive but not negative fluid balance increased the risk of ventilator-associated events, with higher positive fluid balance more likely to lead to ventilator-associated events.
Safety Profile of Thread Lifts on the Face and Neck: An Evidence-Based Systematic Review
Authors: Pham Christine T. , Chu Sherman , Foulad Delila P. , Mesinkovska Natasha A.
Published: August 2021

BACKGROUND

“Thread lifting” has quickly gained popularity as a minimally invasive treatment for facial rejuvenation. However, the effectiveness is questionable, and the safety and adverse effects are often not discussed.

OBJECTIVE

To identify and discuss the adverse effects associated with various types of threads.

MATERIALS AND METHODS

Studies describing the use of thread lifts were identified using a PubMed search. Inclusion criteria included studies in which barbed and nonbarbed threads were used for the face and neck.

RESULTS

Fifty-nine articles consisting of 14,222 patients (14,134 barbed, 81 nonbarbed, and 7 combined cases) were included. The most common side effects overall were facial asymmetry (n = 6,143), edema/tumefaction (n = 453), and ecchymosis (n = 407). Serious adverse effects were rare and consisted of paresthesias, alopecia, and injuries to vessels/glands. Most adverse effects were transient and self-resolving, with the exception of contour irregularities, injuries to vessels/glands, infections, and inflammatory reactions.

CONCLUSION

Most side effects associated with threads were self-resolving, whereas more serious cases subsided with treatment. Future studies are critical to further determine whether thread lifting provides long-lasting, safe, and satisfying results.
Anatomical Landmarks of the Beard Region
Authors: Durgun Ufuk , Ergün Selma Sönmez , Gayretli Özcan , Kelahmetoğlu Osman , Çamli Mehmet F.
Published: August 2021

BACKGROUND

With recent advancements in hair restoration techniques, hair can be transplanted into nonscalp areas, such as the beard region, and the result looks natural. Although scalp zones and landmarks have been available for planning and designing the hairline, landmarks that will determine the beard lines are yet to be presented and made known for clinical practice.

OBJECTIVE

This study aimed to determine and analyze the beard lines and anatomical boundaries of the beard area to provide a more natural restoration/reconstruction appearance.

MATERIALS AND METHODS

The soft-tissue landmarks of the face that will enable physicians to create natural-looking beard lines were determined. Based on these important points, beard lines were analyzed with anthropometric methods by using the photographs of 32 male volunteers.

RESULTS

The ideal upper and lower beard lines and the anatomical boundaries of the beard area were determined using these landmarks.

CONCLUSION

These lines ensure that beard restoration/reconstruction provides a more natural appearance.
Weight Change and the Onset of Cardiovascular Diseases: Emulating Trials Using Electronic Health Records
Authors: Katsoulis Michail , Stavola Bianca D. , Diaz-Ordaz Karla , Gomes Manuel , Lai Alvina , Lagiou Pagona , Wannamethee Goya , Tsilidis Konstantinos , Lumbers R. Thomas , Denaxas Spiros , Banerjee Amitava , Parisinos Constantinos A. , Batterham Rachel , Patel Riyaz , Langenberg Claudia , Hemingway Harry
Published: August 2021

Background:

Cross-sectional measures of body mass index (BMI) are associated with cardiovascular disease (CVD) incidence, but less is known about whether weight change affects the risk of CVD.

Methods:

We estimated the effect of 2-y weight change interventions on 7-y risk of CVD (CVD death, myocardial infarction, stroke, hospitalization from coronary heart disease, and heart failure) by emulating hypothetical interventions using electronic health records. We identified 138,567 individuals with 45–69 years of age without chronic disease in England from 1998 to 2016. We performed pooled logistic regression, using inverse-probability weighting to adjust for baseline and time-varying confounders. We categorized each individual into a weight loss, maintenance, or gain group.

Results:

Among those of normal weight, both weight loss [risk difference (RD) vs. weight maintenance = 1.5% (0.3% to 3.0%)] and gain [RD = 1.3% (0.5% to 2.2%)] were associated with increased risk for CVD compared with weight maintenance. Among overweight individuals, we observed moderately higher risk of CVD in both the weight loss [RD = 0.7% (−0.2% to 1.7%)] and the weight gain group [RD = 0.7% (−0.1% to 1.7%)], compared with maintenance. In the obese, those losing weight showed lower risk of coronary heart disease [RD = −1.4% (−2.4% to −0.6%)] but not of stroke. When we assumed that chronic disease occurred 1–3 years before the recorded date, estimates for weight loss and gain were attenuated among overweight individuals; estimates for loss were lower among obese individuals.

Conclusion:

Among individuals with obesity, the weight-loss group had a lower risk of coronary heart disease but not of stroke. Weight gain was associated with increased risk of CVD across BMI groups. See video abstract at, http://links.lww.com/EDE/B838.
CLINICAL FEATURES AND SURGICAL OUTCOMES OF ENCIRCLING SCLERAL BUCKLING WITH CRYOTHERAPY IN FAMILIAL EXUDATIVE VITREORETINOPATHY-ASSOCIATED RHEGMATOGENOUS RETINAL DETACHMENT
Authors: Huang Liuhui , Liang Tingyi , Lyu Jiao , Jin Haiying , Zhao Peiquan
Published: August 2021

Purpose:

To report the clinical features and surgical outcomes of encircling scleral buckling surgery with cryotherapy in familial exudative vitreoretinopathy (FEVR) patients with rhegmatogenous RD.

Methods:

This study was a consecutive, retrospective interventional case series. Clinical features, including the FEVR stage, proliferative vitreoretinopathy grade, range of RD and degeneration, and presence of retinal breaks, and surgical outcomes, including the success rate, best-corrected visual acuity, and myopic shift, were analyzed.

Results:

There were 16 eyes with Stage 3A FEVR and eight eyes with Stage 4A FEVR. 13 eyes had Grade A proliferative vitreoretinopathy, and 11 eyes had Grade B proliferative vitreoretinopathy. Retinal reattachment was achieved in 22 of 24 eyes (91.67%) with FEVR-rhegmatogenous RD after initial encircling scleral buckling surgery. The best-corrected visual acuity improved from a mean of 1.08 ± 0.86 logarithm of the minimum angle of resolution preoperatively to 0.45 ± 0.41 logarithm of the minimum angle of resolution postoperatively (P < 0.01). A myopic shift of −2.39 ± 1.38 (range, −1 to −6) diopter (P < 0.01) was observed. The mean follow-up period was 34.5 ± 27.7 (range, 7–104) months.

Conclusion:

Our study clarified the efficacy of encircling scleral buckling surgery with cryotherapy in FEVR-rhegmatogenous RD with Stage 3A or 4A FEVR and Grade A or B proliferative vitreoretinopathy, especially in patients with multiple retinal holes.
IMPACT OF FLUID COMPARTMENTS ON FUNCTIONAL OUTCOMES FOR PATIENTS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION
Authors: Chaudhary Varun , Matonti Frédéric , Zarranz-Ventura Javier , Stewart Michael W.
Published: August 2021

Purpose:

Understanding the impact of fluid in different retinal compartments is critical to developing treatment paradigms that optimize visual acuity and reduce treatment burden in neovascular age-related macular degeneration. This systematic review aimed to determine the impact of persistent/new subretinal fluid, intraretinal fluid, and subretinal pigment epithelial fluid on visual acuity over 1 year of treatment.

Methods:

Publication eligibility and data extraction were conducted according to Cochrane methods: 27 of the 1,797 screened records were eligible.

Results:

Intraretinal fluid negatively affected visual acuity at baseline and throughout treatment, with foveal intraretinal fluid associated with lower visual acuity than extrafoveal intraretinal fluid. Some studies found that subretinal fluid (particularly subfoveal) was associated with higher visual acuity at Year 1 and longer term, and others suggested subretinal fluid did not affect visual acuity at Years 1 and 2. Data on the effects of subretinal pigment epithelial fluid were scarce, and consensus was not reached. Few studies reported numbers of injections associated with fluid status.

Conclusion:

To optimally manage neovascular age-related macular degeneration, clinicians should understand the impact of fluid compartments on visual acuity. After initial treatment, antivascular endothelial growth factor regimens that tolerate stable subretinal fluid (if visual acuity is stable/improved) but not intraretinal fluid may enable patients to achieve their best possible visual acuity. Confirmatory studies are required to validate these findings.
COVID-19–associated Acute Disseminated Encephalomyelitis–like Disease in 2 Children
Authors: Akçay Nihal , Bektaş Gonca , Menentoğlu Mehmet Emin , Oğur Mustafa , Sofuoğlu Ayşe İrem , Palabiyik Figen Bakirtaş , Şevketoğlu Esra
Published: August 2021

Background:

The coronavirus disease 2019 pandemic was caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although the predominant clinical presentation is a respiratory disease, neurologic manifestations are being recognized increasingly.

Case Report:

We report 2 children 9 years of age who developed acute disseminated encephalomyelitis-like disease associated with SARS-CoV-2. Seizures and encephalopathy were the main central nervous system symptoms. The cerebrospinal fluid analysis performed within the first week of disease onset showed elevated protein in both children with normal cell count and no evidence of infection including negative SARS-CoV-2 by antibody and polymerase chain reaction. Brain magnetic resonance imaging revealed T2A, fluid-attenuated inversion recovery cortical and subcortical hyperintensity without restricted diffusion consistent with acute disseminated encephalomyelitis–like disease. They received methylprednisolone followed by therapeutic plasma exchange. One of them showed complete clinical improvement and resolution in magnetic resonance imaging findings. The other developed laminar necrosis in brain magnetic resonance imaging and showed significant clinical improvement after therapeutic plasma exchange. He was positive for positive SARS-CoV-2 antibody in cerebrospinal fluid on day 55 of admission. They were both positive for SARS-CoV-2 antibodies in serum after 2 weeks.

Conclusions:

Our two cases highlight the occurrence of acute disseminated encephalomyelitis–like disease as a postinfectious/immune-mediated complication of SARS-CoV-2 infection.
Chronic Obstructive Pulmonary Disease is a Risk Factor for Sensorineural Hearing Loss: A US Population Study
Authors: Sharma Rahul K. , Chern Alexander , Begasse de Dhaem Olivia , Golub Justin S. , Lalwani Anil K.
Published: August 2021

Objectives:

The goal of this study is to determine if chronic obstructive pulmonary disease (COPD) is associated with sensorineural hearing loss (SNHL) in a national database.

Study Design:

Cross-sectional study.

Setting:

National sample of the United States population.

Patients:

Adults with audiometric and spirometry data from the National Health and Nutrition Examination Study (NHANES) database.

Interventions:

None.

Methods:

A total of 2,464 adults with spirometry and audiometry data from the NHANES database (2009–2012) were studied. Outcome measures included hearing, measured by high-frequency pure tone average (HFPTA; 3, 4, 6, 8 kHz) and low-frequency pure tone average (LFPTA; .5, 1, 2 kHz) frequencies. SNHL was defined as a HFPTA or LFPTA threshold more than 25 decibels (dB) in the better ear. Multivariable regression analyses explored the association between hearing loss and COPD.

Results:

The prevalence of COPD was 19.8% in individuals with SNHL in the better ear and 4.7% in individuals with normal hearing (p < 0.001). Presence of COPD was associated with elevated hearing thresholds (worse hearing) at each individual frequency. The presence of COPD was independently associated with a 3.29 dB (95% CI: 1.48, 5.09) increase in HFPTA (p < 0.001), and 2.32 dB (1.13, 3.50) increase in LFPTA (p < 0.001) after controlling for medical, social, and environmental covariates. The presence of COPD was independently associated with a 1.85-fold (1.12, 3.06) increased odds of isolated low-frequency SNHL (p = 0.017).

Conclusions:

COPD was independently associated with sensorineural hearing loss after controlling for multiple confounding factors. These results contribute to the evidence that COPD and pulmonary dysfunction can be comorbid with hearing decline.
Effect of community-based nutritional counseling intervention on children's eating habits
Authors: Dike Ibiwari Caroline , Ebizie Elizabeth N. , Chukwuone Chiamaka Adaobi , Ejiofor Ngozi Juliana , Anowai Chinwe Christiana , Ogbonnaya Ezeda Kalu , Ugwu Eunice Ifenyinwa , Nkechinyere Udeagha Scholastica , Chigbu Eberechukwu Francisca , Ezeaku Margret N. , Nnadi Grace Chinyere , Ihuoma Ekomaru Chinyere , Gera Nguvan Patience , Chikwendu Justina Ndirika
Published: August 2021

Aim:

This study aimed to assess the outcome of community-based nutritional counseling interventions on eating habits of rural-dwelling children.

Methods:

A group-randomized trial design was used in this study. A total of 108 rural-dwelling children from a community in the Enugu North agricultural zone, Enugu State, who participated in the study. The children were randomly assigned to 2 groups: the treatment group (n = 54) and the no-treatment control group (n = 54). The child eating behavior questionnaire was used for data collection. Parents of the participating children within each study group completed the child eating behavior questionnaire at 3 time points. The data collected were analyzed using an independent sample t test at a probability level of .05.

Result:

The outcome of the study showed that the children's eating habits in the treatment group improved positively following the community-based nutritional counseling intervention. The positive gain from exposure to the community-based nutritional counseling intervention program was sustained during follow-up for children in the treatment group compared with the no-treatment group.

Conclusion:

The community-based nutrition counseling intervention carried out among children in rural communities had a positive adjustment in children's eating habits. The intervention requires the constant collaboration of professional childhood educators, caregivers, home economists, school staff, healthcare specialists, families, and the children themselves. Furthermore, there is a need for future long-term evaluations of the effects of community-based nutritional counseling interventions on children's nutrition and eating habits.
Psychological nursing intervention improve the mental health status of young patients with lung cancer surgery during the perioperative period
Authors: Zhao Li , Ma Lina , Chen Xiaomin , Liu Zhuo
Published: August 2021

Background:

To explore the effects of psychological nursing on improving the mental health status of young patients with lung cancer surgery during the perioperative period.

Methods:

seventy-eight young patients (From February 2018 to February 2019) underwent lung cancer operation were selected. All these patients were randomly allocated to intervention group and control group. The patients in the control group were treated with general routine care. The patients in the intervention group were treated with a comprehensive and systematic family participation psychological nursing. The mental health status of the patients in the 2 groups were compared and analyzed.

Results:

The self-rating anxiety scale scores and self-rating depression scale scores of patients were significantly reduced in the intervention group compared with the control group (P < .05). The scores of somatization, obsessive symptoms, interpersonal relationship, depression, anxiety, hostile, phobic neurosis, stubborn, paranoia and psychosis were also significantly reduced in the intervention group compared with the control group (P < .05).

Conclusion:

the comprehensive and systematic psychological nursing intervention improved the mental health status of young patients with lung cancer surgery during the perioperative period.
Recovery of an injured arcuate fasciculus via transcallosal fiber in a stroke patient
Authors: Jang Sung Ho , Seo Jeong Pyo , Kwon Young Hyeon
Published: August 2021

Rationale:

We report on a patient whose arcuate fasciculus (AF) and corticobulbar tract (CBT) recovered following an infarct in the middle cerebral artery (MCA) territory, demonstrated on serial diffusion tensor tractography (DTT).

Patient concerns:

The patient showed moderate conduction aphasia on the Western Aphasia Battery with an aphasia quotient of 46.5‰ (spontaneous speech: 35.0‰, auditory comprehension: 36.0‰, and naming: 53.1‰) at 1 month after onset. His aphasia improved with an aphasia quotient of 49‰ (spontaneous speech: 71.0‰, auditory comprehension: 52.0‰, and naming: 59.0‰) at 10 months after onset.

Diagnosis:

A 44-year-old right-handed male patient presented with aphasia and quadriplegia, which occurred at the onset of an infarct in the left MCA territory.

Intervention:

Diffusion tensor imaging data were acquired twice (1 month and 10 months after onset).

Outcomes:

On one-month DTT, the discontinuation of the left AF and severe narrowing of the right CBT were observed. However, on ten-month DTT, the left AF was connected to the opposite AF by a new tract that passed through the splenium of corpus callosum, and the right CBT had become thicker.

Lessons:

We believe that our results suggest a recovery mechanism of injured AF and CBT in stroke patients.
Burkitt Lymphoma After Cardiac Transplantation: Therapeutic Considerations
Authors: El-Atoum Batool , Williams Margaret , Molina Kimberly , Orjuela-Grimm Manuela A. , Prince Jeffrey , Afify Zeinab
Published: August 2021

Postsolid organ transplant Burkitt lymphoma (PSOT-BL) is rare but more aggressive than other post-transplant lymphoproliferative disorders (PTLD). Little is known about optimal treatment and outcome of postcardiac transplant Burkitt lymphoma (BL). We report an 8-year-old boy with a history of heart transplant who developed Epstein-Barr virus positive, late-onset PSOT-BL. He was successfully treated with BL specific chemoimmunotherapy and cessation of baseline immunosuppression. In this pediatric case of PSOT-BL, the use of standard intensive pediatric based chemoimmunotherapy regimen without modifications was feasible, well tolerated and resulted in complete remission. Long-term toxicities need further study.
Clinical Utility of Total Oxidative Stress and Total Antioxidant Capacity in Childhood Febrile Neutropenia
Authors: Kara Buket , Akyurek Fikret , Akbas Hilal , Ertan Kubra , Vatansev Husamettin , Koksal Yavuz
Published: August 2021

The aim is to determine the oxidative status of children with febrile neutropenia (FEN). Blood samples were collected to determine the total antioxidant capacity (TAC) and total oxidative status (TOS) of healthy children (once) and children with FEN after 0, 48, and 96 hours. Eighteen patients with FEN were evaluated. The baseline TAC level of patients was significantly higher than that of the controls (P<0.0001). The TAC levels of patients with FEN with and without antibiotic modification were higher than those of the controls (P=0.002 and 0.02, respectively). The TAC levels of the patients with FEN with antibiotic modification were lower than those of the patients without antibiotic modification (P=0.0224). The oxidative stress index (OSI), calculated TOS/TAS, value of the children with FEN was lower than that of the controls (P<0.0001). The OSI values of the patients with FEN with and without antibiotic modification were lower than those of the control group (P=0.001 and <0.0001, respectively). The TAC values of the patients with antibiotic modification were higher than those of the patients without antibiotic modification (P=0.02). In conclusion, the oxidative status of the children with FEN was affected, and it can give information about the follow-up of FEN.
Sampling Multiple Catheter Lumens to Improve Detection of Bloodstream Infection in Pediatric Oncology Patients
Authors: Rider Erica , Ligon John A. , Voskertchian Annie , Milstone Aaron M. , Toltzis Philip
Published: August 2021

Current guidelines recommend sampling each central-access lumen during the initial evaluation of febrile pediatric oncology patients. We investigated this recommendation’s validity at centers implementing a diagnostic stewardship program to reduce blood cultures in critically ill children. Among 146 oncology patients admitted to the intensive care unit, there were 34 eligible blood culture-sets. Eleven (34%) sets yielded discordant results, most commonly cultivating a likely pathogen from one lumen and no growth from another. As hospitals move toward reducing testing overuse, these results emphasize the continued importance of culturing each central-access lumen to optimize the detection of bacteremia in the initial evaluation of critically ill pediatric oncology patients.
Caring for the Mental Health of Youth and Families
Authors: Bonham Elizabeth , Kwasky Andrea
Published: August 2021

Purpose/Objectives

Children in our nation are experiencing the social, emotional, and physical impacts of an unprecedented time in history. Advanced practice nurses prepared as psychiatric clinical nurse specialists and nurse practitioners bring therapeutic interventions, psychopharmacologic management, and systems thinking to clinical environments of care. Insight into the mental health of youth and families and how clinical nurse specialists may provide solutions for forthcoming challenges is discussed.

Description of the Project/Program

Barriers to mental healthcare such as the invisibility of nurses at state and federal levels must be eradicated to mitigate the mental health challenges that youth, families, and communities endure. Contemporary issues such as effects of social media, stigma, and suicide present burdens that can be moderated through nursing interventions.

Outcome

The psychiatric clinical nurse specialist provides evidence and community-based nursing interventions that, through early identification and advocacy, contribute to positive mental health outcomes for youth and families.

Conclusion

The need for well-educated advanced practice nurses has never been greater for our vulnerable populations of children, adolescents, and families with mental health challenges. Nurse-delivered programs demonstrate that interventions are necessary for communication, psychoeducation, and prevention of consequences from unacknowledged social media, stigma, and suicide problems.
Telomere Shortening and Fusions: A Link to Aneuploidy in Early Human Embryo Development
Authors: Kohlrausch Fabiana B. , Wang Fang , Chamani Isaac , Keefe David L.
Published: August 2021

Importance

It is known that oocytes undergo aging that is caused by exposure to an aged ovarian microenvironment. Telomere length in mouse and bovine oocytes declines with age, and age-associated telomere shortening in oocytes is considered a sign of poor development competency. Women with advanced age undergoing assisted reproductive technologies have poor outcomes because of increasing aneuploidy rates with age. Research has shown that aneuploidy is associated with DNA damage, reactive oxygen species, and telomere dysfunction.

Objective

In this review, we focus on the possible relationship between telomere dysfunction and aneuploidy in human early embryo development and several reproductive and perinatal outcomes, discussing the mechanism of aneuploidy caused by telomere shortening and fusion in human embryos.

Evidence Acquisition

We reviewed the current literature evidence concerning telomere dysfunction and aneuploidy in early human embryo development.

Results

Shorter telomeres in oocytes, leukocytes, and granulosa cells, related to aging in women, were associated with recurrent miscarriage, trisomy 21, ovarian insufficiency, and decreasing chance of in vitro fertilization success. Telomere length and telomerase activity in embryos have been related to the common genomic instability at the cleavage stage of human development. Complications of assisted reproductive technology pregnancies, such as miscarriage, birth defects, preterm births, and intrauterine growth restriction, also might result from telomere shortening as observed in oocytes, polar body, granulosa cells, and embryos.

Conclusions and Relevance

Telomere length clearly plays an important role in the development of the embryo and fetus, and the abnormal shortening of telomeres is likely involved in embryo loss during early human development. However, telomere fusion studies have yet to be performed in early human development.

Target Audience

Obstetricians and gynecologists, family physicians

Learning Objectives

After completing this activity, the learner should be better able to identify telomere dysfunction; describe telomere length and aneuploidy during early development of preimplantation embryos in humans; and explain the possible effects of telomere fusions during early development of preimplantation embryos in humans.
HPV-negative Squamous Cell Carcinomas of the Cervix With Special Focus on Intraepithelial Precursor Lesions
Authors: Regauer Sigrid , Reich Olaf , Kashofer Karl
Published: August 2021

Recently, the World Health Organization (WHO) recognized human papilloma virus (HPV)-independent invasive cervical squamous cell carcinoma (SCC) without recognizing the existence of precursor lesions. This is a detailed characterization of 3 preinvasive lesions and 6 invasive SCC negative for HPV-DNA (32 genotypes), HPV-mRNA (14 genotypes) and genomic HPV sequencing. We evaluated histologic features, expression of p16ink4a, p53, CK7, and CK17, aberrations in 50 cancer genes and chromosomal copy number variations. HPV-negative preinvasive lesions were extensive basaloid or highly differentiated keratinizing intraepithelial proliferations of 3 to 20 cell layers thickness, partly with prominent cervical gland involvement. Overall, 2/3 intraepithelial lesions and the in situ component of 1/6 SCC showed p16ink4a block staining, while 1/6 in situ component revealed heterogenous p16ink4a staining. All invasive components of keratinizing SCC were p16ink4a-negative. Preinvasive and invasive SCC showed inconsistent CK7 and CK17 staining. Nuclear p53 overexpression was restricted to the TP53 gene mutated SCC. The highly vascularized peritumoral stroma showed a dense inflammatory infiltrate including plasma cells and intratumoral and peritumoral eosinophilic granulocytes. Inconsistent somatic gene mutations (PIK3CA, STK11, TP53, SMARC2B, and GNAS) occurred predominantly in nonhotspot locations at low mutational frequency in 3/6 SCC. Consistent aberrations included the pathogenic (angiogenic) germline polymorphism Q472H in the KDR gene (7/9 patients), and chromosome 3q gains (4/9 patients). In conclusion, HPV-negative intraepithelial cervical precancerous lesions exist, either as highly differentiated keratinized intraepithelial proliferations reminiscent of differentiated vulvar intraepithelial neoplasia, or undifferentiated basaloid intraepithelial lesions with occasional p16ink4a block staining resembling high-grade squamous intraepithelial lesion. Gains of chromosome 3q, angiogenic germline variants the inflammatory infiltrate may contribute to progression of HPV-negative cervical carcinogenesis.
Integrating New Therapies for Chronic Lymphocytic Leukemia
Authors: Burger Jan A.
Published: August 2021

Over the last 2 decades, treatment of chronic lymphocytic leukemia (CLL) therapy has drastically changed, resulting in greatly improved survival and treatment tolerance with current targeted therapies. First, the transition from chemotherapy (alkylating agents, nucleoside analogs) to chemoimmunotherapy with the addition of anti-CD20 antibodies resulted in deeper and more complete remissions, with an improvement in progression-free and overall survival. Over the last few years, chemoimmunotherapy has gradually been replaced by new targeted agents, based on further improvement in survival, especially in patients with high-risk CLL, and fewer adverse effects, that is, a lack of myelosuppression and lack of DNA damage and associated risk of secondary acute myeloid leukemia/myelodysplastic syndrome. The most active targeted treatments for CLL patients are the kinase inhibitors, which inhibit signaling of surface receptors, especially the B-cell antigen receptor, and the BCL-2 antagonist venetoclax. Among the kinase inhibitors, Bruton tyrosine kinase inhibitors are highly effective and generally well-tolerated and induce durable responses in the vast majority of patients. PI3 kinase inhibitors are alternatives for patients with intolerance to Bruton tyrosine kinase inhibitors. This review discusses the rationale for the transition from chemotherapy–based treatment to the novel agents, the activity, adverse effects, sequencing, and combinations of the novel agents and provides an outlook into future CLL therapy for the next decade.
An Outcomes Review of 330 Sternal Wound Reconstructions: Timing of Closure Does Make a Difference
Authors: Levy Adam S. , Altchek Chloe L. , McMillen Elizabeth M. , Karinja Sarah J. , Tiao Jonathan R. , Smith Craig R. , Ascherman Jeffrey A.
Published: August 2021

Background:

Sternal wound infection and dehiscence following cardiac surgery remain difficult clinical problems with high morbidity. Older classification systems regarding timing to reconstruction do not take into account recent improvements in critical care, wound vacuum-assisted closure use, or next-generation antibiotic therapies, which may prolong time to reconstruction.

Methods:

Records of patients undergoing sternal wound reconstruction performed by the senior author (J.A.A.) from 1996 to 2018 at a high-volume cardiac surgery center were reviewed. Indications included sternal wound infection or dehiscence. All patients underwent single-stage removal of hardware, débridement, and flap closure. Patients were divided into two groups based on timing of wound closure after cardiac surgery: less than 30 days or greater than or equal to 30 days.

Results:

Of the 505 patients identified during the study period, 330 had sufficient data for analysis. Mean time to sternal wound surgery was 15.7 days in the early group compared to 64.4 days (p < 0.01) beyond 30 days. Postdébridement cultures were positive in 72 percent versus 62.5 percent of patients (p = 0.11), whereas rates of postoperative infection were significantly higher in the delayed group: 1.9 percent versus 9.5 percent (p < 0.01). Partial wound dehiscence rates were also higher after 30 days (1.9 percent versus 11.3 percent; p < 0.01), whereas total length of stay was decreased. Use of wound vacuum-assisted closure was significantly associated with reconstruction beyond 30 days (p < 0.01).

Conclusions:

Although performing sternal wound reconstruction more than 30 days after initial cardiac surgery was associated with a shorter overall hospital length of stay and higher extubation rates in the operating room, these patients also had elevated postoperative infection and wound complication rates. The authors thus recommend not delaying definitive surgical reconstruction when possible.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Obstructive and Nonobstructive Hypertrophic Cardiomyopathy
Authors: Palmisano Vitanio , Cossa Stefano , Esposito Antonio , Bassareo Pier P. , Porcu Michele , Cau Riccardo , Pontone Gianluca , Suri Jasjit S. , Saba Luca
Published: August 2021

Purpose:

To evaluate any significant differences in myocardial strain between hypertrophic obstructive cardiomyopathy (HOCM) and nonobstructive ones (HNCM), as assessed by cardiac magnetic resonance feature tracking (CMR-FT).

Materials and Methods:

A total of 17 patients (mean age: 54±14 y) with echocardiographic diagnosis of HOCM (left ventricular outflow tract obstruction peak gradient ≥30 mm Hg), 19 patients (mean age: 49±16 y) with HNCM (peak gradient <30 mm Hg), and 18 age-matched and gender-matched healthy controls (mean age: 42±14 y). All patients underwent cardiac MRI with SSFP-cine to assess left ventricular global and segmental strain analysis by CMR-FT. Late gadolinium enhancement (LGE) sequences were used for semiautomatic quantification of LGE volume, mass, and percentage.

Results:

The magnitude of global radial, circumferential, and longitudinal strain as well as strain rate were significantly lower in all patients in comparison to controls (P<0.001), except for radial and circumferential strain between HOCM and controls (P=0.270; P=0.154). The latter strain parameters were significantly higher in HOCM than HNCM (radial strain: 31.67±7.55 vs. 21.26±7.10, P<0.001; circumferential strain: −17.94±2.78 vs. −13.46±3.42, P<0.001). Radial and circumferential strain and circumferential diastolic strain rate were higher in mid-anterior (P<0.001), mid-anteroseptal (P<0.001), and all apical segments (P<0.005) between the 2 groups of patients. Moreover, longitudinal strain was higher only in apical segments in HOCM (P<0.02).

Conclusions:

HOCM patients showed higher left ventricular apical, mid-anterior, and mid-anteroseptal strain parameters compared with HNCM. These differences were independent of corresponding segmental thickness and LGE amount.
Gender Affirming Mastectomy Improves Quality of Life in Transmasculine Patients
Authors: Lane Megan , Kirsch Michael J. , Sluiter Emily C. , Svientek Shelby R. , Hamill Jennifer B. , Morrison Shane D. , Ives Graham C. , Alman Emma , Gilman Robert H. , Kuzon William M. , Cederna Paul S. , Wilkins Edwin G.
Published: August 2021

Objective:

To determine the impact of gender-affirming mastectomy on depression, anxiety, and body image.

Background:

There are many cross-sectional and ad-hoc studies demonstrating the benefits of gender-affirming surgery. There are few prospective investigations of patient-reported outcomes in gender-affirming surgery using validated instruments.

Methods:

In this prospective study, patients presenting to the University of Michigan for gender-affirming Mastectomy were surveyed preoperatively and 6-months postoperatively. Primary outcomes were patient-reported measurements of anxiety measured by General Anxiety Disorder-7, depression measured by Patient Health Questionnaire-9, body image measured by BODY-Q and Body Image Quality of Life Index, psychosocial and sexual functioning measured by BREAST-Q, and satisfaction with decision measured by BREAST-Q. Linear regression analysis was used to control for presence of complication and existing history of mental health conditions.

Results:

A total of 70 patients completed the study. The average age of participants was 26.7. The mean Patient Health Questionnaire-9 score pre-operatively was 7.8 and postoperatively was 5.4 (P=0.001). The mean preoperative and postoperative General Anxiety Disorder-7 scores were 7.6 and 4.6, respectively (P<0.001). There were significant improvements in both psychosocial (35 to 79.2, P<0.001) and sexual (33.9 to 67.2, P< 0.001) functioning related to chest appearance as measured by the BREAST-Q and global psychosocial functioning (–15.6 to +32, P<0.001) as measured by the Body Image Quality of Life Index. Satisfaction with chest contour (14.3 to 93.8, P<0.001) and nipple appearance (29.3 to 85.9, P<0.001) measured by the BODY-Q significantly improved. Patients had a mean satisfaction with outcome score of 93.1.

Conclusions:

Patients undergoing gender-affirming mastectomy in this single-center prospective study reported significant improvements in anxiety, depression, body image, psychosocial, and sexual functioning after this procedure. Patients were extremely satisfied with the decision to undergo this operation.
Personalized AAC Intervention to Increase Participation and Communication for a Young Adult With Down Syndrome
Authors: Babb Salena , Jung Sojung , Ousley Ciara , McNaughton David , Light Janice
Published: August 2021

Many adults with Down syndrome (DS) experience difficulty with speech production, and intelligibility challenges and communication breakdowns are common. Augmentative and alternative communication (AAC) intervention can provide important supports for persons with these complex communication needs but must be customized to address the goals, strengths, and needs of the individual. This article provides a description of a personalized AAC intervention for a young adult with DS whose speech was frequently unintelligible. The AAC intervention made use of a video visual scene display (VSD) approach and was investigated in 2 separate studies in 2 key community settings: An inclusive post–secondary education program (a single-case reversal ABAB design), and a community shopping activity (a nonexperimental AB case study design). The participant demonstrated sharp increases in successful communication and participation in both settings following the introduction of the video VSD, and both the participant and the key stakeholders viewed the intervention positively. The results provide preliminary evidence that personalized AAC intervention, including the use of a video VSD approach, can provide important supports for communication and participation in community settings for adults with DS and complex communication needs.
The winding path towards symbiotic autonomous systems
Authors: Saracco Roberto , Grise Kathy , Martinez Terence
Published: August 2021

Over the next 10 years, we are likely to see the convergence of two independent evolutionary paths: one leading to an augmentation of machine capabilities; the other with the augmentation of human capabilities. This convergence will not happen at a specific point in time; instead, it will be the result of progressive overlapping, to the point that it might be difficult to identify a defining moment. The following decade will likely be quite different from the present one. 5G will probably be remembered as a transitional system, artificial intelligence (AI) as a misplaced objective. We are looking forward to a communications fabric created by autonomous systems that will exist both in the physical world as well as in cyberspace, determining a continuum that gives rise to digital reality and where intelligence is an emerging property of the ambient. Hence, the dichotomy between AI and natural intelligence will no longer exist and AI will be considered as a tool for human augmentation and as the glue connecting minds and machines.

This article is part of the theme issue ‘Towards symbiotic autonomous systems’.
Digital twins as run-time predictive models for the resilience of cyber-physical systems: a conceptual framework
Authors: Flammini Francesco
Published: August 2021

Digital twins (DT) are emerging as an extremely promising paradigm for run-time modelling and performability prediction of cyber-physical systems (CPS) in various domains. Although several different definitions and industrial applications of DT exist, ranging from purely visual three-dimensional models to predictive maintenance tools, in this paper, we focus on data-driven evaluation and prediction of critical dependability attributes such as safety. To that end, we introduce a conceptual framework based on autonomic systems to host DT run-time models based on a structured and systematic approach. We argue that the convergence between DT and self-adaptation is the key to building smarter, resilient and trustworthy CPS that can self-monitor, self-diagnose and—ultimately—self-heal. The conceptual framework eases dependability assessment, which is essential for the certification of autonomous CPS operating with artificial intelligence and machine learning in critical applications.

This article is part of the theme issue ‘Towards symbiotic autonomous systems’.
Paracoccus onubensis sp. nov., a novel alphaproteobacterium isolated from the wall of a show cave
Authors: Gutierrez-Patricio Sara , Gonzalez-Pimentel Jose L. , Miller Ana Zelia , Hermosin Bernardo , Saiz-Jimenez Cesareo , Jurado Valme
Published: August 2021

A novel facultatively anaerobic, non-motile, Gram-stain-negative, non-endospore-forming alphaproteobacterium, strain 1011MAR3C25T, was isolated from a white biofilm colonizing the walls of the Andalusian show cave Gruta de las Maravillas (Huelva, Spain). Strain 1011MAR3C25T grew at 8–42 °C (optimum, 20–30 °C), at pH 5.0–9.0 (optimum, pH 5.0–6.0) and in the presence of 0–12 % (w/v) NaCl (optimum 3–5 %). Cells were catalase- and oxidase-positive. The strain grew heterotrophically with various carbon sources and chemoautotrophically with thiosulfate under aerobic conditions. Results of phylogenetic analysis showed that strain 1011MAR3C25T was related to

Paracoccus saliphilus

DSM 18447T and

Paracoccus alkanivorans

LMG 30882T (97.90 % and 97.32 % 16S rRNA sequence identity values, respectively). The major respiratory quinone was ubiquinone Q-10 and the predominant fatty acid was C18 : 1 ω7c. The polar lipid profile consisted of diphosphatidylglycerol, phosphatidylcholine, phosphatidylglycerol, an unidentified aminolipid, an unidentified glycolipid and an unidentified polar lipid. The DNA G+C content was 60.3 mol%. Based on a polyphasic taxonomic study it is proposed that strain 1011MAR3C25T (=CECT 9092T=LMG 29414T) represents a novel species of the genus

Paracoccus

, for which the name Paracoccus onubensis sp. nov. is proposed.
Immunogenicity after the first dose of the BNT162b2 mRNA Covid-19 vaccine: real-world evidence from Greek healthcare workers
Authors: Kontopoulou Konstantina , Ainatzoglou Alexandra , Ifantidou Athina , Nakas Christos T. , Gkounti Georgia , Adamopoulos Vasilios , Papadopoulos Nikitas , Papazisis Georgios
Published: August 2021

Real-world data regarding the effectiveness, safety and immunogenicity of the Pfizer-BioNTech BNT162b2 mRNA vaccine are accumulating in the literature, suggesting that this vaccine generates high titres of S1-binding IgG antibodies that exhibit potent virus neutralization capacity. This is the first phase IV immunogenicity study to recruit a large number of Greek healthcare workers (n=425) including 63 previously-infected subjects. We measured titres of neutralizing IgGs against the receptor-binding domain of the S1 subunit of the spike protein of SARS-CoV-2 14 days post-immunization with the first dose, employing the SARS-CoV-2 IgG II Quant assay. A total of 92.24 % of our study cohort received a positive assay outcome and titres varied with age. Post-hoc analysis revealed that although titres did not significantly differ among participants aged 20–49 years, a significant decline was marked in the age group of 50–59 years, which was further accentuated in subjects aged over 60. Antibody titres escalated significantly among the previously-infected, indicating the potential booster effect of the first dose in that group.
Deep Learning Classification of Lake Zooplankton
Authors: Kyathanahally S. , Hardeman T. , Merz E. , Kozakiewicz T. , Reyes M. , Isles P. , Pomati F. , Baity-Jesi M.
Published: August 2021

Plankton are effective indicators of environmental change and ecosystem health in freshwater habitats, but collection of plankton data using manual microscopic methods is extremely labor-intensive and expensive. Automated plankton imaging offers a promising way forward to monitor plankton communities with high frequency and accuracy in real-time. Yet, manual annotation of millions of images proposes a serious challenge to taxonomists. Deep learning classifiers have been successfully applied in various fields and provided encouraging results when used to categorize marine plankton images. Here, we present a set of deep learning models developed for the identification of lake plankton, and study several strategies to obtain optimal performances, which lead to operational prescriptions for users. To this aim, we annotated into 35 classes over 17900 images of zooplankton and large phytoplankton colonies, detected in Lake Greifensee (Switzerland) with the Dual Scripps Plankton Camera. Our best models were based on transfer learning and ensembling, which classified plankton images with 98% accuracy and 93% F1 score. When tested on freely available plankton datasets produced by other automated imaging tools (ZooScan, FlowCytobot and ISIIS), our models performed better than previously used models. Our annotated data, code and classification models are freely available online.