bluuebunny/crossref_metadata_2025 huggingface dataset:
JAK1: Number one in the family; number one in inflammation?
Authors: Spinelli Francesca Romana , Colbert Robert A , Gadina Massimo
Published: January 2021

Several cytokines involved in inflammatory pathologies signal via the Janus kinase-signal transducer and activator of transcription pathway. Four JAKs are known: JAK1, JAK2, JAK3 and TYK2. The specific activation of JAKs and STATs determines the biological effects of each cytokine. JAK1 is involved in the signalling of ‘γc’ receptor cytokines (IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21), pro-inflammatory cytokines including IL-6, as well as IFN. The critical position of JAK1 downstream of these cytokines suggests that JAK1-selective inhibitors are comparable to non-selective ones, without the unwanted consequences of JAK2- or JAK3-blockade. JAK inhibition has led to a better understanding of the biology of synovial inflammation and bone homeostasis. Moreover, the efficacy of non-selective JAK inhibitors and novel JAK1-selective drugs in RA supports a role for JAK1 in its pathogenesis. JAK1-selective drugs are also showing promise in axial spondyloarthritis, suggesting that they may target additional regulatory pathways that impact cytokines such as TNF and IL-17A, which do not use JAKs. Additionally, evidence now supports a JAK1 predominance in the signalling of IL-6 and oncostatin M, and indirectly, of TNF in synovial fibroblasts, macrophages and endothelial cells. Notably, bone homeostasis is also dependent on cytokines relying on JAK1 signalling to promote receptor activator of NF-κB ligand expression in osteoblasts and T cells, contributing to osteoclastogenesis. Here, the contribution of JAK1 over other kinases is unclear. While beneficial effects of JAK inhibitors on bone erosion are supported by preclinical and clinical data, effects on new bone formation in axial spondyloarthritis requires additional study.
Lifting the Veil on Campus Sexual Assault: Morehouse College, Hegemonic Masculinity, and Revealing Racialized Rape Culture through the Du Boisian Lens
Authors: Grundy Saida
Published: January 2021

As national rates of sexual assault continue to fall, sexual assault rates for colleges and universities remain stagnant. Researchers ask why rates of sexual assault on college campuses differ from rates across the nation. One approach examines the contexts in which college men “do” rape culture. How men are racialized, however, is a critically missing context in understanding the cultures in which gender violence persists. Although race is one of the most pronounced ways that college men see themselves and their interactions, it is overlooked in extant literature. In failing to apply race theories to college men, researchers have missed an opportunity to unveil how their rape cultures operate as racialized rape cultures. Interviews with 32 graduates of Morehouse College, the nation’s only historically Black college for men, reveal that race is a modality through which men make meanings of masculinity, sex, women, competition, and the repercussions of sexual assault in ways that preserve gender violence on campus. Through a Du Boisian lens of double consciousness, this study finds that rape culture is not only how these men do gender, but is also a formative means by which they do race and are racialized throughout their college experience.
An ‘Omics Approach to Unraveling the Paradoxical Effect of Diet on Perfluorooctanesulfonic Acid (PFOS) and Perfluorononanoic Acid (PFNA)-Induced Hepatic Steatosis
Authors: Pfohl Marisa , Marques Emily , Auclair Adam , Barlock Benjamin , Jamwal Rohitash , Goedken Michael , Akhlaghi Fatemeh , Slitt Angela L
Published: January 2021

Perfluoroalkyl substances (PFAS) are a family of toxicants universally detected in human serum and known to cause dyslipidemia in animals and humans. Hepatic steatosis, which is defined as lipid deposition in the liver, is known to be a consequence of poor diet. Similarly, PFAS are known to induce hepatic steatosis in animals on a low-fat chow. This study explored diet-PFAS interactions in the liver and their potential to modulate hepatic steatosis. Male C57BL/6J mice were fed with either a low-fat diet (10% kcal from fat, LFD) or a moderately high-fat diet (45% kcal from fat, HFD) with or without perfluorooctanesulfonic acid (3 ppm, PFOS) or perfluorononanoic acid (3 ppm, PFNA) in feed for 12 weeks. Livers were excised for histology and quantification of PFAS and lipids. The PFOS and PFNA coadministration with HFD reduced the hepatic accumulation of lipid and PFAS relative to the LFD treatment groups. Furthermore, transcriptomic analysis revealed that PFAS administration in the presence of an HFD significantly reduces expression of known hepatic PFAS uptake transporters, organic anion transporter proteins. Transcriptomics and proteomics further revealed several pathways related to lipid metabolism, synthesis, transport, and storage that were modulated by PFAS exposure and further impacted by the presence of dietary fat. Both dietary fat content and the chemical functional head group exerted significant influence on hepatic PFAS accumulation and the resulting biochemical signature, suggesting that diet and structure should be considered in the design and interpretation of research on PFAS induced hepatic steatosis.
Photoprotective compounds as early markers to predict holm oak crown defoliation in declining Mediterranean savannahs
Authors: Encinas-Valero Manuel , Esteban Raquel , Hereş Ana-Maria , Becerril José María , García-Plazaola José Ignacio , Artexe Unai , Vivas María , Solla Alejandro , Moreno Gerardo , Curiel Yuste Jorge
Published: January 2021

Dehesas, human-shaped savannah-like ecosystems, where the overstorey is mainly dominated by the evergreen holm oak (Quercus ilex L. subsp. ballota (Desf.) Samp.), are classified as a global conservation priority. Despite being Q. ilex a species adapted to the harsh Mediterranean environmental conditions, recent decades have witnessed worrisome trends of climate-change-induced holm oak mortality. Holm oak decline is evidenced by tree vigour loss, gradual defoliation and ultimately, death. However, before losing leaves, trees undergo leaf-level physiological adjustments in response to stress that may represent a promising field to develop biochemical early markers of holm oak decline. This study explored holm oak photoprotective responses (pigments, tocopherols and photosynthetic performance) in 144 mature holm oak trees with different health statuses (i.e., crown defoliation percentages) from healthy to first-stage declining individuals. Our results indicate differential photochemical performance and photoprotective compounds concentration depending on the trees' health status. Declining trees showed higher energy dissipation yield, lower photochemical efficiency and enhanced photoprotective compounds. In the case of total violaxanthin cycle pigments (VAZ) and tocopherols, shifts in leaf contents were significant at very early stages of crown defoliation, even before visual symptoms of decline were evident, supporting the value of these biochemical compounds as early stress markers. Linear mixed-effects models results showed an acute response, both in the photosynthesis performance index and in the concentration of foliar tocopherols, during the onset of tree decline, whereas VAZ showed a more gradual response along the defoliation gradient of the crown. These results collectively demonstrate that once a certain threshold of leaf physiological damage is surpassed, that leaf cannot counteract oxidative stress and progressive loss of leaves occurs. Therefore, the use of both photosynthesis performance indexes and the leaf tocopherols concentration as early diagnostic tools might predict declining trends, facilitating the implementation of preventive measures to counteract crown defoliation.
Matching the Pieces: The Presence of Idiosyncratic Deals and Their Impact on Retirement Preferences Among Older Workers
Authors: Jonsson Robin , Hasselgren Caroline , Dellve Lotta , Seldén Daniel , Larsson Daniel , Stattin Mikael
Published: January 2021

Despite working life prolongation having been at the center of the policy agenda in Europe for the last two decades, organizations’ engagement in formal age-management activities intended to strengthen older workers’ motivation and work ability appears limited. Given policies to extend working lives, negotiated individualized work arrangements—often called idiosyncratic deals (I-deals)—can be an informal and complementary approach to formalized age-management practices, improving the person–job fit and helping older workers extend their working lives. Nevertheless, research on I-deals and retirement preferences remains scarce in the Nordic context, where collective agreements regulate conditions of employment and the employer–employee relationship. Using confirmatory factor analysis and structural equation modeling, this study examines five areas of I-deals (i.e., Task and Work Responsibilities, Workload Reduction, Schedule Flexibility, Location Flexibility, and Financial Incentives) and their relationships with retirement preferences among Swedish public-sector employees aged 55 years or older (n = 4,499). Findings show that I-deals are generally less prevalent among women and older employees, as well as among those with poor health, in lower socioeconomic positions, and with shorter organizational tenure. Regarding retirement preferences, we found Task and Work Responsibilities to be related to later preferred retirement age, while, surprisingly, the opposite was observed for Workload Reduction, probably because individuals who received workload reductions also reported poorer health. Comparatively, factors such as matching employees’ competence, experience, and growth opportunities seem to be the most important for public-sector employees’ retirement preferences.
Pilonidal Sinus Disease: An Analysis of the Factors Affecting Recurrence
Authors: Kanlioz Murat , Ekici Uğur , Tatli Faik , Karatas Turgay
Published: January 2021

OBJECTIVE

To assess the success of treatment methods at reducing recurrence, the most important problem in pilonidal sinus disease (PSD), along with factors affecting the occurrence of PSD and posttreatment recurrence.

METHODS

The researchers retrospectively analyzed files of patients treated for PSD between 2003 and 2018. Three study groups were created: G1, G2, and G3. G1 included all PSDs with recurrence, and a comparable number of cases without recurrence were selected randomly for the G2 group. The control group, G3, included healthy individuals without PSD. In all groups, the following were recorded: body mass index, skin color and oiliness, family history of PSD, hair overgrowth, smoking habit, time spent sitting per day, and number of baths per week. The following were additionally recorded for G1 and G2: treatment methods, follow-up periods, pretreatment abscess(es), and time of onset of complaints before treatment. The number of recurrences and the period between last treatment and recurrence were also recorded for G1.

RESULTS

G1 comprised 234 patients; G2, 247 patients; and G3, 128 healthy individuals. The significant factors causing recurrence included body mass index, family history, bathing habits, hair overgrowth, skin color and oiliness, time spent sitting per day, smoking habit, abscess(es), and duration of symptom(s) (P < .05). Limberg flap repair was the most successful treatment method. Sixty-three (27%), 135 (58%), and 185 (79%) recurrences occurred in the first 6 months, in the first year, and in the first 2 years, respectively.

CONCLUSIONS

The researchers recommend Limberg flap repair for treatment. It is possible to reduce recurrence by taking preventable factors into consideration.
Understanding gastroesophageal reflux disease in children
Authors: Friedman Chloe , Sarantos Gianna , Katz Sarah , Geisler Sheryl
Published: January 2021

Gastroesophageal reflux disease (GERD) is a common disorder with increasing prevalence in children. The diagnosis and management of GERD remains a challenge because of its nonspecific symptomatology from infancy through adolescence. Certain presenting alarm symptoms warrant a further, more extensive workup. Treatment of pediatric GERD begins with lifestyle and nonpharmacologic management, including postural adjustments, dietary changes, and weight loss if indicated. Pharmacologic interventions can be prescribed to relieve symptoms for patients whose disease does not respond to lifestyle management. Patients with refractory symptoms can be managed with surgical intervention. Complications may arise if GERD remains untreated, ranging from worsening oral health to failure to thrive.
Changes in the Frequency of Cesarean Delivery in Nulliparous Women in Labor in a Canadian Population, 1992–2018
Authors: Wood Stephen , Tang Selphee
Published: January 2021

OBJECTIVE:

To examine the relative contribution of changes in patient demographics and physician management to changes in the cesarean delivery rate in labor among nulliparous women.

METHODS:

We conducted a retrospective cohort study of 485,451 births to nulliparous women who experienced labor at or beyond 35 weeks of gestation in Alberta, Canada, from 1992 to 2018. The data were from a province-wide perinatal database. The primary outcome was cesarean delivery. Multivariate logistic regression and calculation of population attributable risk for identified risk factors were performed.

RESULTS:

The cesarean delivery rate increased from 12.5% in 1992 to 24% in 2018. The prevalence of maternal risk factors for cesarean delivery such as obesity, maternal age 35 years or older at delivery, and comorbidities increased over the study period. However, this did not account for the increase in cesarean delivery, because the frequency of cesarean delivery increased irrespective of risk status. Additionally, the population-attributable risk for each risk factor was stable across the study period. For example, for maternal age 35 years or older at delivery, the number of cesarean deliveries attributable to this factor (the population-attributable risk) was 0.9 per 100 deliveries in 1992–1998 and 1 per 100 in 2014–2018. The proportion of cesarean deliveries in which nonreassuring fetal status was the indication increased from 30.1% in 1992 to 51.1% in 2018. The absolute rate of cesarean delivery in the second stage of labor increased from 3.1% in 1992 to 5.9% in 2018. This was due to a significant increase, among those who entered the second stage, in cesarean delivery without a trial of forceps, from 2.5% in 1992 to 7.0% in 2018.

CONCLUSION:

The observed doubling of the rate of cesarean delivery in labor in first-time mothers was not driven by patient risk factors. Increases in the rate of cesarean delivery for nonreassuring fetal status and decreased operative vaginal deliveries were important factors.
Expanded Carrier Screening and the Complexity of Implementation
Authors: Silver Julia , Norton Mary E.
Published: January 2021

Advances in genetic technology have allowed for the development of multiplex panels that can test for hundreds of genetic disorders at the same time; these large panels are referred to as expanded carrier screening. This process can screen couples for far more conditions than the gene-by-gene approach used with traditional carrier screening; however, although expanded carrier screening has been promoted as an efficient means of detecting many more disorders, the complexities of genetic sequencing raise substantial challenges and concerns. In our practice, we have seen a number of complex cases in which only attention to detail on the part of thorough genetic counselors allowed identification of misclassified variants that could have resulted in significant patient harm. We raise issues that require urgent attention by professional societies, including: whether to endorse testing that uses sequencing compared with genotyping; required components of pretest and posttest counseling; reclassification of variants; whether obstetric health care professionals have a responsibility to assure that patients understand the iterative process of variant interpretation and how it relates to carrier screening results; and the question of rescreening in subsequent pregnancies. Implementation of expanded carrier screening needs to be considered thoughtfully in light of the complexity of genetic sequencing and limited knowledge of genetics of most front-line obstetric health care professionals.
Prophylactic Negative Pressure Wound Therapy After Laparotomy for Gynecologic Surgery
Authors: Leitao Mario M. , Zhou Qin C. , Schiavone Maria B. , Cowan Renee A. , Smith Evan S. , Iasonos Alexia , Veith Mitchell , Rafizadeh Michael , Curran Katherine , Ramesh Bhavani , Chang Kaity , Chi Dennis S. , Sonoda Yukio , Brown Amy K. , Cosin Jonathan A. , Abu-Rustum Nadeem R. , Martino Martin A. , Mueller Jennifer J. , Long Roche Kara , Jewell Elizabeth L. , Broach Vance , Lambrou Nicholas C. , Diaz John P. , Zivanovic Oliver
Published: January 2021

OBJECTIVE:

To estimate the effectiveness of prophylactic negative pressure wound therapy in patients undergoing laparotomy for gynecologic surgery.

METHODS:

We conducted a randomized controlled trial. Eligible, consenting patients, regardless of body mass index (BMI), who were undergoing laparotomy for presumed gynecologic malignancy were randomly allocated to standard gauze or negative pressure wound therapy. Patients with BMIs of 40 or greater and benign disease also were eligible. Randomization, stratified by BMI, occurred after skin closure. The primary outcome was wound complication within 30 (±5) days of surgery. A sample size of 343 per group (N=686) was planned.

RESULTS:

From March 1, 2016, to August 20, 2019, we identified 663 potential patients; 289 were randomized to negative pressure wound therapy (254 evaluable participants) and 294 to standard gauze (251 evaluable participants), for a total of 505 evaluable patients. The median age of the entire cohort was 61 years (range 20–87). Four hundred ninety-five patients (98%) underwent laparotomy for malignancy. The trial was eventually stopped for futility after an interim analysis of 444 patients. The rate of wound complications was 17.3% in the negative pressure wound therapy (NPWT) group and 16.3% in the gauze group, absolute risk difference 1% (90% CI −4.5 to 6.5%; P=.77). Adjusted odds ratio controlling for estimated blood loss and diabetes was 0.99 (90% CI 0.62–1.60). Skin blistering occurred in 33 patients (13%) in the NPWT group and in three patients (1.2%) in the gauze group (P<.001).

CONCLUSION:

Negative pressure wound therapy after laparotomy for gynecologic surgery did not lower the wound complication rate but did increase skin blistering.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT02682316.

FUNDING SOURCE:

The protocol was supported in part by KCI/Acelity.
Evolving the Preconception Health Framework
Authors: Dehlendorf Christine , Akers Aletha Y. , Borrero Sonya , Callegari Lisa S. , Cadena Denicia , Gomez Anu Manchikanti , Hart Jamie , Jimenez Laura , Kuppermann Miriam , Levy Barbara , Lu Michael C. , Malin Kiko , Simpson Monica , Verbiest Sarah , Yeung Miriam , Crear-Perry Joia
Published: January 2021

Over the past decade, increasing attention has been paid to intervening in individuals’ health in the “preconception” period as an approach to optimizing pregnancy outcomes. Increasing attention to the structural and social determinants of health and to the need to prioritize reproductive autonomy has underscored the need to evolve the preconception health framework to center race equity and to engage with the historical and social context in which reproduction and reproductive health care occur. In this commentary, we describe the results of a meeting with a multidisciplinary group of maternal and child health experts, reproductive health researchers and practitioners, and Reproductive Justice leaders to define a new approach for clinical and public health systems to engage with the health of nonpregnant people. We describe a novel “Reproductive and Sexual Health Equity” framework, defined as an approach to comprehensively meet people's reproductive and sexual health needs, with explicit attention to structural influences on health and health care and grounded in a desire to achieve the highest level of health for all people and address inequities in health outcomes. Principles of the framework include centering the needs of and redistributing power to communities, having clinical and public health systems acknowledge historical and ongoing harms related to reproductive and sexual health, and addressing root causes of inequities. We conclude with a call to action for a multisectoral effort centered in equity to advance reproductive and sexual health across the reproductive life course.
Congenital Kyphosis: Progressive Correction With an Instrumented Posterior Epiphysiodesis: A Preliminary Report
Authors: Rocos Brett , Lebel David E. , Zeller Reinhard
Published: January 2021

Purpose:

Congenital kyphosis is a rare condition. In this case series we sought to identify the outcomes and complications of posterior instrumented fusion and the resultant epiphysiodesis effect in uniplanar congenital kyphosis in pediatric patients.

Method:

Pediatric patients were included if treated for a uniplanar congenital kyphotic deformity treated with posterior instrumented spinal fusion between October 2006 and August 2017, with a minimum of 2 years of follow-up. Patients were excluded if a coronal deformity >10 degrees was present.

Results:

Six patients met the inclusion criteria. Mean age at surgery was 3.6 years. The mean kyphotic deformity before surgery was 49.7 degrees. All patients underwent posterior instrumented fusion with autogenous iliac crest graft and a cast or brace postoperatively. One patient showed a loss of motor evoked potential on prone positioning which returned to normal on supine positioning. No patient showed any postoperative neurological deficits. One patient was diagnosed with a wound infection which was successfully treated with oral antibiotics.

By a follow-up of 5.4 years (range, 2.2 to 10.9 y) there was no failure of instrumentation. An epiphysiodesis effect (a difference of ≥5 degrees in the kyphotic deformity measured between the immediate postoperative and final follow-up lateral whole spine XR) of 16.2 degrees (range, 7.2 to 30.9 degrees) was seen in 5 patients. The mean annual epiphysiodesis effect was 2.7 degrees (95% confidence interval, 1.4-4.1 degrees). No kyphosis proximal to the instrumentation was observed for the duration of follow-up.

Conclusion:

Posterior instrumented fusion and epiphysiodesis is safe and effective. The epiphysiodesis effect occurs in 5/6 of cases, and our data suggests that the procedure is associated with an acceptable blood loss and a low incidence of neurological complications.
Risk Factors for Revision Surgery After Primary Adult Thoracolumbar Deformity Surgery
Authors: Varshneya Kunal , Stienen Martin N. , Medress Zachary A. , Fatemi Parastou , Pendharkar Arjun V. , Ratliff John K. , Veeravagu Anand
Published: January 2021

Study Design:

This is a retrospective cohort study.

Objective:

The aim was to identify the risk factors for revision surgery within 2 years of patients undergoing primary adult spinal deformity (ASD) surgery.

Summary of Background Data:

Previous literature reports estimate 20% of patients undergoing thoracolumbar ASD correction undergo reoperation within 2 years. There is limited published data regarding specific risk factors for reoperation in ASD surgery in the short term and long term.

Methods:

The authors queried the MarketScan database in order to identify patients who were diagnosed with a spinal deformity and underwent ASD surgery from 2007 to 2015. Patient-level factors and revision risk were investigated during 2 years after primary ASD surgery. Patients under the age of 18 years and those with any prior history of trauma or tumor were excluded from this study.

Results:

A total 7422 patients underwent ASD surgery during 2007–2015 in the data set. Revision rates were 13.1% at 90 days, 14.5% at 6 months, 16.7% at 1 year, and 19.3% at 2 years. In multivariate multiple logistic regression analysis, obesity [adjusted odds ratio (OR): 1.58, P<0.001] and tobacco use (adjusted OR: 1.38, P=0.0011) were associated with increased odds of reoperation within 2 years. Patients with a combined anterior-posterior approach had lower odds of reoperation compared with those with posterior only approach (adjusted OR: 0.66, P=0.0117).

Conclusions:

Obesity and tobacco are associated with increased odds of revision surgery within 2 years of index ASD surgery. Male sex and combined surgical approach are associated with decreased odds of revision surgery.
Tocilizumab in Coronavirus Disease 2019-Related Critical Illness: A Propensity Matched Analysis
Authors: Rajendram Prabalini , Sacha Gretchen L. , Mehkri Omar , Wang Xiaofeng , Han Xiaozhen , Vachharajani Vidula , Duggal Abhijit
Published: January 2021

Objectives:

The primary objective was to evaluate ICU mortality at 28 days in patients with severe hypoxemic respiratory failure due to coronavirus disease 2019 infection who received tocilizumab. The secondary objectives were to evaluate ICU-, hospital-, mechanical ventilation-, and vasopressor-free days at day 28 and development of secondary infections.

Design:

Retrospective, observational, multicenter, cohort study between March 15, 2020, and May 31, 2020. Using propensity score matching based on ICU admission source, C-reactive protein, Sequential Organ Failure Assessment score, vasopressor use, age, race, weight, and mechanical ventilation, patients who received tocilizumab were matched to patients who did not receive tocilizumab.

Setting:

Ten hospitals within the Cleveland Clinic Enterprise.

PATIENTS:

Adult patients admitted to a medical, surgical, neurosciences, or mixed ICU with severe acute respiratory syndrome coronavirus 2 infection.

Interventions:

None.

Measurements and Main Results:

Four-hundred forty-four patients were included: 342 patients (77%) did not receive tocilizumab and 102 patients (23%) received tocilizumab. Of those, 82 patients in each arm were matched. Before matching, patients who received tocilizumab had higher Sequential Organ Failure Assessment scores (6.1 ± 3.4 vs 4.7 ± 3.6), higher C-reactive protein (21.0 ± 10.2 vs 13.7 ± 9.6 mg/dL), higher frequency of intubation, vasopressor requirement, and paralytics. After matching, characteristics were more balanced and over 85% of patients required mechanical ventilation. ICU mortality was lower in tocilizumab group (23.2% vs 37.8%; risk difference, –15%; 95% CI, –29% to –1%), with more ICU-, hospital-, and vasoactive-free days at day 28 compared with those who did not receive tocilizumab. There was no difference in mechanical ventilation-free days at day 28 or development of secondary infections.

Conclusions:

Tocilizumab use was associated with a significant decrease in ICU mortality in critically ill coronavirus disease 2019 patients with severe hypoxemic respiratory failure. Future randomized controlled trials limited to tocilizumab administration in critically ill coronavirus disease 2019 patients, with severe hypoxemic respiratory failure, are needed to support these findings.
Age–period–cohort effects in utilization of diagnostic procedures leading to incidental colorectal cancer detection
Authors: Salvatori Andrea , Andreano Anita , Decarli Adriano , Russo Antonio Giampiero
Published: January 2021

Background and aim

Despite the overall decrease in colorectal cancer (CRC) incidence, a small but constant rise has been recently observed in people younger than 50 years across several countries. This phenomenon can be explained by environmental or lifestyle factors, but it may also be partially justified by an increasing tendency in younger cohorts to undertake diagnostic procedures that may lead to CRC incidental diagnosis.

Methods

We performed an age–period–cohort analysis on 1 815 694 diagnostic procedures undertook by the population of the City of Milan, served by the Agency for Health Protection of Milan, between 1999 and 2018. We considered all instances of colonoscopy, rectoscopy, fecal occult blood test (FOBT) and ultrasonography. We stratified by gender, nationality and quintile of socioeconomic deprivation.

Results

Incidence of utilization rose with age for all procedures but rectoscopy; there was a marked increase from 2005 to 2010 for FOBT and colonoscopy. A strong all-procedures cohort effect was observed, greater for FOBT and colonoscopy. A steady increase of diagnostic procedures utilization started in cohorts born in the late 1950s, with a relative effect rising from 0.91 [95% confidence interval (CI) 0.90–0.92] for the 1950 cohort to 5.03 (95% CI, 4.58–5.48) for the 1990 one.

Conclusion

We found a growing tendency in younger cohorts to undertake diagnostic procedures, explainable by inappropriate access to endoscopic procedures, that can lead to an incidental diagnosis of CRC. This finding may at least partially explain the observed rising incidence of early-onset CRC.
Expanded Tumor-infiltrating Lymphocytes From Soft Tissue Sarcoma Have Tumor-specific Function
Authors: Mullinax John E. , Hall MacLean , Beatty Matthew , Weber Amy M. , Sannasardo Zachary , Svrdlin Tanja , Hensel Jonathan , Bui Marilyn , Richards Allison , Gonzalez Ricardo J. , Cox Cheryl A. , Kelley Linda , Mulé James J. , Sarnaik Amod A. , Pilon-Thomas Shari
Published: January 2021

Adoptive cell transfer (ACT) with tumor-infiltrating lymphocytes (TILs) can generate durable clinical responses in patients with metastatic melanoma and ongoing trials are evaluating efficacy in other advanced solid tumors. The aim of this study was to develop methods for the expansion of tumor-reactive TIL from resected soft tissue sarcoma to a degree required for the ACT. From 2015 to 2018, 70 patients were consented to an institutional review board–approved protocol, and fresh surgical specimens were taken directly from the operating room to the laboratory. Fragments of the tumor (1 mm3) or fresh tumor digest were placed in culture for a period of 4 weeks. Successfully propagated TIL from these cultures were collected and analyzed by flow cytometry. TIL were cocultured with autologous tumor and function was assessed by measurement of interferon-γ in the supernatant by enzyme-linked immunosorbent assay. Initial TIL cultures were further expanded using a rapid expansion protocol. Nearly all specimens generated an initial TIL culture (91% fragment method, 100% digest method). The phenotype of the TIL indicated a predominant CD3+ population after culture (43% fragment, 52% digest) and TIL were responsive to the autologous tumor (56% fragment, 40% digest). The cultured TIL expanded to a degree required for clinical use following rapid expansion protocol (median: 490-fold fragment, 403-fold digest). The data demonstrate the feasibility of TIL culture from fresh soft tissue sarcoma. The derived TIL have tumor-specific reactivity and can be expanded to clinically relevant numbers. An active ACT clinical trial using the methods described in this report is now approved for patients with metastatic soft tissue sarcoma.
The role of cardiorespiratory fitness on quality of life in midlife women
Authors: Flesaker Michelle Q. , Serviente Corinna , Troy Lisa M. , Witkowski Sarah
Published: January 2021

Objective:

We aimed to characterize the relationship between cardiorespiratory fitness and quality of life in a sample of healthy midlife women aged 40 to 65 years.

Methods:

Cardiorespiratory fitness was measured with a VO2max test. Quality of life was assessed with the menopause-specific Utian Quality of Life scale (UQOL). The UQOL measures overall quality of life, which comprises health, emotional, occupational, and sexual domains. Simple and multiple linear regression models were built to analyze relationships between cardiorespiratory fitness and overall quality of life as well as the separate UQOL domains.

Results:

Forty-nine women with an average age of 52.5 years were included in the analysis. In simple linear models, cardiorespiratory fitness was related to overall (R

2
 = 0.34, P < 0.001), health (R

2
 = 0.55, P < 0.001), emotional (R

2
 = 0.08, P = 0.05), and occupational (R

2
 = 0.09, P = 0.03) quality of life. In multiple regression models, cardiorespiratory fitness was associated with overall (P < 0.01) and health (P < 0.001) quality of life, after controlling for physical activity, age, body mass index, and time sedentary.

Conclusions:

Higher cardiorespiratory fitness is associated with better quality of life during midlife, particularly in the health domain. Increasing cardiorespiratory fitness may be a useful means to promote quality of life in this population.
Cognitive changes during the menopausal transition: a longitudinal study in women with and without HIV
Authors: Maki Pauline M. , Springer Gayle , Anastos Kathryn , Gustafson Deborah R. , Weber Kathleen , Vance David , Dykxhoorn Derek , Milam Joel , Adimora Adaora A. , Kassaye Seble G. , Waldrop Drenna , Rubin Leah. H.
Published: January 2021

Objective:

To assess longitudinal changes in cognitive performance across menopause stages in a sample comprised primarily of low-income women of color, including women with HIV (WWH).

Methods:

A total of 443 women (291 WWH; 69% African American; 18% Hispanic; median age = 42 y) from the Women's Interagency HIV Study completed tests of verbal learning and memory, attention/working memory, processing speed, verbal fluency, motor skills, and executive function first at an index premenopausal visit and thereafter once every 2 years for up to six visits (mean follow-up = 5.7 y). General linear-mixed effects regression models were run to estimate associations between menopause stages and cognition, in the overall sample and in WWH. We examined both continuous scores and categorical scores of cognitive impairment (yes/no >1 standard deviation below the mean).

Results:

Adjusting for age and relevant covariates, the overall sample and WWH showed longitudinal declines in continuous measures of learning, memory, and attention/working memory domains from the premenopause to the early perimenopause and from the premenopause to the postmenopause, Ps < 0.05 to < 0.001. Effects on those same domains were also evident in categorical scores of cognitive impairment, with the increased odds of impairment ranging from 41% to 215%, Ps < 0.05 to < 0.001. The increase in predicted probability of impairment by menopausal stage (% affected) ranged from 4% to 13%.

Conclusions:

Menopause stage was a key determinant of cognition in a sample of low-income women of color, including WWH. Many of these changes reached a clinically significant level of cognitive impairment.
Individual and additive-effect relationships of sleep problems and severe menopausal symptoms among women in menopausal transition
Authors: Li Yuanyuan , Zhao Di , Lv Gaorong , Mao Cui , Zhang Yunxue , Xie Zihui , Li Ping
Published: January 2021

Objective:

Sleep problems and menopausal symptoms are both common complaints among midlife women. However, the associations of the quality and quantity of sleep problems with the severity of menopausal symptoms have not been well studied. Thus, this study aims to examine the relationships between individual sleep problems and the additive number of sleep problems with severe menopausal symptoms among women during the menopausal transition.

Methods:

Using the convenience sampling, a total of 848 middle-aged women in China were investigated from December 2017 to August 2018. All participants completed a questionnaire on sleep problems, Menopause Rating Scale, and the general information questionnaire. Based on the cutoff of the Menopause Rating Scale, participants were divided into the nonsevere menopausal symptom group and severe menopausal symptoms group. Propensity score matching was used to balance covariates between the two groups. Stepwise binary logistic regression and restricted cubic spline were applied to analyze the associations of individual and additive sleep problems with severe menopausal symptoms.

Results:

After propensity score matching, no significant difference was observed between the nonsevere menopausal symptoms group and severe menopausal symptoms group (Ps > 0.05). Logistic regression analysis showed that five sleep problems (“feeling too hot,” “having pain,” “restless legs syndrome,” “taking medicine to help sleep,” and “having trouble staying awake”) were closely associated with severe menopausal symptoms. The restricted cubic spline curve showed an upward trend in odds ratios between the number of these five sleep problems and severe menopausal symptoms, and women were more than twice as likely to suffer severe menopausal symptoms when they experienced more than three of these individual sleep problems.

Conclusion:

Both the individual and additive number of sleep problems exerted significant effects on severe menopausal symptoms. It might be useful for healthcare providers to set guidelines to support a healthy menopausal transition for midlife women.
Menopausal status and observed differences in the gut microbiome in women with and without HIV infection
Authors: Peters Brandilyn A. , Xue Xiaonan , Wang Zheng , Usyk Mykhaylo , Santoro Nanette , Sharma Anjali , Anastos Kathryn , Tien Phyllis C. , Golub Elizabeth T. , Weber Kathleen M. , Gustafson Deborah , Kaplan Robert C. , Burk Robert , Qi Qibin
Published: January 2021

Objective:

Gut microbiota respond to host physiological phenomena, yet little is known regarding shifts in the gut microbiome due to menopausal hormonal and metabolic changes in women. HIV infection impacts menopause and may also cause gut dysbiosis. We therefore sought to determine the association between menopausal status and gut microbiome composition in women with and without HIV.

Methods:

Gut microbiome composition was assessed in stool from 432 women (99 premenopausal HIV+, 71 premenopausal HIV−, 182 postmenopausal HIV+, 80 postmenopausal HIV−) via 16S rRNA gene sequencing. We examined cross-sectional associations of menopause with gut microbiota overall diversity and composition, and taxon and inferred metagenomic pathway abundance. Models were stratified by HIV serostatus and adjusted for age, HIV-related variables, and other potential confounders.

Results:

Menopause, ie post- versus premenopausal status, was associated with overall microbial composition only in women with HIV (permutational MANOVA of Jensen Shannon Divergence: P = 0.01). In women with HIV, menopause was associated with enrichment of gram-negative order Enterobacteriales, depletion of highly abundant taxa within Prevotella copri, and alterations in other low-abundance taxa. Additionally, menopause in women with HIV was associated with enrichment of metagenomic pathways related to Enterobacteriales, including degradation of amino acids and phenolic compounds, biosynthesis of enterobactin, and energy metabolism pathways. Menopause-related differences in some low-abundance taxa were also observed in women without HIV.

Conclusions:

A changing gut microbiome may be an overlooked phenomenon of reproductive aging in women with HIV. Longitudinal assessments across all reproductive stages are necessary to confirm these findings and identify health implications.
Change in Covid-19 infection and mortality rates in postmenopausal women
Authors: Cagnacci Angelo , Xholli Anjeza
Published: January 2021

Objective:

To evaluate whether the rates of COVID-19 infection and death in women versus men differ with age.

Methods:

From data provided by the Italian National Institute of Statistics, we calculated the respective proportions of women among COVID-infected versus noninfected populations and male versus female infection and death rates, stratifying the results into 10-year age groups.

Results:

The prevalence of COVID-19 infection was 3.6% higher in women than in the general population from 20 to 59 years of age, then decreased to −13.3% below that of the general population between 60 and 89 years of age. Death rates among infected women showed the opposite age-related trend. In infected women, the mortality rate was −77.4% lower than that of men aged 20 to 59 years. Between 60 and 89 years of age, the difference in women decreases to −34.5% below that of men.

Conclusions:

Our results indicate opposing age-related trends among women in infection and death rates due to COVID-19. Further studies are needed to examine the contribution of the phases of the female reproductive cycle to the observed variations.
Amniotic Membrane-Covered Conformer and Fibrin Glue for Toxic Epidermal Necrolysis
Authors: Chan Sarah , Gole Glen A. , Lee Graham A.
Published: January 2021

Purpose:

Stevens-Johnson syndrome and its more severe form, toxic epidermal necrolysis, are immunologic disorders that cause widespread blistering of the skin and mucous membranes. Its incidence is higher in children and can lead to long-term disabling ocular surface complications that can be averted with amniotic membrane transplantation early in the disease. To introduce an amniotic membrane treatment technique that is time efficient and minimally invasive but still allows for extensive coverage of the ocular mucosal surfaces to prevent and lessen the severity of the complications from ocular surface sequelae.

Methods:

The procedure was undertaken in the operating room under general anesthesia. Symblephara were divided before an amniotic membrane-covered conformer was placed into the fornices. Fibrin glue was used to secure the conformer and to keep the palpebral aperture closed. Topical chloramphenicol 0.5% and prednisolone 0.5% were prescribed 4 times a day.

Results:

After 7 days, the conformers were removed and new amniotic membrane-covered conformers were reapplied in both eyes for a further week. After the second round of treatment, the conformers were left out for 3 days. Inferior symblephara reformed in the left lower fornix, and therefore, a third round of treatment was undertaken in the left eye only, which was then removed after 7 days. A follow-up at 8 weeks revealed 20/20 vision with minimal symblephara in either eye.

Conclusions:

This novel technique, using an amniotic membrane-covered conformer in combination with fibrin glue, allows for the coverage of the entire ocular surface and protection of the lid margins while requiring minimal preparation and surgical time. This technique could also be used in patients with other cicatrizing ocular surface conditions, such as chemical or thermal injuries or postreconstructive surgery of the fornices.
A Water-free 0.1% Cyclosporine A Solution for Treatment of Dry Eye Disease: Results of the Randomized Phase 2B/3 ESSENCE Study
Authors: Sheppard John D. , Wirta David L. , McLaurin Eugene , Boehmer Blair E. , Ciolino Joseph B. , Meides Alice S. , Schlüter Thomas , Ousler George W. , Usner Dale , Krösser Sonja
Published: January 2021

Purpose:

To assess the efficacy, safety, and tolerability of a topical water-free cyclosporine A formulation (CyclASol 0.1% ophthalmic solution) in comparison with vehicle for the treatment of dry eye disease (DED).

Methods:

Three hundred twenty-eight patients were enrolled in this prospective, 12-week, multicenter, randomized, double-masked, confirmatory, vehicle-controlled clinical study. After a 2-week run-in period, eligible DED patients were randomized 1:1 to either CyclASol 0.1% or vehicle twice daily. The primary efficacy endpoint was change from baseline in total corneal fluorescein staining (National Eye Institute scale), and the second hierarchical primary efficacy endpoint was change from baseline in the Ocular Surface Disease Index score, both at 4 weeks. Secondary efficacy and safety assessments included conjunctival lissamine green staining (Oxford scale), visual analog scales for dry eye symptoms, and adverse event.

Results:

Treatment with CyclASol 0.1% was superior to vehicle in the primary endpoint: total corneal fluorescein staining at week 4 (Δ −0.8; 95% confidence interval, −1.3 to −0.4; P = 0.0002, analysis of covariance). This difference had already reached statistical significance after 2 weeks and was maintained throughout the study. The study did not statistically meet its second hierarchically tested primary endpoint: Ocular Surface Disease Index score (P = 0.2634). However, CyclASol 0.1% treatment showed statistically significant improvement compared with that of vehicle in the eye dryness score at week 4 (Δ −4.783; 95% confidence interval, −9.129 to −0.438; P = 0.0311).

Conclusions:

CyclASol 0.1% was effective in treating signs and symptoms of DED. It significantly reduced corneal and conjunctival staining and improved ocular dryness compared with vehicle. CyclASol 0.1% was safe and showed excellent tolerability.
Practice patterns of corneal transplantation in Europe: first report by the European Cornea and Cell Transplantation Registry
Authors: Dunker Suryan L. , Armitage W. John , Armitage Margareta , Brocato Lucia , Figueiredo Francisco C. , Heemskerk Martin B.A. , Hjortdal Jesper , Jones Gary L.A. , Konijn Cynthia , Nuijts Rudy M.M.A. , Lundström Mats , Dickman Mor M.
Published: January 2021

Purpose:

To report practice patterns of corneal transplantation in Europe.

Setting:

Corneal clinics in 10 European member states (MS), the United Kingdom, and Switzerland.

Design:

Multinational registry study.

Methods:

Corneal transplant procedures registered in the European Cornea and Cell Transplantation Registry were identified. Preoperative donor and recipient characteristics, indication and reason for transplantation, and surgical techniques were analyzed.

Results:

A total of 12 913 corneal transplants were identified from 10 European Union MS, the United Kingdom, and Switzerland. Most countries were self-sufficient with regard to donor tissue. Fuchs endothelial corneal dystrophy was the most common indication (41%, n = 5325), followed by regraft (16%, n = 2108), pseudophakic bullous keratopathy (12%, n = 1594), and keratoconus (12%, n = 1506). Descemet stripping automated endothelial keratoplasty (DSAEK, 46%, n = 5918) was the most commonly performed technique, followed by penetrating keratoplasty (30%, n = 3886) and Descemet membrane endothelial keratoplasty (9%, n = 1838). Vision improvement was the main reason for corneal transplantation (90%, n = 11 591). Surgical technique and reason for transplantation differed between indications.

Conclusions:

This report provides the most comprehensive overview of corneal transplantation practice patterns in Europe to date. Fuchs endothelial dystrophy is the most common indication, vision improvement the leading reason, and DSAEK the predominant technique for corneal transplantation.