bluuebunny/crossref_metadata_2025 huggingface dataset:
Invited review: strategic adoption of antibiotic-free pork production: the importance of a holistic approach
Authors: Patience John F , Ramirez Alejandro
Published: May 2022

The discovery of the use of antibiotics to enhance growth in the 1950s proved to be one of the most dramatic and influential in the history of animal agriculture. Antibiotics have served animal agriculture, as well as human and animal medicine, well for more than seven decades, but emerging from this tremendous success has been the phenomenon of antimicrobial resistance. Consequently, human medicine and animal agriculture are being called upon, through legislation and/or marketplace demands, to reduce or eliminate antibiotics as growth promotants and even as therapeutics. As explained in this review, adoption of antibiotic-free (ABF) pork production would represent a sea change. By identifying key areas requiring attention, the clear message of this review is that success with ABF production, also referred to as “no antibiotics ever,” demands a multifaceted and multidisciplinary approach. Too frequently, the topic has been approached in a piecemeal fashion by considering only one aspect of production, such as the use of certain feed additives or the adjustment in health management. Based on the literature and on practical experience, a more holistic approach is essential. It will require the modification of diet formulations to not only provide essential nutrients and energy, but to also maximize the effectiveness of normal immunological and physiological capabilities that support good health. It must also include the selection of effective non-antibiotic feed additives along with functional ingredients that have been shown to improve the utility and architecture of the gastrointestinal tract, to improve the microbiome, and to support the immune system. This holistic approach will require refining animal management strategies, including selection for more robust genetics, greater focus on care during the particularly sensitive perinatal and post-weaning periods, and practices that minimize social and environmental stressors. A clear strategy is needed to reduce pathogen load in the barn, such as greater emphasis on hygiene and biosecurity, adoption of a strategic vaccine program and the universal adoption of all-in-all-out housing. Of course, overall health management of the herd, as well as the details of animal flows, cannot be ignored. These management areas will support the basic biology of the pig in avoiding or, where necessary, overcoming pathogen challenges without the need for antibiotics, or at least with reduced usage.
Climate change impacts shifting landscape of the dairy industry in Hawai‘i
Authors: Adhikari Mandeep , Longman Ryan J , Giambelluca Thomas W , Lee C N , He Yanghua
Published: May 2022

Proper knowledge and understanding of climatic variability across different seasons are important in farm management. To learn more about the potential effects of climate change on dairying in Hawaii, we conducted a study on site-specific climate characterization using several variables including rainfall, wind speed (WS), solar radiation, and temperature, at two dairy farms located on Hawai`i Island, Hawai`i, in Ookala named “OK DAIRY” and in Upolu Point named “UP DAIRY.” Temperature–humidity index (THI) and WS variations in the hottest four months (June to September) were analyzed to determine when critical thresholds that affect animal health are exceeded. Rainfall data were used to estimate the capacity of forage production in 6-mo wet (November to April) and dry (May to October) seasons. Future projections of temperature and rainfall were assessed using mid- and end-century gridded data products for low (RCP 4.5) and high emissions (RCP 8.5) scenarios. Our results showed that the “OK DAIRY” site received higher rainfall than the “UP DAIRY” site, favoring grass growth and forage availability. In addition, the “UP DAIRY” site was more stressful for animals during the summer (THI 69 to 73) than the “OK DAIRY” site (THI 67 to 70) as the THI exceeded the critical threshold of 68, which is conducive for high-lactating cattle. On the “UP DAIRY” site, the THI did not drop below 68 during the summer nights, which created fewer opportunities for cattle to recover from heat stress. Future projections indicated that air temperature would increase 1.3 to 1.8 °C by mid-century and 1.6 to 3.2 °C by the end-century at both farms, and rainfall will increase at the “OK DAIRY” site and decrease at the “UP DAIRY” site by the end-century. The agriculture and livestock industries, particularly the dairy and beef subsectors in Hawai`i, are vulnerable to climate changes as higher temperatures and less rainfall will have adverse effects on cattle. The findings in this study demonstrated how both observed and projected changes in climate support the development of long-term strategies for breeding and holistic livestock management practices to adapt to changing climate conditions.
A Revised Markov Model Evaluating Oophorectomy at the Time of Hysterectomy for Benign Indication
Authors: Rush Shannon K. , Ma Xiuyu , Newton Michael A. , Rose Stephen L.
Published: May 2022

OBJECTIVE:

To perform an updated Markov modeling to assess the optimal age for bilateral salpingo-oophorectomy (BSO) at the time of hysterectomy for benign indication.

METHODS:

We performed a literature review that assessed hazard ratios (HRs) for mortality by disease, age, hysterectomy with or without BSO, and estrogen therapy use. Base mortality rates were derived from national vital statistics data. A Markov model from reported HRs predicted the proportion of the population staying alive to age 80 years by 1-year and 5-year age groups at time of surgery, from age 45 to 55 years. Those younger than age 50 years were modeled as either taking postoperative estrogen or not; those 50 and older were modeled as not receiving estrogen. Computations were performed with R 3.5.1, using Bayesian integration for HR uncertainty.

RESULTS:

Performing salpingo-oophorectomy before age 50 years for those not taking estrogen yields a lower survival proportion to age 80 years than hysterectomy alone before age 50 years (52.8% [Bayesian CI 40.7–59.7] vs 63.5% [Bayesian CI 62.2–64.9]). At or after age 50 years, there were similar proportions of those living to age 80 years with hysterectomy alone (66.4%, Bayesian CI 65.0–67.6) compared with concurrent salpingo-oophorectomy (66.9%, Bayesian CI 64.4–69.0). Importantly, those taking estrogen when salpingo-oophorectomy was performed before age 50 years had similar proportions of cardiovascular disease, stroke, and people living to age 80 years as those undergoing hysterectomy alone or those undergoing hysterectomy and salpingo-oophorectomy at age 50 years and older.

CONCLUSION:

This updated Markov model argues for the consideration of concurrent salpingo-oophorectomy for patients who are undergoing hysterectomy at age 50 and older and suggests that initiating estrogen in those who need salpingo-oophorectomy before age 50 years mitigates increased mortality risk.
County-Level Associations Between Pregnancy-Related Mortality Ratios and Contextual Sociospatial Indicators
Authors: Barrera Chloe M. , Kramer Michael R. , Merkt Peter T. , Petersen Emily E. , Brantley Mary D. , Eckhaus Lindsay , Beauregard Jennifer L. , Goodman David A.
Published: May 2022

OBJECTIVE:

To characterize county-level differences in pregnancy-related mortality as a function of sociospatial indicators.

METHODS:

We conducted a cross-sectional multilevel analysis of all pregnancy-related deaths and all live births with available ZIP code or county data in the Pregnancy Mortality Surveillance System during 2011–2016 for non-Hispanic Black, Hispanic (all races), and non-Hispanic White women aged 15–44 years. The exposures included 31 conceptually-grounded, county-specific sociospatial indicators that were collected from publicly available data sources and categorized into domains of demographic; general, reproductive, and behavioral health; social capital and support; and socioeconomic contexts. We calculated the absolute difference of county-level pregnancy-related mortality ratios (deaths per 100,000 live births) per 1-unit increase in the median absolute difference between women living in counties with higher compared with lower levels of each sociospatial indicator overall and stratified by race and ethnicity.

RESULTS:

Pregnancy-related mortality varied across counties and by race and ethnicity. Many sociospatial indicators were associated with county-specific pregnancy-related mortality ratios independent of maternal age, population size, and Census region. Across domains, the most harmful indicators were percentage of low-birth-weight births (absolute ratio difference [RD] 6.44; 95% CI 5.36–7.51), percentage of unemployed adults (RD 4.98; 95% CI 3.91–6.05), and food insecurity (RD 4.92; 95% CI 4.14–5.70). The most protective indicators were higher median household income (RD −2.76; 95% CI −3.28 to −2.24), percentage of college-educated adults (RD −2.28; 95% CI −2.81 to −1.75), and percentage of owner-occupied households (RD −1.66; 95% CI −2.29 to −1.03). The magnitude of these associations varied by race and ethnicity.

CONCLUSION:

This analysis identified sociospatial indicators of pregnancy-related mortality and showed an association between pregnancy-related deaths and place of residence overall and stratified by race and ethnicity. Understanding county-level context associated with pregnancy-related mortality may be an important step towards building public health evidence to inform action to reduce pregnancy-related mortality at local levels.
Association of Pharmacist Prescription of Contraception With Breaks in Coverage
Authors: Rodriguez Maria I. , Manibusan Brynna , Kaufman Menolly , McConnell K. John
Published: May 2022

OBJECTIVE:

To assess whether pharmacist prescription of combined hormonal contraception is associated with 12-month contraceptive continuation rates or breaks in contraceptive coverage.

METHODS:

We conducted a retrospective cohort study of all short-acting, hormonal contraceptive users (pill, patch, ring, injectable) in Oregon's All Payer All Claims database from January 1, 2016, to December 31, 2018. We captured contraceptive use using diagnosis and National Drug Classification codes. We used logistic regression to measure the association between prescription by a pharmacist and 12-month contraceptive continuation rates and breaks in contraceptive coverage. Model covariates included age, rurality, and payer.

RESULTS:

Our study sample consisted of 172,325 contraceptive users, of whom 1,512 (0.9%) received their prescriptions from a pharmacist. Pharmacists were significantly more likely than clinicians to prescribe to women between the ages of 25 and 34 years (50.5% vs 36.9%, P<.05), in urban settings (88.4% vs 81.7%, P<.05), and with commercial insurance (89.2% vs 59.5%, P<.05). We found that the rate of 12 months contraceptive continuation was higher among the population receiving a pharmacist prescription (34.3% vs 21.0%, P<.01). In an adjusted model, the odds of contraceptive continuation at 12 months were 61.0% higher for individuals with any pharmacist prescription (adjusted odds ratio [aOR] 1.61, 95% CI 1.44–1.79) compared with those with clinician prescriptions. Over 6 months, most contraceptive users in both groups experienced a break in coverage, defined as a gap of 1–29 days between prescriptions (61.6% vs 61.9%, P=.89). Breaks in contraceptive use were not significantly associated with prescriber type (aOR 1.03, 95% CI 0.90–1.18).

CONCLUSION:

Compared with clinician prescriptions, pharmacist prescription of contraception is associated with increased odds of 12-month contraceptive continuation rates. However, the frequency of breaks in contraceptive coverage was similar among pharmacist and clinic-based prescribers.

FUNDING SOURCE:

Arnold Ventures.
Association of Body Mass Index With the Use of Health Care Resources in Low-Risk Nulliparous Pregnancies After 39 Weeks of Gestation
Authors: Costantine Maged M. , Sandoval Grecio J. , Grobman William A. , Reddy Uma M. , Tita Alan T.N. , Silver Robert M. , El-Sayed Yasser Y. , Wapner Ronald J. , Rouse Dwight J. , Saade George R. , Thorp John M. , Chauhan Suneet P. , Chien Edward K. , Casey Brian M. , Srinivas Sindhu K. , Swamy Geeta K. , Simhan Hyagriv N. ,   for the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units (MFMU) Network
Published: May 2022

OBJECTIVE:

To compare health care medical resource utilization in low-risk nulliparous pregnancies according to body mass index (BMI, calculated as weight in kilograms divided by height in meters squared) categories.

METHODS:

This is a secondary analysis of a multicenter randomized controlled trial of induction of labor between 39 0/7 39 and 4/7 weeks of gestation compared with expectant management in low-risk nulliparous pregnant people, defined as those without standard obstetric indications for delivery at 39 weeks. Body mass index at randomization was categorized into four groups (lower than 25, 25–29, 30–39, and 40 or higher). The primary outcome of this analysis was time spent in the labor and delivery department from admission to delivery. Secondary outcomes included length of stay (LOS) postdelivery, total hospital LOS, and antepartum, intrapartum, and postpartum resource utilization, which were defined a priori. Multivariable generalized linear modeling and logistic regressions were performed, and 99% CIs were calculated.

RESULTS:

A total of 6,058 pregnant people were included in the analysis; 640 (10.6%) had BMIs of lower than 25, 2,222 (36.7%) had BMIs between 25 and 29, 2,577 (42.5%) had BMIs of 30–39, and 619 (10.2%) had BMIs of 40 or higher. Time spent in the labor and delivery department increased from 15.1±9.2 hours for people with BMIs of lower than 25 to 23.5±13.6 hours for people with BMIs of 40 or higher, and every 5-unit increase in BMI was associated with an average 9.8% increase in time spent in the labor and delivery department (adjusted estimate per 5-unit increase in BMI 1.10, 99% CI 1.08–1.11). Increasing BMI was not associated with an increase in antepartum resource utilization, except for blood tests and urinalysis. However, increasing BMI was associated with higher odds of intrapartum resource utilization, longer total hospital LOS, and postpartum resource utilization. For example, every 5-unit increase in BMI was associated with an increase of 26.1% in the odds of antibiotic administration, 57.6% in placement of intrauterine pressure catheter, 5.1% in total inpatient LOS, 31.0 in postpartum emergency department visit, and 23.9% in postpartum hospital admission.

CONCLUSION:

Among low-risk nulliparous people, higher BMI was associated with longer time from admission to delivery, total hospital LOS, and more frequent utilization of intrapartum and postpartum resources.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT01990612.
Contemporary Use and Techniques of Laparoscopic Sacrocolpopexy With or Without Robotic Assistance for Pelvic Organ Prolapse
Authors: Culligan Patrick J. , Saiz Cristina M. , Rosenblatt Peter L.
Published: May 2022

The past 4 years have been consequential in the world of surgery to correct pelvic organ prolapse. In 2018, results of a large, multicenter randomized trial demonstrated very disappointing cure rates of traditional native tissue repairs at 5 years or more. In 2019, a vaginal mesh hysteropexy kit was removed from the market by the U.S. Food and Drug Administration only to subsequently demonstrate it provided better cure rates and similar risk profile to vaginal hysterectomy plus native tissue repair in its own 5-year study published in 2021. Meanwhile, the use and techniques of laparoscopic sacrocolpopexy with or without robotic assistance have evolved such that it is commonly adapted to treat all support defects for patients with uterovaginal or posthysterectomy prolapse. This article is intended to provide an overview of the contemporary use and techniques of laparoscopic sacrocolpopexy based on the evidence and our clinical experience.
Use of Estrogen Therapy After Surgical Menopause in Women Who Are Premenopausal
Authors: Suzuki Yukio , Huang Yongmei , Melamed Alexander , Clair Caryn M. St. , Hou June Y. , Khoury-Collado Fady , Gockley Allison , Accordino Melissa , Hershman Dawn L. , Wright Jason D.
Published: May 2022

OBJECTIVE:

To examine the use of estrogen therapy (ET) and patterns of follow-up evaluation for sequelae of estrogen deprivation among women who were premenopausal who underwent bilateral salpingo-oophorectomy (BSO) for benign gynecologic diseases.

METHODS:

The IBM Watson Health MarketScan Research Databases were used to identify women between age 18 and 50 years who underwent BSO from 2008 to 2019. Estrogen therapy was defined as any prescription of estrogen filled from 6 weeks before BSO to 36 months after BSO. Patterns of follow-up testing including bone mineral density and lipid testing were examined.

RESULTS:

We identified a total of 61,980 women who underwent BSO for benign indications. Overall, 64.5% (95% CI 64.1–64.9%) of women received ET. The rate of ET use within 36 months of surgery declined from a peak of 69.5% in 2008 to 58.2% in 2016. The median duration of continuous ET was 5.3 months. Estrogen therapy use declined with increasing age. The cumulative rate of ET use at 36 months after surgery was 79.1% (95% CI 76.9–81.1) in those aged 18–29 years, 75.9% (95% CI 74.5–77.3%) in those aged 30–34 years, 70.2% (95% CI 69.1–71.2%) in those aged 35–39 years, 66.1% (95% CI 65.3–66.9%) in those aged 40–44 years, and 60.0% (95% CI 59.4–60.6%) in those aged 45–50 years. In a multivariable model, women who underwent surgery more recently and those with medical comorbidities were less likely to receive ET, whereas younger women, those with Medicaid insurance, those outside of the northeast, and those who underwent concurrent hysterectomy were more likely to receive ET.

CONCLUSION:

Estrogen therapy use in women who are premenopausal who underwent BSO for benign gynecologic diseases has declined substantially over the past decade.
Apical Support Procedures at the Time of Hysterectomy for Benign Indications
Authors: Wang Rui , Tulikangas Paul , Harvie Heidi S.
Published: May 2022

OBJECTIVE:

To assess the cost effectiveness of performing routine concurrent apical support procedures at the time of hysterectomy for benign indications.

METHODS:

We developed a Markov decision model from the health care sector perspective to compare concurrent apical support (ie, McCall culdoplasty) at the time of hysterectomy for benign indications compared with hysterectomy alone. We modeled Markov transitions between asymptomatic, prolapse without treatment, and treated prolapse states for 3 years. Our primary outcome was incremental cost-effectiveness ratio, defined as the difference between groups in mean cost (2019 U.S. dollars) divided by the difference in mean quality-adjusted life-years (QALYs). Model parameter estimates were taken from the published medical literature. Cost estimates were obtained from Medicare reimbursement rates and the literature. One-way, two-way, and probabilistic sensitivity analyses were performed.

RESULTS:

We assumed a base-case scenario of 13% posthysterectomy prolapse after hysterectomy alone and 2.1% after concurrent apical support, 5.8% and 0.9% undergoing subsequent surgical treatment for prolapse, respectively. Concurrent apical support at the time of hysterectomy had higher costs ($1,667 vs $1,423) but was more effective (2.34 vs 2.31 QALYs) than hysterectomy alone. Concurrent apical support was cost effective with an incremental cost-effectiveness ratio of $11,988/QALY, compared with general willingness-to-pay ranges of $50,000–150,000/QALY. In sensitivity analyses, concurrent apical support remained cost effective as long as the rate of posthysterectomy prolapse after concurrent apical support remained less than 8.7%. Monte Carlo simulation showed that concurrent apical support was cost effective in more than 60% of the simulated iterations.

CONCLUSION:

Apical support at the time of hysterectomy for benign indications is cost effective compared with hysterectomy alone from the health care sector perspective at 3 years. Our results suggest that encouraging concurrent apical support procedures at time of hysterectomy is a cost-effective strategy in preventing posthysterectomy vaginal prolapse.
Severity of Pancreatic Leak in Relation to Gut Restoration After Pancreaticoduodenectomy
Authors: Smyrniotis Vasileios , Parasyris Stavros , Gemenetzis Georgios , Margaris Ioannis , Petropoulou Zoe , Papadoliopoulou Maria , Sidiropoulos Theodoros , Dellaportas Dionysios , Vezakis Antonios , Polydorou Andreas , Kokoropoulos Panagiotis , Theodoraki Kassiani , Matsota Paraskevi , Vassiliu Panteleimon , Arkadopoulos Nikolaos
Published: May 2022

Background:

Pancreatic leak after pancreaticoduodenectomy and gut restoration via a single jejunal loop remains the crucial predictor of patients’ outcome. Our reasoning that active pancreatic enzymes may be more disruptive to the pancreatojejunostomy prompted us to explore a Roux-en-Y configuration for the gut restoration, anticipating diversion of bile salts away from the pancreatic stump. Our study aims at comparing two techniques regarding the severity of postoperative pancreatic fistula (POPF) and patients’ outcome.

Methods:

The files of 415 pancreaticoduodenectomy patients were retrospectively reviewed. Based on gut restoration, the patients were divided into: cohort A (n = 105), with gut restoration via a single jejunal loop, cohort B (n = 140) via a Roux-en-Y technique assigning the draining of pancreatic stump to the short limb and gastrojejunostomy and bile (hepaticojejunostomy) flow to long limb, and cohort C (n = 170) granting the short limb to the gastric and pancreatic anastomosis, whereas hepaticojejunostomy was performed to the long limp. The POPF-related morbidity and mortality were analyzed.

Results:

Overall POPF in cohort A versus cohorts B and C was 19% versus 12.1% and 9.4%, respectively (P = 0.01 A vs B + C). POPF-related morbidity in cohort A versus cohorts B and C was 10.5% versus 7.3% and 6.3%, respectively (P = 0.03 A vs B+C). POPF-related total hospital mortality in cohorts A versus B and C was 1.9% versus 0.8% and 0.59%, respectively (P = 0.02 A vs B+C).

Conclusion:

Roux-en-Y configuration showed lower incidence and severity of POPF. Irrespective of technical skill, creating a gastrojejunostomy close to pancreatojejunostomy renders the pancreatic enzymes less active by leaping the bile salts away from the pancreatic duct and providing a lower pH.
Estimating Skeletal Maturity Using Wrist Radiographs During Preadolescence: The Epiphyseal:Metaphyseal Ratio
Authors: Huang Lauren F. , Furdock Ryan J. , Uli Naveen , Liu Raymond W.
Published: May 2022

Background:

Although skeletal maturity is most relevant during adolescence, it has utility in treatment of younger patients in some circumstances, such as scoliosis, limb length discrepancy, or endocrinopathies. Currently, a quick, accurate, and reproducible method of estimating skeletal maturity in preadolescents using wrist radiographs is lacking.

Methods:

Serial anteroposterior wrist radiographs taken at historical growth study visits leading up to the chronological age (CA) associated with 90% of the final height (an enhanced skeletal maturity standard as compared with peak height velocity) were analyzed in 102 children. Epiphyseal and metaphyseal widths of 5 physes were evaluated: distal radius, distal ulna, first metacarpal, third metacarpal, and fifth metacarpal. Ulnar styloid height and radial styloid height were also measured, for a total of 7 epiphyseal:metaphyseal radiographic parameters. Greulich and Pyle (GP) bone age was also measured. A combination of stepwise linear regression and generalized estimating equation analyses was used to produce a skeletal maturity estimation model incorporating demographics (CA and sex) and the epiphyseal:metaphyseal ratios significantly correlated with skeletal maturity.

Results:

A total of 273 left anteroposterior hand-wrist radiographs from 56 girls (163 radiographs, range 4 to 13 y) and 46 boys (112 radiographs, range 3.8 to 15 y) were included. The demographics+ratios model had better prediction accuracy than GP only and GP with demographics (0.44, 0.87, and 0.47 y mean discrepancy from actual skeletal age, P<0.05 for both comparisons). There was no significant difference in the rate of outlier skeletal age estimates, defined as an estimate >1 year off from the true skeletal age, between the demographics+ratios model and the demographics+GP model (5.9% vs. 8.4%, P=0.12).

Conclusions:

When combined with CA and sex data, measurement of the epiphyseal:metaphyseal ratios of the left first and third metacarpals allows for improved skeletal maturity estimation compared with the GP technique.

Clinical Relevance:

Our modified wrist skeletal maturity system offers a relatively quick and reproducible method for estimating skeletal maturity extending into the juvenile age range. This study is a level III retrospective study of longitudinal human growth data obtained from the Bolton Brush Collection in Cleveland, Ohio.
Treatment of STAT5b-RARA positive acute promyelocytic leukemia by Venetoclax combining with homoharringtonine, cytarabine: A case report and literature review
Authors: Zhang Guangji , Song Yang , Wan Li , Liu Kaiqi , Qiu Shaowei , Wang Jianxiang , Mi Yingchang
Published: May 2022

Introduction:

Acute promyelocytic leukemia (APL) is mostly due to the chromosome translocation t (15; 17) (q22; q12), leading to the formation of PML-RARA fusion protein. Some patients carried rare translocation involving RARA gene, who were called variant APL caused by RAR family (RARA, RARB, and RARG) and partner genes. STAT5b-RARA was a rare type of molecular genetic abnormality with unfavorable prognosis which have been reported in only 18 cases in variant APL. Knowledge of STAT5b-RARA (+) APL treatment is still limited.

Case report:

We presented a 38-year-old female variant APL case, who was STAT5b-RARA positive detected by reverse transcription polymerase chain reaction. The patient failed to respond after four-drug combined induction chemotherapy: idarubicin, cytarabine, all trans retinoic acid, and arsenic trioxide (As2O3). Then, the patient was re-induced with azacytidine, but still failed to achieve complete remission (CR). Next, she was treated with Venetoclax combining with homoharringtonine and cytarabine as the salvage therapy and achieved CR. Later, the patient received hematopoietic stem cell transplantation after 4 cycles of consolidation therapy.

Conclusion:

Venetoclax combining with homoharringtonine and cytarabine has been used as the salvage therapy in the STAT5b-RARA positive APL successfully.
Pembrolizumab-induced Myasthenia Gravis: Literature Review of Ocular Manifestations and a Refractory Case
Authors: Dugena Oliver , Zheng Chaolan , Taylor Jennifer , Wong Annie
Published: May 2022

Immune checkpoint inhibition is a new and promising therapy approved for the treatment of various malignancies. Pembrolizumab is a potent tumor suppressor that acts by upregulating the immune system to recognize cancer cells which may result in disrupted self-tolerance. We describe a case and perform a literature review of myasthenia gravis with ocular manifestations after treatment with pembrolizumab. Our case had bilateral ptosis refractory to conventional treatment, and she remained functionally blind as a result. The literature review included 28 cases of immune-related myasthenia gravis, and a 30% mortality rate excluding deaths from primary cancer progression was shown. Under half had full symptom resolution (n=13, 46%), and there was no clear correlation between specific management strategies and prognosis. Patients with isolated ocular myasthenia gravis (n=9, 32%) were twice as likely to be symptom-free after treatment compared with generalized myasthenia gravis (75% vs. 39%). Respiratory involvement was associated with twice the mortality rate (60% vs. 33%) and triple the risk of noncomplete symptom resolution (20% vs. 61%). The majority of cases had their pembrolizumab discontinued (n=20, 71%), but 3 were successfully rechallenged by utilizing prophylactic low-dose steroids. Patients with immune-related myasthenia gravis experience increased mortality and morbidity but if steroid-responsive, may benefit from the reintroduction of anti–programmed cell death protein 1 therapy for end-stage malignancy with close monitoring. A high index of clinical suspicion for immune-related adverse effects are critical in an era of rising immunotherapy use.
EFFICIENCY OF LASER PHOTOCOAGULATION ON THE PREVENTION OF RETINAL DETACHMENT IN ACUTE RETINAL NECROSIS
Authors: Chen Man , Zhang Meiqin , Chen Haoyu
Published: May 2022

Background:

Retinal detachment is a severe complication of acute retinal necrosis, threatening vision. The published articles on the effectiveness of laser in preventing retinal detachment in acute retinal necrosis are controversial. Therefore, we aim to evaluate whether prophylactic laser is effective for retinal detachment after acute retinal necrosis.

Methods:

PubMed, Embase, and Cochrane databases were searched, and the retrieved records were screened. Each included study has well-defined laser-treated group and control group without laser treatment or with enough data for manual grouping. The quality of the included studies was assessed using ROBINS-I (“Risk Of Bias In Nonrandomized Studies—of Interventions”). Meta-analysis was conducted to calculate the pooled odds ratios and their 95% confidence interval. Sensitivity analysis was used to test the solidarity, and subgroup analysis was performed to determine the source of heterogeneity.

Results:

Fourteen studies with a total of 532 eyes were eventually included. The quality of the included studies was moderate. The combined results showed that the pooled odds ratio was 0.61 (95% confidence interval [0.41∼0.90], P < 0.05, I2 = 27%). Sensitivity analysis showed that the odds ratios were similar when excluding any study. Subgroup analysis showed moderate heterogeneity among three subgroups (I2 = 48.0%, P = 0.15 for heterogeneity), and the odds ratio in antiviral therapy and steroid combined with prophylactic laser was 0.43 (95% confidence interval [0.25∼0.74], P < 0.05, I2 = 0%).

Conclusion:

In patients with acute retinal necrosis, laser photocoagulation is an effective treatment to prevent retinal detachment, especially in the subgroup combined with antiviral therapy and steroid.
Yellow Plaques Around the Eyes
Authors: Medepalli Vidya M. , Langley Collins , Mockbee Chelsea S. , Brodell Robert T. , Nahar Vinayak K.
Published: May 2022

A 67-year-old Black man was found to have skin-colored papules and plaques on the eyelids with a yellow hue on routine annual skin examination. The patient was asymptomatic. The differential diagnosis for papules and plaques on the eyelids is reviewed based on presentations, patient histories, and distinguishing visual features. Lesions in skin of color may present a diagnostic challenge as the appearance of the same lesion in a variety of skin tones may not appear commonly in textbooks. The purpose of this case is to improve knowledge of the appearance of a common skin condition in skin of color. A primary care provider's prompt recognition of this diagnosis may promote workup and treatment for possible underlying systemic diseases, leading to decreased morbidity and improved health outcomes.
Factors Contributing to Burnout and Well-Being in Physical Therapist Students
Authors: Smith Allison , Ellison Jennifer , Bogardus Jennifer , Gleeson Peggy
Published: May 2022

Introduction.

Burnout is a syndrome resulting from chronic workplace stress that has not been successfully managed. Prevention and management of burnout in the doctor of physical therapy (DPT) student population may help reduce the development of burnout later in their work life.

Review of Literature.

Few published studies assessing burnout have been conducted with physical therapist students. In studies with medical and nursing students, individual factors that influence the development of burnout include reduced level of physical activity, reduced level of social support, not experiencing positive life events, increased fatigue, increased stress, and decreased resilience. Environmental factors that influence the development of burnout include grading scheme and perceptions of the learning environment.

Subjects.

Participants included 20 DPT students from across the United States.

Method.

A total of 522 students from a previous study who volunteered for the present grounded theory qualitative study were stratified by burnout group (burnout and nonburnout) and geographic region. Once stratified, students were randomized and then contacted through email to set up an interview time to participate in a Zoom audio interview. A total of 20 semistructured interviews were completed ranging from 20 to 40 minutes.

Results.

Three major themes emerged from the data, each with 3 subthemes. The major themes included burnout experience, factors that negatively affected well-being, and factors that positively affected well-being.

Discussion and Conclusion.

The results of this study indicate that DPT students experienced burnout as a combination of exhaustion, disengagement, and chronic overload. Factors that negatively affected well-being while in DPT school included unmanageable stress, an excessive workload, and time pressures. Factors that positively affected well-being while in DPT school included prioritizing time, support from faculty, friends, and family, and self-awareness.
Improving Extracorporeal Membrane Oxygenation Survival in COVID-19. Effect of a Bundle of Care
Authors: Salazar Leonardo , Bermon Anderson , Vasquez Raul , Castillo Mario , Mendoza-Monsalve Alejandra , Landinez Maria F. , Ortiz-Cordoba Angelica L. , Meneses Karenth J. , Ferrer Wilfran J. , Ballesteros Juliana , Espinosa Andres , Pizarro Maria P. , Pinilla-Ojeda Jorge , Mayorga-Suarez Cinthia P. , Pardo Elkin J. , Merchán Ivan H. , Alvarez Javier , Diaz Rodrigo , Pizarro Camilo E.
Published: May 2022

Veno-venous extracorporeal membrane oxygenation (ECMO) support surged during the COVID-19 pandemic. Our program changed the model of care pursuing to protect the multidisciplinary team from the risk of infection and to serve as many patients as possible. Patient–healthcare interactions were restricted, and the ECMO bed capacity was increased by reducing the ECMO specialist–patient ratio to 1:4 with non-ECMO trained nurses support. The outcomes worsened and we paused while we evaluated and modified our model of care. The ECMO bed capacity was reduced to allow a nurse ECMO–specialist nurse ratio 2:1 with an ECMO trained nurse assistant’s support. Intensivists, general practitioners, nurse assistants, and physical and respiratory therapists were trained on ECMO. Tracheostomy, bronchoscopy, and microbiological molecular diagnosis were done earlier, and family visits and rehabilitation were allowed in the first 48 hours of ECMO cannulation. There were 35 patients in the preintervention cohort and 66 in the postintervention cohort. Ninety days mortality was significantly lower after the intervention (62.9% vs. 31.8%, p = 0.003). Factors associated with increased risk of death were the need for cannulation or conversion to veno arterial or veno arterio venous ECMO, hemorrhagic stroke, and renal replacement therapy during ECMO. The interventions associated with a decrease in the risk of death were the following: early fiberoptic bronchoscopy and microbiological molecular diagnostic tests. Increasing the ECMO multidisciplinary team in relation to the number of patients and the earlier performance of diagnostic and therapeutic interventions, such as tracheostomy, fiberoptic bronchoscopy, molecular microbiological diagnosis of pneumonia, rehabilitation, and family support significantly decreased mortality of patients on ECMO due to COVID-19.
Intracranial Volumes of Healthy Children in the First 3 Years of Life: An Analysis of 270 Magnetic Resonance Imaging Scans
Authors: Brandel Michael G. , Kamel George N. , Carbulido Kristine , Belza Caitlyn , Modi Rishi , McKee Ryan , Cronin Brendan J. , Ewing Emily , Lance Samuel H. , Gosman Amanda A.
Published: May 2022

Background:

There is a paucity of data on normal intracranial volumes for healthy children during the first few years of life, when cranial growth velocity is greatest. The aim of this study was to generate a normative predictive model of intracranial volumes based on brain magnetic resonance imaging from a large sample of healthy children to serve as a reference tool for future studies on craniosynostosis.

Methods:

Structural magnetic resonance imaging data for healthy children up to 3 years of age was acquired from the National Institutes of Health Pediatric MRI Data Repository. Intracranial volumes were calculated using T1-weighted scans with FreeSurfer (version 6.0.0). Mean intracranial volumes were calculated and best-fit logarithmic curves were generated. Results were compared to previously published intracranial volume curves.

Results:

Two-hundred seventy magnetic resonance imaging scans were available: 118 were collected in the first year of life, 97 were collected between years 1 and 2, and 55 were collected between years 2 and 3. A best-fit logarithmic growth curve was generated for male and female patients. The authors’ regression models showed that male patients had significantly greater intracranial volumes than female patients after 1 month of age. Predicted intracranial volumes were also greater in male and female patients in the first 6 months of life as compared to previously published intracranial volume curves.

Conclusions:

To the authors’ knowledge, this is the largest series of demographically representative magnetic resonance imaging–based intracranial volumes for children aged 3 years and younger. The model generated in this study can be used by investigators as a reference for evaluating craniosynostosis patients.
Endoscope-Assisted Fronto-Orbital Distraction Osteogenesis
Authors: Kalmar Christopher L. , Carlson Anna R. , Kosyk Mychajlo S. , Zapatero Zachary D. , Heuer Gregory G. , Taylor Jesse A.
Published: May 2022

Anterior cranial vault fronto-orbital distraction osteogenesis is a promising treatment modality for children with unicoronal craniosynostosis. A minimally invasive, endoscope-assisted approach offers the additional potential benefits of less scalp scarring, decreased blood loss, and decreased scalp dissection. In this article, the authors present a novel technique for minimally invasive, endoscope-assisted fronto-orbital distraction osteogenesis.
School-Based Telepractice Assessment (STA)
Authors: Lundblom Erin , Cohn Ellen R. , Tindall Covert Lyn
Published: May 2022

Over 50% of American Speech-Language-Hearing Association (ASHA)-certified speech–language pathologists (SLPs) are employed in schools (ASHA, n.d.). Speech–language pathologists increasingly provide services to students with speech and language disorders via telepractice. ASHA's Roles and Responsibilities of Speech-Language Pathologists in Schools document states that telepractice services must be comparable to in-person services (ASHA, 2010). This article presents the School-Based Telepractice Assessment (STA; Lundblom et al., 2021), comprising aspirational questions related to compliance with federal legislation; personnel; roles and responsibilities of school-based SLPs; and privacy and security issues. The STA is designed for use by SLPs, school administrators, and contracted providers. The guide comprehensively evaluates the range of school-based telepractice components such as diagnostic and therapeutic services, the use of support personnel consultation, preventative services, integration with the school culture and curricula, and compliance with federal regulations. The STA can guide both school-based SLPs and administrators as they prepare for telepractice service delivery and later appraise whether the telepractice services are comparable to in-person school-based practice.
Online Language Assessment of School-Age Students
Authors: Kester Ellen Stubbe
Published: May 2022

The purpose of this tutorial is to guide speech–language pathologists in conducting speech and language evaluations remotely. Practical considerations, such as setting up the testing environment and the importance of conducting a pre-evaluation check, are discussed. Different item types and assessments are discussed with consideration of the technology requirements for different tools. Issues such as testing fidelity when remotely administering assessments that were normed with in-person testing and ways to use standardized tools in nonstandardized ways are addressed. The benefits of remote testing are discussed.
The Effect of Rotigotine on Cognitive Function, Daytime Sleepiness, and Sleep Problems in Parkinson Disease: An Open-Label Pilot Study
Authors: Suzuki Keisuke , Funakoshi Kei , Fujita Hiroaki , Hirata Koichi
Published: May 2022

Background

We hypothesized that rotigotine may have a positive effect on cognitive function in patients with Parkinson disease (PD) by improving daytime motor function and sleep status.

Methods

Fifteen PD patients with sleep disturbances, defined as a PD Sleep Scale (PDSS)-2 score of 15 or greater, were included in this single-center, 3-month open-label study. Participants received 2 to 4 mg/24 h (patch content: 4.5–9 mg) rotigotine for a 3-month period. At baseline and 3 months, the patients were evaluated on the Movement Disorder Society Revision of the Unified PD Rating Scale (MDS-UPDRS) parts III and IV and cognitive assessments, such as the Mini-Mental State Examination, frontal assessment battery, and Montreal Cognitive Assessment (MoCA). The Epworth Sleepiness Scale (ESS) and PDSS-2 were administered at baseline and at 1, 2, and 3 months.

Results

At 3 months, the MDS-UPDRS part III (−11.1, P < 0.0001) and MDS-UPDRS part IV (−1.1, P = 0.0013) scores significantly decreased, and off time significantly decreased (−34.6 minutes, P = 0.0085) from baseline. The PDSS-2 scores significantly decreased from baseline at 1 month (−4.2, P < 0.01), 2 months (−7.7, P < 0.0001), and 3 months (−7.3, P < 0.0001). The ESS also decreased at 1 month (−2.5, P < 0.05) and 3 months from baseline (−4.5, P < 0.01). The MoCA scores (1.6, P = 0.0029) significantly improved, but the Mini-Mental State Examination or frontal assessment battery scores did not significantly change. The mean changes from baseline to 3 months in the MoCA were negatively correlated with mean changes in the ESS scores.

Conclusions

We suggest that rotigotine could improve cognitive function by improving motor symptoms, sleep disturbance, and daytime sleepiness in patients with PD.
Impacts of Mycoplasma agalactiae restriction-modification systems on pan-epigenome dynamics and genome plasticity
Authors: Dordet-Frisoni Emilie , Vandecasteele Céline , Contarin Rachel , Sagné Eveline , Baranowski Eric , Klopp Christophe , Nouvel Laurent-Xavier , Citti Christine
Published: May 2022

DNA methylations play an important role in the biology of bacteria. Often associated with restriction modification (RM) systems, they are important drivers of bacterial evolution interfering in horizontal gene transfer events by providing a defence against foreign DNA invasion or by favouring genetic transfer through production of recombinogenic DNA ends. Little is known regarding the methylome of the

Mycoplasma

genus, which encompasses several pathogenic species with small genomes. Here, genome-wide detection of DNA methylations was conducted using single molecule real-time (SMRT) and bisulphite sequencing in several strains of

Mycoplasma agalactiae

, an important ruminant pathogen and a model organism. Combined with whole-genome analysis, this allowed the identification of 19 methylated motifs associated with three orphan methyltransferases (MTases) and eight RM systems. All systems had a homolog in at least one phylogenetically distinct

Mycoplasma

spp. Our study also revealed that several superimposed genetic events may participate in the

M. agalactiae

dynamic epigenomic landscape. These included (i) DNA shuffling and frameshift mutations that affect the MTase and restriction endonuclease content of a clonal population and (ii) gene duplication, erosion, and horizontal transfer that modulate MTase and RM repertoires of the species. Some of these systems were experimentally shown to play a major role in mycoplasma conjugative, horizontal DNA transfer. While the versatility of DNA methylation may contribute to regulating essential biological functions at cell and population levels, RM systems may be key in mycoplasma genome evolution and adaptation by controlling horizontal gene transfers.
The respiratory lipoquinone, menaquinone, functions as an inducer of genes regulated by the Mycobacterium smegmatis repressor MSMEG_2295
Authors: Barman Anik , Patra Madhu Manti , Das Gupta Sujoy K.
Published: May 2022

A previous study reported that the

Mycobacterium smegmatis

(Msm) protein MSMEG_2295 is a repressor controlling the expression of several genes, including that for MSMEG_5125, a putative isoprenoid binding protein belonging to the YceI family, and DinB2, a DNA damage repair enzyme. This repressor is encoded by the first gene of the operon that also expresses the gene for DinB2. Targeted inhibition of MSMEG_5125 using CRISPRi technology resulted in a significant loss of Msm’s respiratory activity and viability. Since this protein has been predicted to be an isoprenoid binding protein, we suspected a role of menaquinones, which are isoprenoid naphthoquinones, in the observed phenomenon. Accordingly, we tested whether MSMEG_5125’s deficiency-induced lethality could be reversed by adding menaquinone. The result was positive, implying cooperation between MSMEG_5125 and menaquinone in bringing about respiration. Inhibition of MSMEG_5125 expression led to the induction of MSMEG_0089 and 2296, two hallmark genes of the MSMEG_2295 regulon. This result suggests that when MSMEG_5125 becomes limiting, a feedback-loop derepresses the MSMEG_2295 regulon genes, including its own. Interestingly, menaquinone functioned as an inducer of MSMEG_5125, indicating that it is likely to mediate the feedback mechanism. This result also strengthens our hypothesis that the functions of menaquinone and MSMEG_5125 are interrelated. Menaquinone also induced the MSMEG_2295-controlled operon MSMEG_2295–2294 (dinB2) not induced following the inactivation of MSMEG_5125. Therefore, the activation mechanism of MSMEG_2295-regulated genes may not be the same for all, although derepression is likely to be a common feature. In vitro, menaquinone abolished MSMEG_2295’s DNA binding activity by interacting with it, confirming its role as an inducer. Therefore, a menaquinone–MSMEG_5125-regulated gene expression circuit controls Msm respiration and possibly oxidative stress-induced DNA damage repair.
Quantitative analysis of diffraction by liquids using a pink-spectrum X-ray source
Authors: Singh Saransh , Coleman Amy L. , Zhang Shuai , Coppari Federica , Gorman Martin G. , Smith Raymond F. , Eggert Jon H. , Briggs Richard , Fratanduono Dayne E.
Published: May 2022

A new approach for performing quantitative structure-factor analysis and density measurements of liquids using X-ray diffraction with a pink-spectrum X-ray source is described. The methodology corrects for the pink beam effect by performing a Taylor series expansion of the diffraction signal. The mean density, background scale factor, peak X-ray energy about which the expansion is performed, and the cutoff radius for density measurement are estimated using the derivative-free optimization scheme. The formalism is demonstrated for a simulated radial distribution function for tin. Finally, the proposed methodology is applied to experimental data on shock compressed tin recorded at the Dynamic Compression Sector at the Advanced Photon Source, with derived densities comparing favorably with other experimental results and the equations of state of tin.