bluuebunny/crossref_metadata_2025 huggingface dataset:
Palliative Care Nurse Perceptions of Nonpharmacological Sleep-Promoting Interventions
Authors: Capezuti Elizabeth
Published: January 2021

Poor quality of sleep is common among those with advanced serious illness. Several interventions have been demonstrated to improve sleep; however, the extent to which these are used is unknown. This study describes nurses' perceptions of 36 nonpharmacological sleep-promoting interventions as well as facilitators and barriers to implementing nonpharmacological interventions. A descriptive survey design was used to collect data via an online, anonymous survey from nurses throughout the United States that included demographic items and open-ended questions (barriers and facilitators). The 108 respondents were nurses working in either a hospital (33.3%) or home care/outpatient (54.6%) setting. Among 36 interventions presented, a mean (SD) total score of feasible interventions per respondent was 27.1 (6.5). There were no significant differences in the mean total feasibility score due to practice site, nurse type, or years of experience. Most thought individual belief in the efficacy of the nonpharmacological intervention was an important facilitator whereas perceived lack of value and institutional support were the major barriers. There was an overall appreciation and positive perception of nonpharmacological, sleep-promoting interventions by palliative care nurses. Increasing use will depend on overcoming barriers by identification of specific patient/caregiver and institutional factors in each setting or patient population.
The Milan System for Reporting Salivary Gland Cytopathology: Benefits and Cautions
Authors: van Zante Annemieke , Ha Patrick , Pusztaszeri Marc Philippe
Published: January 2021

Fine-needle aspiration (FNA) is a well-established procedure for the diagnosis and management of salivary gland lesions despite challenges imposed by their diversity, complexity, and cytomorphological overlap. Until recently, the reporting of salivary gland FNA specimens was inconsistent among different institutions throughout the world, leading to diagnostic confusion among pathologists and clinicians. In 2015, an international group of pathologists initiated the development of an evidence-based tiered classification system for reporting salivary gland FNA specimens, the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC). A corresponding MSRSGC Atlas was published in February 2018. The MSRSGC consists of 6 diagnostic categories that incorporate the morphologic heterogeneity and overlap among various nonneoplastic, benign, and malignant lesions of the salivary glands. In addition, each diagnostic category is associated with a risk of malignancy and management recommendations. The main goal of the MSRSGC is to improve communication between cytopathologists and treating clinicians, while also facilitating cytologic-histologic correlation, quality improvement, and sharing of data from different laboratories for research. Herein, we review the benefits and the limitations of the MSRSGC, as well as the challenges of implementing this new reporting system in routine practice.
Physical Medicine and Rehabilitation Program Directors’ Perspectives on US Medical Licensing Examination Step 1 Scoring Changes
Authors: Chator Areeb A. , Ganesh Kumar Nishant , Drolet Brian C. , Sullivan William J. , Kennedy David J.
Published: January 2021

In response to increasing dependence on US Medical Licensing Examination Step 1 scores for resident selection, and to improve medical student well-being and education, the Federation of State Medical Boards and the National Board of Medical Examiners announced that no sooner than 2022, Step 1 score reporting would change from numeric to pass/fail. To gauge the impact that this change will have on the residency application process in physical medicine and rehabilitation, an anonymous survey was electronically distributed to program directors of all accredited physical medicine and rehabilitation residency programs in the United States. A response rate of 49% was obtained. In total, 13% of program directors agreed that the scoring change was a good idea. Eighty percent of program directors felt that the change would increase emphasis on Step 2 clinical knowledge in the application process and that it will be more difficult to objectively compare applicants. Among free-text responses to the survey, 70% disapproved, 10% approved, and the remaining 20% were neutral to the change. The results of this survey show that many physical medicine and rehabilitation program directors are concerned about the implications of the Step 1 score reporting change. These data can serve as a helpful guide to program directors and students preparing for a pass/fail Step 1.
Design and conduct of confirmatory chronic pain clinical trials
Authors: Katz Nathaniel
Published: January 2021

The purpose of this article is to provide readers with a basis for understanding the emerging science of clinical trials and to provide a set of practical, evidence-based suggestions for designing and executing confirmatory clinical trials in a manner that minimizes measurement error. The most important step in creating a mindset of quality clinical research is to abandon the antiquated concept that clinical trials are a method for capturing data from clinical practice and shifting to a concept of the clinical trial as a measurement system, consisting of an interconnected set of processes, each of which must be in calibration for the trial to generate an accurate and reliable estimate of the efficacy (and safety) of a given treatment. The status quo of inaccurate, unreliable, and protracted clinical trials is unacceptable and unsustainable. This article gathers aspects of study design and conduct under a single broad umbrella of techniques available to improve the accuracy and reliability of confirmatory clinical trials across traditional domain boundaries.
Oncologic Considerations for Safe Gender-Affirming Mastectomy: Preoperative Imaging, Pathologic Evaluation, Counseling, and Long-Term Screening
Authors: Salibian Ara A. , Axelrod Deborah M. , Smith Julia A. , Fischer Beverly A. , Agarwal Cori , Bluebond-Langner Rachel
Published: January 2021

There remain significant gaps in the evidence-based care of patients undergoing gender-affirming mastectomy with regard to implications for breast cancer development and screening. The current clinical evidence does not demonstrate an increased risk of breast cancer secondary to testosterone therapy in transgender patients. Gender-affirmation mastectomy techniques vary significantly with regard to the amount of residual breast tissue left behind, which has unknown implications for the incidence of postoperative breast cancer and need for screening. Subcutaneous mastectomy should aim to remove all gross breast parenchyma, although this is limited in certain techniques. Tissue specimens should also be routinely sent for pathologic analysis. Several cases of incidental breast cancer after subcutaneous mastectomy have been described. There is little evidence on the need for or types of postoperative cancer screening. Chest awareness is an important concept for patients that have undergone subcutaneous mastectomies, as clinical examination remains the most common reported method of postmastectomy malignancy detection. In patients with greater known retained breast tissue, such as those with circumareolar or pedicled techniques, consideration may be given to alternative imaging modalities, although the efficacy and cost-utility of these techniques must still be proven. Preoperative patient counseling on the risk of breast cancer after gender-affirming mastectomy in addition to the unknown implications of residual breast tissue and long-term androgen exposure is critical. Patient awareness and education play an important role in shared decision-making, as further research is needed to define standards of medical and oncologic care in this population.
Topographic and Neural Anatomy of the Depressor Anguli Oris Muscle and Implications for Treatment of Synkinetic Facial Paralysis
Authors: Krag Andreas E. , Dumestre Danielle , Hembd Austin , Glick Samuel , Mohanty Ahneesh J. , Rozen Shai M.
Published: January 2021

Background:

Synkinetic patients often fail to produce a satisfactory smile because of antagonistic action of a hypertonic depressor anguli oris muscle and concomitantly weak depressor labii inferioris muscle. This study investigated their neurovascular anatomy to partially explain this paradoxical depressor anguli oris hypertonicity and depressor labii inferioris hypotonicity and delineated consistent anatomical landmarks to assist in depressor anguli oris muscle injection and myectomy.

Methods:

Ten hemifaces from five fresh human cadavers were dissected to delineate the neurovascular supply of the depressor anguli oris and depressor labii inferioris muscles in addition to the depressor anguli oris muscle relation to consistent anatomical landmarks.

Results:

The depressor anguli oris muscle received innervation from both lower buccal and marginal mandibular facial nerve branches, whereas the depressor labii inferioris muscle was solely innervated by marginal mandibular branches. The mandibular depressor anguli oris origin was on average 39 mm wide, and its medial and lateral borders were located 17 mm from the symphysis and 41 mm from the mandibular angle, respectively. The depressor anguli oris fibers consistently passed anterior to the first mandibular molar toward their insertion into the modiolus, which was located 10 mm lateral and 10 mm caudal to the oral commissure.

Conclusions:

Depressor anguli oris muscle dual innervation versus depressor labii inferioris single innervation may explain why depressor anguli oris hypertonicity and depressor labii inferioris weakness are commonly observed concomitantly in synkinetic patients. Based on treatment goals, diagnostic percutaneous injection with lidocaine can be performed on the depressor anguli oris muscle along a cutaneous line from the modiolus to the mandibular first molar border, and an intraoral depressor anguli oris myectomy can be performed along that same transmucosal line.
The Business of Plastic Surgery: Employment Contracts
Authors: Johnson Debra J. , Adatto, J.D. Bradford E. , Byrd, J.D. Michael S.
Published: January 2021

Plastic surgeons are increasingly choosing to practice as employed physicians: either in an academic position, a single-specialty or multispecialty group, or within a franchise-type business. Employment offers advantages with regard to immediate income, minimal investment in practice start-up costs, and easier access to prospective patients. Surgeons considering such employment must perform due diligence to determine whether the position offered is a good fit. Once the decision is made to offer the plastic surgeon a position, an employment contract is negotiated. It is imperative that all parties understand the provisions of the contract, so that there are no misunderstandings between the employer and employee for the duration of the term. This article introduces physician recruitment offers and employment contracting. The key components of a contract are described, and compensation options are explained. Negotiation of the contract is critical so that all aspects are understood and agreed on, and the responsibilities of all parties are delineated.
Implications of Free Temporoparietal Fascial Flap Reconstruction in the Pediatric Population
Authors: Hamidian Jahromi Alireza , Horen Sydney R. , Konofaos Petros
Published: January 2021

The temporoparietal fascial flap (TPFF) is a versatile tool that can be used in the reconstruction of head and neck and distal upper and lower extremity defects. The TPFF may be harvested as a pedicle or free flap as well as with the temporalis muscle and/or adjacent calvarial bone as a composite flap. As a free flap, the TPFF has been used as a joint gliding surface with coverage of nerves and tendons, for extremity soft tissue repair, for tracheal and pharyngeal coverage and for defects of the nose, scalp, and auricle. This article focuses on the use of the free TPFF in the pediatric population through systemic review of the medical literature. Current perspectives on the use of this flap and microsurgery in general in pediatric patients are addressed.
Preoperative Anxiety in Patients With Nonmelanoma Skin Tumors of the Face
Authors: Karypidis Dimitrios , Vakis Georgios , Giannikou Paraskevi , Karagouni Aikaterini
Published: January 2021

The manifestation of preoperative anxiety often emerges when a patient is about to experience a surgical procedure. Especially in facial plastic surgery, where the reconstruction region is very strictly confined and the visibility of the outcome is undeniable, an upcoming surgery may easily provoke the feeling of anxiety. The aim of this study is to assess the number of patients that undergo preoperative anxiety and to associate it with several factors found to be concerning for them. Two hundred twenty-eight adult (>18 years) patients with facial nonmelanoma skin tumors, from a Plastic Surgery Clinic in a major Oncology Hospital in Athens, were included in the study and were given questionnaires and a Numeric Rating Scale in order to qualitate and quantitate their preoperative anxiety. Their responses were categorized and examined using the method of content analysis. 93.8% (n = 214) reported feeling anxious preoperatively, while the remaining 6.2% (n = 14) stated the opposite. Data showed that higher scores were documented when the patients were older, had had previous surgeries or had previously undergone general anesthesia, major procedures or procedures in the periorbital area. Gender was not found to be associated with preoperative anxiety. The main concern, finally, of most patients was the success of the outcome of the surgery.
Predictors of Opioid Prescription After Orthognathic Surgery in Opioid Naive Adults From a Large Database
Authors: Pakvasa Mikhail , Abbasi Ali , Boachie-Mensah Michael , Chattha Anmol , Reid Russell R.
Published: January 2021

Background:

Orthognathic surgery often requires postoperative opioid pain management. The goal of this study was to examine opioid prescribing patterns in adults after orthognathic surgery and to analyze factors associated with high-dose postoperative opioid administration and persistent opioid use.

Methods:

We included opioid naive adults in the IBM MarketScan Databases who had undergone orthognathic surgery from 2003 to 2017. Three outcomes were examined: presence of a perioperative outpatient opioid claim; total oral morphine milliequivalents (MMEs) in the perioperative period; and persistent opioid use. Univariate analysis and multiple regression were used to determine associations between the outcomes and independent variables.

Results:

Our study yielded a cohort of 8163 opioid naive adults, 45.6% of whom had an opioid claim in the perioperative period. The average prescribed MMEs in the perioperative period was 466 MMEs total, and 66 MMEs daily. Of patients with an opioid claim, 17.9% had persistent opioid use past 90 days. The presence of a complication was a predictor of having an opioid claim (P<0.001). Increasing age (P<0.001) and days hospitalized (P < 0.001) were associated with increased opioid usage. Persistent opioid use was associated with being prescribed more than 600 MMEs in the perioperative period (P < 0.001), as well as increasing age and days hospitalized. Interestingly, patients undergoing double-jaw surgery did not have significantly more opioids prescribed than those undergoing single-jaw surgery.

Conclusions:

Prescription opioids are relatively uncommon after jaw surgery, although 17.9% of patients continue to use opioids beyond 3 months after surgery. Predictors of persistent opioid use in this population include the number of days hospitalized, increasing age, and increasing amount of opioid prescribed postoperatively.
Novel intraperitoneal hemostasis device prolongs survival in a swine model of noncompressible abdominal hemorrhage
Authors: McCracken Brendan M. , Tiba Mohamad Hakam , Colmenero Carmen I. , Leander Danielle C. , Greer Nicholas L. , Plott Jeffery S. , Shih Albert J. , Ward Kevin R.
Published: January 2021

BACKGROUND

Noncompressible torso hemorrhage (NCTH) of the abdomen is a challenge to rapidly control and treat in the prehospital and emergency department settings. In this pilot study, we developed a novel intraperitoneal hemostasis device (IPHD) prototype and evaluated its ability for slowing NCTH and prolonging survival in a porcine model of lethal abdominal multiorgan hemorrhage.

METHODS

Yorkshire male swine (N = 8) were instrumented under general anesthesia for monitoring of hemodynamics and blood sampling. Animals were subjected to a 30% controlled arterial hemorrhage followed by lacerating combinations of the liver, spleen, and kidney. The abdomen was closed and after 2 minutes of NCTH, and the IPHD was inserted into the peritoneal cavity via an introducer (n = 5). The balloon was inflated and maintained for 60 minutes. At 60 minutes postdeployment, the balloon was deflated and removed, and blood resuscitation was initiated followed by gauze packing for hemostasis. The remaining animals (n = 3) were used as controls and subjected to the same injury without intervention.

RESULTS

All animals managed with IPHD intervention (5 of 5 swine) survived the duration of the intervention period (60 minutes), while all control animals (3 of 3 swine) died at a time range of 15 to 43 minutes following organ injury (p = 0.0042). Animals receiving IPHD remained hemodynamically stable with a mean arterial pressure range of 44.86 to 55.10 mm Hg and experienced increased cardiac output and decreased shock index after treatment. Controls experienced hemodynamic decline in all parameters until endpoints were met. Upon IPHD deflation and removal, all treated animals began to hemorrhage again and expired within 2 to 132 minutes despite packing.

CONCLUSION

Our data show that the IPHD concept is capable of prolonging survival by temporarily stanching lethal NCTH of the abdomen. This device may be an effective temporary countermeasure to NCTH of the abdomen that could be deployed in the prehospital environment or as a bridge to more advanced therapy.
Clinical utilization of deployed military surgeons
Authors: Hall Andrew B. , Qureshi Iram , Gurney Jennifer M. , Shackelford Stacy , Taylor Jonathan , Mahoney Christopher , Trask Scott , Walker Avery , Wilson Ramey L.
Published: January 2021

BACKGROUND

Combat casualty care has been shaped by the prolonged conflicts in Southwest Asia, namely Afghanistan, Iraq, and Syria. The utilization of surgeons in austere locations outside of Southwest Asia and its implication on skill retention and value have not been examined. This study hypothesizes that surgeon utilization is low in the African theater. This lack of activity is potentially damaging to surgical skill retention and patient care.

METHODS

Military case logs of surgeons deployed to Africa under command of Special Operations Command Africa between January 1, 2016, and January 1, 2020, were examined. Cases were organized based on population served, general type of procedure, current procedural terminology codes, and location.

RESULTS

Twenty deployment caseloads representing 74% of the deployments during the period were analyzed. In 3,294 days, 101 operations were performed, which included 45 on combat/terrorism related injuries and 19 on US personnel. East and West African deployments, combat, and noncombat zones, respectively, were compared. East Africa averaged 4.1 ± 3.8 operations per deployment, and West Africa, 7.3 ± 8.0 (p = 0.2434). In East Africa, 56.1% of total operations were related to combat/terrorism, compared with 29.6% of total operations in West Africa (p = 0.0077). West Africa had a significantly higher proportion of elective (p = 0.0002) and humanitarian cases (p = <0.0001).

CONCLUSION

Surgical cases for military surgeons were uncommon in Africa. The low volumes have implications for skill retention, morale, and sustainability of military surgical end strength. Reduction in deployment lengths, deployment location adjustments, and/or skill retention strategies are required to ensure clinical peak performance and operational readiness. Failure to implement changes to current practices to optimize surgeon experience will likely decrease surgical readiness and could contribute to decreased retention of deployable military surgeons to support global operations.

LEVEL OF EVIDENCE

Economic/decision, level III
External Validation of a Predictive Model to Estimate Renal Function After Living Donor Nephrectomy
Authors: Benoit Thibaut , Prudhomme Thomas , Adypagavane Aurélien , Malavaud Bernard , Soulié Michel , Gamé Xavier , Kamar Nassim , Dariane Charles , Legendre Christophe , Méjean Arnaud , Roumiguié Mathieu , Timsit Marc Olivier
Published: January 2021

Background.

Transplantation from living donor nephrectomy (LDN) is the best treatment for end-stage renal disease but observed decrease in donor renal function is a major concern. The aim of this study was to externally validate a predictive model to estimate 1-y postdonation estimated glomerular filtration rate (eGFR) and risk of chronic kidney disease (CKD) in living donors.

Methods.

All LDN performed at Necker Hospital from January 2006 to May 2018 were retrospectively included. Observed eGFR (using CKD-EPI formula) at 1-y post LDN was compared with the predicted eGFR calculated with a formula developed at Toulouse-Rangueil and based on predonation eGFR and age. Pearson correlation, receiver operating characteristics curve (ROC curve), and calibration curve were used to assess external validity of the proposed prognostic model to predict postoperative eGFR and occurrence of CKD in donors.

Results.

Four hundred donors were evaluated with a mean postoperative eGFR of 62.1 ± 14 mL/min/1.73m2. Significant correlation (Pearson r = 0.66; P < 0.001) and concordance (Bradley-Blackwood F = 49.189; P < 0.001) were observed between predicted and observed 1-y eGFR. Area under the receiver operating characteristic curve of the model relevant accuracy was 0.86 (95% CI, 0.82-0.89).

Conclusions.

This study externally validated the formula to predict 1-y postdonation eGFR. The calculator could be an accurate tool to improve the selection of living kidney donor candidate.
Effect of Nonalcoholic Fatty Liver Disease and Metabolic Risk Factors on Waitlist Outcomes in Patients With Hepatocellular Carcinoma
Authors: Weinfurtner Kelley , Dodge Jennifer L. , Yao Francis Y. K. , Mehta Neil
Published: January 2021

Background.

Nonalcoholic fatty liver disease (NAFLD) is a leading cause of hepatocellular carcinoma (HCC) in the United States. Prior data suggest that NAFLD-HCC patients are less likely to receive liver transplantation (LT) and have worse overall survival; however, the reason for this discrepancy is unknown.

Methods.

We conducted a retrospective study of 631 HCC patients listed for LT at a large academic center from 2004 to 2013. Waitlist dropout and LT were analyzed using competing risk regression.

Results.

Compared with other-HCC patients (n = 589), NAFLD-HCC patients (n = 42, 6.7%) were older (65 versus 58, P < 0.001) with more women (50.0 versus 23.6%, P < 0.001), Hispanic ethnicity (40.5 versus 17.7%, P = 0.001), obesity (69.0 versus 29.9%, P < 0.001), diabetes mellitus (59.5 versus 27.8%, P < 0.01), insulin-dependence (23.8 versus 10.2%, P = 0.007), hyperlipidemia (40.5 versus 10.5, P < 0.001), and statin use (33.3 versus 5.3%, P < 0.001). Cumulative incidence of waitlist dropout at 2 y was 17.4% (95% confidence intervals, 7.7-30.4) for NAFLD HCC and 25.4% (95% confidence intervals, 21.9-29.0) for other HCC (P = 0.28). No difference in waitlist dropout or receipt of LT between NAFLD HCC and other HCC was found on regression analysis. Similarly, NAFLD and obesity, obesity alone, diabetes mellitus, insulin-dependence, hyperlipidemia, and statin use were not associated with waitlist outcomes. Finally, we observed no statistically significant difference in 5-y survival from HCC diagnosis between NAFLD HCC and other HCC (78.5% versus 66.9%, P = 0.9).

Conclusions.

In our single-center cohort, we observed no difference in waitlist outcomes or survival in NAFLD HCC, although conclusions are limited by the small number of NAFLD-HCC patients. Notably, the inclusion of patients with obesity in the NAFLD-HCC group and stratification by individual metabolic factors also showed no difference in waitlist outcomes.
Plasma Donor-derived Cell-free DNA Levels Are Increased During Acute Cellular Rejection After Lung Transplant: Pilot Data
Authors: Sayah David , Weigt S. Samuel , Ramsey Allison , Ardehali Abbas , Golden Jeff , Ross David J.
Published: January 2021

Background.

Telehealth platforms with remote phlebotomy and biomarker implementation represent a novel paradigm for surveillance after lung transplantation (LT). In a pilot study, we investigated donor-derived cell-free DNA (dd-cfDNA) in plasma using a clinical-grade “next-generation sequencing” assay.

Methods.

dd-cfDNA levels determined in biorepository venous plasma samples obtained during the lung allograft rejection gene expression observation study, implementing a clinical-grade next-generation sequencing assay. Sixty-nine unique LT patients encompassing 9 LT centers, with associated clinical-histopathologic diagnoses, were examined—allograft infection (n = 26), normal histopathology without infection (n = 30), and acute cellular rejection (ACR; n = 13).

Results.

dd-cfDNA in ACR patients were significantly elevated (1.52%; interquartile range [IQR], 0.520-2.2550) compared with the normal stable patients (0.485%; IQR, 0.220-0.790) (P = 0.026). During allograft infection, dd-cfDNA values were not different (0.595; IQR, 0.270-1.170) from normal (P = 0.282) and ACR (P = 0.100). AUC-receiver operator characteristics curve analysis for allograft ACR was 0.717 (95% confidence interval, 0.547-0.887; P = 0.025). At a 0.87% threshold dd-cfDNA—sensitivity = 73.1%, specificity = 52.9%, positive predictive value = 34.1%, and negative predictive value = 85.5%.

Conclusions.

dd-cfDNA assessment holds promise as a noninvasive biomarker of “allograft injury” with acute rejection following LT while prospective, multicenter studies should further refine utility across the spectrum of allograft rejection and infection.
Gender Disparities in Authorships and Citations in Transplantation Research
Authors: Benjamens Stan , Banning Louise B.D. , van den Berg Tamar A.J. , Pol Robert A.
Published: January 2021

Background.

Over the past decades, there has been a rapid change in the gender ratio of medical doctors, whereas gender differences in academia remain apparent. In transplantation research, a field already understaffed with female doctors and researchers, there is little published data on the development in proportion, citations, and funding of female researchers over the past years.

Methods.

To evaluate the academic impact of female doctors in transplantation research, we conducted a bibliometric analysis (01 January 1999 to 31 December 2018) of high-impact scientific publications, subsequent citations, and funding in this field. Web of Science data was used in combination with software R-Package “Gender,” to predict gender by first names.

Results.

For this study, 15 498 (36.2% female; 63.8% male) first and 13 345 (30.2% female; 69.8% male) last author gender matches were identified. An increase in the percentage of female first and last authors is seen in the period 1999–2018, with clear differences between countries (55.1% female authors in The Netherlands versus 13.1% in Japan, for example). When stratifying publications based on the number of citations, a decline was seen in the percentage of female authors, from 34.6%–30.7% in the first group (≤10 citations) to 20.8%–23.2% in the fifth group (>200 citations), for first (P < 0.001) and last (P = 0.014) authors, respectively. From all first author name-gender matches, 6574 (41.6% female; 58.4% male, P < 0.001) publications reported external funding, with 823 (35.5% female; 64.5% male, P = 0.701) reported funding by pharmaceutical companies and 1266 (36.6% female; 63.4% male, P < 0.001) reporting funding by the National Institutes of Health.

Conclusions.

This is the first analysis of gender bias in scientific publications, subsequent citations, and funding in transplantation research. We show ongoing differences between male and female authors in citation rates and rewarded funding in this field. This requires an active approach to increase female representation in research reporting and funding rewarding.
Combining an alarmin HMGN1 peptide with PD-L1 blockade facilitates stem-like CD8+ T cell expansion and results in robust antitumor effects
Authors: Chen Chang-Yu , Ueha Satoshi , Ishiwata Yoshiro , Shichino Shigeyuki , Yokochi Shoji , Yang De , Oppenheim Joost J. , Ogiwara Haru , Deshimaru Shungo , Kanno Yuzuka , Ogawa Tatsuro , Shibayama Shiro , Matsushima Kouji
Published: January 2021

Background

The expansion of intratumoral stem-like CD8+ T (Tstem) cells provides a potential approach to improving the therapeutic efficacy of immune checkpoint blockade (ICB). Thus, here we demonstrate a strategy to facilitate Tstem cell expansion by combining an alarmin high-mobility group nucleosome binding domain 1 (HMGN1) peptide with programmed death-ligand 1 (PD-L1) blockade.

Methods

The antitumor effects of HMGN1, anti-PD-L1 antibody, and their combined treatment were monitored in the B16F10, LLC, Colon26, or the EO771 tumor-bearing mice. The comprehensive immunologic analyses, such as high-dimensional flow cytometry, transcriptome analysis, and single-cell RNA sequencing, were used to investigate the cellular and molecular mechanisms of antitumor immune responses after treatments.

Results

The HMGN1 peptide synergizes with PD-L1 blockade in augmenting the number of mature DCs enriched in immunoregulatory molecules (mregDCs) in tumors, and enhancing their MHC class I antigen-presenting program, which is correlated with the expansion of intratumoral Tstem cells, specifically promoting the Tstem cells but restricting terminally exhausted CD8+ T (Tex) cells, owing to the regulatory molecules expressed on mregDCs.

Conclusion

Our results indicate that HMGN1 peptide serves as an immunoadjuvant to promote effective anti-PD-L1 immunotherapy and implicate that mregDCs play a role beyond facilitating Tstem cell expansion.
Comparison study of commercial COVID-19 RT-PCR kits propose an approach to evaluate their performances
Authors: Krismawati Hana , Mahendra Caroline , Hartanto Annabelle , Rokhmad Muhammad Fajri , Sandi Semuel , Irwanto Astrid
Published: January 2021

With the increasing number of COVID-19 cases in Indonesia, scalable and high-throughput diagnostic testing is essential nationwide. Currently, RT-PCR has been the preferred method of viral detection and many manufacturers offer commercial kits for routine clinical diagnostics. In response to the incoming of various kits, there is a need to assess their performance and compatibility of use in clinical laboratories. Kit characteristics impact the testing workflow of these laboratories and some factors can render a kit to perform sub-optimally, leading to false results that are misleading for public safety. Here, we evaluated six commercial kits that are predominantly distributed to appointed testing facilities across Indonesia. Their performance was assessed based on their ease of use, availability, robustness and accuracy for scalable testing in a manual set-up. Our findings demonstrated that all six kits are suitable for use in routine diagnostics, but their considerations for use may vary according to different use-cases. To better guide considerations in procurement of kits, our study provided a systematic approach for laboratories to assess the performance of new incoming kits.
Development and validation of gradient boosting decision tree models for predicting care needs using a long-term care database in Japan
Authors: Lin Huei-Ru , Fujiwara Koki , Sasaki Minoru , Ishiyama Ko , Ikeda-Sonoda Shino , Takahashi Arata , Miyata Hiroaki
Published: January 2021

Objective

The purpose of the study was to develop machine learning models using data from long-term care (LTC) insurance claims and care needs certifications to predict the individualized future care needs of each older adult.

Methods

We collected LTC insurance-related data in the form of claims and care needs certification surveys from a municipality of Kanagawa Prefecture from 2009 to 2018. We used care needs certificate applications for model generation and the validation sample to build gradient boosting decision tree (GBDT) models to classify if 1) the insured’s care needs either remained stable or decreased or 2) the insured’s care needs increased after three years. The predictive model was trained and evaluated via k-fold cross-validation. The performance of the predictive model was observed in its accuracy, precision, recall, F1 score, area under the receiver-operator curve, and confusion matrix.

Results

Long-term care certificate applications and claim data from 2009–2018 were associated with 92,239 insureds with a mean age of 86.1 years old at the time of application, of whom 67% were female. The classifications of increase in care needs after three years were predicted with AUC of 0.80.

Conclusions

Machine learning is a valuable tool for predicting care needs increases in Japan’s LTC insurance system, which can be used to develop more targeted and efficient interventions to proactively reduce or prevent further functional deterioration, thereby helping older adults maintain a better quality of life.
The usefulness of a quantitative olfactory test for the detection of COVID-19
Authors: Lessa Marcos A , Cotta-Pereira Stella M , Ferreira Frederico A , Castiñeiras Therezinha Marta P P , Galliez Rafael M , Faffe Débora S , Leitão Isabela de C , Mariani Diana , Nascimento Erica R , Lessa Flávia S , Succi Isabela Brasil , Pedreira Carlos A
Published: January 2021

Background

During the COVID-19 pandemic, olfactory dysfunction (anosmia or hyposmia) has been reported by many patients and recognized as a prevalent and early symptom of infection. This finding has been associated with viral-induced olfactory neuron dysfunction rather than the nasal congestion typically found in cold- or flu-like states. In literature, the prevalence of anosmia varies from 15% to 85%, and the studies, in general, were based on the subjective evaluation of patients’ self-reports of loss of smell (yes or no question). In the present study, we quantitatively evaluated olfactory dysfunction and the prevalence of fever in symptomatic patients suspected of having COVID-19 using a scratch-and-sniff olfactory test and infrared temperature testing with RT-PCR as the gold-standard comparator method to diagnose COVID-19 infection.

Methods

Outpatients had their forehead temperature checked with an infrared non-contact thermometer (temperature guns). After that, they received two olfactory smell identification test (SIT) cards (u-Smell-it™; CT, USA) that each had 5 scent windows and were asked to scratch with a pencil and sniff each of the 10 small circles containing the microencapsulated fragrances and mark the best option on a response card. Nasopharyngeal swabs were then collected for Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) to determine if the patients were positive or negative for COVID-19 infection. We considered the number of ‘hits’ (correct answers) ≤ 5 as positive for loss of smell (LOS) in the olfactory test; ≥ 6 hits was considered negative for LOS (i.e. normal olfactory function). All data were analyzed using Excel and Matlab software.

Results

In the present study, 165 patients were eligible for the olfactory test and nasopharyngeal swab collection RT-PCR. Five patients were excluded because of inconclusive PCR results (n=2) and missing data (n=3). A total of 160 patients completed all the protocols. The RT-PCR positivity rate for COVID-19 was 27.5% (n=44), and PCR+ patients scored significantly worse in the olfactory test (5.5±3.5) compared to RT-PCR-patients (8.2±1.8, p<0.001). 0/44 PCR+ patients presented with a fever (≥37.8°C). In contrast an olfactory SIT had a specificity of 94.8% (95% CI, 89.1 – 98.1), sensitivity of 47.7% (95% CI, 32.7 – 63.3), accuracy of 0.82 (95% CI, 0.75 – 0.87), positive predictive value of 77.8% (95% CI, 59.6 – 88.8), negative predictive value of 82.7% (85% CI, 78.7 – 86.7), and odds ratio of 16.7.

Conclusion

Our results suggest that temperature checking failed to detect COVID-19 infection, while an olfactory test may be useful to help identify COVID-19 infection in symptomatic patients.
Prediction of Celiac Disease Severity and Associated Endocrine Morbidities through Deep Learning-based Image Analytics
Authors: Ehsan Lubaina , Khan Marium , Sali Rasoul , Catalano Alexis M. , Adorno William , Kowsari Kamran , Cheng Lin , Pramoonjago Patcharin , Raghavan Shyam , Silvester Jocelyn , DeBoer Mark , Moskaluk Christopher A. , Moore Sean R. , Brown Donald E. , Syed Sana
Published: January 2021

Objective

Develop a deep learning-based methodology using the foundations of systems pathology to generate highly accurate predictive tools for complex gastrointestinal diseases, using celiac disease (CD) as a prototype.

Design

To predict the severity of CD, defined by Marsh–Oberhüber classification, we used deep learning to develop a model based on histopathologic features.

Results

The study was based on a pediatric cohort of 124 patients identified with different classes of CD severity. The model predicted CD with an overall 88.7% accuracy with the highest for Marsh IIIc (91.0%; 95% sensitivity; 91% specificity). The model identified EECs as a defining feature of children with Marsh IIIc CD and endocrinopathies which was confirmed using immunohistochemistry.

Conclusion

This deep learning image analysis platform has broad applications in disease treatment, management, and prognostication and paves the way for precision medicine.

What is already known about this subject?

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Deep Learning has the potential to generate predictive models for complex gastrointestinal diseases.

What are the new findings?

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Our deep learning-based model used the foundations of systems pathology to generate a highly accurate predictive tool for complex gastrointestinal diseases, using a celiac disease (CD) pediatric cohort as a prototype.

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The model predicated CD severity with high accuracy and identified enteroendocrine cells as a defining feature of children with severe CD and endocrinopathies.

How might it impact on clinical practice in the foreseeable future?

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Assessment of histopathological markers at the time of diagnosis that can predict risk of severity or complications can have broad applications in disease treatment, management, and prognostication and pave the way for precision medicine.
Genomic insights into early SARS-CoV-2 strains isolated in Reunion Island
Authors: Wilkinson David A , Lebarbenchon Camille , Atyame Célestine , Hafsia Sarah , Jaffar-Bandjee Marie-Christine , Yemadje-Menudier Luce , Tanaka Sébastien , Meilhac Olivier , Mavingui Patrick
Published: January 2021

The relative isolation of many island communities provides some protection from the COVID-19 pandemic, as imported cases can be limited and traced effectively. Until recently, this was true for the population of the French overseas department, Reunion Island, where only limited numbers of autochthonous cases were observed prior to August 2020. Since the report of the first case of COVID-19, contact tracing has been carried out for each new case identified in Reunion Island to identify transmission and clusters. To contribute to the public health response and understand the diffusion of SARS-Cov-2 strains in Reunion Island, we established in-house genome sequencing capability in Reunion using Oxford nanopore technology (MinION) as an inexpensive option for genomic typing of SARS-CoV-2 lineages on the island, and cross-validated typing results between viral isolation methods and different sequencing technologies. The results of our work during the early phase of the epidemics are presented herein.

Article Summary Line

The COVID-19 pandemic has had an unprecedented impact on the global community. Here we provide epidemiological and genomic details of the early stages of the pandemic on Reunion Island.
A Reproducible Protocol to Assess Arrhythmia Vulnerability in Silico: Pacing at the End of the Effective Refractory Period
Authors: Azzolin Luca , Schuler Steffen , Loewe Axel , Dössel Olaf
Published: January 2021

In both clinical and computational studies, different pacing protocols are used to induce arrhythmia and non-inducibility is often considered as the endpoint of treatment. The need for a standardized methodology is urgent since the choice of the protocol used to induce arrhythmia could lead to contrasting results, e.g., in assessing atrial fibrillation (AF) vulnerabilty. Therefore, we propose a novel method – pacing at the end of the effective refractory period (PEERP) – and compare it to state-of-the-art protocols such as phase singularity distribution (PSD) and rapid pacing (RP) in a computational study. All methods were tested by pacing from 227 evenly distributed endocardial points in a bi-atrial geometry. 6 different atrial models were implemented: 4 cases without specific AF-induced remodelling but with decreasing global conduction velocity and 2 persistent AF cases with an increasing amount of fibrosis resembling different substrate remodeling stages. Compared with PSD and RP, PEERP induced a larger variety of arrhythmia complexity requiring, on average, only 2.7 extra-stimuli and 3 s of simulation time to initiate reentry. Moreover, PEERP and PSD were the protocols which unveiled a larger number of areas vulnerable to sustain stable long living reentries compared to RP. Finally, PEERP can foster standardization and reproducibility, since, in contrast to the other protocols, it is a parameter-free method. Furthermore, we discuss its clinical applicability. We conclude that the choice of the inducing protocol has an influence on both initiation and maintenance of AF and we propose and provide PEERP as a reproducible method to assess arrhythmia vulnerability.
Understanding Vaccine Hesitancy: Empirical Evidence from India*
Authors: Sur Pramod Kumar
Published: January 2021

Why do vaccination rates remain low even in countries where long-established immunization programs exist and vaccines are provided for free? We study this paradox in the context of India, which contributes to the world’s largest pool of under-vaccinated children and about one-third of all vaccine-preventable deaths globally. Combining historical records with survey datasets, we examine the Indian government’s forced sterilization policy, a short-term aggressive family planning program implemented between 1976 and 1977. Using multiple estimation methods, including an instrumental variable (IV) and a geographic regression discontinuity design (RDD) approach, we document that the current vaccination completion rate is low in places where forced sterilization was high. We also explore the heterogeneous effects, mechanisms, and reasons for the mechanism. Finally, we examine the enduring consequence and present evidence that places more exposed to forced sterilization have an average 60 percent higher child mortality rate today. Together, these findings suggest that government policies implemented in the past can have persistent adverse impacts on demand for health-seeking behavior, even if the burden is exceedinglyhigh.
Adherence to the CONSORT statement and risk of bias assessment in Randomized Controlled Trials in rehabilitation journals: a protocol for a meta-research study
Authors: Innocenti Tiziano , Giagio Silvia , Salvioli Stefano , Feller Daniel , Minnucci Silvia , Brindisino Fabrizio , Ostelo Raymond , Chiarotto Alessandro
Published: January 2021

Objective

The aim of this study will be to assess the adherence to the reporting quality standards set forth in the CONSORT Statement checklist of a random sample of randomized controlled trials (RCTs) published in rehabilitation journals, and to assess the association between this adherence and the risk of bias of these RCTs.

Methods and Analysis

A cross-sectional analysis is planned on a random sample of 200 RCTs published between 2011and 2020 in the 68 journals indexed under “rehabilitation” category in InCites Journal Citation Report.

Randomization will be stratified by publication date and journal ranking (quartile range; Q1-2 and Q3-4) to include an equal number of studies from 2011 to 2015 (Q1-Q2=50 and Q3-Q4=50) and from 2016 to 2020 (Q1-Q2=50 and Q3-Q4=50). RCT with parallel group design will be included. Observational or cohort studies, interim analyses, economic analyses of RCTs, RCT protocols, quasi-experimental design post-trial follow-up studies, subgroup and secondary analyses of previously reported RCTs, RCT with cross-over design, pilot feasibility RCTs, n-of-1 trials, cluster trials, editorials, letters and news reports will be excluded. The primary analysis will address the completeness of the reporting for each study and the relationship between CONSORT adherence and risk of bias. This will be a descriptive analysis through descriptive statistics and graphical representation.

Ethics and Dissemination

Several studies have shown the positive influence of reporting guidelines on the completeness of research reporting but no one investigated the use and the appropriateness of reporting guidelines in physical therapy research. Therefore, this study will add relevant knowledge that may contribute to improve further the reporting of rehabilitation research. The results of this research will be published in a peer-reviewed journal and will be presented at relevant (inter)national scientific events.
Adherence to the PRISMA statement and risk of bias assessment in Systematic Reviews in rehabilitation journals: a protocol for a meta-research study
Authors: Innocenti Tiziano , Feller Daniel , Giagio Silvia , Salvioli Stefano , Minnucci Silvia , Brindisino Fabrizio , Chiarotto Alessandro , Ostelo Raymond
Published: January 2021

Objective

The aim of this study will be to assess the adherence to the reporting quality standards set forth in the PRISMA Statement checklist of a random sample of systematic reviews (SRs) published in rehabilitation journals, and to assess the association between this adherence and the risk of bias of these SRs.

Methods and Analysis

A cross-sectional analysis is planned on a random sample of 200 SRs published between 2011and 2020 in the 68 journals indexed under “rehabilitation” category in InCites Journal Citation Report.

Randomization will be stratified by publication date and journal ranking (quartile range; Q1-2 and Q3-4) to include an equal number of studies from 2011 to 2015 (Q1-Q2=50 and Q3-Q4=50) and from 2016 to 2020 (Q1-Q2=50 and Q3-Q4=50). SRs (with or without meta-analysis) published between 2011 and 2020 as full-text scientific articles in the 68 rehabilitation journals will be included. Narrative reviews, mixed-methods reviews, meta-ethnography reviews, umbrella reviews, scoping reviews, editorials, letters and news reports will be excluded. The primary analysis will address the completeness of the reporting for each study and the relationship between PRISMA adherence and risk of bias. This will be a descriptive analysis through descriptive statistics and graphical representation.

Ethics and Dissemination

Several studies have shown the positive influence of reporting guidelines on the completeness of research reporting but no one investigated the use and the appropriateness of reporting guidelines in physical therapy research. Therefore, this study will add relevant knowledge that may contribute to improve further the reporting of rehabilitation research. The results of this research will be published in a peer-reviewed journal and will be presented at relevant (inter)national scientific events.