bluuebunny/crossref_metadata_2025 huggingface dataset:
SAUSAGING AND BULBOSITIES OF THE CHOROIDAL VEINS IN CENTRAL SEROUS CHORIORETINOPATHY
Authors: Spaide Richard F. , Ngo Wei Kiong , Barbazetto Irene , Sorenson John A.
Published: May 2022

Purpose:

To evaluate the caliber of the choroidal veins in central serous chorioretinopathy, a disease proposed to be associated with overloading of choroidal venous outflow.

Methods:

Widefield indocyanine green angiograms of eyes with central serous chorioretinopathy were graded for sausaging defined as three or more contiguous fusiform dilations that vary by at least 50% from the narrowest to largest diameters. A bulbosity was defined as a focal 2X dilation of a blood vessel as compared with the diameter of the surrounding host vessel. The data underwent statistical analysis including the use of generalized estimating equations.

Results:

There were 73 eyes of 41 patients with a mean age of 53.5 years. Sausaging of vessels was seen in a mean and median of three quadrants per eye. Using generalized estimating equations, the only significant risk factor for sausaging was the use of corticosteroids. The two significant predictors of subfoveal choroidal thickness using generalized estimating equations were age (P = 0.021) and proportion of quadrants involved by sausaging (P < 0.001). The decrease in choroidal thickness per year of age was estimated to be 3.7 µm, while the increase with four quadrant involvement with sausaging was estimated to be 236 µm. There were a total of 39 bulbosities in 26 eyes (35.6%), preferentially involving intervortex venous anastomoses.

Conclusion:

Variations in the venous caliber are very common in eyes with central serous chorioretinopathy and seems to be associated with pathophysiologic alterations related to increased pressure within and remodeling of the larger choroidal veins. This may lead to overloading of the choriocapillaris with leakage as one manifestation.
Perioperative oxidative stress predicts subsequent pain-related outcomes in the 6 months after total knee arthroplasty
Authors: Bruehl Stephen , Milne Ginger , Schildcrout Jonathan , Shi Yaping , Anderson Sara , Shinar Andrew , Polkowski Gregory , Mishra Puneet , Billings Frederic T.
Published: May 2022

Total knee arthroplasty (TKA) is effective for pain reduction in most patients, but 15% or more report unsatisfactory long-term pain outcomes. We tested whether oxidative stress (OS) related to extended tourniquet application during TKA and subsequent ischemic reperfusion (IR) contributed to adverse post-TKA pain outcomes. Blood samples were obtained in 91 patients with osteoarthritis (63% female) undergoing TKA before tourniquet placement (T1), 45 minutes after tourniquet inflation (T2), and 15 minutes after tourniquet removal (T3). Plasma levels of F2-isoprostanes and isofurans, the most specific measures of in vivo OS, were quantified. Pain intensity and function were assessed at baseline and again at 6 weeks and 6 months after TKA. Results indicated that higher Combined OS (F2-isoprostanes + isofurans/2) at T1 baseline and larger increases in Combined OS from T1 to T2 were associated with higher baseline-corrected past 24-hour worst and average pain intensity (numeric rating scale) and higher past week McGill Pain Questionnaire-2 total scores at 6-month follow-up (P's < 0.05). Increases in Combined OS from T1 to T3, which should most directly capture OS and IR injury related to tourniquet use, were not associated with short-term or long-term post-TKA pain outcomes. Longer ischemia duration was unexpectedly associated with lower baseline-corrected pain intensity at 6-month follow-up. Combined OS was not linked to functional outcomes at either follow-up. Elevated perioperative OS seems to exert small but significant adverse effects on long-term post-TKA pain outcomes, although this OS seems unrelated to IR injury associated with extended tourniquet use.
Characteristics of Extracorporeal Membrane Oxygenation Education Vary in Entry-Level Doctor of Physical Therapy Programs
Authors: Driscoll Jenna , Elkins Jeananne
Published: May 2022

Background/Purpose:

Extracorporeal membrane oxygenation (ECMO) with high risks of mismanagement is being used more frequently in critical care for cardiorespiratory failure. The safety and feasibility of physical therapy (PT) for patients on ECMO have been established. Little is known about ECMO education and training for entry-level physical therapist students. The purpose of this study is to determine the characteristics of ECMO education in entry-level doctor of physical therapy (DPT) educational programs and examine any correlations among these characteristics.

Methods:

A survey was developed on the basis of a literature search and author experience. The anonymous survey was disseminated electronically to directors of all Commission on Accreditation in Physical Therapy Education (CAPTE)–accredited DPT programs in the United States.

Results:

Faculty from 31 (12.8%) programs responded. Some level of ECMO-related education was included in 25 (80.65%) programs. Content of didactic education varied across programs. Other modes of ECMO education included case study discussions, simulation training, and hands-on experience. Statistically significant relationships were identified among university affiliation with an academic medical center and the presence of case studies (n = 6, P < .05) and hands-on experience (n = 8, P = .001), as well as between instructor cardiovascular and pulmonary specialist credentials and the presence of hands-on experience (n = 12, P < .001).

Discussion/Conclusion:

The extent and characteristics of ECMO-related education vary among entry-level DPT programs. Programs affiliated with academic medical centers and specialty-certified instructors may provide exposure to broader critical care content, such as ECMO. Formalized curricular guidelines may be necessary to help adequately prepare students for clinical practice. Entry-level clinicians should advocate for advanced training when appropriate.
Clinical outcomes of Eustachian tube dysfunction in chronic rhinosinusitis following endoscopic sinus surgery
Authors: Chen Wei-Chih , Yang Kun-Lin , Lin Wei-Che , Fang Kuan-Chung , Wu Ching-Nung , Luo Sheng-Dean
Published: May 2022

Background:

The effects of endoscopic sinus surgery (ESS) on the symptom burden of Eustachian tube dysfunction (ETD) in chronic rhinosinusitis (CRS) patients were investigated.

Methods:

Ninety-two patients with CRS following ESS were prospectively enrolled and followed up every 3 months for 1 year. The 7-item ETD Questionnaire (ETDQ-7) and 22-item Sino-Nasal Outcome Test (SNOT-22) were administered before ESS and at each visit following ESS.

Results:

Before surgery, 25% of patients reported ETDQ-7 scores ≥ 14.5, indicating the presence of ETD. The mean preoperative ETDQ-7 and SNOT-22 scores were 13.3 and 40.0, respectively. The mean ETDQ-7 and SNOT-22 scores were significantly decreased to 8.2 and 17.0 at 1 year following ESS, respectively. Most patients reported alleviation of their symptoms within the first 3 months, and the prevalence of ETD had decreased to 3.3% at 1 year. Patients who received revision surgery had higher ETDQ-7 scores during the follow-up period. Additionally, 5.4% of patients reported worsening of their symptoms.

Conclusion:

ETD symptoms can be effectively alleviated in most patients within 3 months following ESS. However, 5.4% of patients reported worsening of their symptoms at the 1-year follow-up. Additional objective studies should be conducted to evaluate Eustachian tube function thoroughly in CRS patients.
Efficacy of cetuximab-containing regimens in the treatment of recurrent/metastatic head and neck cancer after progression to immune checkpoint inhibitors
Authors: Lai Cheng-Lun , Chen Tien-Hua , Chang Peter Mu-Hsin , Tai Shyh-Kuan , Chu Pen-Yuan , Yang Muh-Hwa
Published: May 2022

Background:

The antiepidermal growth factor receptor (EGFR) monoclonal antibody cetuximab and immune checkpoint inhibitors (ICIs) are the current front-line treatment for recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC). However, understanding of the efficacy of cetuximab-containing regimens in patients who fail ICI treatments is limited. In this study, we present the efficacy of cetuximab-based regimens in heavily pretreated R/M HNSCC patients after progression to ICIs.

Methods:

This was a retrospective study that analyzed patients diagnosed with R/M HNSCC who progressed after ICIs and then received their first-time cetuximab-based regimens at Taipei Veterans General Hospital from January 2017 to December 2020. The response rate, overall survival, and progression-free survival were measured.

Results:

A total of 28 patients were included in this study. Most patients had received pembrolizumab as an ICI. The median duration of cetuximab-based regimens prescribed was 4.5 months. The objective response rate (ORR) was 32.1% (95% confidence interval [CI], 17.9%-50.6%), and the disease control rate (DCR) was 53.6% (95% CI, 42.4%-76.4%). The median overall survival and median progression-free survival were 9.1 months (95% CI, 1.3-16.8) and 2.9 months (95% CI, 2.2-3.5), respectively. The incidence of cetuximab-related adverse events was reported as 39.2%.

Conclusion:

A cetuximab-based regimen is still an effective and tolerable treatment for R/M HNSCC after progression on ICIs. Future prospective studies are needed to identify better treatments for previously ICI-treated or heavily treated R/M HNSCC patients.
Effectiveness of Tai Chi in Patients With Hypertension
Authors: Tam Hon Lon , Leung Leona Yuen Ling , Chan Alex Siu Wing
Published: May 2022

Background

Hypertension affects more than 1 billion people worldwide. Hypertension management guidelines recommend regular exercise to control blood pressure. Tai Chi is a low-impact, low- to moderate-intensity exercise that has numerous health benefits.

Objective

The aim of this study is to perform a review of meta-analyses and summarize the existing information on the health benefits of Tai Chi for patients with hypertension.

Methods

This review was guided by the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Eight health-related databases were systematically searched from their inception to March 2021 to identify the relevant meta-analyses. Two reviewers independently assessed the methodological quality of the evidence.

Results

A total of 6 relevant meta-analyses were included in this review: 3 were rated as critically low in quality, 2 were rated low, and 1 was rated high. In the included meta-analyses, Tai Chi showed many benefits for patients with hypertension. In addition to improving blood pressure, the blood lipid profile, blood sugar, body measurements, and quality of life of patients improved significantly after practicing Tai Chi.

Conclusion

Tai Chi may be considered an effective and safe alternative exercise for patients with hypertension.
Impact of Selected Initial Titration Schedules on Safety and Long-Term Effectiveness of Lamotrigine for the Treatment of Mood Disorders
Authors: Nakamura Tomoyuki , Tomita Masaru , Hirota Susumu , Matsunaga Takamasa , Uchimura Naohisa
Published: May 2022

Purpose

Lamotrigine (LTG) is used for treatment of mood disorders, but it is associated with the risk of rash occurrence in the initial administration phase. Although slow titration reduces this risk, its effectiveness in the treatment of mood disorders has not been verified. The effects of titration method on the safety and effectiveness of LTG for the treatment of mood disorders were examined in this study.

Methods

This retrospective cohort study included 312 patients with mood disorders who underwent initiation of LTG therapy. Data regarding baseline demographics, titration schedules, concomitant medications, and time to and cause of discontinuation of LTG were collected. A multivariate analysis was used to evaluate the effects of the titration schedules. The 12-month effectiveness was also evaluated.

Results

The 12-month discontinuation rate of LTG was 16.7%. The most frequent cause of discontinuation was development of a rash (47.7%, n = 312). Fast titration (adjusted odds ratio, 8.15) significantly increased the risk of rash development, and slow titration (adjusted odds ratio, 0.29) significantly decreased this risk. The time to all-cause discontinuation was not significantly different between the slow and standard titration groups (n = 303). After 12 months of treatment, the condition of 46.7% patients were rated much or very much improved using CGI-C.

Conclusions

Although slow titration of LTG reduces the occurrence of a rash, it is not more effective than standard titration in the long term. Optimizing the initial LTG titration schedule for patients with mood disorders is challenging.
Clinical characteristics and long-term outcomes of hospitalised patients with ischemic colitis with different degrees of haematochezia: a retrospective study
Authors: An Qin , Yuan Baisi- , Guo Zhen , Wu Lin , Yang Miaofang- , Shi Shaopei- , Tang Guoxing- , Wang Fangyu-
Published: May 2022

Background

Based on the literature, haematochezia is associated with a benign clinical course of ischaemic colitis. However, most cases in the literature presented mild haematochezia associated with ischaemic colitis. Therefore, we aimed to investigate the impact of different degrees of haematochezia on the clinical outcomes of ischaemic colitis.

Methods

Patients were divided into nonhaematochezia, mild-haematochezia, and severe-haematochezia cohorts stratified by the degree of haematochezia. The clinical characteristics and prognoses were retrospectively reviewed.

Results

Haematochezia cohort (n = 89) was associated with a lower rate of severe illness (25% vs. 52%, P = 0.001), lower rate of isolated right colon ischaemia (7% vs. 28%,P = 0.001), lower surgery rates (13% vs. 36%, P = 0.001), and shorter hospital stay (12 vs. 17 days, P < 0.001) compared with nonhaematochezia cohort (n = 50). Severe-haematochezia cohort (n = 11) had a higher frequency of severe illness (73% vs. 18%, P < 0.001), higher surgical intervention rate (55% vs. 6%, P < 0.001), higher nonsurgical complication rate, higher in-hospital mortality (45% vs. 0%, P < 0.001), and longer hospital stay (28 vs. 10  days, P = 0.001), compared with mild-haematochezia cohort (n = 78). Additionally, in-hospital mortality (45% vs. 6%, P = 0.003) and nonsurgical complication rate were higher in the severe-haematochezia than in the nonhaematochezia cohort. However, the three cohorts had comparable prognoses for long-term survival and recurrence.

Conclusions

Mild haematochezia was related to a benign clinical course of ischaemic colitis, while lack of haematochezia or severe haematochezia was associated with worse hospitalisation outcomes.
Physiological tracer distribution and benign lesion incidental uptake of Al18F-NOTA-FAPI-04 on PET/CT imaging
Authors: Kou Ying , Jiang Xuemei , Yao Yutang , Shen Jiaqi , Jiang Xiao , Chen Shirong , Lu Hao , Wang Xiaoxiong , Zhao Meng , Xiao Dingqiong , Shen Taipeng , Zhang Wei , Cheng Zhuzhong
Published: May 2022

Objective

To systematically investigate the physiological distribution and benign lesion incidental uptake of Al18F-NOTA-FAPI-04 (18F-FAPI) in cancer patients to establish the normal uptake range in relevant organs and lesions.

Methods

Twenty patients who underwent 18F-FAPI PET/CT imaging were retrospectively assessed. Organ and benign lesion tracer uptake was quantified based on standardized uptake values (SUVmax and SUVmean). We compared the variation in tracer uptake in certain organs between men and women, analyzed the possible reasons for diffuse uptake in the thyroid, and assessed tracer uptake variations in the uterus in different menstrual cycle phases. Incidental tracer uptake in benign lesions was also assessed.

Results

Physiological 18F-FAPI uptake was observed in the urinary tract, biliary tract system, submandibular glands, pancreas, thyroid, uterus, intestine, prostate gland, parotid gland, myocardium, kidney cortex, and muscles, but not the brain, lungs, liver, spleen, colon, and breasts. The SUVmean for each organ was similar for women and men (all P > 0.05). Diffuse tracer uptake in the thyroid was caused by normal thyroid or thyroiditis; there were no statistically significant differences between them (SUVmax: t = −1.3, P = 0.25; SUVmean: t = −1.1, P = 0.31). There was a significant difference for uterus uptake among different menstrual cycle phases (SUVmax: F = 5.08, P = 0.04; SUVmean: F = 5.19, P = 0.04). Incidental benign lesion tracer uptake was observed in patients with esophagitis, thyroiditis, arthritis, fractures, and uterine fibroids.

Conclusion

This study provides a reference range for 18F-FAPI uptake in relevant organs and benign lesions. Benign lesion 18F-FAPI uptake may reduce 18F-FAPI PET/CT specificity.
Research progress on the role of fibroblast activation protein in diagnosis and treatment of cancer
Authors: Wu Zhaoye , Hua Yuqi , Shen Qiaoling , Yu Chunjing
Published: May 2022

Fibroblast activation protein (FAP) is a type II transmembrane protein, which is over-expressed in cancer-associated fibroblasts (CAFs). CAFs are tumor stromal cells that constitute a major component of cancer volume and are reportedly related to tumorigenesis, angiogenesis, metastasis, promotion of drug resistance and induction of tumor immunity. FAP is widely acknowledged as the signature protein of CAFs. At present, FAP inhibitors (FAPI) have achieved ideal results in tumor PET/computed tomography (CT) imaging. Theoretically, FAP-targeted drugs can inhibit tumor progression. Nonetheless, no satisfactory therapeutic effect has been observed so far, which has impeded their implementation in clinical practice. In this review, we describe the characteristics of FAP and its role in the occurrence and development of cancer. We also highlight the potential value of targeting FAP to improve current diagnostic and therapeutic approaches.
Prognostic value of fluorodeoxyglucose positron emission tomography derived metabolic parameters and textural features in pediatric sarcoma
Authors: Aydos Uğuray , Sever Tayyibe , Vural Özge , Topuz Türkcan Büşra , Okur Arzu , Akdemir Ümit Özgür , Poyraz Aylar , Pinarli Faruk Güçlü , Atay Lütfiye Özlem , Karadeniz Ceyda
Published: May 2022

Purpose

The aim of this study was to evaluate the prognostic value of PET-derived metabolic features and textural parameters of primary tumors in pediatric sarcoma patients.

Methods

The imaging findings of 43 patients (14 girls and 29 boys; age 11.4 ± 4.4 years) who underwent 18-fluorodeoxyglucose positron emission tomography (PET)/computed tomography for primary staging prior to therapy between 2005 and 2020 were retrospectively evaluated. The diagnoses were osteosarcoma in 10, rhabdomyosarcoma in 10, and Ewing sarcoma in 23 patients. PET metabolic data and textural features of primary tumors were obtained. Cox proportional hazards regression models were used to identify predictors for progression-free survival and overall survival. Survival curves were estimated by using the Kaplan-Meier method.

Results

Distant metastases were detected in primary staging in 13 patients (30.2%). The median follow-up duration after diagnosis was 28 months (range: 10–171 months). In multivariate Cox regression analysis, the presence of distant metastasis and neighborhood grey-level difference matrix_Contrast (ngldm_Contrast) were found as independent predictors for both progression-free survival and overall survival. Grey-level zone length matrix_Zone-length nonuniformity (glzlm_ZLNU) was also found as an independent predictor for overall survival. The Kaplan–Meier survival analysis showed that higher ngldm_Contrast and glzlm_ZLNU values of primary tumors were significantly associated with shorter progression-free survival and overall survival.

Conclusion

In addition to the presence of distant metastasis at initial diagnosis, textural features of primary tumors may be used as prognostic biomarkers to identify patients with worse prognosis in pediatric sarcoma. Higher tumor heterogeneity is significantly associated with shorter progression-free survival and OS.
Management of Preterm Premature Rupture of Membranes in the Late Preterm Period
Authors: Freeman Sarah W. , Denoble Annalies , Kuller Jeffrey A. , Ellestad Sarah , Dotters-Katz Sarah
Published: May 2022

Importance

For patients who present with prelabor rupture of membrane (PROM) in the late preterm period (34 to 36 6/7 weeks), management remains unclear due to lack of consensus. However, recent guidelines have suggested that shared decision-making may be used and expectant management can be considered up to 37 0/7 weeks.

Objective

In this article, we review the contemporary studies comparing the risks and benefits of immediate delivery versus expectant management for patients with late preterm prelabor rupture of membranes (PPROM).

Evidence Acquisition

Original research articles, review articles, and guidelines on management of late PPROM.

Results

Three randomized clinical trials and 2 meta-analyses comparing expectant management and immediate delivery outcomes in late PPROM showed no significant difference in neonatal sepsis rates between groups. Expectant management increased the likelihood that pregnancies reached term while decreasing the rate of cesarean delivery. However, data suggest an increased risk of antepartum hemorrhage among patients in the expectant management groups, as well as higher rates of histologic chorioamnionitis.

Conclusions and Relevance

We recommend that clinicians offer expectant management as an alternative to immediate delivery in the setting of late PPROM through a shared decision-making process that clearly outlines the risks and benefits.

Target Audience

Obstetricians and gynecologists, family physicians.

Learning Objectives

After participating in this activity, the provider should be better able to summarize current evidence regarding fetal, maternal, and obstetric outcomes between immediate delivery and expectant management of patients with PPROM in the late preterm period; describe clinical evaluation of women who present with PPROM in the late preterm period; and plan adequate counseling on the risk and benefits of immediate delivery or expectant management to women who present with PPROM in the later preterm period.
Clinical and Patient Reported Outcomes Pre- and Postsurgical Treatment of Symptomatic Uterine Leiomyomas: A12-Month Follow-up Review of TRUST, a Surgical Randomized Clinical Trial Comparing Laparoscopic Radiofrequency Ablation (LAP-RFA) and Myomectomy
Authors: Yu Steve , Bhagavath Bala , Shobeiri S. Abbas , Eisenstein David , Levy Barbara
Published: May 2022

(Abstracted from J Minim Invasive Gynecol 2022; doi: 10.1016/j.jmig.2022.01.009)

Uterine leiomyomas (ULs) affect a large population of women in the United States. Despite the high incidence of women with symptomatic ULs, the number of surgical procedures performed annually is fewer than 250,000.
Interpersonal Violence and Painful Bladder Symptoms in Community-Dwelling Midlife to Older Women
Authors: Raphael Eva , Van Den Eeden Stephen K. , Gibson Carolyn J. , Tonner Chris , Thom David H. , Subak Leslee , Huang Alison J.
Published: May 2022

(Abstracted from Am J Obstet Gynecol 2022;226:230.e1–230.e11)

The chronic pain, pressure, and discomfort associated with the bladder pain syndrome (BPS) have a major impact on a woman’s quality of life. Bladder pain syndrome is one of the most common reasons for invasive urological or gynecological procedures.
Association Between the Physician Quality Score in the Merit-Based Incentive Payment System and Hospital Performance in Hospital Compare in the First Year of the Program
Authors: Glance Laurent G. , Thirukumaran Caroline P. , Feng Changyong , Lustik Stewart J. , Dick Andrew W.
Published: May 2022

(Abstracted from JAMA Network Open 2021;4(8):e2118449)

In an effort to deliver better patient outcomes at a lower cost, the Centers for Medicare & Medicaid Services (CMS) mandates eligible clinicians to participate in either the Merit-Based Incentive Payment System (MIPS) or Advanced Alternative Payment Models. Physicians or physician groups being evaluated through MIPS can receive a maximum of 60 points for quality, composed of 6 measurement categories that they may select.
Changes in Delivery Timing for High-Risk Pregnancies in the United States
Authors: Little Sarah E. , Robinson Julian N. , Zera Chloe A.
Published: May 2022

(Abstracted from Am J Perinatol 2021;38:1373–1379)

Awareness of increased morbidity in neonates born at 34 to 37 weeks' gestation (late preterm) and 37 to 39 weeks' gestation (early term), compared with those born at ≥39 weeks' gestation, has grown over the past decade. As a result, efforts have been put in place in hospitals and at state and national levels to reduce deliveries at <39 weeks of gestation that are not medically indicated.
Factors Affecting Nonurgent Pediatric Emergency Department Visits and Parental Emergency Overestimation
Authors: Pehlivanturk-Kizilkan Melis , Ozsezen Beste , Batu Ezgi Deniz
Published: May 2022

Objectives

Understanding the factors causing nonurgent visits to the pediatric emergency departments (PED) is essential for developing effective interventions. Sociodemographic factors might have a direct effect, or they might be associated with other potential causal factors such as access, perceived severity, and convenience. Therefore, we aimed to evaluate the factors that might have an effect on nonurgent PED visits and parental overestimation of emergency severity.

Methods

Data of a total of 974 patients who have been administered to the PED of a district state hospital were collected with a cross-sectional, self-administered survey. Level 5 was accepted as nonurgent cases according to the Pediatric Canadian Triage and Acuity Scale. Parents' assessment of their child's emergency status was assessed along with the age and sex of the child, the number of children, presence of a chronic illness, presence of fever, admission time, parental age, education status and occupation, transportation method, and living distance to emergency department.

Results

Sixty-eight percent of visits were nonurgent. Among these visits, 51.6% were perceived as urgent, and 11.5% as extremely urgent by the parents. We identified that infancy age group (P = 0.001), father's unemployment status (P = 0.038), presence of a chronic disease (P = 0.020), and a previous visit to the PED in the last week (P = 0.008) are associated with urgent visits. Having a fever (P = 0.002), younger mother (P = 0.046) and father age (P = 0.007), mother not having an income (P = 0.034), and father's lower level of education (P = 0.036) increased the likelihood of overestimating the emergency severity.

Conclusions

Nonurgent visits constitute most of the PED admissions. Several factors were found to be associated with nonurgent visits either by causing a direct effect or by indirectly impacting the perceived severity. Health literacy–based interventions targeting common symptoms like fever and especially younger parent groups might be beneficial in lowering the patient burden of PEDs.
ACR-ACNM-ASTRO-SNMMI Practice Parameter for Lutetium-177 (Lu-177) DOTATATE Therapy
Authors: Love Charito , Desai Neil B. , Abraham Tony , Banks Kevin P. , Bodei Lisa , Boike Thomas , Brown Richard K. J. , Bushnell David L. , DeBlanche Lorraine E. , Dominello Michael M. , Francis Tony , Grady Erin C. , Hobbs Robert F. , Hope Thomas A. , Kempf Jeffrey S. , Pryma Daniel A. , Rule William , Savir-Baruch Bital , Sethi Ila , Subramaniam Rathan M. , Xiao Ying , Schechter Naomi R.
Published: May 2022

Objectives

This practice parameter (PP) for Lutetium-177 (Lu-177) DOTATATE peptide receptor radionuclide therapy (PRRT) aims to guide authorized users in selection of appropriate adult candidates with gastroeneropancreatic neuroendocrine tumors (GEP-NETs) from foregut, midgut, and hindgut. The essential selection criteria include somatostatin receptor-positive GEP-NETs, which are usually inoperable and progressed despite standard therapy. Lu-177 DOTATATE is a radiopharmaceutical with high avidity for somatostatin receptors that are overexpressed by these tumors. This document ensures safe handling of Lu-177 DOTATATE by the authorized users and safe management of affected patients.

Methods

The document was developed according to the systematic process developed by the American College of Radiology (ACR) and described on the ACR Web site (https://www.acr.org/Clinical-Resources/Practice-Parameters-and-Technical-Standards). The PP development was led by 2 ACR Committees on Practice Parameters (Nuclear Medicine and Molecular Imaging and Radiation Oncology) collaboratively with the American College of Nuclear Medicine, American Society of Radiation Oncology, and Society of Nuclear Medicine and Molecular Imaging.

Results

The Lu-177 DOTATATE PP reviewed pharmacology, indications, adverse effects, personnel qualifications, and required clinical evaluation before starting the treatment, as well as the recommended posttherapy monitoring, quality assurance, documentation, and appropriate radiation safety instructions provided in written form and explained to the patients.

Conclusions

Lu-177 DOTATATE is available for therapy of inoperable and/or advanced GEP-NETs when conventional therapy had failed. It can reduce tumor size, improve symptoms, and increase the progression free survival. The PP document provides clinical guidance for authorized users to assure an appropriate, consistent, and safe practice of Lu-177 DOTATATE.
BNT–15: Revised Performance Validity Cutoffs and Proposed Clinical Classification Ranges
Authors: Abeare Kaitlyn , Cutler Laura , An Kelly Y. , Razvi Parveen , Holcomb Matthew , Erdodi Laszlo A.
Published: May 2022

Background:

Abbreviated neurocognitive tests offer a practical alternative to full-length versions but often lack clear interpretive guidelines, thereby limiting their clinical utility.

Objective:

To replicate validity cutoffs for the Boston Naming Test—Short Form (BNT–15) and to introduce a clinical classification system for the BNT–15 as a measure of object-naming skills.

Method:

We collected data from 43 university students and 46 clinical patients. Classification accuracy was computed against psychometrically defined criterion groups. Clinical classification ranges were developed using a z-score transformation.

Results:

Previously suggested validity cutoffs (≤11 and ≤12) produced comparable classification accuracy among the university students. However, a more conservative cutoff (≤10) was needed with the clinical patients to contain the false-positive rate (0.20–0.38 sensitivity at 0.92–0.96 specificity). As a measure of cognitive ability, a perfect BNT–15 score suggests above average performance; ≤11 suggests clinically significant deficits. Demographically adjusted prorated BNT–15 T-scores correlated strongly (0.86) with the newly developed z-scores.

Conclusion:

Given its brevity (<5 minutes), ease of administration and scoring, the BNT–15 can function as a useful and cost-effective screening measure for both object-naming/English proficiency and performance validity. The proposed clinical classification ranges provide useful guidelines for practitioners.
The spatial and temporal distribution of females influence the evolution of testes size in Australian rodents
Authors: Firman Renée C. , Rubenstein Dustin R. , Buzatto Bruno A.
Published: May 2022

Male–male competition after mating (sperm competition) favours adaptations in male traits, such as elevated sperm numbers facilitated by larger testes. Ultimately, patterns of female distribution will affect the strength of sperm competition by dictating the extent to which males are able to prevent female remating. Despite this, our understanding of how the spatial and temporal distributions of mating opportunities have shaped the evolutionary course of sperm competition is limited. Here, we use phylogenetic comparative methods to explore interspecific variation in testes size in relation to patterns of female distribution in Australian rodents. We find that as mating season length (temporal distribution of females) increases, testes size decreases, which is consistent with the idea that it is difficult for males to prevent females from remating when overlap among oestrous females is temporally concentrated. Additionally, we find that social species (spatially clustered) have smaller testes than non-social species (spatially dispersed). This result suggests that males may be effective in monopolizing reproduction within social groups, which leads to reduced levels of sperm competition relative to non-social species where free-ranging females cannot be controlled. Overall, our results show that patterns of female distribution, in both space and time, can influence the strength of post-mating sexual selection among species.
A probabilistic framework for windows of opportunity: the role of temporal variability in critical transitions
Authors: van Belzen Jim , Fivash Gregory S. , Hu Zhan , Bouma Tjeerd J. , Herman Peter M. J.
Published: May 2022

The establishment of young organisms in harsh environments often requires a window of opportunity (WoO). That is, a short time window in which environmental conditions drop long enough below the hostile average level, giving the organism time to develop tolerance and transition into stable existence. It has been suggested that this kind of establishment dynamics is a noise-induced transition between two alternate states. Understanding how temporal variability (i.e. noise) in environmental conditions affects establishment of organisms is therefore key, yet not well understood or included explicitly in the WoO framework. In this paper, we develop a coherent theoretical framework for understanding when the WoO open or close based on simple dichotomous environmental variation. We reveal that understanding of the intrinsic timescales of both the developing organism and the environment is fundamental to predict if organisms can or cannot establish. These insights have allowed us to develop statistical laws for predicting establishment probabilities based on the period and variance of the fluctuations in naturally variable environments. Based on this framework, we now get a clear understanding of how changes in the timing and magnitude of climate variability or management can mediate establishment chances.
Modelling the emergence of cities and urban patterning using coupled integro-differential equations
Authors: Whiteley Timothy D. , Avitabile Daniele , Siebers Peer-Olaf , Robinson Darren , Owen Markus R.
Published: May 2022

Human residential population distributions show patterns of higher density clustering around local services such as shops and places of employment, displaying characteristic length scales; Fourier transforms and spatial autocorrelation show the length scale between UK cities is around 45 km. We use integro-differential equations to model the spatio-temporal dynamics of population and service density under the assumption that they benefit from spatial proximity, captured via spatial weight kernels. The system tends towards a well-mixed homogeneous state or a spatial pattern. Linear stability analysis around the homogeneous steady state predicts a modelled length-scale consistent with that observed in the data. Moreover, we show that spatial instability occurs only for perturbations with a sufficiently long wavelength and only where there is a sufficiently strong dependence of service potential on population density. Within urban centres, competition for space may cause services and population to be out of phase with one another, occupying separate parcels of land. By introducing competition, along with a preference for population to be located near, but not too near, to high service density areas, secondary out-of-phase patterns occur within the model, at a higher density and with a shorter length scale than in phase patterning. Thus, we show that a small set of core behavioural ingredients can generate aggregations of populations and services, and pattern formation within cities, with length scales consistent with real-world data. The analysis and results are valid across a wide range of parameter values and functional forms in the model.
A novel methodological approach to simultaneously extract high-quality total RNA and proteins from cortical and trabecular bone
Authors: Faraldi Martina , Mangiavini Laura , Conte Caterina , Banfi Giuseppe , Napoli Nicola , Lombardi Giovanni
Published: May 2022

Molecular differences between cortical and trabecular bone, of relevance to understanding the pathophysiological basis of bone diseases, can be determined only through effective isolation methods for RNA and proteins. Here we present a TRIzol-based method, which combines bone pulverization and homogenization to extract simultaneously total RNA and proteins from human cortical and trabecular bone from the same carrot. RNA integrity and purity were determined as the 260/280 nm and 260/230 nm absorbance ratios and the 28S/18S rRNA ratio. Protein integrity and quality were evaluated by Coomassie blue staining. Reverse transcription quantitative polymerase chain reaction and immunoblotting for bone-specific genes and proteins were performed to verify the suitability of the isolated material in downstream applications. The 260/280 nm and 260/230 nm absorbance ratios were, on average, less than or equal to 1.8. Bands on agarose gel were consistent with intact RNA, with mean 28S/18S ratios of 1.68 ± 0.35 and 1.88 ± 0.10 for cortical and trabecular bone, respectively. Band patterns after Coomassie blue staining confirmed protein integrity. Successful gene and protein expression analysis, with relevant differences between the two compartments, highlighted the suitability of the material in downstream applications. The method presented here is appropriate and effective for the study of human bone.
Source terms for benchmarking models of SARS-CoV-2 transmission via aerosols and droplets
Authors: Stettler Marc E. J. , Nishida Robert T. , de Oliveira Pedro M. , Mesquita Léo C. C. , Johnson Tyler J. , Galea Edwin R. , Grandison Angus , Ewer John , Carruthers David , Sykes David , Kumar Prashant , Avital Eldad , Obeysekara Asiri I. B. , Doorly Denis , Hardalupas Yannis , Green David C. , Coldrick Simon , Parker Simon , Boies Adam M.
Published: May 2022

There is ongoing and rapid advancement in approaches to modelling the fate of exhaled particles in different environments relevant to disease transmission. It is important that models are verified by comparison with each other using a common set of input parameters to ensure that model differences can be interpreted in terms of model physics rather than unspecified differences in model input parameters. In this paper, we define parameters necessary for such benchmarking of models of airborne particles exhaled by humans and transported in the environment during breathing and speaking.
Folding arrays of uniform-thickness panels to compact bundles with a single degree of freedom
Authors: Yang Jingyi , Zhang Xiao , Chen Yan , You Zhong
Published: May 2022

Flat arrays consisting of panels of finite thickness are widely used in aerospace applications such as solar panels and reflectarray antennas. Packaging them into compact bundles without any voids and then deploying them bi-directionally to flat, continuous and accurate surfaces with a single degree of freedom (DoF) has challenged engineers for decades. Here, we present a solution based on origami of thick panels. In modular construction, we first created two deployable unit arrays, each of which comprises four eight-panel elements where panels in regular shapes are connected by simple but robust rotational joints. We prove that these units have only a single DoF, and they can be folded from a flat array to compact bundles without any voids. We then show that the units can be tessellated to form larger flat arrays where a single-DoF deployment and compact packaging properties are intact. A parametric study is carried out, which provides a precise design range that prevents the panels from physical interference during deployment. Physical models were constructed that have successfully validated the concepts. Our work is directly applicable to the design of future flat arrays that can be controlled with ease.
An efficient multiscale bi-directional PBM-DEM coupling framework to simulate one-dimensional aggregation mechanisms
Authors: Das Ashok , De Tarun , Kaur Gurmeet , Dosta Maksym , Heinrich Stefan , Kumar Jitendra
Published: May 2022

The mesoscale population balance modelling (PBM) technique is widely used in predicting aggregation processes. The accuracy and efficiency of PBM depend on the formulation of its kernels. A model of the volume- and time-dependent one-dimensional aggregation kernel is developed for predicting the temporal evolution of the considered particulate system. To make the developed model physically relevant, the PBM model needs three unknown parameters as input: volume-dependency in collisions, collision frequency per particle and aggregation probability. For this, the microscale discrete element model (DEM) is used. The system’s collision frequency is extracted periodically using a novel collision detection algorithm that detects and ignores duplicate collisions.

Finally, a multiscale bi-directional PBM–DEM coupling framework is presented to simulate the aggregation mechanism. PBM and DEM simulations take place periodically to update the particle size distribution (PSD) and extract the collision-frequency, respectively. The coupling framework successfully explains the dependence between the PSD and the collision frequency. Additionally, computational cost of the algorithm is optimized while maintaining the accuracy of the results. Lastly, the accuracy and efficiency of the developed framework are verified using two different test cases. In one of the examples, a simple aggregation is simulated directly inside the DEM for the first time.
Stochastic establishment of β-lactam-resistant
Escherichia coli
mutants reveals conditions for collective resistance
Authors: Saebelfeld Manja , Das Suman G. , Hagenbeek Arno , Krug Joachim , de Visser J. Arjan G. M.
Published: May 2022

For antibiotic resistance to arise, new resistant mutants must establish in a bacterial population before they can spread via natural selection. Comprehending the stochastic factors that influence mutant establishment is crucial for a quantitative understanding of antibiotic resistance emergence. Here, we quantify the single-cell establishment probability of four
Escherichia coli
strains expressing β-lactamase alleles with different activity against the antibiotic cefotaxime, as a function of antibiotic concentration in both unstructured (liquid) and structured (agar) environments. We show that concentrations well below the minimum inhibitory concentration (MIC) can substantially hamper establishment, particularly for highly resistant mutants. While the pattern of establishment suppression is comparable in both tested environments, we find greater variability in establishment probability on agar. Using a simple branching model, we investigate possible sources of this stochasticity, including environment-dependent lineage variability, but cannot reject other possible causes. Lastly, we use the single-cell establishment probability to predict each strain's MIC in the absence of social interactions. We observe substantially higher measured than predicted MIC values, particularly for highly resistant strains, which indicates cooperative effects among resistant cells at large cell numbers, such as in standard MIC assays.
Unravelling the causes and consequences of dispersal syndromes in a wild passerine
Authors: Nicolaus Marion , Wang Xuelai , Lamers Koosje P. , Ubels Richard , Both Christiaan
Published: May 2022

Evidence accumulates that dispersal is correlated with individual behavioural phenotype (dispersal syndrome). The evolutionary causes and consequences of such covariation depend on the degree of plasticity versus inheritance of the traits, which requires challenging experiments to implement in mobile organisms. Here, we combine a forced dispersal experiment, natural colonization and longitudinal data to establish if dispersal and aggression levels are integrated and to test their adaptive nature in pied flycatchers (
Ficedula hypoleuca
). We found that (forced) dispersers behaved more aggressively in their first breeding year after dispersal and decreased their aggression in following years. Strength of dispersal syndrome and direction of fecundity selection on aggression in newly colonized areas varied between years. We propose that the net benefits of aggression for dispersers increase under harsh conditions (e.g. low food abundance). This hypothesis now warrants further testing. Overall, this study provides unprecedented experimental evidence that dispersal syndromes can be remodelled via adaptive plasticity depending on the individuals' local breeding experience and/or year-specific ecological conditions. It highlights the importance of individual behavioural variation in population dynamics.
The source of individual heterogeneity shapes infectious disease outbreaks
Authors: Elie Baptiste , Selinger Christian , Alizon Samuel
Published: May 2022

There is known heterogeneity between individuals in infectious disease transmission patterns. The source of this heterogeneity is thought to affect epidemiological dynamics but studies tend not to control for the overall heterogeneity in the number of secondary cases caused by an infection. To explore the role of individual variation in infection duration and transmission rate in parasite emergence and spread, while controlling for this potential bias, we simulate stochastic outbreaks with and without parasite evolution. As expected, heterogeneity in the number of secondary cases decreases the probability of outbreak emergence. Furthermore, for epidemics that do emerge, assuming more realistic infection duration distributions leads to faster outbreaks and higher epidemic peaks. When parasites require adaptive mutations to cause large epidemics, the impact of heterogeneity depends on the underlying evolutionary model. If emergence relies on within-host evolution, decreasing the infection duration variance decreases the probability of emergence. These results underline the importance of accounting for realistic distributions of transmission rates to anticipate the effect of individual heterogeneity on epidemiological dynamics.