bluuebunny/crossref_metadata_2025 huggingface dataset:
Mediastinal Germ Cell Tumors: A Review and Update on Pathologic, Clinical, and Molecular Features
Authors: El-Zaatari Ziad M. , Ro Jae Y.
Published: May 2021

Mediastinal germ cell tumors (MGCTs) are the most common extragonadal germ cell tumors (GCTs) and most often arise in the anterior mediastinum with a male predilection. MGCTs also have a predilection for patients with Klinefelter syndrome and possibly other genetic conditions. MGCTs, as GCTs at other extragonadal sites, are thought to arise from germ cells improperly retained during migration along the midline during embryogenesis. Similar to their counterparts in the testes, MGCTs are classified into seminomatous and nonseminomatous GCTs. Seminomatous MGCT represents pure seminoma, whereas nonseminomatous MGCTs encompass pure yolk sac tumors, embryonal carcinoma, choriocarcinoma, mature or immature teratoma, and mixed GCTs with any combination of GCT types, including seminoma. Somatic-type or hematologic malignancies can also occur in association with a primary MGCT. MGCTs share molecular findings with GCTs at other sites, most commonly the presence of chromosome 12p gains and isochromosome i(12p). Treatment includes neoadjuvant chemotherapy followed by surgical resection of residual tumor, with the exception of benign teratomas, which require only surgical resection without chemotherapy. In this review, we highlight and provide an update on pathologic, clinical, and molecular features of MGCTs. Immunohistochemical profiles of each tumor type, as well as differential diagnostic considerations, are discussed.
Ultrasound Assessment of Quadriceps Femoris Muscle Thickness in Critically Ill Children*
Authors: Hoffmann Robert M. , Ariagno Katelyn A. , Pham Ivy V. , Barnewolt Carol E. , Jarrett Delma Y. , Mehta Nilesh M. , Kantor David B.
Published: May 2021

OBJECTIVES:

Evaluate the reliability of ultrasound to measure quadriceps femoris muscle thickness in critically ill children and to describe serial changes in quadriceps femoris muscle thickness in relation to fluid balance and nutritional intake.

DESIGN:

Prospective observational study.

SETTING:

Tertiary care children’s hospital.

PATIENTS:

Inpatients age 3 months to 18 years recently admitted to the ICU who were sedated and mechanically ventilated at the time of the first ultrasound scan.

METHODS:

Prospective observational study to examine the reliability of averaged ultrasound measurements of quadriceps femoris muscle thickness. Change in average quadriceps femoris muscle thickness over time was correlated with fluid balance and nutritional intake.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Averaged quadriceps femoris muscle thickness demonstrated good to excellent reliability when comparing pediatric critical care providers to pediatric radiologists and when comparing between different pediatric critical care providers. We found no significant association between fluid balance over 1 or 3 days and change in quadriceps femoris muscle thickness over the same time frame. However, there was a significant association between percent of goal calories (p < 0.001) or percent of goal protein (p < 0.001) over 6 days and change in quadriceps femoris muscle thickness over the same time frame.

CONCLUSIONS:

Averaged ultrasound measurements of quadriceps femoris muscle thickness demonstrate good to excellent reliability, are not confounded by fluid balance, and are useful for tracking changes in muscle thickness that are associated with nutritional intake. Ultrasound-based assessment of quadriceps femoris is a clinically useful tool for evaluating muscle mass and may be a proxy for nutritional status.
Characterizing Sleep Disruption and Delirium in Children After Cardiac Surgery: A Feasibility Study
Authors: Gregory Jillian L. , Brown Anna T. , Kudchadkar Sapna R.
Published: May 2021

OBJECTIVES:

Patients in the pediatric cardiac ICU are frequently exposed to pharmacologic and environmental factors that predispose them to sleep disturbances and may increase the risk of delirium. In this pilot study, we sought to demonstrate the feasibility of actigraphy monitoring in pediatric cardiac ICU patients to investigate the association between sleep characteristics and delirium development.

DESIGN:

Prospective observational pilot study.

SETTING:

Pediatric cardiac ICU in an academic children’s hospital in the United States.

PATIENTS:

Children admitted to the pediatric cardiac ICU after cardiac surgery.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Nineteen enrolled patients wore actigraphy watches that provided data for a total of 63 pediatric cardiac ICU days. The median pediatric cardiac ICU length of stay was 2 days (interquartile range, 1–3 d). The median sleep episode among all patients was 37 minutes in duration (interquartile range, 18–46 min), and the longest sleep episode was a median of 117 minutes (interquartile range, 69–144 min). Sixty-one percent of patients (95% CI, 36–83%) screened positive for delirium at least once during admission, and the median number of delirious days among those who were positive was 2 days (interquartile range, 1–3 d). The median percent sleep time was 43% for delirious patients and 49% for those with no delirium, with similar median sleep and longest sleep episodes. The median ratio of daytime activity/24-hr activity was 54% (interquartile range, 49–59%) in both groups.

CONCLUSIONS:

Actigraphy monitoring in conjunction with delirium screening is feasible in infants and children admitted to the pediatric cardiac ICU after cardiac surgery. Our data suggest that most children in the pediatric cardiac ICU experience severe sleep disruption and delirium is common. These pilot data provide important insights for the design of a large-scale observational study to investigate potential causal relationships between sleep disruption and delirium in the pediatric cardiac ICU.
The Efficacy of a Home-Based, Self-Administered Hand Exercise Program for Patients With Systemic Sclerosis
Authors: Gokcen Neslihan , Badak Suade Ozlem , Sarpel Tunay , Sertdemir Yasar , Erken Eren
Published: May 2021

Background

For patients with systemic sclerosis (SSc), hand involvement is an underrated clinical manifestation. Therefore, the aim of this study was to investigate the efficacy of a hand exercise program and to demonstrate its effect on hand function, quality of life, anxiety, and depression in patients with SSc.

Methods

This study was designed as a single blind, randomized controlled comparative study. Sixty-two female patients with SSc were randomized into an exercise group (n = 32) or a control group (n = 30). After some were lost to follow-up, 25 patients were analyzed in each group. In the exercise group, the 8-week intervention consisted of isometric hand exercises and self-administered stretching repeated 10 times/2 sets per day. All patients were assessed using the Hand Mobility in Scleroderma (HAMIS) test, the Duruoz Hand Index (DHI), grip strength, the 36-item short form, Health Assessment Questionnaire–Disability Index (HAQ-DI), Beck Anxiety Inventory (BAI), and the Beck Depression Inventory (BDI) at baseline and then again 4 and 8 weeks later. Within-group comparisons over time were analyzed using the Friedman test. Post hoc analysis was performed using the Wilcoxon signed rank test. A multiple linear regression analysis was used to define the impact of exercise on clinical status.

Results

Of the 50 total patients, the median age and the median body mass index were 55.5 years and 25.9 kg/m2. The median disease duration was 10.0 years. Thirty-four patients (68.0%) were diffuse cutaneous systemic sclerosis (dcSSC), whereas 16 (32.0%) were limited cutaneous systemic sclerosis (lcSSc). The primary outcome of handgrip strength, as well as the HAMIS, DHI, HAQ-DI, and BDI, significantly improved over time (p < 0.001, p < 0.001, p < 0.001, p < 0.001, and p = 0.005, respectively). The between-group comparison indicated significant improvement in DHI, handgrip strength, HAQ-DI, BAI, and BDI in the exercise group (p = 0.02, p = 0.013, p < 0.001, p = 0.015, and p = 0.036, respectively). In the multiple linear regression analysis, exercise was found to be the most efficient factor affecting the improvement in HAMIS, DHI, HAQ-DI, and grip strength.

Conclusions

The 8-week intervention composed of isometric hand exercises and self-administered stretching provided a significant improvement in handgrip strength, general health, quality of life, and psychological status for patients with SSc.
131I Ablation of an Entire Thyroid Gland in Locally Invasive Differentiated Thyroid Cancer Without Surgery
Authors: Yung Grace , Forwood Nicholas , Russo Robert , Ganda Kirtan , Mansberg Robert
Published: May 2021

A 79-year-old man with locally metastatic papillary thyroid cancer to left-sided cervical lymph nodes was referred for radioiodine therapy. He was considered unfit for thyroidectomy due to extensive local involvement and severe interstitial lung disease requiring continuous oxygen. The patient was treated with low doses of radioiodine (approximately 30 mCi) every 6 months with corticosteroid cover for 3 years with good effect. Sequential 131I scanning and serum thyroglobulin levels confirmed virtual complete ablation of the thyroid gland. The patient remained well on thyroid hormone replacement.
Incidental Finding of Endometrioid Adenocarcinoma of the Ovary on 131I Whole-Body Scan
Authors: Mohd Rohani Mohd Fazrin , Amir Hassan Siti Zarina
Published: May 2021

A 57-year-old woman was referred for radioactive iodine therapy 12 weeks after completion thyroidectomy and left modified radical neck dissection for pT2N1Mx follicular variant papillary thyroid carcinoma. After 4 weeks of l-thyroxine withdrawal, stimulated serum thyroglobulin level was less than 0.1 ng/mL with positive thyroglobulin antibody. Posttherapy 131I scintigraphy with SPECT/CT of the head and abdominopelvic region showed thyroid residual in the neck, occipital bone metastasis, and heterogenous tracer uptake in a large peritoneal mass, likely arising from the left ovary. Left salpingo-oophorectomy was performed, and histopathologic examination revealed endometrioid carcinoma of left ovary.
68Ga-FAPI PET/CT Imaging of Graves Ophthalmopathy in a Patient With Esophageal Cancer
Authors: Liu Huipan , Yang Xiao , Wang Yingwei , Wang Peng , Chen Yue
Published: May 2021

68Ga-FAPI PET/CT has been used in the assessment of a variety of malignancies. In addition, FAPI uptake in nonmalignant diseases has also been reported. Herein, we present a case of Graves ophthalmopathy detected by 68Ga-FAPI PET/CT.
De-epithelialized Skin Flaps to Minimize Complications in Large Breast Reconstruction
Authors: Lanitis Sophocles , Kontos Michalis , Chortis Panagiotis , Gkanis Vasilios , Peristeraki Styliani , Lainas Spyridon , Hadjiminas Dimitri J.
Published: May 2021

Mastectomy and immediate reconstruction may be challenging in patients with large breasts, especially when significant ptosis is also present. Skin-reducing mastectomy (SRM) is usually indicated in these cases, although with increased morbidity. The aims of the study were to introduce 2 modifications of the classic technique and to incorporate them in the management algorithm to improve the outcomes.

Twenty patients fulfilling the criteria for SRM underwent mastectomy and reconstruction either with the “classic SRM” (8 patients) or with 1 of the 2 modifications described here: modification A “vertical limb bridging” (for patients with very large breasts, 2 patients) and modification B “dual coverage” (for patients with moderate breasts, 10 patients). All reconstructions were performed using a slow progressive expansion of the implant. Herein, we describe the techniques along with the proposed indications for each one of them.

There was no reconstruction failure, and all patients were satisfied with the final results. There were 2 cases with T junction, lateral skin flap partial ischemia managed with delayed revision of the wound on the fifth postoperative day to allow less skin excision. One patient (smoker) developed severe lower pole cellulitis, which was managed conservatively. Finally, 1 patient who underwent radiotherapy developed a late infected seroma, which was managed successfully with drainage and antibiotics. Overall, there was good lower pole projection even with the dual-coverage modification.

Skin-reducing mastectomy can be tailored according to individual patient anatomy, and the high reported complication rate associated with this technique can be minimized using certain surgical modifications, tissue expanders with progressive inflation, and good patient selection.
Formulating an Easy, Affordable, and Reproducible Method for Virtual Planning and 3D Reconstruction
Authors: Gupta Samarth , Goil Pradeep
Published: May 2021

Introduction

Free fibula flap is now regarded as the criterion standard for mandibular reconstruction after oncological resection. However, the results are often confounded due to inappropriate estimate of defect or inappropriate angulation of osteotomy. Three-dimensional (3D) printing and virtual planning can be an effective tool to help in planning osteotomies, therefore simplifying the process. Unfortunately, in developing countries, it is considered to be an expensive and a time-consuming affair, refraining the surgeons to use this technology. We have devised a cheap (less than $35), rapid, and reproducible method for this process that can be performed by residents with the help of the operating surgeon using a freely available software.

Materials and Methods

The study was conducted over a span of 5 years from 2016 to 2020. Forty patients were randomly categorized into 2 groups of 20 each, one of which underwent conventional free fibula flap and the other group consisted of those for whom 3D printing and virtual planning were used. Aesthetic outcome was measured by preoperative and postoperative CT scans with 3D reconstruction. Furthermore, the reconstruction time and total operative time were also measured in both these groups.

Results

Comparative study clearly demonstrated a significantly better aesthetic outcome in the 3D printing and virtual planning group. The use of this modality significantly reduced the reconstruction time, which was 83.9 minutes in the cases group and 124 minutes in the control group.

Conclusions

Three-dimensional printing and virtual planning help to improve the quality of mandibular reconstruction giving a better aesthetic outcome. Besides, it also reduces the operative time and gives us a chance to use prebent implants used for reconstruction. Our methodology is simple, quick, and cost-effective; therefore, we believe that this tool can be incorporated often in free fibula flaps for mandibular reconstruction in developing countries such as ours.
Clinical Outcomes After Neurolysis for the Treatment of Peroneal Nerve Palsy
Authors: Chow Amanda L. , Levidy Michael F. , Luthringer Margaret , Vasoya Devin , Ignatiuk Ashley
Published: May 2021

Background

Neurolysis techniques have been adapted for decompression of peripheral nerves in multiple locations, including the common peroneal nerve (CPN) at the fibular neck. The aim of this study was to conduct a systematic review and meta-analysis to summarize the clinical outcomes of neurolysis for the management of peroneal nerve palsy (PNP).

Methods

Preferred Reporting Systems for Systematic Reviews and Meta-Analyses guidelines were followed for this meta-analysis. Four databases were queried, and randomized clinical trials, cohort studies, case-control studies, and case series with n > 10 published in English that evaluated clinical outcomes of neurolysis for the treatment of PNP and foot drop were included. Two reviewers completed screening and data extraction. Methodological quality was evaluated using the Newcastle-Ottawa Scale.

Results

A total of 493 articles were identified through literature search. Title and abstract screening identified 39 studies for full-text screening. Ten articles met the inclusion criteria for qualitative analysis, and 8 had complete data for meta-analysis.

Overall, there were 368 patients (370 nerves) who had neurolysis of the CPN for PNP, of which 59.2% (n = 218) were men and 40.8% (n = 150) were women. The mean age of the patients was 47.1 years (SD, 10.0 years), mean time to surgery was 9.65 months (SD, 6.3 months), and mean follow-up time was 28 months (SD, 14.0 months). The median preoperative Medical Research Council (MRC) score was 1 (IQR 0, 3), with 42.2% (n = 156) having MRC score of 0. The median postoperative MRC score was 5 (IQR 4, 5), with 53.9% (n = 199) having MRC score of 5. Complications of neurolysis of the peroneal nerve for treatment of PNP included postoperative infection (0.54%, n = 2), wound dehiscence (0.27%, n = 1), hematoma (0.54%, n = 2), bleeding (0.27%, n = 1), relapse of PNP (0.27%, n = 1), and 1 case of mortality due to sepsis.

Conclusions

Our meta-analysis shows that neurolysis of the CPN is safe and improves ankle dorsiflexion strength in patients with PNP. Future studies should use a standardized method of measuring sensory outcomes, and studies of higher levels of evidence are needed to better assess the clinical outcomes of neurolysis for treatment of PNP.
Does Complexity Always Correlate With Compensation? An Analysis of Work Relative Value Units in 3 Common Nerve Decompression Syndromes
Authors: Doval Andres F. , Boochoon Kieran , Le Hung B. , Mehra Nikhilesh V. , Liberman Shari , Harris Joshua D. , Echo Anthony
Published: May 2021

Background

Work relative value units (wRVUs) are part of Resource Based Relative Value Scale system. It is expected that a more difficult and time-consuming procedure would yield higher wRVUs. Brachial plexus nerve decompression surgery is a more time-consuming procedure compared with carpal and cubital tunnel procedures. The aim of this study was to analyze physician reimbursement in upper limb decompression procedures by comparing mean operative times, wRVUs per minute, and dollars per minute.

Methods

A retrospective cohort study was conducted from June 2016 to June 2019, including all patients who underwent carpal tunnel, cubital tunnel, and brachial plexus release procedures. Operating time was collected, and calculations of mean operative time, wRVUs per minute, and dollars per minute were performed and compared between groups.

Results

A total of 209 cases were included. Carpal tunnel accounted for 75.1% of the cases, followed by cubital tunnel and brachial plexus releases. Brachial plexus release had the highest median operative time (147 minutes), followed by cubital tunnel (57 minutes) and carpal tunnel release (16 minutes, P < 0.0001). Carpal tunnel release procedures had a significantly higher wRVUs per minute (0.310) when compared with cubital tunnel and brachial pleaxus release procedures, 0.127 and 0.077, respectively (P < 0.0001). Same was true for dollars per minute; carpal tunnel procedures yielded significantly more compensation than cubital tunnel and thoracic outlet procedures (P < 0.0001).

Conclusions

More complex and time-consuming procedures yielded a lower reimbursement for physicians. The current work relative unit system does not account adequately for the time spent in each procedure.
Cost-effectiveness of Staple Line Reinforcement in Laparoscopic Sleeve Gastrectomy
Authors: Highet Alexandra , Johnson Emily H. , Bonham Aaron J. , Hutton David W. , Zhou Shuhao , Thalji Ameen S. , Ghaferi Amir A.
Published: May 2021

Objective:

To perform a cost-effectiveness analysis of staple-line reinforcement in laparoscopic sleeve gastrectomy.

Summary of Background Data:

Exponential increases in surgical costs have underscored the critical need for evidence-based methods to determine the relative value of surgical devices. One such device is staple-line reinforcement, thought to decrease bleeding rates in laparoscopic sleeve gastrectomy.

Methods:

Two intervention arms were modeled, staple-line reinforcement and standard nonreinforced stapling. Bleed and leak rates and 30-day treatment costs were obtained from national and state registries. Quality-adjusted life-year (QALY) values were drawn from previous literature. Device prices were drawn from institutional data. A final incremental cost-effectiveness ratio was calculated, and one-way and probabilistic sensitivity analyses were performed.

Results:

A total of 346,530 patient records from 2012 to 2018 were included. Complication rates for the reinforced and standard cohorts were 0.05% for major bleed in both cohorts (P = 0.8841); 0.45% compared with 0.59% for minor bleed (P < 0.0001); and 0.24% compared with 0.26% for leak (P = 0.4812). Median cost for a major bleed was $5552 ($3287, $16,817) and $2406 ($1861, $3484) for a minor bleed. Median leak cost was $9897 ($4589, $21,619) and median cost for patients who did not experience a bleed, leak, or other serious complication was $1908 ($1712, $2739). Mean incremental cost of reinforced stapling compared with standard was $819.60/surgery. Net QALY gain with reinforced stapling compared with standard was 0.00002. The resultant incremental cost-effectiveness ratio was $40,553,000/QALY. One-way and probabilistic sensitivity analyses failed to produce a value below $150,000/QALY.

Conclusions:

Compared with standard stapling, reinforced stapling reduces minor postoperative bleeding but not major bleeding or leaks and is not cost-effective if routinely used in laparoscopic sleeve gastrectomy.
Development of a Low-Fidelity Laparoscopic Sacrocolpopexy Simulation Model and Evaluation of Curriculum
Authors: Karaoğlan Tunahan , Aydin Serdar , Bilginer Umur
Published: May 2021

Objectives

Minimally invasive sacrocolpopexy (SCP) is a compelling surgical procedure that requires advanced laparoscopic suturing and dissection skills and knowledge of pelvic retroperitoneal anatomy. The aim of this study was to develop a low-cost laparoscopic SCP model and educational curriculum to improve dissection and suturing skills along with anatomic knowledge to avoid complications.

Methods

The pelvic SCP model was developed with easily available material that was placed on the commercial pelvic bone model to construct a vagina, major vessels, ureter, peritoneum, and areolar tissue. A comprehensive curriculum encompassing didactic and technical skills components on the pelvic model was used to teach laparoscopic SCP. Participants completed precurriculum and postcurriculum multiple-choice questionnaires to evaluate the didactic component. A modified Objective Structured Assessment of Technical Skills (OSATS) tool was used to measure technical skills before and after technical skills curriculum.

Results

Among the 10 senior residents, 6 (60%) were studying at their fourth postgraduate year, and 3 (30%) were studying at their third postgraduate year. Postcurriculum test scores (14.5 vs 10.6) for assessment of cognitive knowledge were significantly improved (P < 0.001). The median postcurriculum OSATS scores (26.5; range, 18–30) were significantly improved (P = 0.005). Laparoscopic SCP OSATS scores increased from median 21 to median 26.5 after cognitive and technical curriculum, showing a 21.4% improvement. The majority (70%) of residents believed that the SCP model would be useful to enhance skills acquisition before performing the skill in the operating room.

Conclusions

A low-fidelity laparoscopic SCP curriculum showed improvement in cognitive knowledge and technical skills.
Stability of Anti-HLA Sensitization Profiles in Highly Sensitized Kidney Transplantation Candidates: Toward a Rational Serological Testing Strategy
Authors: Wojciechowski Elodie , Jambon Frédéric , Cargou Marine , Guidicelli Gwendaline , Merville Pierre , Couzi Lionel , Taupin Jean-Luc , Visentin Jonathan
Published: May 2021

Background.

Highly sensitized (HS) anti-HLA patients awaiting kidney transplantation benefit from specific allocation programs. Serological monitoring at 3-mo intervals is recommended to prevent unexpected positive crossmatch (XM), but this strategy is not evidence-based. Therefore, we assessed its relevance when using single-antigen flow bead (SAFB) and screening flow bead (SFB) assays.

Methods.

We included 166 HS patients awaiting a transplant and assessed their SAFB profile during the year preceding their inclusion. Anti-HLA antibodies were evaluated by SAFB assay and compared within patients as serum pairs at 3, 6, and 9 mo. We assessed the performance of SFB for detecting changes in SAFB profiles with 35 serum pairs.

Results.

On comparing 354, 218, and 107 serum pairs at 3, 6, and 9 mo, respectively, only 0.6%, 0.7%, and 1% of all antigens tested exceeded for the first time the unacceptable antigen threshold (mean fluorescence intensity ≥2000) in the most recent sample. Irrespective of the follow-up period, the calculated panel-reactive antibodies increased by a mean of 1%, and there was no significant increase in the proportion of donors at risk for positivity of flow- or complement-dependent cytotoxicity XM. The SFB did not accurately detect the variations of SAFB profiles.

Conclusions.

Changes in HS patient profiles are anecdotal and show little association with transplant access or risk for positive XM. Less-frequent monitoring in HS patients should be considered to improve cost-effectiveness without affecting transplant safety.
Frailty Measures in Patients Listed for Lung Transplantation
Authors: Montgomery Elyn , Newton Phillip J. , Chang Sungwon , Peng Wenbo , Jha Sunita R. , Wilhelm Kay , Macdonald Peter S. , Malouf Monique
Published: May 2021

Background.

The study aimed to determine whether the addition of cognitive impairment, depression, or both, to the assessment of physical frailty (PF) is associated with the risk of lung transplant (LTX) waitlist mortality.

Methods.

Since March 2013, all patients referred for LTX evaluation underwent PF assessment. Cognition was assessed using the Montreal Cognitive Assessment and depression assessed using the Depression in Medical Illness questionnaire. We assessed the association of 4 composite frailty measures: PF ≥3 of 5 = frail, cognitive frailty (CogF ≥3 of 6 = frail), depressive frailty (DepF ≥3 of 6 = frail), and combined frailty (ComF ≥3 of 7 = frail) with waitlist mortality.

Results.

The prevalence of PF was 78 (22%), CogF 100 (28%), DepF 105 (29%), and ComF 124 (34%). Waitlist survival in the non-PF group was 94% ± 2% versus 71% ± 7% in the PF group (P < 0.001). Cox proportional hazards regression analysis demonstrated that PF (adjusted hazard ratio [HR], 4.88; 95% confidence interval [CI], 2.06-11.56), mild cognitive impairment (adjusted HR, 3.03; 95% CI, 1.05-8.78), and hypoalbuminemia (adjusted HR, 0.89; 95% CI, 0.82-0.97) were independent predictors of waitlist mortality. There was no significant difference in the area under the curve of the 4 frailty measures.

Conclusions.

The addition of cognitive function and depression variables to the PF assessment increased the number of patients classified as frail. However, the addition of these variables does not strengthen the association with LTX waitlist mortality compared with the PF measure.
Exploration of Rapid Automatized Naming and Standard Visual Tests in Prodromal Alzheimer Disease Detection
Authors: Wu Shirley Z. , Nolan-Kenney Rachel , Moehringer Nicholas J. , Hasanaj Lisena F. , Joseph Binu M. , Clayton Ashley M. , Rucker Janet C. , Galetta Steven L. , Wisniewski Thomas M. , Masurkar Arjun V. , Balcer Laura J.
Published: May 2021

Background:

Visual tests in Alzheimer disease (AD) have been examined over the last several decades to identify a sensitive and noninvasive marker of the disease. Rapid automatized naming (RAN) tasks have shown promise for detecting prodromal AD or mild cognitive impairment (MCI). The purpose of this investigation was to determine the capacity for new rapid image and number naming tests and other measures of visual pathway structure and function to distinguish individuals with MCI due to AD from those with normal aging and cognition. The relation of these tests to vision-specific quality of life scores was also examined in this pilot study.

Methods:

Participants with MCI due to AD and controls from well-characterized NYU research and clinical cohorts performed high and low-contrast letter acuity (LCLA) testing, as well as RAN using the Mobile Universal Lexicon Evaluation System (MULES) and Staggered Uneven Number test, and vision-specific quality of life scales, including the 25-Item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) and 10-Item Neuro-Ophthalmic Supplement. Individuals also underwent optical coherence tomography scans to assess peripapillary retinal nerve fiber layer and ganglion cell/inner plexiform layer thicknesses. Hippocampal atrophy on brain MRI was also determined from the participants' Alzheimer disease research center or clinical data.

Results:

Participants with MCI (n = 14) had worse binocular LCLA at 1.25% contrast compared with controls (P = 0.009) and longer (worse) MULES test times (P = 0.006) with more errors in naming images (P = 0.009) compared with controls (n = 16). These were the only significantly different visual tests between groups. MULES test times (area under the receiver operating characteristic curve [AUC] = 0.79), MULES errors (AUC = 0.78), and binocular 1.25% LCLA (AUC = 0.78) showed good diagnostic accuracy for distinguishing MCI from controls. A combination of the MULES score and 1.25% LCLA demonstrated the greatest capacity to distinguish (AUC = 0.87). These visual measures were better predictors of MCI vs control status than the presence of hippocampal atrophy on brain MRI in this cohort. A greater number of MULES test errors (r
s = −0.50, P = 0.005) and worse 1.25% LCLA scores (r
s = 0.39, P = 0.03) were associated with lower (worse) NEI-VFQ-25 scores.

Conclusions:

Rapid image naming (MULES) and LCLA are able to distinguish MCI due to AD from normal aging and reflect vision-specific quality of life. Larger studies will determine how these easily administered tests may identify patients at risk for AD and serve as measures in disease-modifying therapy clinical trials.
Clinical outcomes after clozapine discontinuation in responders versus nonresponders: a retrospective chart review
Authors: Watanabe Maiko , Misawa Fuminari , Miura Gentaro , Fujii Yasuo , Takeuchi Hiroyoshi
Published: May 2021

No studies have compared clinical outcomes after discontinuation of clozapine between patients who responded to clozapine and those who did not. Therefore, we examined 1-year clinical outcomes after clozapine discontinuation in responders and nonresponders. We reviewed data on patients who discontinued clozapine and retrospectively followed them for 1 year. Clinical information was collected from medical records starting at the initiation of clozapine administration, at discontinuation and at 1 year after discontinuation. In addition, clinical status was assessed using the Clinical Global Impression – Severity (CGI-S) and Clinical Global Impression – Improvement (CGI-I) scales. We classified the patients into clozapine responder and nonresponder groups according to the CGI-I score. Thirty-nine patients were enrolled in this study. Olanzapine was the most common antipsychotic prescribed after clozapine discontinuation in both the responder and nonresponder groups. The mean CGI-S score significantly increased 1 year after clozapine discontinuation in the responder group and significantly decreased in the nonresponder group; there was a significant difference in changes in the CGI-S scores between the groups. The difference remained significant after controlling for clozapine dose and duration of treatment. The findings suggest that clinicians may consider continuing and discontinuing clozapine treatment for patients who responded to clozapine and those who did not, respectively.
The clinical intervention choice for pediatric tic disorder patients from a tertiary children’s hospital in China: a large-scale retrospective study based on electronic medical records
Authors: Wang Fang , Ma Zihan , Li Ying , Wen Fang , Yu Liping , Yan Junjuan , Liu Jingran , Zhang Jishui , Cui Yonghua
Published: May 2021

Pharmacological intervention played an important role in the management of tic disorder. Large-scale prescription data for pediatric tic disorder patients in the real-world setting were scarce. The demographic and prescription data of tic disorder were extracted from the electronic medical records database of Beijing Children’s Hospital from 2018 to 2020. The intervention choice for outpatient pediatric tic disorder patients was analyzed. A total of 20 417 patients were included, 28.1% (n = 5028) of them did not receive any pharmacological treatment. Over 70% were prescribed with anti-tic medication. For children less than 6 years of age, clonidine adhesive patches (CAPs) and traditional Chinese medicine (TCM) were the common choice. With the age growing, the use of antipsychotics was on the rise; 22% (n = 3389) were prescribed for at least two anti-tic medication, and the most common medication combination group was tiapride and TCM (33.7%), followed by CAP and TCM (22.1%). The clinical intervention choice for tic disorder is highly individualized. The pharmacological choice was influenced by severity, duration of symptom, age, the acceptance of parents and other factors.
Infection is associated with elevated serum concentrations of antipsychotic drugs
Authors: Zhang Yuan-Yuan , Zhou Xie-Hai , Shan Feng , Liang Jun
Published: May 2021

We aimed to investigate the effects of infection on serum concentrations of different antipsychotics in inpatients with respiratory tract infections treated with psychiatric drugs, including risperidone, clozapine, quetiapine, and aripiprazole. All patients underwent therapeutic drug monitoring (TDM) and routine blood tests during infection and noninfection periods. The Wilcoxon signed-rank test was used to analyze intra-individual differences in dose-corrected serum concentrations (C/D) levels in infection and noninfection periods. To study the effects of infection intensity on drug concentrations, white blood cells (WBCs) parameters and C/D levels were analyzed by Spearman’s correlation analysis using all samples. The median C/D levels of risperidone (risperidone + 9-OH, n = 36) and clozapine (n = 42) were significantly higher (P < 0.001), whereas the median C/D levels of quetiapine (n = 21) and aripiprazole (n = 13) were slightly significantly higher (P < 0.01) in infection than in noninfection period. A significant positive association between C/D levels and WBC parameters was observed for risperidone, clozapine, and quetiapine. These results indicated reduced clearance of all drugs evaluated, especially clozapine and risperidone, due to infection. Therefore, during infection in patients receiving risperidone, clozapine, quetiapine, or aripiprazole, TDM should be performed to minimize the possible adverse effects associated with elevated drug concentrations.
Axisymmetry of critical points for the Onsager functional
Authors: Ball J. M.
Published: May 2021

A simple proof is given of the classical result (Fatkullin I, Slastikov V. 2005 Critical points of the Onsager functional on a sphere.
Nonlinearity
18
, 2565–2580 (
doi:10.1088/0951-7715/18/6/008
); Liu H
et al.
2005 Axial symmetry and classification of stationary solutions of Doi-Onsager equation on the sphere with Maier-Saupe potential.
Commun. Math. Sci.
3
, 201–218 (
doi:10.4310/CMS.2005.v3.n2.a7
)) that critical points for the Onsager functional with the Maier-Saupe molecular interaction are axisymmetric, including the case of stable critical points with an additional dipole-dipole interaction (Zhou H
et al.
2007 Characterization of stable kinetic equilibria of rigid, dipolar rod ensembles for coupled dipole-dipole and Maier-Saupe potentials.
Nonlinearity
20
, 277–297 (
doi:10.1088/0951-7715/20/2/003
)). The proof avoids spherical polar coordinates, instead using an integral identity on the sphere
S
2
. For general interactions with absolutely continuous kernels the smoothness of all critical points is established, generalizing a result in (Vollmer MAC. 2017 Critical points and bifurcations of the three-dimensional Onsager model for liquid crystals.
Archive for Rational Mechanics and Analysis
226
, 851–922 (
doi:10.1007/s00205-017-1146-8
)) for the Onsager interaction. It is also shown that non-axisymmetric critical points exist for a wide variety of interactions including that of Onsager.

This article is part of the theme issue ‘Topics in mathematical design of complex materials’.
Chromonic liquid crystals and packing configurations of bacteriophage viruses
Authors: Hiltner Lindsey , Carme Calderer M. , Arsuaga Javier , Vázquez Mariel
Published: May 2021

We study equilibrium configurations of hexagonal columnar liquid crystals in the context of characterizing packing structures of bacteriophage viruses in a protein capsid. These are viruses that infect bacteria and are currently the focus of intense research efforts, with the goal of finding new therapies for bacteria-resistant antibiotics. The energy that we propose consists of the Oseen–Frank free energy of nematic liquid crystals that penalizes bending of the columnar directions, in addition to the cross-sectional elastic energy accounting for distortions of the transverse hexagonal structure; we also consider the isotropic contribution of the core and the energy of the unknown interface between the outer ordered region of the capsid and the inner disordered core. The problem becomes of free boundary type, with constraints. We show that the concentric, azimuthal, spool-like configuration is the absolute minimizer. Moreover, we present examples of toroidal structures formed by DNA in free solution and compare them with the analogous ones occurring in experiments with other types of lyotropic liquid crystals, such as food dyes and additives.

This article is part of the theme issue ‘Topics in mathematical design of complex materials’.
Efficacy and safety of novel probiotic formulation in adult Covid19 outpatients: a randomized, placebo-controlled clinical trial
Authors: Gutiérrez-Castrellón Pedro , Gandara-Martí Tania , Abreu Ana Teresa , Nieto-Rufino Cesar D. , López-Orduña Eduardo , Jiménez-Escobar Irma , Jiménez-Gutiérrez Carlos , López-Velazquez Gabriel , Espadaler-Mazo Jordi
Published: May 2021

Background

Probiotics have been proposed as adjuvants for Coronavirus Disease 2019 (Covid19) but randomized controlled trials (RCT) are lacking.

Methods

Single-center, quadruple-blinded RCT. Symptomatic Covid 19 outpatients (aged 18 to 60 years) with positive SARS-CoV2 nucleic acids test were randomized to active (n=150; ≥2×109 colony-forming units (CFU) of probiotic strains Lactiplantibacillus plantarum KABP022, KABP023 and KAPB033, plus strain Pediococcus acidilactici KABP021) or placebo (n=150), take orally once daily for 30 days. Oral acetaminophen was allowed and controlled as co-intervention. Primary endpoint included: i) proportion of patients in complete remission (both symptoms and nucleic acids test) or progressing to moderate or severe disease with hospitalization; ii) death rate and duration on Intensive Care Unit (ICU). Safety was assessed in all patients. This study is registered at ClinicalTrials.gov (NCT04517422).

Findings

300 subjects were randomized (median age 37.0 years [range 18 to 60], 161 [53.7%] women, 126 [42.0%] having known metabolic risk factors), and 293 completed the study (97.7%). Remission was achieved by 78 of 147 (53.1%) in the active group compared to 41 of 146 (28.1%) in placebo (P<0.0001; ARR=25.0% [95%CI 14.1-35.9%]), still significant after multiplicity correction for the primary endpoint. No hospitalizations or deaths occurred during the study, precluding the assessment of efficacy on these endpoints. No serious adverse events occurred during the study. Replication studies with this probiotic formula are warranted.
RT-qPCR detection of SARS-CoV-2 mutations S 69-70 del, S N501Y and N D3L associated with variants of concern in Canadian wastewater samples
Authors: Peterson Shelley W. , Lidder Ravinder , Daigle Jade , Wonitowy Quinn , Nagasawa Audra , Mulvey Michael R. , Mangat Chand S.
Published: May 2021

SARS-CoV-2 variants of concern (VoC) have been increasingly detected in clinical surveillance in Canada and internationally. These VoC are associated with higher transmissibility rates and in some cases, increased mortality. In this work we present a national wastewater survey of the distribution of three SARS-CoV-2 mutations found in the B.1.1.7, B.1.351, and P.1 VoC, namely the S-gene 69-70 deletion, N501Y mutation, and N-gene D3L. RT-qPCR allelic discrimination assays were sufficiently sensitive and specific for detection and relative quantitation of SARS-CoV-2 variants in wastewater to allow for rapid population-level screening and surveillance. We tested 261 samples collected from 5 Canadian cities (Vancouver, Edmonton, Toronto, Montreal, and Halifax) and 6 communities in the Northwest Territories from February 16th to March 28th, 2021. VoC were not detected in the Territorial communities, suggesting the absence of VoC SARS-CoV-2 cases in those communities. Percentage of variant remained low throughout the study period in the majority of the sites tested, however the Toronto sites showed a marked increase from ~25% to ~75% over the study period.

The results of this study highlight the utility of population level molecular surveillance of SARS-CoV-2 VoC using wastewater. Wastewater monitoring for VoC can be a powerful tool in informing public health responses, including monitoring trends independent of clinical surveillance and providing early warning to communities.
Trajectory of Growth of SARS-CoV-2 Variants in Houston, Texas, January through May 2021 Based on 12,476 Genome Sequences
Authors: Olsen Randall J. , Christensen Paul A. , Long S. Wesley , Subedi Sishir , Hodjat Parsa , Olson Robert , Nguyen Marcus , Davis James J. , Yerramilli Prasanti , Saavedra Matthew Ojeda , Pruitt Layne , Reppond Kristina , Shyer Madison N. , Cambric Jessica , Gadd Ryan , Thakur Rashi M. , Batajoo Akanksha , Finkelstein Ilya J. , Gollihar Jimmy , Musser James M.
Published: May 2021

Genetic variants of the SARS-CoV-2 virus are of substantial concern because they can detrimentally alter the pandemic course and disease features in individual patients. Here we report SARS-CoV-2 genome sequences from 12,476 patients in the Houston Methodist healthcare system diagnosed from January 1, 2021 through May 31, 2021. The SARS-CoV-2 variant designated U.K. B.1.1.7 increased rapidly and caused 63%-90% of all new cases in the Houston area in the latter half of May. Eleven of the 3,276 B.1.1.7 genomes had an E484K change in spike protein. Compared with non-B.1.1.7 patients, individuals with B.1.1.7 had a significantly lower cycle threshold value (a proxy for higher virus load) and significantly higher rate of hospitalization. Other variants (e.g., B.1.429, B.1.427, P.1, P.2, and R.1) also increased rapidly, although the magnitude was less than for B.1.1.7. We identified 22 patients infected with B.1.617 “India” variants; these patients had a high rate of hospitalization. Vaccine breakthrough cases (n=207) were caused by a heterogeneous array of virus genotypes, including many that are not variants of interest or concern. In the aggregate, our study delineates the trajectory of concerning SARS-CoV-2 variants circulating in a major metropolitan area, documents B.1.1.7 as the major cause of new cases in Houston, and heralds the arrival and spread of B.1.617 variants in the metroplex.
Feasibility of Rapid Case Ascertainment for Cancer in East Africa: An Investigation of Community-Representative Kaposi Sarcoma in the Era of Antiretroviral Therapy
Authors: Semeere Aggrey , Byakwaga Helen , Laker-Oketta Miriam , Freeman Esther , Busakhala Naftali , Wenger Megan , Kasozi Charles , Ssemakadde Matthew , Bwana Mwebesa , Kanyesigye Michael , Kadama-Makanga Philippa , Rotich Elyne , Kisuya Job , Sang Edwin , Wools-Kaloustian Kara , Maurer Toby , Kambugu Andrew , Martin Jeffrey
Published: May 2021

BACKGROUND

Rapid case ascertainment (RCA) refers to the expeditious and detailed examination of patients with a potentially rapidly fatal disease shortly after diagnosis. RCA is frequently performed in resource-rich settings to facilitate cancer research. Despite its utility, RCA is rarely implemented in resource-limited settings and has not been performed for malignancies. One cancer and context that would benefit from RCA in a resource-limited setting is HIV-related Kaposi sarcoma (KS) in sub-Saharan Africa.

METHODS

To determine the feasibility of RCA of KS, we searched for all potential newly diagnosed KS among HIV-infected adults attending three community-based facilities in Uganda and Kenya. Searching involved querying of electronic medical records, pathology record review, and notification by clinicians. Upon identification, a team verified eligibility and attempted to locate patients to perform RCA, which included epidemiologic, clinical and laboratory measurements.

RESULTS

We identified 593 patients with suspected new KS. Of the 593, 171 were ineligible, mainly because biopsy failed to confirm KS (65%) or KS was not new (30%). Among the 422 remaining, RCA was performed within 1 month for 56% of patients and within 3 months for 65% (95% confidence interval: 59 to 70%). Reasons for not performing RCA included intervening death (47%), inability to contact (44%), refusal/unsuitable to consent (8.3%), and patient re-location (0.7%).

CONCLUSIONS

We found that RCA — an important tool for cancer research in resource-rich settings — is feasible for the investigation of community-representative KS in East Africa. Feasibility of RCA for KS suggests feasibility for other cancers in Africa.
Multi-trait GWAS of atherosclerosis detects novel pleiotropic loci
Authors: Bellomo Tiffany R. , Bone William P. , Chen Brian Y. , Gawronski Katerina A. B. , Zhang David , Park Joseph , Levin Michael , Tsao Noah , Klarin Derek , Lynch Julie , Assimes Themistocles L. , Gaziano J. Michael , Wilson Peter W. , Cho Kelly , Vujkovic Marijana ,   the VA Million Veteran Program, O’Donnell Christopher J. , Chang Kyong-Mi , Tsao Phil S. , Rader Daniel J. , Ritchie Marylyn D. , Voight Benjamin F. , Damrauer Scott M.
Published: May 2021

Rationale

Although affecting different arterial territories, the related atherosclerotic vascular diseases coronary artery disease (CAD) and peripheral artery disease (PAD) share similar risk factors and have shared pathobiology. Analysis of their shared genetic architecture, along with that of common risk factors, may identify novel common biology.

Objective

To identify novel pleiotropic genetic loci associated with atherosclerosis and provide a better understanding of biological pathways underlying atherosclerosis.

Methods and Results

Summary statistics from genome wide association studies (GWAS) of nine known atherosclerotic (CAD, PAD) or atherosclerosis risk factors (body mass index, smoking initiation, type 2 diabetes, low density lipoprotein (LDL), high density lipoprotein, total cholesterol, and triglycerides) were combined to perform 15 separate multi-trait genetic association scans which resulted in 31 unique novel pleiotropic loci not yet reported as genome-wide significant for their respective traits. Colocalization with single-tissue eQTLs identified 34 candidate causal genes across 14 of the detected signals. Notably, the signal between PAD and CAD at theVDAC2locus (rs7088974) colocalized withVDAC2expression in aorta and tibial artery tissues. Additionally, the signal between PAD and LDL at thePCSK6locus (rs1531817) affectsPCSK6splicing in human liver tissue and induced pluripotent derived hepatocyte like cells.

Conclusions

Joint analysis of related atherosclerotic disease traits and their risk factors allowed identification of unified biology that may offer the opportunity for therapeutic manipulation.VDAC2andPCSK6represent possible shared causal biology where existing inhibitors may be able to be leveraged for novel therapies.