bluuebunny/crossref_metadata_2025 huggingface dataset:
Electrical storm due to Epstein-Barr virus-induced lymphoma of a transplanted heart: a case report
Authors: Charbonneau Etienne , Galand Vincent , Flécher Erwan
Published: June 2022

Background

Cancers, and specifically lymphomas, are one of the main causes of morbidity and mortality after heart transplantation. Sixteen percent of heart transplant recipients develop cancer within 5 years and lymphomas represent 10% of these patients.

Case summary

We report the case of an Epstein–Barr Virus–induced primary cardiac lymphoma on the graft. The patient initially present an electrical storm quickly controlled under medical treatment. The multimodal exploration led us to the diagnosis of lymphoma. The lymphoma has spread quickly in spite of the numerous treatments we have tried and has resulted in arrhythmia complications.

Discussion

This case report highlights the challenging management of heart transplant lymphoma and its treatment. Primary cardiac lymphoma on the graft is highly rare with poor prognosis and arrhythmia complications.
Tradeoffs in milk immunity affect infant infectious disease risk
Authors: Wander Katherine , Fujita Masako , Mattison Siobhan M , Duris Margaret , Gauck Megan , Hopt Tessa , Lacy Katherine , Foligno Angela , Ulloa Rebecca , Dodge Connor , Mowo Frida , Kiwelu Ireen , Mmbaga Blandina T
Published: June 2022

Background and objectives

The human immune system has evolved to balance protection against infection with control of immune-mediated damage and tolerance of commensal microbes. Such tradeoffs between protection and harm almost certainly extend to the immune system of milk.

Methodology

Among breastfeeding mother–infant dyads in Kilimanjaro, Tanzania, we characterized in vitro proinflammatory milk immune responses to Salmonella enterica (an infectious agent) and Escherichia coli (a benign target) as the increase in interleukin-6 after 24 h of incubation with each bacterium. We characterized incident infectious diseases among infants through passive monitoring. We used Cox proportional hazards models to describe associations between milk immune activity and infant infectious disease.

Results

Among infants, risk for respiratory infections declined with increasing milk in vitro proinflammatory response to S. enterica (hazard ratio [HR]: 0.68; 95% confidence interval [CI]: 0.54, 0.86; P: 0.001), while risk for gastrointestinal infections increased with increasing milk in vitro proinflammatory response to E. coli (HR: 1.44; 95% CI: 1.05, 1.99; P: 0.022). Milk proinflammatory responses to S. enterica and E. coli were positively correlated (Spearman’s rho: 0.60; P: 0.000).

Conclusions and implications

These findings demonstrate a tradeoff in milk immune activity: the benefits of appropriate proinflammatory activity come at the hazard of misdirected proinflammatory activity. This tradeoff is likely to affect infant health in complex ways, depending on prevailing infectious disease conditions. How mother–infant dyads optimize proinflammatory milk immune activity should be a central question in future ecological–evolutionary studies of the immune system of milk.
Short acting intravenous beta-blocker as a first line of treatment for atrial fibrillation after cardiac surgery: a prospective observational study
Authors: Chapalain X , Oilleau J F , Henaff L , Lorillon PharmD P , Saout D Le , Kha P , Pluchon K , Bezon E , Huet O
Published: June 2022

Post-operative atrial fibrillation (POAF) defined as a new-onset of atrial fibrillation (AF) following surgery occurs frequently after cardiac surgery. For non-symptomatic patients, rate control strategy seems to be as effective as rhythm control one in surgical patients. Landiolol is a new highly cardio-selective beta-blocker agent with interesting pharmacological properties that may have some interest in this clinical situation. This is a prospective, monocentric, observational study. All consecutive adult patients (age >18 years old) admitted in the intensive care unit following cardiac surgery with a diagnosed episode of AF were eligible. Success of landiolol administration was defined by a definitive rate control from the beginning of infusion to the 72th h. We also evaluated rhythm control following landiolol infusion. Safety analysis was focused on haemodynamic, renal and respiratory side effects. From 1 January 2020 to 30 June 2021, we included 54 consecutive patients. A sustainable rate control was obtained for 49 patients (90.7%). Median time until a sustainable rate control was 4 h (1, 22). Median infusion rate of landiolol needed for a sustainable rate control was 10 µg/kg/min (6, 19). Following landiolol infusion, median time until pharmacological cardioversion was 24 h. During landiolol infusion, maintenance of mean arterial pressure target requires a concomitant very low dose of norepinephrine. We did not find any other side effects. Low dose of landiolol used for POAF treatment was effective and safe for a rapid and sustainable rate and rhythm control after cardiac surgery.
LTBK-06. Memantine increases dendritic arborization and integration of immature neurons after cranial irradiation
Authors: Zisiadis Georgios , Rodrigues Carlos , Pizzirusso Giusy , Arroyo-García Luis , Osman Ahmed , Blomgren Klas
Published: June 2022

Cranial irradiation (IR) is a cornerstone in the treatment of high-grade pediatric brain tumors. While lifesaving, it is associated with severe sequalae in 50-90 % of the survivors, as they often show disabling cognitive dysfunction, declined IQ, impaired processing speed, anxiety and posttraumatic stress symptoms, resulting in poorer academic accomplishments and social isolation. Memantine (Mem) is a non-competitive NMDA receptor antagonist and a potent enhancer of neural plasticity. It is used in the clinical setting in the treatment of Alzheimer’s disease and dementias and has been shown to enhance cognition in post-IR cancer survivors. Nevertheless, while an improvement in synaptic plasticity has been documented in association to hippocampal neurogenesis, the exact mechanisms underlying Mem’s actions are yet poorly understood. The goal of this project is to further dissect the actions of Mem and identify factors that contribute to hippocampal neurogenesis. To this end, 20-day-old C57BL6/J mice were subjected to a single dose of 7 Gy whole brain irradiation and then supplied with Mem in the drinking water to obtain a steady-state plasma concentration of the drug. Animals were then sacrificed at different time points and the brains harvested for immunohistochemical staining, bulk-RNA sequencing and electrophysiological studies. Sholl analysis of the morphological data of the new-born neurons of Mem treated animals showed a statistically significant increase in coverage area (500µm2 vs. 250µm2, p= <0,0001) and number of dendrites (15 vs. 5, p= <0,0001) compared to non-treated individuals. Preliminary analysis of the electrophysiological responses revealed no changes in the gamma oscillations in Mem treated irradiated mice. The attained results will shed light on the mechanisms of action and take steps towards establishing Mem as a neoadjuvant therapy for children undergoing IR. Ultimately, we aim to ameliorate IR-associated neurocognitive impairment and improve the quality of life of pediatric cancer survivors.
Effect of treatment adherence on the association between sex and unfavourable treatment outcomes among tuberculosis patients in Puducherry, India: a mediation analysis
Authors: Barathi Arivarasan , Krishnamoorthy Yuvaraj , Sinha Pranay , Horsburgh Charles , Hochberg Natasha , Johnson Evan , Salgame Padmini , Govindarajan Soundappan , Senbagavalli P B , Lakshinarayanan Subitha , Roy Gautam , Ellner Jerrold , Sarkar Sonali
Published: June 2022

Background

A better understanding of the complex interplay between risk factors of tuberculosis (TB) is essential. This study was part of the Regional Prospective Observational Research for Tuberculosis (RePORT) India consortium and includes newly diagnosed TB patients in Puducherry between 2014 and 2018. We employed mediation analysis to identify the effect of treatment adherence on association between sex and unfavourable TB treatment outcomes.

Methods

Required demographic and treatment-related variables were extracted from the RePORT India consortium database and causal mediation analysis using parametric regression models was done.

Results

Of the 712 TB patients, ~87 (12.2%) had unfavourable TB treatment outcomes. Total effect of male sex was significantly associated with the unfavourable TB treatment outcomes [adjusted odds ratio (aOR) = 2.48; 95% confidence interval (CI): 1.11–5.55]. However, the overall association between male sex and TB treatment outcomes was dominated by the indirect pathway, as the direct pathway does not show significant association (aOR = 1.67; 95% CI: 0.75–3.75), while the indirect pathway shows significantly higher odds of TB treatment outcomes (aOR = 1.48; 95% CI:1.27–1.73), indicating complete mediation by the treatment adherence.

Conclusions

The study has shown a complete mediation of sexes through TB treatment adherence for unfavourable treatment outcomes. Developing of treatment strategies require better understanding between the biological and social factors related to TB.
Temporal Trends in Cervical Cancer Screening Practices and Associated Downstream Abnormalities and Procedures Among Women With Insurance in the United States
Authors: Liao Lillian , Chen Ling , Gockley Allison , Melamed Alexander , St Clair Caryn M. , Hou June Y. , Khoury-Collado Fady , Accordino Melissa , Hershman Dawn L. , Wright Jason D.
Published: June 2022

OBJECTIVE:

To examine temporal trends in cervical cancer screening practices and associated downstream abnormalities and procedures.

METHODS:

Women aged 18–64 years with commercial insurance or Medicaid insurance from 2008 to 2019 were identified using the IBM MarketScan databases. The annual rates of screening overall and by type of test (cytology, co-testing, or primary human papillomavirus testing) were examined. Downstream abnormal cytologic and histologic test results, colposcopies, and excisional procedures were examined, and rates were reported for the population of eligible patients with continuous insurance and for those who underwent screening. Changes over time in testing and outcomes were compared using χ2 tests and Spearman's correlation.

RESULTS:

From 2008 to 2019, the annual screening prevalence decreased from 42.6% to 29.4% in women with commercial insurance (P<.001) and from 27.9% to 12.4% among women with Medicaid insurance (P<.001). In the cohort of women with commercial insurance, cytology usage decreased from 79.4% to 38.9% and co-testing increased from 20.1% to 59.6% (P<.001). Per 1,000 women screened, the rate of abnormal histologic and cytologic test results rose from 96 to 119 (P<.001) and colposcopies rose from 33 to 42 (P<.001); excisional procedures remained relatively constant. Per 1,000 eligible women, the rate of abnormal histologic and cytologic test results decreased from 41 to 35 (P<.001), colposcopies declined from 14 to 12, and excisional procedures decreased from 3 to 2.

CONCLUSION:

Human papillomavirus testing has been rapidly incorporated into cervical cancer screening and is associated with an increasing trend of downstream abnormalities and procedures among screened women but a declining trend at the population level.
Comparison of Relative Value Units and 30-Day Outcomes Between Primary and Revision Pediatric Spinal Deformity Surgery
Authors: Song Junho , Katz Austen D. , Dalal Sidhant , Silber Jeff , Essig David , Qureshi Sheeraz , Virk Sohrab
Published: June 2022

Study Design:

Retrospective cohort study.

Objective:

The aim of this study was to compare the relative value units (RVUs) and 30-day outcomes between primary and revision pediatric spinal deformity (PSD) surgery.

Summary of Background Data:

PSD surgery is frequently complicated by the need for reoperation. However, there is limited literature on physician reimbursement rates and short-term outcomes following primary versus revision spinal deformity surgery in the pediatric population.

Materials and Methods:

This study utilizes data obtained from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) Pediatric database. Patients between 10 and 18 years of age who underwent posterior spinal deformity surgery between 2012 and 2018 were included. Univariate and multivariate regression were used to assess the independent impact of revision surgery on RVUs and postoperative outcomes, including 30-day readmission, reoperation, morbidity, and complications.

Results:

The study cohort included a total of 15,055 patients, with 358 patients who underwent revision surgery. Patients in the revision group were more likely to be younger and male sex. Revision surgery more commonly required osteotomy (13.7% vs. 8.3%, P=0.002).

Univariate analysis revealed higher total RVUs (71.09 vs. 60.51, P<0.001), RVUs per minute (0.27 vs. 0.23, P<0.001), readmission rate (6.7% vs. 4.0%, P=0.012), and reoperation rate (7.5% vs. 3.3%, P<0.001) for the revision surgery group. Morbidity rates were found to be statistically similar. In addition, deep surgical site infection, pulmonary embolism, and urinary tract infection were more common in the revision group. After controlling for baseline differences in multivariate regression, the differences in total RVUs, RVUs per minute, reoperation rate, and rate of pulmonary embolism between primary and revision surgery remained statistically significant.

Conclusions:

Revision PSD surgery was found to be assigned appropriately higher mean total RVUs and RVUs per minute corresponding to the higher operative complexity compared with primary surgery. Revision surgery was also associated with poorer 30-day outcomes, including higher frequencies of reoperation and pulmonary embolism.

Level of Evidence:

Level III.
A Real-World Study of the Incidence and Outcomes of Early-Onset Well-differentiated Neuroendocrine Neoplasms
Authors: Abdel-Rahman Omar , Ghosh Sunita
Published: June 2022

Objective:

The objective of this study was to evaluate the incidence and outcomes of adults with early-onset (20 to 34 y) diagnosis of well-differentiated neuroendocrine neoplasms.

Methods:

Surveillance, Epidemiology, and End Results (SEER)-18 database was accessed, and patients with well-differentiated lung or digestive tract neuroendocrine neoplasms diagnosed 2000 to 2018 were reviewed. Annual percent changes (APCs) were calculated for the 3 disease subsites (foregut, midgut, and hindgut) stratified by age group. Kaplan-Meier survival estimates/log-rank testing were used to examine differences in overall survival between the 3 age groups. Multivariable Cox regression analyses were used to evaluate factors affecting overall and cancer-specific survivals.

Results:

Throughout the study period, patients with early-onset disease (20 to 34 y) have experienced the greatest APC (20 to 34 y: 9.7; 35 to 49 y: 5.4; ≥50 y: 4.1). When APCs were stratified by disease subsite, this difference in APCs appears to be driven by midgut tumors (20 to 34 y: 19.2; 35 to 49: 8.4; ≥50 y: 3.8). Using multivariable Cox regression modeling, the following variables were associated with a higher risk of all-cause death (worse overall survival): male sex (hazard ratio [HR] 1.27; 95% confidence interval [CI]: 1.22-1.31), African American race (HR vs. white race: 1.20; 95% CI: 1.15-1.26), nonhindgut primary (HR foregut vs. hindgut primary: 2.02; 95% CI: 1.91-2.13; HR midgut vs. hindgut primary: 2.09; 95% CI: 1.95-2.24), distant disease (HR vs. regional disease: 2.06; 95% CI: 1.96-2.18), no surgery to the primary (HR: 2.34; 95% CI: 2.24-2.46), and older age (HR: 5.80; 95% CI: 4.87-6.91).

Conclusion:

Cases of early-onset well-differentiated neuroendocrine neoplasms have disproportionately increased over the past 2 decades (compared with other age groups), and this appears to have been driven mainly by midgut tumors.
Acute glucagon-like peptide-1 receptor agonist liraglutide prevents cue-, stress-, and drug-induced heroin-seeking in rats
Authors: Douton Joaquin E. , Acharya Nikhil K. , Stoltzfus Brooke , Sun Dongxiao , Grigson Patricia S. , Nyland Jennifer E.
Published: June 2022

Substance use disorder is challenging to treat due to its relapsing nature. In the last decade, opioid use disorder has been a threat to public health, being declared an epidemic by the Centers for Disease Control and Prevention. This is a tragic situation, considering there currently are only three effective, yet not ideal, treatments to prevent relapse to opioids. Recent research has shown that hormones that modulate hunger and satiety also can modulate motivated behavior for drugs of abuse. For example, the short-acting analog of glucagon-like peptide-1 (GLP-1), an incretin hormone that regulates homeostatic feeding, has been shown to reduce responding for rewarding stimuli such as food, cocaine, heroin, and nicotine when administered over several days or weeks. This may serve as an effective adjuvant during treatment; however, whether it would be effective when used acutely to bridge a patient between cessation of use and onset of medication for the treatment of an opioid addiction is unknown. Here, we tested the acute effects of the longer acting GLP-1 analog, liraglutide, on heroin-seeking. In rats with heroin self-administration experience, we found that subcutaneous administration of an acute dose of 0.3-mg/kg liraglutide was effective in preventing drug-seeking after exposure to three major precipitators: drug-associated cues, stress (yohimbine-induced), and the drug itself. Finally, we confirmed that the reduction in drug-seeking is not due to a locomotor impairment, as liraglutide did not significantly alter performance in a rotarod test. As such, acute use of GLP-1 analogs may serve as a new and effective nonopioid bridge to treatment.
Factors Impacting HIV Postexposure Prophylaxis Among Sexually Assaulted Patients Presenting to Two Urban Emergency Departments
Authors: Scannell Meredith J. , Rodgers Rachel F. , Molnar Beth E. , Guthrie Barbara J.
Published: June 2022

Introduction

Sexually assaulted patients who seek care in emergency departments are often recommended for nonoccupational HIV postexposure prophylaxis treatment. HIV postexposure prophylaxis is an effective method in preventing HIV transmission if the treatment is administered promptly and if a full 28-day course is completed. However, research has shown that only a fraction of patients who start the treatment will complete a 28-day course. Research is needed to explore factors that may be associated with compliance to postexposure prophylaxis so that interventions can be designed to address the factors that put patients at risk for noncompletion.

Methods

A retrospective chart review was conducted examining 246 medical records of sexually assaulted female patients who presented to one of two urban hospitals. A number of patient and event-related factors were examined to determine whether they were associated with HIV postexposure prophylaxis adherence among patients presenting at an emergency room after a sexual assault.

Results

Results revealed that five factors showed significant associations with sexually assaulted female patients completing HIV postexposure prophylaxis treatment. These factors include educational level, employment, health insurance, vaginal injuries, and tongue–mouth assaults.

Implications for Practice

The results of this study represent a starting point from which to inform the development of targeted interventions such that those most at risk for nonadherence can receive additional support or services to improve HIV postexposure prophylaxis adherence.
The Negative Prognostic Role of Inflammatory Biomarkers in Patients With Chronic Cerebrospinal Venous Insufficiency
Authors: Song Si-ying , Lan Duo , Jiao Bao-lian , Liu Yun-huan , Ding Yu-chuan , Ji Xun-ming , Meng Ran
Published: June 2022

Background:

The pathologic consequences of inflammatory responses in chronic cerebrospinal venous insufficiency (CCSVI) remains poorly understood. Hence, this study was aimed to evaluate the peripheral inflammatory biomarkers in patients with intracranial and extracranial CCSVI pathology. In addition, the relationship between inflammatory cytokine profile and CCSVI prognosis was also evaluated.

Methods:

Patients diagnosed with CCSVI between July 2017 and July 2019 were included and subsequently divided into 3 groups based on the location of stenosis. The inflammatory biomarker assay included neutrophil-to-lymphocyte ratios (NLRs), platelet-to-lymphocyte ratios (PLRs), red blood cell distribution widths (RDW), C-reactive protein (CRP) levels, interleukin-6 (IL-6) levels, and neuron-specific enolase levels. Clinical outcomes were assessed using the modified Rankin Scale and Patient Global Impression of Change score. Univariate and multivariate regression analyses were performed to identify significant prognostic factors for poorer outcomes. Finally, we established a nomogram based on the multivariate regression analysis.

Results:

We enrolled 248 patients in total, including 102 males and 146 females, with an average age of 57.85±12.28 years. Compared with patients with internal jugular vein stenosis, cerebral venous sinus stenosis (CVSS) patients were mostly younger and had been suffering from headaches and severe papilledema. Higher levels of NLR, RDW, and CRP were also observed in the CVSS group. Multivariate analysis indicated that NLR, PLR, and IL-6 were the independent prognostic factors for poor CCSVI outcomes.

Conclusions:

The clinical presentations and increases in NLR, PLR, IL-6, and CRP levels could be distinctly marked in patients with CVSS-related CCSVI than that in internal jugular vein stenosis–related CCSVI, indicating poor prognostic outcomes in these patients. A proinflammatory state might be associated with CCSVI pathology.
Physician-Specific Utilization of an Electronic Best Practice Alert for Pediatric Sepsis in the Emergency Department
Authors: Souganidis Ellie S. , Patel Binita , Sampayo Esther M.
Published: June 2022

Background

Early recognition of sepsis remains a critical goal in the pediatric emergency department (ED). Although this has led to the development of best practice alerts (BPAs) to facilitate screening and bundled care, research on how individual physicians interact with sepsis alerts and protocols is limited. This study aims to identify common reasons for acceptance and rejection of a sepsis BPA by pediatric emergency medicine (PEM) physicians and understand how the BPA affects physician management of patients with suspected sepsis.

Methods

This is a qualitative study of PEM physicians in a quaternary-care children's hospital. Data were collected through semistructured interviews and analyzed through an iterative coding process until thematic saturation was achieved. Member checking was completed to ensure trustworthiness. Thematic analysis of PEM physicians' rejection reasons in the electronic health record was used to categorize their responses and calculate each theme's frequency.

Results

Twenty-two physicians participated in this study. Seven physicians (32%) relied solely on patient characteristics when deciding to accept the BPA, whereas the remaining physicians considered nonpatient factors specific to the ED environment, individualized practice patterns, and BPA design. Eleven principal reasons for BPA rejection were derived from 1406 electronic health record responses, with clinical appearance not consistent with shock being the most common. Physicians identified the BPA's configuration and incomplete understanding of the BPA as the biggest barriers to utilization and provided strategies to improve the BPA screening process and streamline sepsis care. Physicians emphasized the need for further BPA education for physicians and triage staff and improved transparency of the alert.

Conclusions

Physicians consider patient and nonpatient factors when responding to the BPA. Improved BPA functionality combined with measures to enhance screening, optimize sepsis management, and educate ED providers on the BPA may increase satisfaction with the alert and promote more effective utilization when it fires.
Prevalence and Causes of Subconjunctival Hemorrhage in Children
Authors: Parikh Alomi O. , Christian Cindy W. , Forbes Brian J. , Binenbaum Gil
Published: June 2022

Objective

Subconjunctival hemorrhage (SCH) is a reported sign of occult abusive injury, but there are limited published data about SCH during childhood. We sought to determine the prevalence and causes of SCH in children.

Methods

This is a retrospective cross-sectional study of children seen by pediatric ophthalmologists in an outpatient setting over 4 years. Primary outcomes were prevalence and causes of SCH, based on history, physical ocular and nonocular findings, and laboratory and imaging studies. Subconjunctival hemorrhage prevalence was determined including and excluding eye surgery to reduce bias in the prevalence estimate.

Results

We studied 33,990 children, who underwent 86,277 examinations (median age, 5 years; range, 2 days to 18 years; 9282 younger than 2 years, 13,447 age 2–7 years, 11,261 age 8–18 years). There were 949 cases of SCH (1.1%; 95% confidence interval, 1.0–1.2). When surgery was excluded, there were 313 cases (prevalence, 0.4%; 95% confidence interval, 0.3–0.4), of which 261 (83%) were due to trauma; 40 (13%) ocular surface inflammation, including infectious conjunctivitis; 7 (2%) orbital or conjunctival lesion; 3 (1%) vessel rupture from choking or cough; and 2 (1%) coagulopathy related. Across all ages, including less than 2 years, trauma and inflammation together accounted for 94% to 97% of all cases of SCH.

Conclusions

Subconjunctival hemorrhage is uncommon in children. The great majority of cases are due to trauma. All children with SCH, including infants and young children, should be closely examined to identify other ocular or nonocular signs of trauma.
Response Time in the Transport of Pediatric Patients to a Tertiary Critical Care Unit
Authors: Villacrés Sindy , Katyal Chhavi , Gomez James , Longani Neha , Chang Deidre , Velasco Susan , Zeiman Linda , Choi Steven
Published: June 2022

Introduction:

Various barriers delay the process of patient transfer to critical care units. We implemented quality improvement methods to decrease the time required for interhospital transfer of critical care patients. As a result, we aimed to decrease the time from initial transfer call to specialized transport team arrival at the referring hospital from 150 minutes to <40 minutes over 2 years.

Methods:

Quality improvement initiative monitoring the length of transport time of 245 patients transferred from referral hospitals to a tertiary pediatric intensive care unit for 31 months from March 2013 to October 2015. We reviewed preexisting transport protocols and identified barriers to the timely arrival to the pediatric intensive care unit. We implemented 3 interventions: a transport information line serving as a central communication center to coordinate the transport process between all stakeholders, the formation of a specialized pediatric transport team, and a training program. We collected transport response time data and monitored the impact of interventions via statistical process control charts.

Results:

There was a significant decrease in the length of the time course pre- and postintervention. We noted a special cause to decrease in time from referral hospital call to arrival of our transport team by 76% from 150 minutes to 36 minutes. In addition, the statistical process chart revealed a stable and effective process without significant shifts above the process mean as early as 3 months postintervention.

Conclusions:

By improving our transport services with additional resources and people, we have improved the efficiency of patient transport between institutions.
Assessing Suicide Risk in a Pediatric Outpatient Behavioral Health System: A Quality Improvement Report
Authors: Soffer Stephen L. , Lewis Jason , Lawrence O’Nisha S. , Marroquin Yesenia A. , Doupnik Stephanie K. , Benton Tami D.
Published: June 2022

Introduction:

Standardized suicide risk assessment improves the detection of individuals at risk of suicide. We conducted a quality improvement initiative in a system of outpatient behavioral health practices affiliated with a free-standing children’s hospital to implement standardized suicide risk assessment for new patients.

Methods:

Clinicians received education in suicide risk assessment and were trained to use an evidence-based suicide risk assessment tool, the Columbia Suicide Severity Rating Scale (C-SSRS). We standardized workflow processes and integrated the C-SSRS in the electronic health record with a feature to communicate instances of elevated risk across care teams through a problem list. We analyzed C-SSRS responses and adherence to standardized processes and compared the percentage of patients with a suicide-related item on the problem list before and after implementation. We assessed clinician knowledge through a survey. All patients with identified suicide risk received treatment to reduce their risk of suicide in the context of usual care.

Results:

For 3,972 new patient visits occurring postimplementation (November 2016–December 2018), the average monthly adherence to the standardized process was 97.7%. The mean monthly incidence of nonspecific active suicidal thoughts was 16%, aborted suicide attempts were 2%, and actual suicide attempts were 3%. The mean monthly incidence of a suicide-related item documented on the problem list was 5.66% in the postimplementation period compared with 1.47% in the 1-year preimplementation. Clinicians demonstrated statistically significant increases in knowledge about suicide risk factors and assessment.

Conclusions:

Standardization of suicide risk assessment processes improved detection and documentation of suicide risk in a pediatric outpatient behavioral health setting.
Clinical Effects of PET-CT Before Definite Concurrent Chemoradiotherapy in Patients With Unresectable Stage IIIA–IIIB Squamous Cell Carcinoma of the Lungs
Authors: Lin Wei-Chun , Chen Wang-Ming , Chen Mingchih , Shia Ben-Chang , Wu Szu-Yuan
Published: June 2022

Purpose

No large-scale, retrospective cohort study with a long-term follow-up time has yet evaluated the effects of preoperative 18F-FDG PET-CT on survival in patients with unresectable stages IIIA–IIIB squamous cell lung carcinoma (SqCLC) who received definite concurrent chemoradiotherapy (CCRT).

Methods

We included patients with unresectable stages IIIA–IIIB SqCLC receiving definite CCRT and categorized them into 2 groups. The case group comprised patients who underwent pre-CCRT 18F-FDG PET-CT, and the comparison group comprised patients who did not receive pre-CCRT 18F-FDG PET-CT; the groups were matched at a ratio of 1:1.

Results

The matching process yielded a final cohort of 4042 eligible patients (2021 and 2021 in the case and comparison groups, respectively). Multivariable Cox regression analyses revealed a positive correlation between patients with unresectable stages IIIA–IIIB SqCLC receiving definite CCRT and all-cause death in the pre-CCRT 18F-FDG PET-CT (adjusted hazard ratio, 0.85; 95% confidence interval, 0.80–0.91; P < 0.0001).

Conclusion

Pre-CCRT 18F-FDG PET-CT was associated with more favorable survival in both patients with unresectable clinical stage IIIA and those with stage IIIB receiving definite CCRT.
High 11C-Methionine Uptake in a Parasellar Inflammatory Pseudotumor
Authors: Kaida Hayato , Okuda Takeshi , Hanaoka Kohei , Ishii Kazunari
Published: June 2022

A 20-year-old man had left visual impairment and homonymous hemianopsia. MRI findings suggested enlargement of an optic glioma, because optic glioma was indicated by MRI 14 years earlier without a definite pathological diagnosis. 11C-methionine (MET) PET showed high uptake in the tumor in the parasellar region. Transnasal endoscopic biopsy was performed, and an inflammatory pseudotumor (IPT) was diagnosed based on histopathological findings. High MET uptake in a parasellar IPT has apparently not been previously reported. Clinicians should be aware of the possibility of high MET uptake in IPT, because this image could provide an interpretation pitfall.
Comparison of 68Ga-FAPI PET and 18F-FDG PET Findings in a Patient With Bilateral Breast Cancer of 2 Different Histopathologies
Authors: Choudhury Sayak , Shah Sneha , Shet Tanuja , Agrawal Archi , Purandare Nilendu , Puranik Ameya , Rangarajan Venkatesh
Published: June 2022

We present the findings of 18F-FDG PET and 68Ga–fibroblast activation protein PET scans done in a case of bilateral breast carcinoma with 2 different histopathology, left breast tubulolobular carcinoma and right breast invasive breast carcinoma of no special type.
Clozapine Use in a Movement Disorder Clinic
Authors: Friedman Joseph H. , Hershkowitz Dylan
Published: June 2022

Background

Clozapine is an effective antipsychotic for Parkinson’s disease (PD) that does not worsen motor function and can improve tremor. It is approved for PD psychosis in Europe and Australia.

Objective

The aim of this study was to report on the use of clozapine in a movement disorder clinic.

Methods

We report on patients monitored during the COVID-19 pandemic in clinic over a 7-month period.

Results

Sixty-five patients were seen, of whom 50 had PD. Thirty-one were treated for psychosis, 18 for refractory tremor and 1 for levodopa dyskinesias. The remainder had psychotic symptoms with dementia with Lewy bodies (n = 2) or other movement disorders. Four had clozapine discontinued because of sedation and 1 for agranulocytosis. Three had clozapine temporarily halted because of granulocytopenia but were rechallenged successfully.

Conclusions

When comparing clozapine use in this clinic as compared with others, we deduce that clozapine is likely significantly underutilized in the United States.
Probable Miglustat-Induced Psychosis in a Child With Niemann-Pick Type C
Authors: Koç Yekedüz Merve , Öncül Ümmühan , Köse Engin , Eminoğlu Fatma Tuba
Published: June 2022

Background

Niemann-Pick disease type C (NP-C) is a neurodegenerative lysosomal disease in which psychiatric symptoms, such as psychosis, can also be observed. Miglustat is indicated in cases with progressive neurological manifestations, and although there have been studies reporting that miglustat completely cures psychosis, it has been recently observed that miglustat may also trigger psychosis. We report on a rare case of probable miglustat-induced psychosis in a patient with NP-C.

Case

A 21-year-old female patient presented with a complaint of social isolation that started at the age of 6 years. During clinical follow-up, the patient's clinical progress deteriorated, and ocular apraxia, ataxia, seizures, and dementia developed at the age of 15 years. A genetic investigation was performed, and a homozygous p.P120S (c.358C > T) variant was detected in the NPC2 gene. Miglustat was initiated at the age of 15 years, and during the 6 months of treatment, psychotic symptoms such as unwarranted anger, suspiciousness, and delusions developed. Consequently, the miglustat was discontinued by the parents of the patient, and the psychosis completely disappeared. The patient has experienced no further psychotic episodes in the approximately 5.5 years following the discontinuation of therapy.

Conclusion

Although a positive effect of miglustat on neurological and psychiatric symptoms has been reported, there exists a risk of psychosis being triggered. To the best of our knowledge, this is the first case of pediatric NP-C to develop psychosis after miglustat to be reported in literature. Further studies of such cases are needed to understand the impact of miglustat on psychiatric symptoms in NP-C.
Whole-genome sequencing enhances existing pathogen and antimicrobial-resistance surveillance schemes within a neonatal unit
Authors: Price Vivien , Dunn Steven J. , Moran Robert A. , Swindells Jonathan , McNally Alan
Published: June 2022

In some neonatal units, the screening of isolates for antimicrobial-resistant organisms is a matter of routine, with theoretical benefits including the prevention or early detection of outbreaks. This study sought to use whole-genome sequencing (WGS) retrospectively to characterize the genomic epidemiology of Gram-negative organisms obtained from a screening programme in a 32-bed unit providing intensive, high-dependency and special care at City Hospital, Birmingham, UK, identifying occult transmission events and clinically important antimicrobial-resistance (AMR) genes. WGS was performed for 155 isolates collected from rectal and umbilical screening swabs over a 2 month period from 44 individual neonates. Genomic epidemiological analysis showed possible transmission events involving

Escherichia coli

,

Enterobacter cloacae

,

Klebsiella oxytoca

and

Klebsiella pneumoniae

not detected by routine screening, with eight putative clusters involving different individuals identified. Within phylogenetic clusters, the relatedness of organisms – as determined by the abundance of SNPs – varied widely, indicating that a variety of transmission routes may be implicated. While clinically important AMR genes were not present in the putative transmission clusters, our observation of suspected interspecies horizontal transfer of bla
CTX-M-15 within individuals highlights the potential for their spread between organisms as well as individuals in this environment, with implications for surveillance. Our data show that WGS may reveal occult Gram-negative transmission events, demonstrating the potential of sequencing-based surveillance systems for nosocomial pathogens. Challenges remain in understanding how to utilize WGS surveillance to maximum effect in real-world settings.
Interstitial Notch signaling regulates nephron development via the Gata3-Renin axis in the mouse kidney
Authors: Chung Eunah , Adam Mike , Potter Andrew S. , Marshall Sara M. , Potter S. Steven , Park Joo-Seop
Published: June 2022

Notch signaling in the renal interstitium is known to be required for the formation of mesangial cells and Ren1 (Renin)-expressing cells. However, little is known about how interstitial Notch signaling affects nephron development. We found that blocking Notch signaling in the renal interstitium in mice caused developmental arrest of proximal tubules accompanied by defective formation of mesangial cells. We examined the interstitial Pdgfrb mutant kidney which exhibits a similar mesangial cell defect and found that the Pdgfrb mutant kidney showed normal proximal tubule development, suggesting that the absence of mesangial cells was not the cause of defective proximal tubule development. Our single cell RNA-seq analysis of the interstitial Rbpj mutant kidney showed that a subset of proximal tubule genes were downregulated in the mutant kidney and that Gata3 was downregulated in the mutant interstitium during the development of Ren1-expressing cells. We found that deleting Gata3 in the interstitium caused the loss of Renin and the developmental arrest of proximal tubules, phenocopying the interstitial Notch/Rbpj mutants. Our results suggest that interstitial Notch signaling regulates the development of proximal tubules via the Gata3-Renin axis in the mouse kidney.
CSF p-tau181 Increases in Patients with Neuronal Intranuclear Inclusion Disease without Amyloid Burden
Authors: Kurihara Masanori , Komatsu Hiroki , Sengoku Renpei , Shibukawa Mari , Morimoto Satoru , Matsubara Tomoyasu , Arakawa Akira , Orita Makoto , Ishibashi Kenji , Mitsutake Akihiko , Shibata Shota , Ishiura Hiroyuki , Adachi Kaori , Ohse Kensuke , Hatano Keiko , Ihara Ryoko , Higashihara Mana , Nishina Yasushi , Tokumaru Aya Midori , Ishii Kenji , Saito Yuko , Murayama Shigeo , Kanemaru Kazutomi , Iwata Atsushi
Published: June 2022

Background and Objectives

CSF tau phosphorylated at threonine 181 (p-tau181) is a widely used biomarker for Alzheimer’s disease (AD) and has recently been regarded to reflect amyloid-beta (Aβ) and/or p-tau deposition in the AD brain. Although it is important to know how this biomarker reacts in other neurocognitive diseases, CSF p-tau181 in patients with neuronal intranuclear inclusion disease (NIID) has not been studied.

Methods

CSF concentrations of p-tau181, total tau, amyloid-beta 1-42 (Aβ42), monoamine metabolites homovanillic acid (HVA), and 5-hydroxyindole acetic acid (5-HIAA) were compared between 12 patients with NIID, 120 patients with symptomatic AD biologically confirmed based on CSF biomarker profiles, and patients clinically diagnosed with other neurocognitive disorders (dementia with Lewy bodies [DLB], 24; frontotemporal dementia [FTD], 13; progressive supranuclear palsy [PSP], 21; and corticobasal syndrome [CBS], 13). Amyloid PET using Pittsburgh compound B (PiB) was performed in six NIID patients.

Results

CSF p-tau181 concentration was significantly higher in NIID (72.7 ± 24.8 pg/mL) compared to DLB, PSP, and CBS and was comparable between NIID and AD. CSF p-tau181 was above the cutoff value (50.0 pg/mL) in 11 of 12 NIID patients (91.7%). Within these patients, only two patients showed decreased CSF Aβ42, and these patients showed negative or mild local accumulation in PiB PET, respectively. PiB PET scans were negative in the remaining 4 patients tested. CSF HVA and 5-HIAA concentrations were significantly higher in patients with NIID compared to disease controls.

Discussion

CSF p-tau181 was increased in patients with NIID without amyloid accumulation. Although the deposition of p-tau has not been reported in NIID brains, molecular mechanism of tau phosphorylation or secretion of p-tau may be altered in NIID.
HybAVPnet: a novel hybrid network architecture for antiviral peptides identification
Authors: Ge Ruiquan , Xia Yixiao , Jiang Minchao , Jia Gangyong , Jing Xiaoyang , Li Ye , Cai Yunpeng
Published: June 2022

Motivation

The virus poses a great threat to human production and life, thus the research and development of antiviral drugs is urgently needed. Antiviral peptides play an important role in drug design and development. Compared with the time-consuming and laborious wet chemical experiment methods, accurate and rapid identification of antiviral peptides using computational methods is critical. However, it is still challenging to extract effective feature representations from the sequences for the accurate identification of antiviral peptides.

Results

This study introduces a novel two-step approach, named HybAVPnet, with a hybrid network architecture to identify antiviral peptides based on neural networks and traditional machine learning methods. Firstly, eighteen kinds of features are extracted to predict labels and probabilities by the neural network classifier and LightGBM classifier, respectively. Secondly, the support vector machine classifier is carried out using the predicted probability of the first step to make the final prediction. The experimental result shows HybAVPnet can achieve better and more robust performance compared with the state-of-the-art methods, especially on independent datasets, which makes it useful for the research and development of antiviral drugs. Meanwhile, it can also be extended to other peptide recognition problems because of its generalization ability.

Availability and implementation

The predicted model could be downloaded from:https://github.com/greyspring/HybAVPnet

Contact

gespring@hdu.edu.cn;yp.cai@siat.ac.cn

Supplementary information

Supplementary data are available atBioinformaticsonline.
Silicon Diode based Flexible and Bioresorbable Optoelectronic Interfaces for Selective Neural Excitation and Inhibition
Authors: Huang Yunxiang , Cui Yuting , Deng Hanjie , Wang Jingjing , Hong Rongqi , Hu Shuhan , Hou Hanqing , Dong Yuanrui , Wang Huachun , Chen Junyu , Li Lizhu , Xie Yang , Sun Pengcheng , Fu Xin , Yin Lan , Xiong Wei , Shi Song-Hai , Luo Minmin , Wang Shirong , Li Xiaojian , Sheng Xing
Published: June 2022

The capability to selectively and precisely modulate neural activities represents a powerful tool for neuroscience research and clinical therapeutics. Traditional electrical stimulations associate with bulky and tethered implants, and optogenetic methods rely on genetic modification for cell targeting. Here, we report an optoelectronic, non-genetic strategy for exciting and inhibiting neural activities, accomplished by bioresorbable, thin-film silicon (Si) diodes. Under illumination, these devices establish polarity-dependent, positive or negative voltages at the semiconductor/solution interface. Such photovoltaic signals enable deterministic depolarization and hyperpolarization of cultured neurons, upregulating and downregulating intracellular calcium dynamics in vitro. Furthermore, flexible, thin-film Si based devices mounted on the nerve tissue selectively activate and silence in vivo activities, both in the peripheral nerve and the brain. Finally, these Si membranes naturally dissolve within the animal body. Such a Si-based material and device platform offers broad potential for biomedical applications.
Gli1+ mesenchymal progenitors contribute to multilineage differentiation in a mouse model of post-traumatic joint injury
Authors: Magallanes Jenny , Liu Nancy Q , Zhang Jiankang , Ouyang Yuxin , Mkaratigwa Tadiwanashe , Bian Fangzhou , Van Handel Ben , Skorka Tautis , Petrigliano Frank A. , Evseenko Denis
Published: June 2022

Complex injury and open reconstructive surgeries of the knee often lead to joint dysfunction that may alter the normal biomechanics of the joint. Two major complications that often arise are excessive deposition of fibrotic tissue and acquired heterotopic endochondral ossification. Knee arthrofibrosis is a fibrotic joint disorder where aberrant buildup of scar tissue and adhesions develop around the joint. Heterotopic ossification is ectopic bone formation around the periarticular tissues. Even though arthrofibrosis and heterotopic ossification pose an immense clinical problem, limited studies focus on their cellular and molecular mechanisms. Effective cell-targeted therapeutics are needed, but the cellular origin of both knee disorders remains elusive. Moreover, all the current animal models of knee arthrofibrosis and stiffness are developed in rats and rabbits, limiting genetic experiments that would allow us to explore the contribution of specific cellular targets to these knee pathologies. Here, we present a novel mouse model of post-traumatic joint injury where surgically induced injury and hyperextension of the knee lead to excessive deposition of disorganized collagen in the meniscus, synovium, and joint capsule in addition to formation of extra-skeletal bone in muscle and soft tissues within the joint capsule. As a functional outcome, arthrofibrosis and heterotopic endochondral ossification coupled with a significant increase in total joint stiffness were observed. By employing this model and genetic lineage tracing, we also demonstrate that Gli1+ mesenchymal progenitors proliferate after joint injury and contribute to fibrotic cells in the synovium and ectopic osteoblasts within the joint capsule. These findings demonstrate that Gli1+ cells are a major cellular contributor to knee arthrofibrosis and heterotopic ossification that manifests after knee injury. Our data collectively shows that genetic manipulation of Gli1+ cells in mice may offer a platform for identification of novel therapeutic targets to prevent chronic knee joint dysfunction after chronic injury.