bluuebunny/crossref_metadata_2025 huggingface dataset:
Criteria for Pediatric Sepsis—A Systematic Review and Meta-Analysis by the Pediatric Sepsis Definition Taskforce*
Authors: Menon Kusum , Schlapbach Luregn J. , Akech Samuel , Argent Andrew , Biban Paolo , Carrol Enitan D. , Chiotos Kathleen , Jobayer Chisti Mohammod , Evans Idris V. R. , Inwald David P. , Ishimine Paul , Kissoon Niranjan , Lodha Rakesh , Nadel Simon , Oliveira Cláudio Flauzino , Peters Mark , Sadeghirad Benham , Scott Halden F. , de Souza Daniela C. , Tissieres Pierre , Watson R. Scott , Wiens Matthew O. , Wynn James L. , Zimmerman Jerry J. , Sorce Lauren R. ,   for the Pediatric Sepsis Definition Taskforce of the Society of Critical Care Medicine
Published: October 2021

Objective:

To determine the associations of demographic, clinical, laboratory, organ dysfunction, and illness severity variable values with: 1) sepsis, severe sepsis, or septic shock in children with infection and 2) multiple organ dysfunction or death in children with sepsis, severe sepsis, or septic shock.

Data Sources:

MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched from January 1, 2004, and November 16, 2020.

Study Selection:

Case-control studies, cohort studies, and randomized controlled trials in children greater than or equal to 37-week-old postconception to 18 years with suspected or confirmed infection, which included the terms “sepsis,” “septicemia,” or “septic shock” in the title or abstract.

Data Extraction:

Study characteristics, patient demographics, clinical signs or interventions, laboratory values, organ dysfunction measures, and illness severity scores were extracted from eligible articles. Random-effects meta-analysis was performed.

Data Synthesis:

One hundred and six studies met eligibility criteria of which 81 were included in the meta-analysis. Sixteen studies (9,629 patients) provided data for the sepsis, severe sepsis, or septic shock outcome and 71 studies (154,674 patients) for the mortality outcome. In children with infection, decreased level of consciousness and higher Pediatric Risk of Mortality scores were associated with sepsis/severe sepsis. In children with sepsis/severe sepsis/septic shock, chronic conditions, oncologic diagnosis, use of vasoactive/inotropic agents, mechanical ventilation, serum lactate, platelet count, fibrinogen, procalcitonin, multi-organ dysfunction syndrome, Pediatric Logistic Organ Dysfunction score, Pediatric Index of Mortality-3, and Pediatric Risk of Mortality score each demonstrated significant and consistent associations with mortality. Pooled mortality rates varied among high-, upper middle-, and lower middle-income countries for patients with sepsis, severe sepsis, and septic shock (p < 0.0001).

Conclusions:

Strong associations of several markers of organ dysfunction with the outcomes of interest among infected and septic children support their inclusion in the data validation phase of the Pediatric Sepsis Definition Taskforce.
Preexisting Clinical Frailty Is Associated With Worse Clinical Outcomes in Patients With Sepsis*
Authors: Lee Hong Yeul , Lee Jinwoo , Jung Yoon Sun , Kwon Woon Yong , Oh Dong Kyu , Park Mi Hyeon , Lim Chae-Man , Lee Sang-Min
Published: October 2021

OBJECTIVES:

Frailty is a multidimensional syndrome or state of increased vulnerability to poor resolution of homoeostasis following a stressor event. Frailty is common in patients with sepsis. Sepsis and frailty are both associated with older age and chronic medical conditions. However, there is limited evidence about the direct association between frailty and sepsis. The aim of this study is to determine the association between preexisting clinical frailty and clinical outcomes in patients with sepsis.

DESIGN:

A nationwide propensity score–matched cohort study analyzing data prospectively collected between September 2019 and February 2020.

SETTING:

Nineteen tertiary or university-affiliated hospitals in South Korea.

PATIENTS:

Adult patients who were diagnosed with sepsis.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Frailty status was assessed using the Clinical Frailty Scale. All patients were classified as “frail” (Clinical Frailty Scale score, 5–9) or “nonfrail” (Clinical Frailty Scale score, 1–4). Propensity score matching identified comparable nonfrail patients. The primary outcome was inhospital mortality. Multivariable logistic regression analysis was used to evaluate the association between frailty and inhospital mortality. The propensity score–matched cohort comprised 468 nonfrail patients and 468 frail patients; all covariate imbalances were alleviated. In the matched cohort (mean age, 69 ± 14 yr), 27.2% had septic shock at presentation. Inhospital mortality was 34.2% in the frail group and 26.9% in the nonfrail group (p = 0.019). The adjusted odds ratio for inhospital mortality in the frail group compared with the nonfrail group was 2.00 (95% CI, 1.39–2.89; p < 0.001). Among the patients who survived to discharge, the frail group was less likely to be discharged home compared with the nonfrail group, 64.0% versus 81.3%, respectively (p < 0.001).

CONCLUSIONS:

In patients with sepsis, preexisting clinical frailty is associated with worse clinical outcomes than that in nonfrail patients, including inhospital mortality and discharge to home.
Cardiovascular Manifestations of Systemic Sclerosis: An Overview of Pathophysiology, Screening Modalities, and Treatment Options
Authors: Lee Kyu-In , Manuntag Levy Jo , Kifayat Alina , Manuntag Samantha Eugene , Sperber Kirk , Ash Julia Yegudin , Frishman William H. , Wasserman Amy
Published: October 2021

Systemic sclerosis, previously known as scleroderma, is a heterogeneous, systemic disease that is defined by its 3 pathological hallmarks: the production of autoantibodies, small vessel vasculopathy, and fibroblast dysfunction, leading to an increased deposition of extracellular matrix. We conducted a review of the available literature that covers the cardiovascular manifestations of SSc: electrical conduction abnormalities, pulmonary hypertension, pericardial disease, and atherosclerosis. Within each major category, we will discuss the definition, diagnostics, and available treatment options. Increased mortality from cardiovascular complications necessitates early screening and management. Annual screening with noninvasive modalities is encouraged. The current management of each complication generally follows the management algorithms of patients regardless of SSc status and is dependent on the severity of the patient’s clinical presentation.
Maternal Obesity, Gestational Diabetes, and Fetal Macrosomia: An Incidental or a Mechanistic Relationship?
Authors: Salameh Mohammad A. , Oniya Olubunmi , Chamseddine Reem S. , Konje Justin C.
Published: October 2021

Gestational diabetes mellitus (GDM) is a well-established risk factor for fetal macrosomia. A significant number of patients with GDM also suffer from obesity, a factor associated with fetal macrosomia. An important question is whether GDM is independently associated with fetal macrosomia, or whether this relationship is merely the result of maternal obesity acting as a confounder. In this review of the literature, we attempt to further elucidate the relationship between GDM, maternal obesity, and fetal macrosomia.
Impact of ABCB1 Polymorphisms on Lacosamide Serum Concentrations in Uygur Pediatric Patients With Epilepsy in China
Authors: Zhao Ting , Li Hong-jian , Feng Jie , Zhang Hui-lan , Ting-ting Wang , Ma Long , Yu Jing , Zhao Wen-bo , Sun Li , Yu Lu-hai , Sun Yan
Published: October 2021

Background:

P-glycoprotein, encoded by ABCB1 (or MDR1), may contribute to drug resistance in epilepsy by limiting gastrointestinal absorption and brain access to antiseizure medications. The study aimed to evaluate the impact of ABCB1 polymorphisms on lacosamide (LCM) serum concentrations in Uygur pediatric patients with epilepsy.

Methods:

The serum concentrations of LCM were determined by ultrahigh performance liquid chromatography, and the ABCB1 polymorphism was analyzed through polymerase chain reaction–fluorescence staining in situ hybridization. The χ2 test and the Fisher exact test were used to analyze the allelic and genotypic distributions of ABCB1 polymorphisms between the drug-resistant and drug-responsive patient groups. Differences in steady-state and dose-corrected LCM serum concentrations between different genotypes were analyzed using the one-way analysis of variance and the Mann–Whitney test.

Results:

A total of 131 Uygur children with epilepsy were analyzed, and of them, 41 demonstrated drug resistance. The frequency of the GT genotype of ABCB1 G2677T/A was significantly higher in the drug-resistant group than that in the drug-responsive group (P < 0.05, OR = 1.966, 95% CI, 1.060–3.647). Patients with the G2677T/A-AT genotype had a statistically significantly lower concentration-to-dose (CD) value than patients with the G2677T/A-GG genotype (mean: 0.6 ± 0.2 versus 0.8 ± 0.5 mcg/mL per mg/kg, P < 0.001). Significantly lower LCM serum concentrations were observed in ABCB1 C3435T CT and TT genotype carriers than those in the CC carriers (P = 0.008 and P = 0.002), and a significantly lower LCM CD value was observed in ABCB1 C3435T CT genotype carriers than that in the CC carriers (P = 0.042).

Conclusions:

ABCB1 G2677T/A and C3435T polymorphisms may affect LCM serum concentrations and treatment efficacy in Uygur pediatric patients with epilepsy, leading to drug resistance in pediatric patients.
Vital Anaesthesia Simulation Training (VAST); immersive simulation designed for diverse settings
Authors: Mossenson Adam I. , Mukwesi Christian , Elaibaid Mohamed , Doverty Julie , May Alistair , Murray Michelle , Livingston Patricia L.
Published: October 2021

Simulation-based education (SBE) of health care providers is ubiquitous in well-resourced locations and has been used successfully to teach clinical and nontechnical skills. Numerous barriers prevent this important educational tool from widespread use in resource-limited and remote settings. Vital Anaesthesia Simulation Training (VAST) was founded with the aim of promoting the use of vivid, experiential simulation-based learning regardless of location. As an organization, VAST now offers a range of training opportunities. The 3-day VAST Course is a highly portable program that uses low-cost materials to teach core perioperative practices and non-technical skills for health care practitioners in diverse settings. The VAST Course is paired with the VAST Facilitator Course to build skills for SBE among local educators. The VAST Design Course equips simulation facilitators with tools for developing their own simulation scenarios. The VAST Foundation Year is a 48-week curriculum of active learning sessions for early anesthesia trainees, made available to VAST facilitators. This manuscript describes many of the challenges faced when delivering SBE in varied environments and indicates VAST’s strategies to help overcome potential barriers. An overview of the VAST scenario template and stepwise approach to scenario design is included (Supplemental Digital Content 1, http://links.lww.com/IJSGH/A14). While challenges facing SBE in resource-limited settings are significant, its potential value in this context is immense. VAST offers a viable platform for expanding SBE beyond the traditional simulation center.
Practical Review of the Comprehensive Management of Morel-Lavallée Lesions
Authors: Molina Bianca J. , Ghazoul Erika N. , Janis Jeffrey E.
Published: October 2021

Background:

Morel-Lavallée lesions have been described in the literature since the mid-19th century, yet contemporary clinical management continues to be challenging and remains variable. These closed degloving injuries are usually seen in the setting of blunt trauma and are due to shearing forces, creating a space for the collection of hemolymphatic fluid. These fluid collections can be persistent despite conservative treatment attempts and can require staged surgical interventions.

Methods:

A literature search of peer-reviewed articles pertaining to Morel-Lavallée lesions was performed. Articles relating to the pathophysiology, clinical presentation, diagnosis, treatment, and management of complications of Morel-Lavallée lesions were included to formulate recommendations for clinical management.

Results:

Fifty-six relevant articles were included in the review. Recognition of these lesions may be delayed and the use of imaging is important in diagnosis. Initial attempts at conservative management may be appropriate for smaller, uncomplicated Morel-Lavallée lesions. Surgical interventions such as open debridement, techniques to close dead space, negative pressure wound therapy, and skin grafts or flaps are critical to managing complex or recurring lesions. An algorithm for the treatment of Morel-Lavallée lesions is proposed based on review of the literature.

Conclusions:

Plastic and reconstructive surgeons are frequently involved in more complex Morel-Lavallée lesions such as those exhibiting delayed healing or super-infection. The skillset needed for successful management of patients with Morel-Lavallée lesions is well within the armamentarium of plastic and reconstructive surgeons.
Exercise after Breast Reconstruction Surgery: Evaluating Current Trends and Practices of U.S. Plastic Surgeons
Authors: Alabaster Kelsey , Homsy Christopher , Puyana Salomon , Higgins Margaret , Ferrin Peter , Mulcahey Mary K. , Chaffin Abigail
Published: October 2021

Background:

Breast cancer patients have reported restricted mobility, pain, lymphedema, and impaired sensation and strength after breast reconstruction surgery. Many studies have demonstrated benefits of early exercise intervention (within the first 2 weeks) for functional recovery after breast surgery. From the surgeon’s perspective, there is a concern that early postoperative exercise can potentially lead to complications or even reconstruction failure. The purpose of this study was to evaluate current trends and practices related to patient exercise after breast reconstruction among plastic surgeons in the United States.

Methods:

An anonymous, electronic survey was sent to a random cohort of 2336 active members of the American Society of Plastic Surgeons. The survey consisted of 23 questions and was used to assess how plastic surgeons currently manage patients postoperatively after breast reconstruction.

Results:

Responses were received from 228 plastic surgeons. Thirty-six (18%) respondents reported never prescribing physical therapy (PT) postoperatively. In total, 154 (76%) prescribe PT to less than 50% of their patients, and those who do most commonly prescribe it more than 3 weeks postoperatively. There was no difference in perceived rate of complications by respondents who prescribe early versus late exercise (χ

2
(5) = 8.815, P = 0.117).

Conclusions:

Based on our survey results, only a small percentage of plastic and reconstructive surgeons support early initiation of exercise, and PT is being prescribed to a minority of patients. Surgeons and physical therapists must work together to devise a recovery program that maximizes functional outcomes for patients while also limiting complications.
Synergistic therapeutic effect of low-dose bevacizumab with cisplatin-based chemotherapy for advanced or recurrent cervical cancer
Authors: Liu Chia-Hao , Kung Yen-Hsuan , Chien-Fu Lin Jeff , Chuang Chi-Mu , Wu Hua-Hsi , Jiang Ling-Yu , Shih Ying-Chu , Wang Peng-Hui , Chen Yi-Jen
Published: October 2021

Background:

Cisplatin-based chemotherapy (CBC) is highly efficacious for advanced cervical cancer; its efficacy can be enhanced by combining with 15 mg/kg (standard dose) bevacizumab (BEV). However, this standard dose is associated with various adverse events (AEs). Therefore, in this retrospective study, we analyzed the survival outcomes and AEs in patients with advanced or recurrent cervical cancer treated with CBC in combination with BEV 7.5 mg/kg.

Methods:

Registered patient data were retrieved between October 2014 and September 2019, and 64 patients with advanced or recurrent cervical cancer treated with CBC + BEV (n = 21) or CBC alone (n = 43) were analyzed. The primary endpoints were progression-free survival (PFS) and overall survival (OS); the secondary endpoints were the frequency and severity of AEs. The Cox proportional-hazards model was applied to explore prognostic factors associated with PFS and OS.

Results:

The 1-, 2-, and 3-year PFS rates (95% CI) were 36.24% (22.0-50.5), 20.7% (9.8-34.2), and 17.7% (7.7-31.1) for the CBC group; and 71.4% (47.1-86.0), 51.0% (27.9-70.1), and 51.0% (27.9-70.1) for the CBC + BEV group, respectively. The 1-, 2-, and 3-year OS rates were 62.6% (46.4-75.18), 32.4% (18.8-46.9), and 23.2% (11.2-37.6) for the CBC group; and 85.7% (61.9-95.1), 66.6% (42.5-82.5), and 55.5% (27.1-76.7) for the CBC + BEV group, respectively. The CBC + BEV group presented higher PFS and OS rates, p = 0.003 and p = 0.005, respectively. Proteinuria (6 vs 9, p = 0.025) and hypertension (0 vs 10, p < 0.001) were less common, but anemia was more common in the CBC group (35 vs 11, p = 0.021).

Conclusion:

Overall, CBC + BEV significantly improved the PFS and OS compared with CBC alone. CBC + BEV also prevents severe AEs and hence is an efficacious and safe therapeutic option.
Analysis of Readmissions in a Mobile Integrated Health Transitional Care Program Using Root Cause Analysis and Common Cause Analysis
Authors: Buitrago Ivan , Seidl Kristin L. , Gingold Daniel B. , Marcozzi David
Published: October 2021

Mobile integrated health and community paramedicine (MIH-CP) programs are gaining popularity in the United States as a strategy to address the barriers to healthcare access and appropriate utilization. After one year of operation, leadership of Baltimore City's MIH-CP program was interested in understanding the circumstances surrounding readmission for enrolled patients and to incorporate quality improvement tools to direct program development. Retrospective chart review was performed to determine preventable versus unpreventable readmissions with a hypothesis that deficits in social determinants of health would play a more significant role in preventable readmissions. In the studied population, at least one root cause that can be considered a social determinant of health was present in 75.8% of preventable readmissions versus only 15.2% of unpreventable readmissions. Root Cause Analysis highlighted health literacy, functional status, and behavioral health issues among the root causes that most heavily influence preventable readmissions. Common Cause Analysis results suggest our MIH-CP program should focus its resources on mitigating poor health literacy and functional status. This project's findings successfully directed leadership of the city's MIH-CP program to modify program processes and advocate for the use of these quality improvement tools for other MIH-CP programs.
Uniting the Global Gastroenterology Community to Meet the Challenge of Climate Change and Nonrecyclable Waste
Authors: Leddin Desmond , Omary M. Bishr , Veitch Andrew , Metz Geoffrey , Amrani Naima , Aabakken Lars , Ali Raja A.R. , Alvares-da-Silva Mario R. , Armstrong David , Boyacioglu Sedat , Chen Ye , Elwakil Reda , Fock Kwong-Ming , Hamid Saeed S. , Makharia Govind , Macrae Finlay , Malekzadeh Reza , Mulder Chris J. , Piscoya Alejandro , Perman Mai Ling , Sadeghi Anahita , Sáenz Roque , Saurin Jean-Christophe , Butt Amna S. , Wu Kaichun , Lee Yeong Yeh
Published: October 2021

Climate change has been described as the greatest public health threat of the 21st century. It has significant implications for digestive health. A multinational team with representation from all continents, excluding Antarctica and covering 18 countries, has formulated a commentary which outlines both the implications for digestive health and ways in which this challenge can be faced.
Modeling Patient Risk for Hospital-Acquired Pressure Injuries During COVID-19
Authors: Montgomery Aoyjai P. , Patrician Patricia A. , Hall Allyson , Miltner Rebecca S. , Enogela Ene M. , Polancich Shea
Published: October 2021

Background:

COVID-19 negatively impacts many organ systems including the skin. One of the most significant skin-associated adverse events related to hospitalization are pressure injuries.

Purpose:

The aim of this study was to determine 8 risk factors that would place hospitalized patients at a higher risk for hospital-acquired pressure injuries (HAPIs) during the COVID-19 pandemic.

Methods:

A retrospective, descriptive analysis was conducted in an urban academic health science center located in the southeastern United States.

Results:

There were 247 of 23 093 patients who had pressure injuries and 1053 patients who had a positive COVID-19 diagnosis. Based on the generalized estimating equation model, diagnosis of COVID-19, age, male gender, risk of mortality, severity of illness, and length of stay are statistically significant factors associated with the development of HAPIs.

Conclusions:

Further study should explore pathology of COVID-19 skin changes and what interventions are effective against HAPIs in the COVID-19 population taking into consideration current treatments.
Association of Bipolar Disorder With Major Adverse Cardiovascular Events: A Population-Based Historical Cohort Study
Authors: Foroughi Moein , Medina Inojosa Jose R. , Lopez-Jimenez Francisco , Saeidifard Farzane , Suarez Laura , Stokin Gorazd B. , Prieto Miguel L. , Rocca Walter A. , Frye Mark A. , Morgan Robert J.
Published: October 2021

Objective

This study aimed to assess the association of bipolar disorder (BD) with risk of major adverse cardiac events (MACEs) after adjusting for established cardiovascular disease (CVD) risk factors.

Methods

We conducted a population-based historical cohort study using the Rochester Epidemiology Project. Patients older than 30 years with a clinical encounter from 1998 to 2000 with no prior MACE, atrial fibrillation, or heart failure were followed up through March 1, 2016. BD diagnosis was validated by chart review. Cox proportional hazards regression models were adjusted for established CVD risk factors, alcohol use disorder, other substance use disorders (SUDs), and major depressive disorder (MDD).

Results

The cohort included 288 individuals with BD (0.81%) and 35,326 individuals without BD as the reference group (Ref). Median (interquartile range) follow-up was 16.5 (14.6–17.5) years. A total of 5636 MACE events occurred (BD, 59; Ref, 5577). Survival analysis showed an association between BD and MACE (median event-free-survival rates: BD, 0.80; Ref, 0.86; log-rank p = .018). Multivariate regression adjusting for age and sex also yielded an association between BD and MACE (hazard ratio [HR] = 1.93; 95% confidence interval [CI] = 1.43–2.52; p < .001). The association remained significant after further adjusting for smoking, diabetes mellitus, hypertension, high-density lipoprotein cholesterol, and body mass index (HR = 1.66; 95% CI = 1.17–2.28; p = .006), and for alcohol use disorder, SUD, and MDD (HR = 1.56; 95% CI = 1.09–2.14; p = .010).

Conclusions

In this study, BD was associated with an increased risk of MACE, which persisted after adjusting for established CVD risk factors, SUDs, and MDD. These results suggest that BD is an independent risk factor for major clinical cardiac disease outcomes.
A Functional Connectivity Study to Investigate the Role of the Right Anterior Insula in Modulating Emotional Dysfunction in Borderline Personality Disorder
Authors: Sampedro Frederic , Aracil-Bolaños Ignacio , Carmona i Farrés Cristina , Soler Joaquim , Schmidt Carlos , Elices Matilde , Pomarol-Clotet Edith , Salvador Raymond , Vega Daniel , Pascual Juan C.
Published: October 2021

Objective

Previous imaging studies in patients with borderline personality disorder (BPD) have detected functional brain dysfunctions. Mindfulness training may improve the symptoms of BPD, although the neural mechanisms involved remain poorly understood. This study had several key aims: a) to investigate the role of right anterior insula (rAI) functional connectivity in modulating baseline emotional status in BPD, b) to compare differences in connectivity changes after mindfulness training versus interpersonal effectiveness intervention, and c) to explore the correlation between longitudinal changes in imaging data and clinical indicators.

Methods

Thirty-eight patients with BPD underwent resting-state functional magnetic resonance imaging. Participants completed self-report clinical scales and participated in a dialectical-behavioral therapy (mindfulness versus interpersonal effectiveness modules). Changes in clinical and imaging variables were evaluated longitudinally after completion of the first 10-week sessions of psychotherapeutic intervention.

Results

At baseline, the rAI was strongly connected with the other salience network nodes and anticorrelated with most core nodes of the default mode network (p < .05, corrected). The functional connectivity of the rAI correlated with emotional dysregulation and deficits in mindfulness capacities (p < .05, corrected). After completion of psychotherapeutic intervention, both groups (mindfulness and interpersonal effectiveness) showed divergent posttherapy functional connectivity changes, which were in turn associated with the clinical response.

Conclusions

The functional connectivity of the rAI seems to play an important role in emotion dysregulation and deficits in mindfulness capacities in individuals with BPD. Psychotherapy seems to modulate this functional connectivity, leading to beneficial changes in clinical variables.
Breast Computed Tomography
Authors: Zellweger Caroline , Berger Nicole , Wieler Jann , Cioni Dania , Neri Emanuele , Boss Andreas , Frauenfelder Thomas , Marcon Magda
Published: October 2021

Objectives

This study aimed to evaluate the diagnostic performance of the maximum intensity projection (MIP) reformations of breast computed tomography (B-CT) images as a stand-alone method for the detection and characterization of breast imaging findings.

Materials and Methods

A total of 160 women undergoing B-CT between August 2018 and December 2020 were retrospectively included; 80 patients with known breast imaging findings were matched with 80 patients without imaging findings according to age and amount of fibroglandular tissue (FGT). A total of 71 benign and 9 malignant lesions were included. Images were evaluated using 15-mm MIP in 3 planes by 2 radiologists with experience in B-CT. The presence of lesions and FGT were evaluated, using the BI-RADS classification. Interreader agreement and descriptive statistics were calculated.

Results

The interreader agreement of the 2 readers for finding a lesion (benign or malignant) was 0.86 and for rating according to BI-RADS classification was 0.82. One of 9 cancers (11.1%) was missed by both readers due to dense breast tissue. BI-RADS 1 was correctly applied to 73 of 80 patients (91.3%) by reader 1 and to 74 of 80 patients (92.5%) by reader 2 without recognizable lesions. BI-RADS 2 or higher with a lesion in at least one of the breasts was correctly applied in 69 of 80 patients (86.3%) by both readers. For finding a malignant lesion, sensitivity was 88.9% (95% confidence interval [CI], 51.75%–99.72%) for both readers, and specificity was 99.3% (95% CI, 96.4%–100%) for reader 1 and 100% (95% CI, 97.20%–100.00%) for reader 2.

Conclusions

Evaluation of B-CT images using the MIP reformations may help to reduce the reading time with high diagnostic performance and confidence.
Cerebral Perfusion in Pediatric Stroke: Children Are Not Little Adults
Authors: Lee Sarah , Jiang Bin , Heit Jeremy J. , Dodd Robert L. , Wintermark Max
Published: October 2021

Cerebral perfusion imaging provides useful information about the hemodynamic state of the brain that is relevant to a number of neurologic conditions, including stroke, epilepsy, and brain tumors. Multiple imaging modalities have been developed to evaluate brain perfusion, primarily by the use of different tracers to measure cerebral blood volume and cerebral blood flow. Here, we provide an overview of magnetic resonance imaging perfusion techniques; summarize the role of perfusion imaging in adult stroke; describe changes in cerebral blood flow over childhood; and discuss the relevance and future directions of perfusion imaging in pediatric cerebrovascular disorders and stroke.
The Assessment of Neurosensory Disturbance Following Bilateral Sagittal Split Osteotomy With Subjective and Three-Dimensional Evaluation
Authors: Iscan Duygu , Ozbilen Elvan Onem , Ugurlu Kemal , Acar Ahu
Published: October 2021

Purpose:

Inferior alveolar neurosensory disturbance (IAND) is the most common complication of bilateral sagittal split osteotomy (BSSO). The aim of the present study was to evaluate IAND with subjective tests postoperatively and assess the relationship between three-dimensional measurements of the mandibular canal (MC) and IAND.

Methods:

Eighteen patients (Mean age: 24.05 ± 5.85 years) treated with BSSO were retrieved from the archive. Subjective tests (light touch, tactile sensitivity, 2-point discrimination, brush-stroke directional discrimination, sharp/blunt discrimination, dental vitality, questionnaire) and three-dimensional measurements related to MC and fixation screws were done postoperatively (on average 20.43 ± 8.76 months after surgery). Statistical significance was set at P < 0.05.

Results:

Subjective test results were found compatible with each other except brush-stroke directional discrimination test. According to the questionnaire, IAND was apparent in all patients immediately after surgery, and recovery after 1 to 2 years was statistically significant (P < 0.05). Preoperative ramus width, medial and lateral cancellous bone lengths, the decrease in MC length, and the presence of screw in MC were not related to IAND (P < 0.05).

Conclusions:

There is a high incidence of IAND following BSSO, and the subjective tests are efficient to evaluate the disturbance. Spontaneous recovery of the nerve occurs during the follow-up periods. Instead of preoperative measurements of bone thickness, MC length, and the position of fixation screws, the surgical procedure seems to be more important in IAND occurrence.
An Unusual Abnormal Muscular Response During Microvascular Decompression Under Endoscope Assistance
Authors: Liu Yufei , Liu Lingyu , Wang Jing , Ge Shunnan , Qu Yan
Published: October 2021

Abnormal muscular response (AMR) has been widely used in the intraoperative monitoring of microvascular decompression due to its advantages for the identification of responsible arteries and the evaluation of adequate decompression. Here the authors report a 48-year-old man with an unusual AMR during microvascular decompression under endoscope assistance. The morphology and number of AMRs were influenced by different stimulation and recording sites. Abnormal muscular response disappeared and hemifacial spasm was completely relieved without facial paralysis postoperatively.
The actual, long-term cost of intentional injury care among a cohort of Maryland Medicaid recipients
Authors: Dezman Zachary D.W. , Thurman Paul , Stockwell Ian
Published: October 2021

BACKGROUND

Intentional injury (both self-harm and interpersonal) is a major cause of morbidity and mortality, yet there are little data on the per-person cost of caring for these patients. Extant data focus on hospital charges related to the initial admission but does not include actual dollars spent or follow-up outpatient care. The Affordable Care Act has made Medicaid the primary payor of intentional injury care (39%) in the United States and the ideal source of cost data for these patients. We sought to determine the total and per-person long-term cost (initial event and following 24 months) of intentional injury among Maryland Medicaid recipients.

METHODS

Retrospective cohort study of Maryland Medicaid claims was performed. Recipients who submitted claims after receiving an intentional injury, as defined by the International Classification of Diseases, Tenth Revision, between October 2015 and October 2017, were included in this study. Subjects were followed for 24 months (last participant enrolled October 2017 and followed to October 2019). Our primary outcome was the dollars paid by Medicaid. We examined subgroups of patients who harmed themselves and those who received repeated intentional injury.

RESULTS

Maryland Medicaid paid $11,757,083 for the care of 12,172 recipients of intentional injuries between 2015 and 2019. The per-person, 2-year health care cost of an intentional injury was a median of $183 (SD, $5,284). These costs were highly skewed: min, $2.56; Q
1 = 117.60, median, $182.80; Q
3 = $480.82; and max, $332,394.20. The top 5% (≥95% percentile) required $3,000 (SD, $6,973) during the initial event and $8,403 (SD, $22,024) per served month thereafter, or 55% of the overall costs in this study.

CONCLUSION

The long-term, per-person cost of intentional injury can be high. Private insurers were not included and may experience different costs in other states.

LEVEL OF EVIDENCE

Economic and Value Based Evaluations; level III.
COVID-19 in Solid Organ Transplantation: Results of the National COVID Cohort Collaborative
Authors: Vinson Amanda J. , Agarwal Gaurav , Dai Ran , Anzalone Alfred J. , Lee Stephen B. , French Evan , Olex Amy , Madhira Vithal , Mannon Roslyn B.
Published: October 2021

Background.

Coronavirus disease 2019 (COVID-19) has resulted in significant morbidity and mortality in solid organ transplant (SOT) recipients. The National COVID Cohort Collaborative was developed to facilitate analysis of patient-level data for those tested for COVID-19 across the United States.

Methods.

In this study, we identified a cohort of SOT recipients testing positive or negative for COVID-19 (COVID+ and COVID−, respectively) between January 1, 2020, and November 20, 2020. Univariable and multivariable logistic regression were used to determine predictors of a positive result among those tested. Outcomes following COVID-19 diagnosis were also explored.

Results.

Of 18 121 SOT patients tested, 1925 were positive (10.6%). COVID+ SOT patients were more likely to have a kidney transplant and be non-White race. Comorbidities were common in all SOT patients but significantly more common in those who were COVID+. Of COVID+ SOT, 42.9% required hospital admission. COVID+ status was the strongest predictor of acute kidney injury (AKI), rejection, and graft failure in the 90 d after testing. A total of 40.9% of COVID+ SOT experienced a major adverse renal or cardiac event, 16.3% experienced a major adverse cardiac event, 35.3% experienced AKI, and 1.5% experienced graft loss.

Conclusions.

In the largest US cohort of COVID+ SOT recipients to date, we identified patient factors associated with the diagnosis of COVID-19 and outcomes following infection, including a high incidence of major adverse renal or cardiac event and AKI.
Stenotrophomonas maltophilia as a rare cause of meningitis and ventriculoperitoneal shunt infection
Authors: Manuel Adarsh , Jayachandran Akarsh , Harish Srinivasan , Sunil Thenozhi , K. R. Vishnu Das , K. Rajeev , Jo Joseph , Unnikrishnan Muthukuttiparambil , George Koshy , Bahuleyan Biji
Published: October 2021

Stenotrophomonas maltophilia

is an extremely rare pathogen responsible for ventriculoperitoneal shunt infection and meningitis. This young female patient with history of multiple shunt revisions in the past, came to us with shunt dysfunction and exposure of the ventriculoperitoneal shunt tube in the neck. The abdominal end of the shunt tube was seen migrating into the bowel during shunt revision. The cerebrospinal fluid analysis showed evidence of

Stenotrophomonas maltophilia

growth. This is the first reported case of

Stenotrophomonas maltophilia

meningitis associated with ventriculoperitoneal shunt migration into the bowel.
SARS-CoV-2 PLpro whole human proteome cleavage prediction and enrichment/depletion analysis
Authors: Prescott Lucas
Published: October 2021

A novel coronavirus (SARS-CoV-2) has caused a pandemic that has killed millions of people, worldwide vaccination and herd immunity are still far away, and few therapeutics are approved by regulatory agencies for widespread use. The coronavirus 3-chymotrypsin-like protease (3CLpro) is a commonly investigated target in COVID-19, however less work has been directed toward the equally important papain-like protease (PLpro). PLpro is less characterized due to its fewer and more diverse cleavages in coronavirus proteomes and the assumption that it mainly modulates host pathways with its deubiquitinating activity. Here, I extend my previous work on 3CLpro human cleavage prediction and enrichment/depletion analysis to PLpro.[1] Using three sets of neural networks trained on different taxonomic ranks of dataset with a maximum of 463 different putative PLpro cleavages, Matthews correlation coefficients of 0.900, 0.948, and 0.966 were achieved for Coronaviridae, Betacoronavirus, and Sarbecovirus, respectively. I predict that more than 1,000 human proteins may be cleaved by PLpro depending on diversity of the training dataset and that many of these proteins are distinct from those previously predicted to be cleaved by 3CLpro. PLpro cleavages are similarly nonrandomly distributed and result in many annotations shared with 3CLpro cleavages including ubiquitination, poly(A) tail and 5’ cap RNA binding proteins, helicases, and endogenous viral proteins. Combining PLpro with 3CLpro cleavage predictions, additional novel enrichment analysis was performed on known substrates of cleaved E3 ubiquitin ligases with results indicating that many pathways including viral RNA sensing are affected indirectly by E3 ligase cleavage independent of traditional PLpro deubiquitinating activity. As with 3CLpro, PLpro whole proteome cleavage prediction revealed many novel potential therapeutic targets against coronaviruses, although experimental verification is similarly required.
Evaluation of flow cytometry for cell count and detection of bacteria in biological fluids
Authors: Dossou N. , Gaubert I. , Moriceau C. , Cornet E. , Le Hello S. , Malandain D.
Published: October 2021

The analysis of biological fluids is crucial for the diagnosis and monitoring of diseases causing effusions and helps in the diagnosis of infectious diseases. The gold standard method for cell count in biological fluids is the manual method using counting chambers. The microbiological routine procedures consist of Direct Gram staining and culture on solid or liquid media. We evaluate the analytical performance of SYSMEX UF4000 (Sysmex, Kobe, Japan) and Sysmex XN10 (Sysmex, Kobe, Japan) in comparison with cytological and microbiological routine procedures. A total of 526 biological fluid samples were included in this study (42 ascitic, 31 pleural, 31 peritoneal, 125 cerebrospinal, 281 synovial, and 16 peritoneal dialysis fluids). All samples were analysed by flow cytometry and subsequently processed following cytological and/or microbiological routine procedures. With regards to cell counts, UF4000 (Sysmex, Kobe, Japan) showed a performance which was at least equivalent to those of the reference methods and superior to those of XN10 (Sysmex, Kobe, Japan). Moreover, the bacterial count obtained with UF4000 (Sysmex, Kobe, Japan) was significantly higher among culture or Direct Gram stain positive samples. We established 3 optimal cut-off points to predict Direct Gram stain positive samples for peritoneal (465.0 bacteria/μL), synovial (1200.0 bacteria/μL), and cerebrospinal fluids (17.2 bacteria/μL) with maximum sensitivity and negative predictive values. Cell count and detection of bacteria by flow cytometry could be used upstream cytological and microbiological routine procedures to improve and accelerate the diagnosis of infection of biological fluid samples.
Revealing the function of HMGB1 N-terminal acetylation by a protein semi-synthesis approach
Authors: Wei Tongyao , Liu Jiamei , Tan Yi , Li Can , Wei Ruohan , Wang Jinzheng , Wu Hongxiang , Li Qingrong , Liu Heng , Tang Yubo , Li Xuechen
Published: October 2021

HMGB1 (high-mobility group box 1) protein is a nonhistone chromatin-associated protein that has been widely reported to be a representative damage-associated molecular pattern (DAMP) and to play a pivotal role in proinflammatory process once it is in an extracellular location. Accumulating evidence has shown HMGB1 undergoes extensive PTMs that remarkably regulated its conformation, localization, and intermolecular interaction. However, the PTMrelated study has been dramatically hindered by the difficulty to access to homogenous proteins with site-specific PTMs of interest. Here, we introduce a protein semi-synthesis strategy via salicylaldehyde ester-mediated chemical ligations (Ser/Thr ligation and Cys/Pen ligation, STL/CPL). This methodology has enabled us to generate N-terminal acetylated HMGB1 proteins in high purity. Further studies revealed that the acetylation on N-terminus regulates its interaction with heparin and modulates its stability, representing a regulatory switch to control the HMGB1’s activity.
A Probabilistic Approach for Registration of Multi-Modal Spatial Transcriptomics Data
Authors: Qiang Yu , He Shixu , Ding Renpeng , Ma Kailong , Hou Yong , Zhou Yan , Rohr Karl
Published: October 2021

Observing the spatial characteristics of gene expression by image-based spatial transcriptomics technology allows studying gene activity across different cells and intracellular structures. We present a probabilistic approach for the registration and analysis of transcriptome images and immunostaining images. The method is based on particle filters and jointly exploits intensity information and image features. We applied our approach to synthetic data as well as real transcriptome images and immunostaining microscopy images of the mouse brain. It turns out that our approach accurately registers the multi-modal images and yields better results than a state-of-the-art method.
Machine learning-based tissue of origin classification for cancer of unknown primary diagnostics using genome-wide mutation features
Authors: Nguyen Luan , van Hoeck Arne , Cuppen Edwin
Published: October 2021

Tumor tissue of origin (TOO) is an important factor for guiding treatment decisions. However, TOO cannot be determined for ~3% of metastatic cancer patients and are categorized as cancers of unknown primary (CUP). As whole genome sequencing (WGS) of tumors is now transitioning from the research domain to diagnostic practice in order to address the increasing demand for biomarker detection, its use for detection of TOO in routine diagnostics also starts becoming within reach. While proof of concept for the use of genome-wide features has been demonstrated before, more complex WGS mutation features, including structural variant (SV) driver and passenger events, have never been integrated into TOO-classifiers even though they bear highly characteristic links with tumor TOO. Using a uniformly processed dataset containing 6820 whole-genome sequenced primary and metastatic tumors, we have developed Cancer of Unknown Primary Location Resolver (CUPLR), a random forest based TOO classifier that employs 502 features based on simple and complex somatic driver and passenger mutations. Our model is able to distinguish 33 cancer (sub)types with an overall accuracy of 91% and 89% based on cross-validation (n=6139) and hold out set (n=681) predictions respectively. We found that SV derived features increase the accuracy and utility of TOO classification for specific cancer types. To ensure that predictions are human-interpretable and suited for use in routine diagnostics, CUPLR reports the top contributing features and their values compared to cohort averages. The comprehensive output of CUPLR is complementary to existing histopathological procedures and may thus improve diagnostics for patients with CUP.
Systematic identification of intron retention associated variants from massive publicly available transcriptome sequencing data
Authors: Shiraishi Yuichi , Okada Ai , Chiba Kenichi , Omori Ikuko , Mateos Raúl Nicolás , Iida Naoko , Yamauchi Hirofumi , Kosaki Kenjiro , Yoshimi Akihide
Published: October 2021

Many disease-associated genomic variants disrupt gene function through abnormal splicing. With the advancement of genomic medicine, identifying disease-associated splicing associated variants has become more important than ever. Most bioinformatics approaches to detect splicing associated variants require both genome and transcriptomic data. However, there are not many datasets where both of them are available. In this study, we developed a methodology to detect genomic variants that cause splicing changes (more specifically, intron retention), using transcriptome sequencing data alone. After demonstrating its high sensitivity and precision, we have applied it to 230,988 transcriptome sequencing data from the publicly available repository and identified 27,937 intron retention associated variants (IRAVs). In addition, by exploring positional relationships with variants registered in existing disease databases, we extracted 3,077 putative disease-associated IRAVs, which range from cancer drivers to variants linked with autosomal recessive disorders. The new in-silico screening framework proposed here provides a foundation for a platform that can automatically acquire medical knowledge making the most of massively accumulated publicly available sequencing data. Collections of IRAVs identified in this study are available through IRAVDB (https://iravdb.io/).