bluuebunny/crossref_metadata_2025 huggingface dataset:
The Influence of Hospital Characteristics on Patient Survival in Surgically Managed Metastatic Disease of Bone
Authors: Herbach Emma L. , McDowell Bradley D. , Chrischilles Elizabeth A. , Miller Benjamin J.
Published: July 2022

Objectives:

We investigated whether patients receiving surgical treatment for metastatic disease of bone (MDB) at hospitals with higher volume, medical school affiliation, or Commission on Cancer accreditation have superior outcomes.

Materials and Methods:

Using the Surveillance, Epidemiology, and End Results–Medicare database, we identified 9413 patients surgically treated for extremity MDB between 1992 and 2014 at the age of 66 years or older. Cox proportional hazards models were used to calculate the hazards ratios (HR) for 90-day and 1-year mortality and 30-day readmission according to the characteristics of the hospital where bone surgery was performed.

Results:

We observed no notable differences in 90-day mortality, 1-year mortality, or 30-day readmission associated with hospital volume. Major medical school affiliation was associated with lower 90-day (HR: 0.88, 95% confidence interval [CI]: 0.80-0.96) and 1-year (HR: 0.92, 95% CI: 0.87-0.99) mortality after adjustments for demographic and tumor characteristics. Surgical treatment at Commission on Cancer accredited hospitals was associated with significantly higher risk of death at 90 days and 1 year after the surgery. This effect appeared to be driven by lung cancer patients (1-year HR: 1.17, 95% CI: 1.07-1.27).

Conclusions:

Our findings suggest surgical management of MDB at lower-volume hospitals does not compromise survival or readmissions. There may be benefit to referral or consultation with an academic medical center in some tumor types or clinical scenarios.
Seborrheic Keratosis With Malignant Transformation (Invasive or Noninvasive Squamous Cell Carcinoma Arising in Seborrheic Keratosis): A Clinicopathologic and Immunohistochemical Study of 11 Cases
Authors: Goto Keisuke , Ogawa Kohei , Hishima Tsunekazu , Oishi Naoki , Tomita Ozumi , Tsuyuki Takuji , Oda Takao , Iwahashi Yoshifumi , Inaba Yutaka , Honma Keiichiro
Published: July 2022

Seborrheic keratosis is a common benign neoplasm composed of basaloid keratinocytes. However, little is known about the malignant transformation of the tumor. Eleven cases of seborrheic keratosis with malignant transformation were analyzed. The 11 patients included 5 male patients and 6 female patients with a median age of 75 years at diagnosis (68–90 years). The tumors arose at various sites from the scalp (n = 3) to the lower leg (n = 2). The median tumor size was 12 (10–32) and 40 (20–75) mm in 7 noninvasive and 4 invasive cases, respectively. One patient exhibited in-transit skin metastasis. Histopathology of the malignant components resembled porocarcinoma or inverted follicular keratosis. Bowenoid and pagetoid spreading was frequently observed. The malignant components expressed cytokeratin 5/6 (100%) and GATA3 (73%), but not cytokeratin 7 (0%), cytokeratin 19 (9%), BerEP4 (0%), c-kit (0%), and NUT (0%). No significant immunoreactivity of YAP1 was observed in any of the cases. Mutant-type immunostaining of p53 and PTEN was observed in 91% and 82% of the cases, respectively. An increase in p16 expression was seen in 6 (86%) of the 7 cases with noninvasive carcinoma, although a loss of p16 immunoexpression was seen in the invasive carcinoma component in 3 (75%) of the 4 cases. This study demonstrated that seborrheic keratosis can undergo malignant transformation, particularly in large-sized lesions in elderly patients. Malignant components mimic porocarcinoma or inverted follicular keratosis. Malignant transformation induced by TP53 and PTEN mutations and tumor invasion by CDKN2A inactivating mutations are suggested in this study.
Levosimendan in paediatric cardiac anaesthesiology
Authors: Lapere Matthias , Rega Filip , Rex Steffen
Published: July 2022

BACKGROUND

Low cardiac output syndrome (LCOS) after congenital cardiac surgery has an incidence of up to 25%. Preventing and treating LCOS is of pivotal importance as LCOS is associated with excess morbidity and mortality.

OBJECTIVES

This systematic review assesses the safety and efficacy of peri-operative levosimendan administration in the setting of paediatric cardiac surgery.

DESIGN

Systematic review of randomised controlled trials. Meta-analyses were performed on efficacy and exploratory outcomes.

DATA SOURCES

Literature was searched in the following databases (MEDLINE, EMBASE, Web of Science and CENTRAL) from inception to July 2021.

ELIGIBILITY CRITERIA

Randomised controlled trials comparing levosimendan with other inotropes or placebo in children younger than 18 years of age undergoing cardiac surgery.

RESULTS

Nine studies enrolling a total of 539 children could be included in the systematic review. All trials study the prophylactic administration of levosimendan in comparison with placebo (n 
= 2), milrinone (n = 6) or dobutamine (n 
= 1). Levosimendan dosing varied considerably with only three studies using a loading dose. Levosimendan reduced the incidence of LCOS [risk ratio (RR) 0.80] [95% confidence interval (CI), 0.40 to 0.89, P = 0.01] and increased cardiac index (MD 0.17 l min−1 m−2) (95% CI, 0.06 to 0.28, P = 0.003) without affecting other outcomes (mortality, ICU length of stay, hospital length of stay, duration of mechanical ventilation, serum lactate, central venous oxygen saturation, serum creatine or acute kidney injury).

CONCLUSION

The prophylactic use of levosimendan in children undergoing cardiac surgery reduced the incidence of LCOS and increased cardiac index compared with other inotropes or placebo. This effect did not translate into an improvement of other clinical endpoints.
Comparison of Ischemic and Bleeding Events Between Short-Duration Versus Long-Duration Tirofiban Regimens in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Percutaneous Coronary Intervention
Authors: Denny Olivia , Woodruff Ashley E. , Mills Kevin , Chilbert Maya R.
Published: July 2022

Tirofiban has been used historically as a bridge to platelet inhibition with clopidogrel in ST-segment myocardial infarction (STEMI) during percutaneous coronary intervention (PCI) to prevent stent thrombosis. However, ticagrelor and prasugrel reach similar levels of platelet inhibition at 30 minutes to that of clopidogrel at 6 hours, challenging the need for long-duration tirofiban. This 1-year, retrospective cohort study compared ischemic and bleeding outcomes of short-duration versus long-duration tirofiban regimens in patients with STEMI who received ticagrelor or prasugrel at the time of PCI. The primary outcome was major adverse cardiovascular events (MACEs) including cardiovascular mortality, recurrent myocardial infarction, urgent target vessel revascularization, or stroke. Secondary outcomes included individual MACE, all-cause mortality, bleeding events defined by the International Society on Thrombosis and Hemostasis, thirty-day readmissions for MACE and bleeding, and tirofiban pharmacy cost. A total of 283 charts were reviewed and 177 included (short duration n = 57; long duration n = 120). MACE rates were similar between short-duration and long-duration groups (0 [0%] vs. 5 [4.2%]; P = 0.18), including 4 cardiovascular deaths and 1 recurrent myocardial infarction. Bleeding event rates were also similar in short-duration versus long-duration groups including major bleeds (2 [3.5%] vs. 2 [1.7%]; P = 0.60) and clinically relevant nonmajor bleeds (3 [5.3%] vs. 9 [7.5%]; P = 0.75). Cost analysis indicated lower pharmacy cost with the short-duration group. In this cohort of patients with STEMI receiving a fast-acting P2Y12 inhibitor, the length of tirofiban infusion did not affect ischemic or bleeding outcomes, yet short-duration regimens were lower cost.
Immigration transition and gastrointestinal symptoms during menopausal transition: midlife women in the US
Authors: Im Eun-Ok , Choi Mi-Young , Kim Gayeong , Jin Ruiqi , Chee Wonshik
Published: July 2022

Objectives

This study aimed to explore the associations of immigration transition to gastrointestinal (GI) symptoms experienced during the menopausal transition among 974 midlife women in the US.

Methods

The data from 974 midlife women from 2 national Internet survey studies were used for this secondary analysis. Only the data related to background characteristics and, health/menopausal status, immigration transition, and the Gastrointestinal Symptom Index for Midlife Women were included. The data were analyzed using descriptive and inferential statistics including analyses of covariance, logistic regression analyses, and hierarchical multiple regression analyses.

Results

There were statistical differences in total numbers and total severity scores of total GI symptoms between immigrants and nonimmigrants (F = 7.08 and 6.20, respectively; both P < 0.05); Immigrants had fewer total numbers and lower total severity scores of GI symptoms than nonimmigrants. All immigration transition variables including immigration status, the length of stay in the US, and the acculturation level accounted for 11.8% of the total numbers (F = 32.79, P < 0.001) and 12.5% of the total severity scores of GI symptoms (F = 35.10, P < 0.001). However, only immigration status (being nonimmigrant) was a significant factor that was associated with greater total numbers and higher total severity scores of GI symptoms (β = 0.62, P < 0.001 and β = 0.65, P < 0.001, respectively).

Conclusions

This study supports that immigration status is a significant factor that influences GI symptoms during the menopausal transition.
Poor physical recovery after critical illness: incidence, features, risk factors, pathophysiology, and evidence-based therapies
Authors: Boelens Yente Florine Niké , Melchers Max , van Zanten Arthur Raymond Hubert
Published: July 2022

Purpose of review

To summarize the incidence, features, pathogenesis, risk factors, and evidence-based therapies of prolonged intensive care unit (ICU) acquired weakness (ICU-AW). We aim to provide an updated overview on aspects of poor physical recovery following critical illness.

Recent findings

New physical problems after ICU survival, such as muscle weakness, weakened condition, and reduced exercise capacity, are the most frequently encountered limitations of patients with postintensive care syndrome. Disabilities may persist for months to years and frequently do not fully recover. Hormonal and mitochondrial disturbances, impaired muscle regeneration due to injured satellite cells and epigenetic differences may be involved in sustained ICU-AW. Although demographics and ICU treatment factors appear essential determinants for physical recovery, pre-ICU health status is also crucial. Currently, no effective treatments are available. Early mobilization in the ICU may improve physical outcomes at ICU-discharge, but there is no evidence for benefit on long-term physical recovery.

Impaired physical recovery is observed frequently among ICU survivors. The pre-ICU health status, demographic, and ICU treatment factors appear to be important determinants for physical convalescence during the post-ICU phase. The pathophysiological mechanisms involved are poorly understood, thereby resulting in exiguous evidence-based treatment strategies to date.
Nutrition before, during and after critical illness
Authors: Ridley Emma J. , Lambell Kate
Published: July 2022

Purpose of review

This review describes considerations preintensive care unit (ICU), within ICU and in the post-ICU period regarding nutrition management and the current state of the literature base informing clinical care.

Recent findings

Within ICU, studies have focussed on the first 5–7 days of illness in mechanically ventilated patients who are heterogeneous and with minimal consideration to premorbid nutrition state. Many evidence gaps in the period within ICU remain, with the major ones being the amount of protein to provide and the impact of longer-term nutrition interventions. Personalised nutrition and nutrition in the post-ICU period are becoming key areas of focus.

Nutrition for the critically ill patient should not be viewed in isolated time periods; what happens before, during and after ICU is likely important to the overall recovery trajectory. It is critical that the impact of nutrition on clinical and functional outcomes across hospitalisation is investigated in specific groups and using interventions in ways that are biologically plausible to impact. Areas that show promise for the future of critical care nutrition include interventions delivered for a longer duration and inclusion of oral nutrition support, individualised nutrition regimes, and use of emerging bedside body composition techniques to identify patients at nutritional risk.
Update on glucose control during and after critical illness
Authors: Deane Adam M. , Plummer Mark P. , Ali Abdelhamid Yasmine
Published: July 2022

Purpose of review

There is a complex bidirectional relationship between critical illness and disordered glucose metabolism. This review aims to provide a comprehensive summary of the recent evidence focused on the relationship between critical illness and disordered glucose metabolism through the distinct phases of prior to, during, and after an acute illness that requires admission to the intensive care unit (ICU).

Recent findings

Recent data suggest that preexisting glucose metabolism affects the optimal blood glucose target during critical illness, with preliminary data suggesting that glucose targets should be ‘personalized’ based on preexisting glycemia. Because of the close association between critical illness and disordered glucose metabolism, there is a need to optimize glucose monitoring in the ICU with rapid, precise, and cost-efficient measurements at the bedside. Recent studies have evaluated the use of various methodologies, with a focus on the use of near-continuous glucose monitoring. For those patients with preexisting diabetes who survive ICU, nocturnal hypoglycemia may be an unrecognized and important issue when discharged to the ward. There is increasing evidence that patients with high blood glucose during their acute illness, so called ‘stress hyperglycemia’, are at increased risk of developing diabetes in the years following recovery from the inciting event. Critically ill patients with COVID-19 appear at greater risk.

There have been important recent insights in the approach to glucose monitoring and glucose targets during critical illness, monitoring and administration of glucose-lowering drugs on discharge from the ICU, and longitudinal follow-up of patients with stress hyperglycemia.
Gonococcal Infection and Ventriculoperitoneal Shunts
Authors: Freeman Megan Culler , Lazzara Alexandra , Lennon Tyler , McAteer John , Pease Matthew , Sefcik Roberta , Radovic-Stakic Ana , Milstone Aaron M. , Nowalk Andrew , Trent Maria
Published: July 2022

Neisseria gonorrhoeae and Chlamydia trachomatis are pathogens commonly isolated in pelvic inflammatory disease. Neisseria gonorrhoeae may uncommonly spread outside the urogenital tract to cause complications. We present 2 cases of adolescents with ventriculoperitoneal shunt infection due to N. gonorrhoeae, requiring shunt externalization.
Cost-effectiveness analysis of pembrolizumab versus standard of care in recurrent or metastatic squamous cell carcinoma of the head and neck
Authors: Yeh Justin , Black William , Guddati Achuta K.
Published: July 2022

Increasing costs of cancer treatment and anticancer drugs can create a financial burden on society and the individual. Pembrolizumab is an anti-PD-1 inhibitor immunotherapy approved for use in recurrent or metastatic head and neck squamous cell carcinoma. Limited data exists on the cost-effectiveness of pembrolizumab in this setting. This study compares the costeffectiveness of pembrolizumab against traditional chemotherapy using data from KEYNOTE-040. Published data from KEYNOTE-040 were used to create a model estimating treatment costs and overall survival benefit of pembrolizumab and traditional chemotherapy. Costs of treatment of toxicity-related events were obtained from previous literature and were incorporated into the model. Derivation of survival benefit gained from treatment was measured in quality-adjusted life-years (QALYs). The incremental cost-effectiveness ratio (ICER) of pembrolizumab compared to the investigator's choice (IC) was $801,864/QALY. The average drug cost of pembrolizumab would have to approximately decrease by 63% in order to reach the cost-effective threshold of $100,000/ QALY. Pembrolizumab would have to confer a survival benefit of 0.88 QALYs per patient over the IC to reach the cost-effective threshold. Pembrolizumab is not considered cost effective at a threshold of $100,000/QALY based on survival data reported in KEYNOTE-040. Improved long-term outcomes of patients on this relatively new immunotherapy have yet to be reported. Inclusion of these data in the future would likely improve the cost-effectiveness calculations of pembrolizumab and other immunotherapies.
Twin/Multiple Gestations With a Hydatidiform Mole
Authors: Xing Deyin , Adams Emily , Zou Ying S. , Morsberger Laura , Scanga Lori R. , Gao Faye F. , Barker Norman , Vang Russell , Ronnett Brigitte M.
Published: July 2022

Complete hydatidiform moles (CHMs) and partial hydatidiform moles (PHMs) are abnormal gestations characterized by vesicular chorionic villi accompanied by variable trophoblastic hyperplasia, with or without embryonic development. CHMs are purely androgenetic (only paternal [P] chromosome complements), mostly homozygous/monospermic (~85%) but occasionally heterozygous/dispermic, whereas PHMs are overwhelmingly diandric triploid (2 paternal [P] and 1 maternal [M] chromosome complements) and heterozygous/dispermic (>95%). The presence of a fetus in a molar pregnancy usually indicates a PHM rather than a CHM; however, CHMs and PHMs rarely can be associated with a viable fetus or a nonmolar abortus in twin pregnancies and rare multiple gestation molar pregnancies have been reported. A “one-oocyte-model,” with diploidization of dispermic triploid zygotes, has been proposed for twin CHM with coexisting fetus, and a “two-oocyte-model” has been proposed for twin PHM with coexisting fetus. Among 2447 products of conception specimens, we identified 21 cases of twin/multiple gestations with a molar component, including 20 CHMs (17 twins, 2 triplets, 1 quintuplet) and 1 PHM (twin). P57 immunohistochemistry was performed on all; DNA genotyping of molar and nonmolar components was performed on 9 twin CHMs, 1 triplet CHM, 1 quintuplet CHM, and 1 twin PHM. All CHM components were p57-negative and those genotyped were purely androgenetic. Twin CHMs had genotypes of P1M1+P2P2 in 5, P1M1+P1P1 in 1, and P1M1+P2P3 in 1, consistent with involvement of 1 oocyte and from 1 to 3 sperm—most commonly a homozygous CHM but involving 2 sperm in the whole conception—and compatible with a “one-oocyte-model.” The triplet CHM was P1M1+P1P1+P2M2 and the quintuplet CHM was P1M1+P2M2+P2M2+P3M3+P4P4, consistent with involvement of 2 sperm and at least 2 oocytes for the triplet and 4 sperm and at least 3 oocytes for the quintuplet. The twin PHM had a P1M1+P2P3M2 genotype, consistent with involvement of 2 oocytes and 3 sperm. p57 immunohistochemistry is highly reliable for diagnosis of CHMs in twin/multiple gestations. Refined diagnosis of molar twin/multiple gestations is best accomplished by correlating morphology, p57 immunohistochemistry, and molecular genotyping, with the latter clarifying zygosity/parental chromosome complement contributions to these conceptions.
Momentary Partner Involvement in Diabetes Self-Care and Continuously Measured Glucose: A Dynamic Analysis
Authors: Soriano Emily C. , Lenhard M. James , Gonzalez Jeffrey S. , Tennen Howard , Otto Amy K. , Perndorfer Christine , Shen Biing-Jiun , Siegel Scott D. , Laurenceau Jean-Philippe
Published: July 2022

Objective

This study examined the dynamic, real-time associations between partner involvement in diabetes self-care and continuous glucose monitor (CGM) metrics in adults with type 2 diabetes.

Methods

For 1 week, 63 participants wore Dexcom G4 CGMs and provided momentary reports of partner involvement in diabetes self-care five times per day. Dynamic structural equation models were used to estimate the reciprocal lagged effects of partner involvement on next-hour CGM metrics (and vice versa).

Results

Partner involvement predicted improved next-hour glucose control for five of six CGM metrics in analyses adjusted for time-varying covariates. The hour after partner involvement, the model predicted a 26.34 mg/dl decrease in glucose level (standardized β = −0.19), 30% greater odds of meeting target time in target range (β = 0.07), 48% higher odds of target time below target range (TBR; β = 0.04; the only nonsignificant effect), 47% greater odds of target time above target range (β = 0.11), a 4.20 unit decrease in glucose standard deviation (β = −0.19), and a 0.01 unit decrease in glucose coefficient of variation (β = −0.08; all p values < .05). There was less consistent support for the reverse pathway, with only two metrics significantly related to next-hour partner involvement: glucose level (β = 0.15) and TBR (β = 0.21), such that having higher levels and meeting target TBR were significantly predictive of next-hour partner involvement.

Conclusions

This is the first study showing that partner involvement in daily diabetes management predicts short-term glucose control. More research is needed to understand how partners influence glycemic control and evaluate interventions that promote their involvement in diabetes care.
A Novel Approach for Engagement in Team Training in High-Technology Surgery: The Robotic-Assisted Surgery Olympics
Authors: Cohen Tara N. , Anger Jennifer T. , Kanji Falisha F. , Zamudio Jennifer , DeForest Elise , Lusk Connor , Avenido Ray , Yoshizawa Christine , Bartkowicz Stephanie , Nemeth Lynne S. , Catchpole Ken
Published: July 2022

Introduction

There is ongoing interest in the development of technical and nontechnical skills in healthcare to improve safety and efficiency; however, barriers to developing and delivering related training programs make them difficult to implement. Unique approaches to training such as “serious games” may offer ways to motivate teams, reinforce skill acquisition, and promote teamwork. Given increased challenges to teamwork in robotic-assisted surgery (RAS), researchers aimed to develop the “RAS Olympics,” a game-based educational competition to improve skills needed to successfully perform RAS.

Methods

This pilot study was conducted at an academic medical center in Southern California. Robotic-assisted surgery staff were invited to participate in the “RAS Olympics” to develop their skills and identify opportunities to improve processes. Impact of the activity was assessed using surveys and debriefs.

Results

Sixteen operating room team members participated and reacted favorably toward the RAS-Olympics (average score, 4.5/5). They enjoyed the activity, would recommend all staff participate, felt that it was relevant to their work, and believed that they practiced and learned new techniques that would improve their practice. Confidence in skills remained unchanged. Participants preferred the RAS Olympics to traditional training because it provided an interactive learning environment.

Conclusions

The successful implementation of the RAS Olympics provided insight into new opportunities to engage surgical staff members while also training technical and nontechnical skills. Furthermore, this shared experience allowed surgical staff members to gain a greater appreciation for their teammates and an understanding of the current challenges and methods to improve teamwork and communication while promoting safety and efficiency in RAS.
Impact of COVID-19 on the Postoperative Bariatric Surgery Patient Experience
Authors: Murtha Jacqueline A. , Alagoz Esra , Breuer Catherine R. , Eierman Lindsey , Jawara Dawda , Farrar-Edwards Dorothy , Voils Corrine I. , Funk Luke M.
Published: July 2022

Objective:

To characterize patient and provider perceptions of the impact of coronavirus disease 2019 (COVID-19) on weight loss following bariatric surgery.

Background:

COVID-19 has disrupted routines and healthcare throughout the United States, but its impact on bariatric surgery patients’ postoperative experience is unknown.

Methods:

Semistructured interviews with bariatric surgery patients, primary care providers, and health psychologists were conducted from April to November 2020. As part of a secondary analysis, patients and providers described how the COVID-19 pandemic affected the postoperative experience within 3 domains: dietary habits, physical activity, and follow-up care. Interview guides were created from 2 conceptual models: Torain’s Surgical Disparities Model and Andersen’s Behavioral Model of Health Services Use. Study team members derived codes, which were grouped into themes using conventional content analysis.

Results:

Thirty-four participants were interviewed: 24 patients (12 Roux-en-Y gastric bypass and 12 sleeve gastrectomy), 6 primary care providers, and 4 health psychologists. Patients were predominately female (83%) and White (79%). Providers were predominately female (90%) and White (100%). COVID-19 affected the postoperative bariatric surgery patient experience via 3 mechanisms: (1) it disrupted dietary and physical activity routines due to facility closures and fear of COVID-19 exposure; (2) it required patients to transition their follow-up care to telemedicine delivery; and (3) it increased stress due to financial and psychosocial challenges.

Conclusions:

COVID-19 has exacerbated patient vulnerability. The pandemic is not over, thus bariatric surgery patients need ongoing support to access mental health professionals, develop new physical activity routines, and counteract increased food insecurity.
Prospective Study of Perioperative Circulating Tumor DNA Dynamics in Patients Undergoing Hepatectomy for Colorectal Liver Metastases
Authors: Newhook Timothy E. , Overman Michael J. , Chun Yun Shin , Dasari Arvind , Tzeng Ching-Wei D. , Cao Hop S. Tran , Raymond Victoria , Parseghian Christine , Johnson Benny , Nishioka Yujiro , Kawaguchi Yoshikuni , Uppal Abhineet , Vreeland Timothy J. , Jaimovich Ariel , Arvide Elsa M. , Cristo Jenilette V. , Wei Steven H. , Raghav Kanwal P. , Morris Van K. , Lee Jeffrey E. , Kopetz Scott , Vauthey Jean-Nicolas
Published: July 2022

Objective:

To evaluate the association of perioperative ctDNA dynamics on outcomes after hepatectomy for CLM.

Summary Background Data:

Prognostication is imprecise for patients undergoing hepatectomy for CLM, and ctDNA is a promising biomarker. However, clinical implications of perioperative ctDNA dynamics are not well established.

Methods:

Patients underwent curative-intent hepatectomy after preoperative chemotherapy for CLM (2013–2017) with paired prehepatectomy/postoperative ctDNA analyses via plasma-only assay. Positivity was determined using a proprietary variant classifier. Primary endpoint was recurrence-free survival (RFS). Median follow-up was 55 months.

Results:

Forty-eight patients were included. ctDNA was detected before and after surgery (ctDNA+/+) in 14 (29%), before but not after surgery (ctDNA+/−) in 19 (40%), and not at all (ctDNA−/−) in 11 (23%). Adverse tissue somatic mutations were detected in TP53 (n = 26; 54%), RAS (n = 23; 48%), SMAD4 (n = 5; 10%), FBXW7 (n = 3; 6%), and BRAF (n = 2; 4%). ctDNA+/+ was associated with worse RFS (median: ctDNA+/+, 6.0 months; ctDNA+/−, not reached; ctDNA−/−, 33.0 months; P = 0.001). Compared to ctDNA+/+, ctDNA+/− was associated with improved RFS [hazard ratio (HR) 0.24 (95% confidence interval (CI) 0.1–0.58)] and overall survival [HR 0.24 (95% CI 0.08–0.74)]. Adverse somatic mutations were not associated with survival. After adjustment for prehepatectomy chemotherapy, synchronous disease, and ≥2 CLM, ctDNA+/− and ctDNA−/− were independently associated with improved RFS compared to ctDNA+/+ (ctDNA+/−: HR 0.21, 95% CI 0.08–0.53; ctDNA−/−: HR 0.21, 95% CI 0.08–0.56).

Conclusions:

Perioperative ctDNA dynamics are associated with survival, identify patients with high recurrence risk, and may be used to guide treatment decisions and surveillance after hepatectomy for patients with CLM.
In vivobiomechanical assessment of iridial deformations and muscle contractions in human eyes
Authors: Safa Babak N. , Bahrani Fard Mohammad Reza , Ethier C. Ross
Published: July 2022

The iris is a muscular organ whose deformations can cause primary angle-closure glaucoma (PACG), a leading cause of blindness. PACG risk assessment does not consider iridial biomechanical factors, despite their expected influence on iris deformations. Here, we exploited an existing biometric dataset consisting of near-infrared movies acquired during the pupillary light reflex (PLR) as a unique resource to study iris biomechanics. The PLR caused significant (greater than 100%) and essentially spatially uniform radial strains in the irisin vivo, consistent with previous findings. Inverse finite-element modelling showed that sphincter muscle tractions werecafivefold greater than iridial stroma stiffness (range 4- to 13-fold, depending on sphincter muscle size). This muscle traction is greater than has been previously estimated, which may be due to methodological differences and/or to different patient populations in our study (European descent) versus previous studies (Asian); the latter possibility is of particular interest due to differential incidence rates of PACG in these populations. Our methodology is fast and inexpensive and may be a useful tool in understanding biomechanical factors contributing to PACG.
Intra-seasonal variation in feeding rates and diel foraging behaviour in a seasonally fasting mammal, the humpback whale
Authors: Nichols Ross C. , Cade David E. , Kahane-Rapport Shirel , Goldbogen Jeremy , Stimpert Alison , Nowacek Douglas , Read Andrew J. , Johnston David W. , Friedlaender Ari
Published: July 2022

Antarctic humpback whales forage in summer, coincident with the seasonal abundance of their primary prey, the Antarctic krill. During the feeding season, humpback whales accumulate energy stores sufficient to fuel their fasting period lasting over six months. Previous animal movement modelling work (using area-restricted search as a proxy) suggests a hyperphagic period late in the feeding season, similar in timing to some terrestrial fasting mammals. However, no direct measures of seasonal foraging behaviour existed to corroborate this hypothesis. We attached high-resolution, motion-sensing biologging tags to 69 humpback whales along the Western Antarctic Peninsula throughout the feeding season from January to June to determine how foraging effort changes throughout the season. Our results did not support existing hypotheses: we found a significant reduction in foraging presence and feeding rates from the beginning to the end of the feeding season. During the early summer period, feeding occurred during all hours at high rates. As the season progressed, foraging occurred mostly at night and at lower rates. We provide novel information on seasonal changes in foraging of humpback whales and suggest that these animals, contrary to nearly all other animals that seasonally fast, exhibit high feeding rates soon after exiting the fasting period
Surface damage from perpendicular and oblique bullet impacts in stone
Authors: Campbell Oliver , Blenkinsop Tom , Gilbert Oscar , Mol Lisa
Published: July 2022

Controlled experiments were conducted to investigate the surface damage caused by perpendicular and oblique impacts of bullets into sandstone and limestone targets. Individual bullets fired in conditions simulating modern rifles at typical combat distances excavated craters with diameters from 22 to 74 mm and depths from 3 to 24 mm. Limestone target craters were up to twice as large and deep as those in sandstone. These craters have a complex shape consisting of a central excavation surrounded by a shallow dish, compared to the simple bowl shape of most sandstone impacts. Radial fractures extending to the edge of the target block were common in limestone targets. Impacts at an angle of 45° to the surface in both rock types result in asymmetric craters. Two common types of intermediate cartridge (ammunition) were compared: the steel-tipped 5.56 × 45 mm NATO projectile generally produced larger and deeper craters than the 7.62 × 39 mm projectile that is commonly fired from AK-47 rifles, despite having approximately half the mass of the latter. These results characterize the sort of damage that can be expected at many sites of cultural significance involved in contemporary conflict zones, and have important implications for their conservation: for example building stone with low tensile strength is likely to sustain more damage and be at risk of greater deterioration.
The risk of death in newborn businesses during the first years in market
Authors: Prieto Faustino , Sarabia José María , Calderín-Ojeda Enrique
Published: July 2022

In this paper, we analysed how business age and mortality are related during the first years of life, and tested the different hypotheses proposed in the literature. For that, we used data on US business establishments, with 1-year resolution in the range of age of 0–5 years, in the period 1978–2019, published by the US Census Bureau. First, we explored the adaptation of classical techniques of survival analysis (the life table and Peto–Turnbull methods) to business survival analysis. Then, we considered nine parametric probabilistic models, most of them well known in reliability analysis and in the actuarial literature, with different shapes of the hazard function, that we fitted by maximum-likelihood method and compared with the Akaike information criterion. Our findings show that newborn firms seem to have a decreasing failure rate with age during the first 5 years in market, with the exception of the first months of some years in which the risk can rise.
Shewanella putrefaciens: a rare cause of purulent otorrhea !
Authors: BENAISSA ELMOSTAFA , Maleb Adil , Elouennass Mostafa
Published: July 2022

Shewanella is a genus of the family Shewanellaceae which includes Gram-negative, non-fermentative, motile and oxidase-positive bacilli. Human infections are rare, but have been furthermore reported in recent years, including bacteremia and skin and soft tissue infections. We report the first case in Morocco of a purulent otorrhea caused by Shewanella putrefaciens occurring in a 25-year-old girl who is immunocompetent, afebrile and without deterioration of the general condition, with a notion of swimming at the beach and also describe the bacteriological characteristics of and antibiotic susceptibility results for the isolate.
Integrative analysis of viral entry networks and clinical outcomes identifies a protective role for spironolactone in severe COVID-19
Authors: Cousins Henry , Kline Adrienne Sarah , Wang Chengkun , Qu Yuanhao , Wang Mengdi , Altman Russ , Luo Yuan , Cong Le
Published: July 2022

Treatment strategies that target host entry factors have proven an effective means of impeding viral entry in HIV and may be more robust to viral evolution than drugs targeting viral proteins directly. High-throughput functional screens provide an unbiased means of identifying genes that influence the infection of host cells, while retrospective cohort analysis can measure the real-world, clinical potential of repurposing existing therapeutics as antiviral treatments. Here, we combine these two powerful methods to identify drugs that alter the clinical course of COVID-19 by targeting host entry factors. We demonstrate that integrative analysis of genome-wide CRISPR screening datasets enables network-based prioritization of drugs modulating viral entry, and we identify three common medications (spironolactone, quetiapine, and carvedilol) based on their network proximity to putative host factors. To understand the drugs’ real-world impact, we perform a propensity-score-matched, retrospective cohort study of 64,349 COVID-19 patients and show that spironolactone use is associated with improved clinical prognosis, measured by both ICU admission and mechanical ventilation rates. Finally, we show that spironolactone exerts a dose-dependent inhibitory effect on viral entry in a human lung epithelial cell line. Our results suggest that spironolactone may improve clinical outcomes in COVID-19 through tissue-dependent inhibition of viral entry. Our work further provides a potential approach to integrate functional genomics with real-world evidence for drug repurposing.
Clinical advancement of patients infected with SARS-CoV-2 Omicron variant in Shanghai, China
Authors: Shao Jiasheng , Fan Rong , Zhang Tiejun , Lee Catherine , Huang Xuyuan , Wang Fei , Liang Haiying , Jin Ye , Jiang Ying , Gu Yanhua , Hu Jianrong , Huang Gang
Published: July 2022

Background

Studies on the Omicron variant infection have generally been restricted to descriptions of its initial clinical and epidemiological characteristics. We investigated the timeline-related advancement in individuals with Omicron variant.

Methods

We conducted a retrospective, single-centered study including 226 laboratory-confirmed cases with Omicron variant between April 6th and May 11th, 2022 in Shanghai, China. Final date of follow-up was May 30, 2022.

Results

Among 226 enrolled patients, the median age was 52 years old, and 118 (52.2%) were female. The duration from onset of symptoms to hospitalization was 3 days (interquartile range [IQR]: 2-4 days) for symptomatic patients. Cough occurred in 168 patients (74.3%). The median interval to negative reverse-transcriptase PCR tests of nasopharynx swab was 10 days ([IQR]: 8-13 days). No radiographic progressions were found in 196 patients on the 7th day after onset of symptoms. The median duration of fever in all participants was 5 days (IQR: 4–6 days). The median PCR conversion time of Paxlovid-treated patients was 8 days (IQR: 7-10 days) compared with that of Lianhuaqingwen (10 days, IQR: 8-13 days) (p=0.00056). Booster vaccination can significantly decrease the severity of Omicron infection when compared with unvaccinated, partially or fully vaccinated patients (p=0.009). The median time of PCR conversion in individuals aged under 14 recovered significantly faster than older patients (median 8 days versus 11 days, P < 0.0001). In multivariate logistic analysis, erythrocyte sedimentation rate (ESR) (OR=1.05) was independently related to the severity of the infection.

Conclusions

The majority clinical symptoms of Omicron infection were not severe. Early and aggressive administration of Paxlovid can significantly reduce the PCR conversion time. Booster vaccination should also be highly recommended in population over 14 years old.
Quantitative G6PD point-of-care test can be used reliably on cord blood to identify male and female newborns at increased risk of neonatal hyperbilirubinaemia: a mixed method study
Authors: Bancone Germana , Gilder Mary Ellen , Win Elsie , Gornsawun Gornpan , Penpitchaporn Penporn , Moo Paw Khu , Archasuksan Laypaw , Wai Nan San , Win Sylverine , Aung Ko Ko , Hashmi Ahmar , Hanboonkunupakarn Borimas , Nosten Francois , Carrara Verena I , McGready Rose
Published: July 2022

Introduction

New point-of-care (POC) quantitative G6PD testing devices developed to provide safe radical cure for P. vivax malaria may be used to diagnose G6PD deficiency in newborns at risk of severe neonatal hyperbilirubinaemia, improving clinical care, and preventing related morbidity and mortality. Methods: We conducted a mixed-methods study analyzing technical performance and usability of the “STANDARD G6PD” Biosensor when used by trained midwives on cord blood samples at two rural clinics on the Thailand-Myanmar border.

Results

In 307 cord blood samples, the Biosensor had a sensitivity of 1.000 (95%CI 0.859-1.000) and a specificity of 0.993 (95% CI 0.971-0.999) as compared to gold standard spectrophotometry to diagnose G6PD deficient newborns using a receiving operator characteristic (ROC) analysis-derived threshold of ≤4.8IU/gHb. The Biosensor had a sensitivity of 0.727 (95%CI: 0.498-0.893) and specificity of 0.933 (95%CI: 0.876-0.969) for 30-70% activity range in females using ROC analysis-derived range of 4.9 to 9.9IU/gHb. These thresholds allowed identification of all G6PD deficient neonates and 80% of female neonates with intermediate phenotypes.

Need of phototherapy treatment for neonatal hyperbilirubinaemia was higher in neonates with deficient and intermediate phenotypes as diagnosed by either reference spectrophotometry or Biosensor.

Focus group discussions found high levels of learnability, willingness, satisfaction, and suitability for the Biosensor in this setting. The staff valued the capacity of the Biosensor to identify newborns with G6PD deficiency early (“We can know that early, we can counsel the parents about the chances of their children getting jaundice”) and at the POC, including in more rural settings (“Because we can know the right result of the G6PD deficiency in a short time. Especially for the clinic which does not have a lab”). Conclusions: The Biosensor is a suitable tool in this resource-constrained setting to identify newborns with abnormal G6PD phenotypes at increased risk of neonatal hyperbilirubinaemia.
The association between diabetes and mortality among patients hospitalized with COVID-19: Cohort Study of Hospitalized Adults in Ontario, Canada and Copenhagen, Denmark
Authors: Bogler Orly , Raissi Afsaneh , Colacci Michael , Beaman Andrea , Biering-Sørensen Tor , Cressman Alex , Detsky Allan , Gosset Alexi , Højbjerg Lassen Mats , Kandel Chris , Khaykin Yaariv , Barbosa David , Shaw Lauren Lapointe , MacFadden Derek R. , Pearson Alexander , Perkins Bruce , Rothman Kenneth J. , Skaarup Kristoffer Grundtvig , Weagle Rachael , Yarnell Chris , Sholzberg Michelle , Hodzic-Santor Bena , Lovblom Erik , Zipursky Jonathan , Quinn Kieran L. , Fralick Mike
Published: July 2022

Importance

Diabetes has been reported to be associated with an increased risk of death among patients with COVID-19. However, available studies lack detail on COVID illness severity and measurement of relevant comorbidities.

Design, Setting, and Participants

We conducted a multicenter, retrospective cohort study of patients over the age of 18 years who were hospitalized with COVID-19 between January 1, 2020 and November 30, 2020 in Ontario, Canada and Copenhagen, Denmark. Chart abstraction emphasizing co-morbidities and disease severity was performed by trained research personnel. The association between diabetes and death was measured using Poissson regression.

Main Outcomes and Measures

within hospital 30-day risk of death.

Results

Our study included 1018 hospitalized patients with COVID-19 in Ontario and 305 in Denmark, of whom 405 and 75 patients respectively had pre-existing diabetes. In both Ontario and Denmark, patients with diabetes were more likely to be older, have chronic kidney disease, cardiovascular disease, higher troponin levels, and to receive antibiotics compared with adults who did not have diabetes. In Ontario, the crude mortality rate ratio among patients with diabetes was 1.60 [1.24 – 2.07 95% CI] and in the adjusted regression model was 1.19 [0.86 – 1.66 95% CI]. In Denmark, the crude mortality rate ratio among patients with diabetes was 1.27 (0.68 – 2.36 95% CI) and in the adjusted model was 0.87 (0.49 – 1.54 95% CI)]. Meta-analyzing the two rate ratios from each region resulted in a crude mortality rate ratio of 1.55 (95% CI 1.22,1.96) and an adjusted mortality rate ratio of 1.11 (95% CI 0.84, 1.47).

Conclusions

Presence of diabetes was not strongly associated with in-hospital COVID mortality independent of illness severity and other comorbidities.
Caregiving in a Tertiary Health Institution in North Central Nigeria: Support Types and Financial Burden
Authors: Akande Oluwatosin Wuraola , Fasiku Mojirola Martina , Bolarinwa Oladimeji Akeem , Akande Tanimola Makanjuola
Published: July 2022

Background

Caregivers play an important role in informal patient management. Identification of the support types and the challenges faced by caregivers will provide information on strategies to ease this burden. This study aimed to describe the support types and financial burden among caregivers in a tertiary hospital in North Central Nigeria.

Methods

This was a cross-sectional study conducted among caregivers of in-patients admitted in a tertiary hospital in North Central Nigeria. Data was collected using a pre-tested interviewer-administered questionnaire. Data was analysed using the Statistical Package for Social Sciences package version 23. Results were reported in frequencies and proportions, and presented in prose, tables and charts.

Results

A total of 400 caregivers were recruited. Mean age was 38.32 ± 12.82 years and most (66.0%) were females. Caregivers supported their patients by running errands (96.3%) and 85.3% reported caregiving as stressful. The reported errands were purchase of medications (92.3%), supply of non-medical needs (63.3%), submission of laboratory samples and collection of results (52.3%) and service payment (47.5%). About two thirds (63.2%) reported loss of income while caregiving and about half (50.8%) provided financial support to the patients.

Conclusion

This study suggests that majority of caregivers experience significant physical and financial burden while caregiving. This burden can be eased off by the simplification of payment and laboratory processes, and employment of more staff to support patients admitted in the wards. The financial burden experienced by caregivers reinforces the need to encourage more Nigerians to enrol in a health insurance scheme.
AI-based image quality assessment in CT
Authors: Edenbrandt Lars , Trägårdh Elin , Ulén Johannes
Published: July 2022

Medical imaging, especially computed tomography (CT), is becoming increasingly important in research studies and clinical trials and adequate image quality is essential for reliable results. The aim of this study was to develop an artificial intelligence (AI)-based method for quality assessment of CT studies, both regarding the parts of the body included (i.e. head, chest, abdomen, pelvis), and other image features (i.e. presence of hip prosthesis, intravenous contrast and oral contrast).

Approach

1, 000 CT studies from eight different publicly available CT databases were retrospectively included. The full dataset was randomly divided into a training (n= 500), a validation/tuning (n= 250), and a testing set (n= 250). All studies were manually classified by an imaging specialist. A deep neural network network was then trained to directly classify the 7 different properties of the image.

Results

The classification results on the 250 test CT studies showed accuracy for the anatomical regions and presence of hip prosthesis in the interval 98.4% to 100.0%. The accuracy for intravenous contrast was 89.6% and for oral contrast 82.4%.

Conclusions

We have shown that it is feasible to develop an AI-based method to automatically perform a quality assessment regarding if correct body parts are included in CT scans, with a very high accuracy.