bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunohistochemical Expression Status of p53, CD44v9, and Ki-67 in a Series of Fallopian Tube Lesions of High-grade Serous Carcinoma
Authors: Sugimoto Sumire , Uchiyama Tomoko , Kawahara Naoki , Ohbayashi Chiho , Kobayashi Hiroshi
Published: February 2021

Pelvic high-grade serous carcinoma (HGSC) has been postulated to arise via a stepwise accumulation of (epi)genetic alterations from normal epithelium to secretory cell outgrowth (SCOUT), p53 signature, and serous tubal intraepithelial carcinoma (STIC) to invasive HGSC. The aim of this study is to investigate alterations in p53 and CD44v9 expression and the status of Ki-67 labeling index in a series of fallopian tube lesions of HGSC patients. A total of 45 specimens were analyzed in 16 patients with HGSC, and their lesions were categorized as follows: morphologically normal fallopian tube epithelium (FTE, n=6 samples), SCOUT (n=5), p53 signature (n=4), dormant STIC (n=8), active STIC (n=6), and HGSC (n=16). Morphologic features and immunohistochemical expression patterns of the p53 protein, CD44v9 protein, and Ki-67 antigen were blindly evaluated by 2 pathologists. Increased nuclear p53 protein accumulation was observed in p53 signature, dormant STIC, active STIC and HGSC compared with normal FTE and SCOUT (P<0.001). Immunohistochemistry scores of CD44v9 protein expression were significantly higher in normal FTE, SCOUT, and p53 signature than in dormant STIC, active STIC, and HGSC (P<0.001). Both active STIC and HGSC had significantly higher Ki-67 labeling indices than normal FTE, SCOUT, p53 signature and dormant STIC (P<0.001). CD44v9 loss contributes to the stepwise progression of p53 signature to dormant STIC. In conclusion, p53 mutation followed by CD44v9 loss may be involved in the evolution of STIC, which may confer positive clonal selection with a growth and survival advantage.
Mental Health of Medical Staff During the Coronavirus Disease 2019 Pandemic: A Systematic Review and Meta-Analysis
Authors: Yan Haohao , Ding Yudan , Guo Wenbin
Published: February 2021

Objective

This study aimed to quantify the prevalence of the adverse mental health outcomes in medical staff working in the hospital settings during the coronavirus disease 2019 (COVID-19) pandemic and explore the relative distribution of anxiety and depressive symptoms.

Methods

PubMed, EMBASE, China National Knowledge Infrastructure, WANFANG DATA, and VIP Database for Chinese Technical Periodicals were searched for articles published from January 1, 2019, to April 19, 2020. The prevalence estimates of adverse mental health symptoms in medical staff were pooled using the random-effects model.

Results

A total of 35 articles and data of 25,343 medical staff were used in the final analysis. The pooled prevalence estimates in medical staff during the COVID-19 pandemic were as follows (ordered from high to low): fear-related symptoms, 67% (95% confidence interval [CI] = 61%–73%); high levels of perceived stress, 56% (95% CI = 32%–79%), anxiety symptoms, 41% (95% CI = 35%–47%); insomnia, 41% (95% CI = 33%–50%); posttraumatic stress disorder symptoms, 38% (95% CI = 34%–43%); depressive symptoms, 27% (95% CI = 20%–34%); and somatic symptoms, 16% (95% CI = 3%–36%). The subgroup analysis revealed that the prevalence estimates of fear-related symptoms were consistently high.

Conclusions

Medical staff during the COVID-19 epidemic have a high prevalence of adverse mental health symptoms. Data-based strategies are needed to optimize mental health of medical staff and other health care professionals during times of high demand such as the COVID-19 and other epidemics.

PROSPERO Registration: CRD42020182433.
Medication Safety in Mental Health Hospitals: A Mixed-Methods Analysis of Incidents Reported to the National Reporting and Learning System
Authors: Alshehri Ghadah H. , Keers Richard N. , Carson-Stevens Andrew , Ashcroft Darren M.
Published: February 2021

Background

Medication safety incidents commonly occur in mental health hospitals. There is a need to improve the understanding of the circumstances that are thought to have played a part in the origin of these incidents to design safer systems to improve patient safety.

Aim

This study aimed to undertake a mixed-methods analysis of medication safety incidents reported to the National Reporting and Learning System in England and Wales in 2010 to 2017.

Method

Quantitative analyses of anonymized medication safety incidents occurring in mental health hospitals that were reported to the National Reporting and Learning System during an 8-year period were undertaken to characterize their type, severity, and the medication(s) involved. Second, a content analysis of the free-text reports associated with all incidents of at least moderate harm severity was undertaken to identify the underlying contributory factors.

Results

Overall, 94,134 medication incident reports were examined, of which 10.4% (n = 9811) were reported to have resulted in harm. The 3 most frequent types of reported medication incidents involved omission of medication (17,302; 18.3%), wrong frequency (11,882; 12.6%), and wrong/unclear dose of medication (10,272; 10.9%). Medicines from the central nervous system (42,609; 71.0%), cardiovascular (4537; 7.6%), and endocrine (3669; 6.1%) medication classes were the most frequently involved with incidents. Failure to follow protocols (n = 93), lack of continuity of care (n = 92), patient behaviors (n = 62), and lack of stock (n = 51) were frequently reported as contributory factors.

Conclusions

Medication incidents pose an enduring threat to patient safety in mental health hospitals. This study has identified important targets that can guide the tailored development of remedial interventions.
Cross-Cultural Adaptation, Validation, and Piloting of the Patient Reported Experiences and Outcomes of Safety in Primary Care Questionnaire for Its Use in Spain
Authors: Serrano-Ripoll María J. , Llobera Joan , Valderas José M. , de Labry Lima Antonio Olry , Fiol-deRoque María A. , Ripoll Joana , Ricci-Cabello Ignacio
Published: February 2021

Objective

This study aimed to cross-culturally adapt, validate, and pilot the Patient Reported Experiences and Outcomes of Safety in Primary Care questionnaire for its use in Spain.

Methods

After setting up an expert panel to determine its content validity, the questionnaire was translated and back-translated, and subjected to cognitive testing. The questionnaire was piloted in a cross-sectional study in 10 primary health care centers in Spain. Fifty patients per center completed the questionnaire while waiting for an appointment. We estimated (i) the acceptability of the questionnaire (response rate), (ii) scores distribution (floor and ceiling effects), (iii) internal consistency (Cronbach α), and (iv) construct validity (exploratory factor analyses and correlation between scales). To examine patients’ evaluations of patient safety, we followed a mixed-methods approach: (i) statistical analyses at the scale and item levels based on responses to standardized items and (ii) qualitative content analysis based on responses to open-ended questions.

Results

Complete data were collected from 493 patients (participation rate, 77%). A ceiling effect was observed for 3 scales (“safety problems,” “harm severity,” “harm needs”). The internal consistency was adequate (α > 0.7) for the majority of scales. Exploratory factor analysis and correlation between scales suggested an appropriate construct validity. Two hundred twenty-six (45.8%) respondents experienced at least 1 safety problem, and 109 (23.2%) reported harm in the previous 12 months.

Conclusions

The multidimensional primary health care patient safety instrument Patient Reported Experiences and Outcomes of Safety in Primary Care is now available for its use in Spain. Initial testing demonstrates its potential for use in primary care. Future developments will further address its use in actual clinical practice.
The Trigger Tool Method for Routine Pharmacovigilance: A Retrospective Cohort Study of the Medical Records of Hospitalized Geriatric Patients
Authors: Marseau Floriane , Prud’Homm Joaquim , Bouzillé Guillaume , Polard Elisabeth , Oger Emmanuel , Somme Dominique , Osmont Marie-Noëlle , Scailteux Lucie-Marie
Published: February 2021

Objective

The main objective was to assess the feasibility of the trigger tool method for the retrospective detection of adverse drug reactions (ADRs) in the Rennes University Hospital. The secondary objective was to describe the performance of the method in terms of positive predictive values (PPVs) and severity or preventability of ADRs.

Methods

Using the Rennes University Hospital clinical data warehouse, pharmacovigilance experts performed a retrospective review of a random sample of 30 inpatient hospital medical records per month using the triggers “fall” and “delirium” to identify related ADRs among patients 65 years and older in 2018 in the geriatrics department. Using the Z test, we compared the proportion of medical records with a positive (identified) trigger related to an ADR, which were reviewed within 20 minutes using the reference of 50% reviewed within 20 minutes.

Results

Among the 355 medical records reviewed, 222 had at least 1 trigger and 98 at least 1 related ADR. Among the 222 positive trigger medical records, 99.6% were reviewed in under 20 minutes (P < 0.001). The pharmacovigilance assessment took 3 months. The PPVs reached 53.9% (46.0%–61.7%) for falls and 21.0% (14.3%–27.5%) for delirium. Among the ADRs, 80% were serious and 53% were preventable.

Conclusions

Given the low PPV of the triggers used and the considerable need for technical and human resources, the trigger tool method cannot be used as a routine tool at the pharmacovigilance center. However, it could be implemented occasionally for specific purposes such as monitoring the impact of risk minimization measures to prevent ADRs.
Advanced Medication Alert System Decreased Hospital-Based Outpatient Duplicated Medications: A Longitudinal Hospital Cohort Study
Authors: Kuo Yu-Chun , Cheng Shou-Hsia , Chiu Herng-Chia
Published: February 2021

Objectives

This study aimed to examine the associations between adoption of an advanced medication alert system and decreases in hospital-based outpatient duplicated medication rates in Taiwan.

Methods

The unit of analysis was the hospital. We merged the hospital medication alert system adoption survey data and Taiwan National Health Insurance outpatient claims data. The observation time was 1998 to 2011, divided into 5 periods (T1–T5). The analysis included 216 hospitals, and outcome variable was hospital-based outpatient duplicated medication rates. The system adoption time frame, hospital accreditation level, and number of drugs per prescription were defined as predicted variables. A generalized estimating equation regression model was used.

Results

Adoption of the advanced medication alert system gradually increased, such that 100% of medical centers and 84% of regional hospitals, but less than 50% of district hospitals, had systems by T5. The hospital-based outpatient duplicated medication rate continually decreased, from 29.8% to 11.2%. The generalized estimating equation model showed rates of duplicated medications of b = −8.44 at T2 and b = −17.88 at T5 (P < 0.001) compared with T1. Medical centers and regional hospitals demonstrated much lower duplication rates (b = −13.71, b = −6.82; P < 0.001) compared with district hospitals. Hospitals with more medications per prescription had higher duplication rates than did hospitals with fewer items.

Conclusions

Hospitals accredited at higher levels tended to have advanced medication alert systems. Hospitals that implemented advanced systems decreased hospital-based outpatient duplicated medications, avoiding a potential risk due to inappropriate medication use.
Clinical Utility of β-Amyloid PET Imaging in People Living With HIV With Cognitive Symptoms
Authors: Vera Jaime H. , Eftychiou Nicholas , Schuerer Matti , Rullmann Michael , Barthel Henryk , Sabri Osama , Gisslen Magnus , Zetterberg Henrik , Blennow Kaj , O'Brien Clara , Banerjee Sube , Dizdarevic Sabina
Published: February 2021

Background:

Imaging with β-amyloid (Aβ) positron emission tomography (PET) has the potential to aid the diagnosis of the cause of cognitive impairment affecting people living with HIV (PLWH) when neurodegenerative disorders are considered. We evaluated the clinical utility of [18F]Florbetaben (FBB) in PLWH with cognitive symptoms.

Methods:

Imaging with FBB PET was performed in 20 patients with cognitive concerns about dementia. Neuropsychological testing, plasma neurofilament light protein, plasma Aβ40, Aβ42, and cerebrospinal fluid Aβ42, tau, and HIV RNA were obtained. FBB PET images were assessed visually by 3 readers blinded to the clinical diagnosis and quantitatively by obtaining a composite cortical to cerebellar cortex standardized uptake value ratio (SUVR). FBB SUVR from 10 age-matched healthy controls was compared with SUVR of PLWH.

Results:

Most participants were men (90%) of white ethnicity (90%) with a median age (interquartile range) of 59 (43–79) years. Median CD4 count was 682 (74–1056). All patients were on combination antiretroviral therapy with plasma and cerebrospinal fluid HIV RNA <40 copies/mL. Fourteen patients had objective cognitive impairment including 2 who met clinical criteria for a diagnosis of dementia. No significant differences in composite SUVRs between PLWH and controls [mean (SD): 1.18 (0.03) vs. 1.16 (0.09);P= 0.37] were observed. Four patients were FBB+ with the highest SUVR in the posterior cingulate, superior temporal, and frontal superior lobe. Amyloid PET results contributed to a change in diagnosis and treatment for 10 patients.

Conclusion:

[18F]Florbetaben PET has potential as an adjunctive tool in the diagnosis of PLWH with cognitive impairment, increasing diagnostic certainty and optimizing management.
COVID-19 Burden and Risk Among People With HIV
Authors: Jones Deborah L. , Morgan Kristiana E. , Martinez Paola C , Rodriguez Violeta J. , Vazquez Andres , Raccamarich Patricia D. , Alcaide Maria L.
Published: February 2021

Background:

This study evaluated COVID-19 risk and burden among people with HIV (PWH) in a US city with high rates of HIV and SARS-CoV-2 transmissions and examined the interrelationship between psychosocial factors and COVID-19 risk and burden.

Setting:

Participants were drawn from an existing consent to contact database of PWH. Database candidates were PWH, adults older than 18 years, people who had received HIV care at the University of Miami HIV clinics, people who spoke English or Spanish, and people who had agreed to be contacted for future research.

Methods:

An adapted version of the Multicenter AIDS Cohort Study/Women's Interagency HIV Study Combined Cohort Study COVID-19 survey was telephonically administered, requiring 15–30 minutes.

Results:

Psychological stress was a predictor of COVID-19 burden (financial and social burden) and COVID-19 risk (health factors associated with an increased risk of severe health outcomes due to infection with COVID-19). Having a history of traumatic events was associated with increased COVID-19 risk, and stress was associated with increased COVID-19 burden and COVID-19 risk.

Conclusions:

Overall, results suggest that the intersection of the HIV and COVID-19 pandemics may be most profound among those who have experienced traumatic events; and traumatic events may be associated with heightened vigilance regarding illness and infection.
Prevalence of Type 2 and Type 1 Diabetes in Psoriatic Arthritis
Authors: Ciaffi Jacopo , Mele Giulio , Mancarella Luana , Brusi Veronica , Lisi Lucia , Faranda Cordella Jacopo , Lubrano Ennio , D'Angelo Salvatore , Meliconi Riccardo , Ursini Francesco
Published: February 2021

Objective

Psoriatic arthritis (PsA) is burdened by an increased susceptibility to cardiovascular diseases. Comorbid diabetes may represent one of the key factors contributing to this risk. The aim of our medical records review study was to investigate the prevalence of type 2 diabetes (T2D) and type 1 diabetes (T1D) in an Italian PsA cohort.

Methods

The clinical records of all patients consecutively seen at our clinic with a diagnosis of PsA during a 12-month period were reviewed to identify comorbid T2D or T1D. For comparison, a 1:1 age- and sex-matched group of individuals with noninflammatory diseases was recruited.

Results

The final study cohort comprised 408 patients. The prevalence of T2D was 7.8% (95% confidence interval, 5.6–10.8) in PsA and 4.4% in controls (95% confidence interval, 2.8–6.9; p = 0.04). Two cases (0.49%) of T1D were identified in the PsA cohort, whereas no cases were observed in controls. In a multivariate logistic regression model including age, disease duration, and body mass index (BMI) as covariates, increasing age (odds ratio [OR], 1.079; p = 0.006) and BMI (OR, 1.188; p = 0.011) but not PsA duration predicted being classified as having T2D. In a similar model accounting for age and BMI, average disease activity score including 28 joints and C-reactive protein showed a trend toward significance (OR, 1.639; p = 0.066).

Conclusions

In conclusion, our data provide further support to the emerging evidence of an increased risk of T2D in PsA patients. Cardiometabolic comorbidity represents a significant aspect of integrated arthritis management to improve long-term cardiovascular outcomes and to provide a comprehensive treatment.
Negative-Pressure Wound Therapy in the Prevention and Management of Complications From Prosthetic Breast Reconstruction
Authors: Chicco Maria , Huang Tony Chieh-Ting , Cheng Hsu-Tang
Published: February 2021

Background

Complications from prosthetic breast reconstruction are distressing for patients, and their management is challenging. For decades, negative-pressure wound therapy (NPWT) has been successfully used for the closure of complex wounds. This study analyzes the outcomes of NPWT use in the prevention and management of complications from prosthetic breast reconstruction.

Method

A systematic search of studies published until August 2020 was conducted using the PubMed/MEDLINE, EMBASE, and Ebscohost/CINAHL databases and using the following key words: “negative-pressure wound therapy,” “breast reconstruction,” and “prosthesis” (including breast implants and tissue expanders). Analyzed endpoints were outcomes of NPWT use in prosthetic breast reconstruction compared with conventional dressings. The methodological quality of included studies was assessed independently. Comparative studies were further meta-analyzed to obtain pooled odds ratios (ORs) describing the effectiveness of NPWT in prosthetic breast reconstruction.

Results/Discussion

Ten studies were included with a total of 787 patients (1230 breasts) undergoing prosthetic breast reconstruction with breast implants or tissue expanders. Three case-control studies focused on preventing breast wound complications. The meta-analysis of the 3 studies included 502 breasts receiving NPWT and 698 breasts receiving conventional wound care. The meta-analysis favored NPWT for less mastectomy flap necrosis (5.6% vs 14.3%; OR, 0.46; 95% confidence interval, 0.27 –0.77; P = 0.004; I
2 = 0%) and less overall wound complications (10.6% vs 21.1%; OR, 0.49; 95% confidence interval, 0.35–0.70; P < 0.00001; I
2 = 0%). In the management of nipple-areolar complex venous congestion, 1 case report demonstrated 85% rescue of nipple-areolar complex after using NPWT (−75 mm Hg) for a total of 12 days. In the management of periprosthetic infections, 2 case series used NPWT with instillation. It accelerated the treatment of infection and maintained the breast cavity for future reconstruction. Conventional NPWT also showed good salvage outcome in four studies.

Conclusions

Current evidence suggests that prophylactic use of NPWT in prosthetic breast reconstruction reduces the rate of overall wound complications and mastectomy flap necrosis. In the management of complications from prosthetic breast reconstructions, NPWT may be a promising option showing beneficial results. Additional high-quality trials are warranted to corroborate the findings of this systematic review.
Does the Initial Width of Cleft Lip Play a Role in the Occurrence of Immediate Local Complications Following Primary Cleft Lip Repairs?
Authors: Amoo Abiodun Taofeek , James Olutayo , Adeyemi Michael , Taiwo Abdurrazaq O. , Adeyemo Wasiu Lanre
Published: February 2021

Objective:

Among the several factors implicated in the occurrence of local surgical site complications following cleft lip repair is the initial width of the cleft. The aim of the study was to examine the effect of cleft width in the occurrence of immediate local surgical site complications.

Material and methods:

All consecutive subjects with diagnosis of unilateral or bilateral cleft lip with or without cleft palate who presented at the cleft clinic and satisfied the inclusion criteria were recruited in the study. The width of the cleft lip defect as adopted for the study was measured from the peak of the Cupid bow on the non-cleft side to a point where the white roll begins to thin out on the cleft side. Measurement was done using a Vernier Calliper. Surgery was performed under general anesthesia after which subjects were evaluated for the presence or absence of immediate local surgical site complications which included dehiscence, infection, and vermillion notching of the lip.

Results:

A total of 70 subjects consisting of 36 (51.4%) males and 34 (48.6%) females were included in the study. Mean age (±SD) was 9.0 ± (19.4) months with age range of 3 months to 13 years. The prevalence of early surgical site complications was 24.3%. The width of cleft above a critical level (14 mm) statistically correlate significantly with the occurrence of early surgical site complications (P = 0.048).

Conclusion:

This study showed that the width of cleft lip of and above critical level of 14 mm may be associated with a clinically significant risk of immediate local surgical site complications.
Hemifacial Microsomia: Clinical Features and Associated Anomalies
Authors: Allam Karam A.
Published: February 2021

Hemifacial microsomia (HFM) is the second most common congenital anomaly of the face after cleft lip and palate. There is a considerable variability in the extent and severity of affection of the bones and soft tissues of the face arising from these two arches. Different classification systems have been described for HFM with the mandible and/or the ear defects being key features needed for any classification system. Nowadays, the most widely used system is the orbital, mandibular, ear, facal nerve, soft tissue (OMENS) classification, later modified to the OMENS+ to include extracraniofacial manifestations.

The aim of this study was to review the demographic characteristics and clinical findings of a group of Egyptian patients with HFM and to correlate the findings with data retrieved from the literature.

Thirty-nine patients were identified and included in this study. Right side was predominantly affected in 19 patients (48.7%), 9 patients (23%) had left side affection (23%) and 11 patients (28.3%) had bilateral affection, with overall male-to-female ratio of 1:1.4. The majority of patients had a normal orbit (64%), mildly hypoplastic mandible with functioning temporomandibular joint (58% with type M1 or M2a), normal facial nerve (82%), and minimal to mild soft-tissue hypoplasia (52%). Significant ear deformity affected the bigger percentage of the patients (E3: 44%, E2: 14%)

The data demonstrate the phenotypic variability of HFM and suggest a degree of relationship among the components of HFM. Some epidemiological aspects and clinical findings in our study did not always parallel those reported in western literatures. Small sample size is the main limitation of the study. Further, and if possible multi-center, studies are recommended.
Alloplastic Temporomandibular Joint Reconstruction in Congenital Craniofacial Deformities
Authors: Hodzic Zlatan , Törnwall Jyrki , Leikola Junnu , Heliövaara Arja , Suojanen Juho
Published: February 2021

Temporomandibular joint (TMJ) reconstruction with alloplastic prosthesis is a commonly performed procedure, which can be used as a treatment for improving pathologic conditions affecting the TMJ. Depending of the severity of the condition, the patient's ability to eat can be impaired, which in turn can affect their quality of life. Several syndromes can affect the patient's facial features, and some of those also affect TMJ's. Use of alloplastic prosthesis in TMJ's affecting syndromes, by means of correcting TMJ conditions and mandibular deformities, is still rather uncommon. Purpose of our study is to review the use TMJ total prosthesis as a treatment modality for correcting TMJ conditions and the reconstruction of mandibular deformities in congenital syndromes affecting the facial features. This study consists of a retrospective cohort of patients treated with TMJ reconstruction with alloplastic prosthesis at the Helsinki University Hospital during the past decade. All subjects with congenital syndrome who underwent TMJ reconstruction were included the study. The cohort consisted of seven patients and ten joints treated. Temporomandibular joints affecting syndromes were Goldenhar syndrome, hemifacial macrosomia, Nager syndrome, and Treacher–Collins syndrome. The majority of the patients have had several previous operative treatments on the facial skeleton during their childhood, which in turn probably affected and compromised the TMJ surgery outcome. Mouth opening was sufficiently achieved as average maximal opening was 34 mm (range 24–42 mm) postoperatively. Temporomandibular joint reconstruction with alloplastic prosthesis can offer new tools and approaches for treatment of facial deformities in syndromes with craniofacial abnormalities. Impaired jaw functions and asymmetry can be addressed with the use of alloplastic prostheses, achieving sufficient mouth opening and restoring the symmetry of the lower facial skeleton.
Pancreas Preservation in Modified Histidine-lactobionate Solution Is Superior to That in University of Wisconsin Solution for Porcine Islet Isolation
Authors: Sakai-Yonaha Mayuko , Miyagi-Shiohira Chika , Kuwae Kazuho , Tamaki Yoshihito , Nishime Kai , Yonaha Tasuku , Saitoh Issei , Watanabe Masami , Noguchi Hirofumi
Published: February 2021

Background.

We previously reported that modified extracellular-type trehalose-containing Kyoto (MK) solution, which contains a trypsin inhibitor (ulinastatin), significantly improved the islet yield compared with University of Wisconsin (UW) preservation, which is the gold standard for organ preservation for islet isolation. In this study, we evaluated the efficiency of a modified histidine-lactobionate (MHL) solution in addition to UW or MK solution. The MHL solution has a high sodium-low potassium composition with low viscosity compared with the UW solution. Moreover, similar to MK solution, MHL solution also contains ulinastatin.

Methods.

Porcine pancreata were preserved in UW, MK, or MHL solution, followed by islet isolation. An optimized number (1500 IE) of isolated islets from each group were then transplanted into streptozotocin-induced diabetic mice.

Results.

The islet yield before and after purification was significantly higher in the MHL group than in the UW group. On the contrary, the islet yield before and after purification was not significantly different between the MHL and MK groups. Preserving the porcine pancreata in MHL solution improved the outcome of islet transplantation in streptozotocin-induced diabetic mice compared with that in UW solution.

Conclusions.

Pancreas preservation with MHL solution preserves islet function better than UW solution. The effect of MHL solution is similar to that of MK solution, suggesting that MHL solution can be used as an alternative to MK solution for pancreatic islet transplantation.
Validation of Cognitive Impairment in Combination With Physical Frailty as a Predictor of Mortality in Patients With Advanced Heart Failure Referred for Heart Transplantation
Authors: Aili Samira R. , De Silva Ricardo , Wilhelm Kay , Jha Sunita R. , Fritis-Lamora Rodrigo , Montgomery Elyn , Pierce Rachel , Lam Fiona , Brennan Xavier , Gorrie Natasha , Schnegg Bruno , Jabbour Andrew , Kotlyar Eugene , Muthiah Kavitha , Keogh Anne M. , Jansz Paul C. , Hayward Christopher , Macdonald Peter S.
Published: February 2021

Background.

The aim of this study was to validate our previous finding that frailty predicts early mortality in patients with advanced heart failure (AHF) and that including cognition in the frailty assessment enhances the prediction of mortality.

Methods.

Patients with AHF referred to our Transplant Unit between November 2015 and April 2020 underwent physical frailty assessment using the modified Fried physical frailty (PF) phenotype as well as cognitive assessment using the Montreal Cognitive Assessment to identify patients who were cognitively frail (CogF). We assessed the predictive value of the 2 frailty measures (PF ≥ 3 of 5 = frail; CogF ≥ 3 of 6 = frail) for pretransplant mortality.

Results.

Three hundred thirteen patients (233 male and 80 female; age 53 ± 13 y) were assessed. Of these, 224 patients (72%) were nonfrail and 89 (28%) were frail using the PF. The CogF assessment identified an additional 30 patients as frail: 119 (38%). Frail patients had significantly increased mortality as compared to nonfrail patients. Ventricular assist device and heart transplant-censored survival at 12 mo was 92 ± 2 % for nonfrail and 69 ± 5% for frail patients (P < 0.0001) using the CogF instrument.

Conclusions.

This study validates our previously published findings that frailty is prevalent in patients with AHF referred for heart transplantation. PF predicts early mortality. The addition of cognitive assessment to the physical assessment of frailty identifies an additional cohort of patients with a similarly poor prognosis.
Frailty in Lung Transplantation: Candidate Assessment and Optimization
Authors: Agarwal Ankita , Neujahr David C.
Published: February 2021

The concept of frailty has gained considerable interest in clinical solid-organ transplantation over the past decade. Frailty as a phenotypic construct to describe a patient’s risk from biologic stresses has an impact on posttransplant survival. There is keen interest in characterizing frailty in lung transplantation, both to determine which patients are suitable candidates for listing and also to prepare for their care in the aftermath of lung transplantation. Here, we review the current status of research on frailty in lung transplant candidates and recipients. This review will highlight areas of uncertainty for frailty in clinical lung transplantation that are likely to impact the state-of-the-art in the field for the next decade.
Trained Innate Immunity in Hematopoietic Stem Cell and Solid Organ Transplantation
Authors: Cunningham Kyle T. , Mills Kingston H.G.
Published: February 2021

Although significant progress has been made to improve short-term survival of transplant patients, long-term acceptance of allografts in solid organ and hematopoietic stem cell (HSC) transplantation is still a significant challenge. Current therapeutics for preventing or treating allograft rejection rely on potent immunosuppressive drugs that primarily target T cells of the adaptive immune response. Promising advances in transplant immunology have highlighted the importance of innate immune responses in allograft acceptance and rejection. Recent studies have demonstrated that innate immune cells are capable of mediating memory-like responses during inflammation, a term known as trained innate immunity. In this process, innate immune cells, such as macrophages and monocytes, undergo metabolic and epigenetic changes in response to a primary stimulus with a pathogen or their products that result in faster and more robust responses to a secondary stimulus. There is also some evidence to suggest that innate immune cells or their progenitors may be more anti-inflammatory after initial stimulation with appropriate agents, such as helminth products. Although this phenomenon has primarily been studied in the context of infection, there is emerging evidence to suggest that it could play a vital role in transplantation rejection and tolerance. Mechanisms of training innate immune cells and their progenitors in the bone marrow are therefore attractive targets for mediating long-term solid organ and HSC transplant tolerance. In this review, we highlight the potential role of proinflammatory and anti-inflammatory mechanisms of trained innate immunity in solid organ and HSC transplantation.
Improving Liver Graft Function Using CD47 Blockade in the Setting of Normothermic Machine Perfusion
Authors: Garcia-Aroz Sandra , Xu Min , Ahmed Ola , Hollingshead Joshua , Wang Xuanchuan , Banan Babak , Khan Adeel , Kang Liang-I , Zhang Zhengyan , Upadhya Gundumi , Manning Pamela , Lin Yiing , Chapman William C.
Published: February 2021

Background.

Toward the goal of using more livers for transplantation, transplant centers are looking to increase the use of organs from “marginal” donors. Livers from these donors, however, have been shown to be more susceptible to preservation and reperfusion injury.

Methods.

Using a porcine model of donation after circulatory death, we studied the use of antibody-mediated CD47 blockade to further improve liver graft function undergoing normothermic machine perfusion. Livers from 20 pigs (5 per group) were brought under either 30 or 60 min of warm ischemia time followed by the administration of CD47 monoclonal antibody (CD47mAb) treatment or immunoglobulin G control antibodies and 6 h of normothermic extracorporeal liver perfusion.

Results.

After 6 h of normothermic extracorporeal liver perfusion, CD47mAb-treated livers with 30 or 60 min warm ischemia time had significantly lower alanine transaminase levels and higher bile production compared with their respective control groups. Blockade of the CD47 signaling pathway resulted in significantly lower thrombospondin-1 protein levels, lower expression of caspase-3, and higher expression of phosphorylated extracellular signal-regulated kinase.

Conclusions.

These findings suggested that CD47mAb treatment decreases ischemia/reperfusion injury through CD47/thrombospondin-1 signaling downregulation and the presence of necrosis/apoptosis after reperfusion and could increase liver regeneration during normothermic perfusion of the liver.
Childhood disadvantage, neurocognitive development and neuropsychiatric disorders: Evidence of mechanisms
Authors: Yu Jing , Patel Reeya A. , Gilman Stephen E.
Published: February 2021

Purpose of review

Children living in socioeconomically disadvantaged households have excess risks of neurodevelopmental and neuropsychiatric problems. The purpose of this review is to synthesize evidence for mechanisms that may contribute to these excess risks.

Recent findings

The majority of the 60 studies included in our review focused on children's neurocognitive development and behavioural problems. About half conducted mediation analyses of factors in the family and neighbourhood environments, including access to resources (e.g. cognitive inputs within the home environment) and exposure to stressors (e.g. negative parenting practices), as well as neurobiological embedding of childhood disadvantage. In addition, many studies conducted moderation analyses of factors that were hypothesized to interact with (i.e. exacerbate or mitigate) the harmful effects of childhood disadvantage.

Many of the factors that contribute to the excess risk of neurodevelopmental and neuropsychiatric problems among children in disadvantaged households are potentially modifiable (e.g. cognitively stimulating materials, parental language input, cultural resources, parental stress and psychopathology, negative parenting, neighbourhood violence). If their causality is ultimately established, they could be targets for the prevention and reduction of disparities. The continued search for mechanisms should not detract from work to reduce and hopefully eliminate children's exposure to disadvantage.
The Functional Significance of Bacterial Predators
Authors: Hungate Bruce A. , Marks Jane C. , Power Mary E. , Schwartz Egbert , van Groenigen Kees Jan , Blazewicz Steven J. , Chuckran Peter , Dijkstra Paul , Finley Brianna K. , Firestone Mary K. , Foley Megan , Greenlon Alex , Hayer Michaela , Hofmockel Kirsten S. , Koch Benjamin J. , Mack Michelle C. , Mau Rebecca L , Miller Samantha N. , Morrissey Ember M. , Propster Jeff R. , Purcell Alicia M. , Sieradzki Ella , Starr Evan P. , Stone Bram W. G. , Terrer César , Pett-Ridge Jennifer
Published: February 2021

Predation structures food webs, influences energy flow, and alters rates and pathways of nutrient cycling through ecosystems, effects that are well documented for macroscopic predators. In the microbial world, predatory bacteria are common, yet little is known about their rates of growth and roles in energy flows through microbial food webs, in part because these are difficult to quantify. Here, we show that growth and carbon uptake were higher in predatory bacteria compared to non-predatory bacteria, a finding across 15 sites, synthesizing 82 experiments and over 100,000 taxon-specific measurements of element flow into newly synthesized bacterial DNA. Obligate predatory bacteria grew 36% faster and assimilated carbon at rates 211% higher than non-predatory bacteria. These differences were less pronounced for facultative predators (6% higher growth rates, 17% higher carbon assimilation rates), though high growth and carbon assimilation rates were observed for some facultative predators, such as members of the generaLysobacterandCytophaga, both capable of gliding motility and wolfpack hunting behavior. Added carbon substrates disproportionately stimulated growth of obligate predators, with responses 63% higher than non-predators for the Bdellovibrionales and 81% higher for the Vampirovibrionales, whereas responses of facultative predators to substrate addition were no different from non-predators. This finding supports ecological theory that higher productivity increases predator control of lower trophic levels. These findings also indicate that the functional significance of bacterial predators increases with energy flow, and that predatory bacteria influence element flow through microbial food webs.
Detecting microstructural deviations in individuals with deep diffusion MRI tractometry
Authors: Chamberland Maxime , Genc Sila , Tax Chantal M.W. , Shastin Dmitri , Koller Kristin , Raven Erika P. , Parker Greg D. , Hamandi Khalid , Gray William P. , Jones Derek K.
Published: February 2021

Most diffusion MRI (dMRI) studies of disease rely on statistical comparisons between large groups of patients and healthy controls to infer altered tissue state. Such studies often require data from a significant number of patients before robust inferences can be made, and clinical heterogeneity can greatly challenge their discriminative power. Moreover, for clinicians and researchers studying small datasets, rare cases, or individual patients, this approach is clearly inappropriate. There is a clear and unmet need to shift away from the current standard approach of group-wise comparisons to methods with the sensitivity for detection of altered tissue states at the individual level. This would ultimately enable the early detection and interpretation of microstructural abnormalities in individual patients, an important step towards personalised-medicine in translational imaging. To this end, Detect was developed to advance dMRI-based Tractometry towards single-subject analysis. By: 1) operating on the manifold of white matter pathways; and 2) learning normative microstructural features to better discriminate patients from controls, our framework captures idiosyncrasies in patterns along brain white matter pathways in the individual. This novel approach paves the way from traditional group-based comparisons to true personalised radiology, taking microstructural imaging from the bench to the bedside.
Outcomes of Percutaneous Tracheostomy for Patients with SARS-CoV-2 Respiratory Failure
Authors: Arnold Jason , Gao Catherine A. , Malsin Elizabeth , Todd Kristy , Argento A. Christine , Cuttica Michael , Coleman John M. , Wunderink Richard G. , Smith Sean B. ,   for the NU COVID Investigators
Published: February 2021

Background

SARS-CoV-2 can cause severe respiratory failure leading to prolonged mechanical ventilation. Data are just emerging about the practice and outcomes of tracheostomy in these patients. We reviewed our experience with tracheostomies for SARS-CoV-2 at our tertiary-care, urban teaching hospital.

Methods

We reviewed the demographics, comorbidities, timing of mechanical ventilation, tracheostomy, and ICU and hospital lengths-of-stay (LOS) in SARS-CoV-2 patients who received tracheostomies. Early tracheostomy was considered <14 days of ventilation. Medians with interquartile ranges (IQR) were calculated and compared with Wilcoxon rank sum, Spearman correlation, Kruskal-Wallis, and regression modeling.

Results

From March 2020 to January 2021, our center had 370 patients intubated for SARS-CoV-2, and 59 (16%) had percutaneous bedside tracheostomy. Median time from intubation to tracheostomy was 19 (IQR 17 – 24) days. Demographics and comorbidities were similar between early and late tracheostomy, but early tracheostomy was associated with shorter ICU LOS and a trend towards shorter ventilation. To date, 34 (58%) of patients have been decannulated, 17 (29%) before hospital discharge; median time to decannulation was 24 (IQR 19-38) days. Decannulated patients were younger (56 vs 69 years), and in regression analysis, pneumothorax was associated was associated with lower decannulation rates (OR 0.05, 95CI 0.01 – 0.37). No providers developed symptoms or tested positive for SARS-CoV-2.

Conclusions

Tracheostomy is a safe and reasonable procedure for patients with prolonged SARS-CoV-2 respiratory failure. We feel that tracheostomy enhances care for SARS-CoV-2 since early tracheostomy appears associated with shorter duration of critical care, and decannulation rates appear high for survivors.
Evaluation of COVID-19 as a risk factor for maternal-fetal and neonatal complications: protocol of a systematic review and meta-analysis of cohort and case-control studies
Authors: Bezerra Priscila , de Siqueira Barros Nogueira Fernanda Gabriella , dos Santos Alan Chaves , Lima Anna katharina Souza , Ribeiro Davi Emanuel , Silva Barbosa Elias Almeida , dos Santos Suellen Casado , de Carvalho Clístenes Crístian
Published: February 2021

Background

COVID-19 in pregnant women has been suggested to impair maternal-fetal and neonatal outcomes. We then designed the present systematic review with meta-analysis to evaluate the repercussion of such disease over maternal fetal and neonatal mortality, need for intensive care, way of delivery, premature delivery, birth weight, Apgar score, presence of intrauterine growth restriction (IGR), and presence of amniotic fluid change.

Methods

We will conduct a computerized search through MEDLINE/PubMed, LILACS/BIREME, Web of science, Biorxiv, Medrxiv, and Embase on July 23, 2020. We will include cohort and case-control studies fully reported comparing pregnant women with COVID-19 with those not affected by the disease for maternal fetal and neonatal mortality, need for intensive care, way of delivery, premature delivery occurrence, birth weight, Apgar scores, presence of intrauterine growth restriction, and presence of amniotic fluid change. Three doubles of reviewers will perform in duplicate and independently all steps on screening, risk of bias judgments, and data extraction with ability to discuss disagreements with supervising authors. Pooled effects will be estimated by both fixed and random-effects models and presented according to qualitative and quantitative heterogeneity assessment. Sensitivity analyses will be performed as well as a priori subgroup, meta-regression and multiple meta-regression analyses. We’ll also evaluate the risk of selective publication by assessing funnel plot asymmetry and the quality of the evidence by the application of the GRADE recommendations.

Discussion

This systematic review with meta-analysis aims to assess the repercussion of COVID-19 in pregnant women over maternal-fetal and neonatal outcomes and to help clinicians and health systems improve such population outcomes throughout the current pandemic.

Systematic review registration

This review protocol was also submitted to PROSPERO registration on February 9, 2021.
Vaccine Rollout Strategies: The Case for Vaccinating Essential Workers Early
Authors: Mulberry N. , Tupper P. , Kirwin E. , McCabe C. , Colijn C.
Published: February 2021

In planning for upcoming mass vaccinations against COVID-19, many jurisdictions have proposed using primarily age-based rollout strategies, where the oldest are vaccinated first and the youngest last. In the wake of growing evidence that approved vaccines are effective at preventing not only adverse outcomes, but also infection (and hence transmission of SARS-CoV-2), we propose that such age-based rollouts are both less equitable and less effective than strategies that prioritize essential workers. We demonstrate that strategies that target essential workers earlier consistently outperform those that do not, and that prioritizing essential work-ers provides a significant level of indirect protection for older adults. This conclusion holds across numerous outcomes, including cases, hospitalizations, Long COVID, deaths and net monetary benefit, and over a range of possible values for the efficacy of vaccination against infection. Our analysis focuses on regimes where the pandemic continues to be controlled with distancing and other measures as vaccination proceeds, and where the vaccination strategy is expected to last for over the coming 6-8 months — for example British Columbia, Canada. In such a setting with a total population of 5M, vaccinating essential workers sooner is expected to prevent over 200,000 infections, over 600 deaths, and to produce a net monetary benefit of over $500M.
Regression QSAR Models for Predicting HIV-1 Integrase Inhibitors
Authors: Xuan Christopher Ha Heng , Kion Lee Nung , Rahman Taufiq , San Hwang Siaw , Yam Wai Keat , Chee Xavier
Published: February 2021

The Human Immunodeficiency Virus (HIV) infection is a global pandemic that has claimed 33 million lives to date. One of the most efficacious treatment for naïve or pre-treated HIV patients is with the HIV integrase strand transfer inhibitors (INSTIs). However, given that HIV treatment is life-long, the emergence of HIV-1 strains resistant to INSTIs is an imminent challenge. In this work, we showed two best regression QSAR models that were constructed using a boosted Random Forest algorithmand a boosted K* algorithmto predict the pIC50values of INSTIs. Subsequently, the regression QSAR models were deployed against the Drugbank database for drug repositioning. The top ranked compounds were further evaluated for their target engagement activity using molecular docking studies and their potential as INSTIs evaluated from our literature search. Our study offers the first example of a large-scale regression QSAR modelling effort for discovering highly active INSTIs to combat HIV infection.