bluuebunny/crossref_metadata_2025 huggingface dataset:
Survival on Venoarterial Extracorporeal Membrane Oxygenation in Cardiogenic Shock: Which Lactate Is Most Useful?
Authors: Omar Hesham R. , Handshoe Jonathan W. , Tribble Thomas , Guglin Maya
Published: March 2021

Prognostic significance of elevated serum lactate in patients on venoarterial extracorporeal membrane oxygenation (ECMO) is widely known. Our objective was to study the utility of lactate measured at different points of time and lactate clearance in predicting the two study endpoints: successful ECMO weaning and hospital survival. Among 238 consecutive patients treated with ECMO, lactic acid was collected before initiating ECMO and then on days 1, 3, 5, and 10 while on ECMO. Out of our cohort, 129 (54.2%) were successfully weaned and 98 (41.2%) were discharged alive. Patients successfully weaned from ECMO had a significantly lower lactic acid level pre-ECMO (p = 0.001), at day 1 (p < 0.001), day 3 (p < 0.001), and day 5 (p = 0.001), compared with unsuccessfully weaned patients. Also, patients who survived hospitalization had significantly lower lactic acid pre-ECMO (p = 0.007), at day 1 (p < 0.001), day 3 (p = 0.001), and day 5 (p = 0.001), compared with those who died in-hospital. With regard to hospital survival, day 3 lactic acid was superior to pre-ECMO lactic acid (p = 0.0385), lactic acid on day 1, lactic acid reduction from pre-ECMO to day 1 (p = 0.0177) and from pre-ECMO to day 3 (p = 0.0361), and a day 3 lactic acid ≤ 1.7 meq/L was the optimal value that predicted hospital survival. On multivariable analysis, day 3 lactic acid independently predicted hospital survival after covariate adjustment (odds ratio [OR], 0.505; 95% confidence interval [CI], 0.290–0.880; p = 0.016). In conclusion, the absolute level of lactic acid while on ECMO support is more important for prognosis than a pre-ECMO level or the magnitude of decline from pre-ECMO to on-ECMO.
Inhaled gases as novel neuroprotective therapies in the postcardiac arrest period
Authors: Magliocca Aurora , Fries Michael
Published: March 2021

Purpose of review

The purpose of this review is to summarize recent advances about inhaled gases as novel neuroprotective agents in the postcardiac arrest period.

Recent findings

Inhaled gases, as nitric oxide (NO) and molecular hydrogen (H2), and noble gases as xenon (Xe) and argon (Ar) have shown neuroprotective properties after resuscitation. In experimental settings, the protective effect of these gases has been demonstrated in both in-vitro studies and animal models of cardiac arrest. They attenuate neuronal degeneration and improve neurological function after resuscitation acting on different pathophysiological pathways. Safety of both Xe and H2 after cardiac arrest has been reported in phase 1 clinical trials. A randomized phase 2 clinical trial showed the neuroprotective effects of Xe, combined with targeted temperature management. Xe inhalation for 24 h after resuscitation preserves white matter integrity as measured by fractional anisotropy of diffusion tensor MRI.

Inhaled gases, as Xe, Ar, NO, and H2 have consistently shown neuroprotective effects in experimental studies. Ventilation with these gases appears to be well tolerated in pigs and in preliminary human trials. Results from phase 2 and 3 clinical trials are needed to assess their efficacy in the treatment of postcardiac arrest brain injury.
The Epidemiology of Annular Pancreas in the United States
Authors: Alkhayyat Motasem , Bachour Salam , Abou Saleh Mohannad , Abureesh Mohammad , Almomani Ashraf , Simons-Linares C. Roberto , Mansoor Emad , Sandhu Dalbir , Bhatt Amit , Chahal Prabhleen
Published: March 2021

Background and Aims:

Annular pancreas is a rare congenital condition where the second part of the duodenum is encircled by pancreatic tissue. There is a scarcity of data on its natural history therefore, we aimed to evaluate the epidemiology of annular pancreas and identify underlying associations using a large database.

Methods:

A multi-institutional database (Explorys) was surveyed. A cohort of patients with a Systematized Nomenclature of Medicine—Clinical Terms diagnosis of “MRI, CT, EUS and/or ERCP” between April 2015 and April 2020 was identified. Subsequently a cohort of patients with history of “annular pancreas” was identified.

Results:

There were a total of 40,075,980 individuals in the database with 6,162,600 (15.38%) who had an magnetic resonance imaging, computed tomography, endoscopic retrograde cholangiopancreatography, and/or endoscopic ultrasound. There were 210 (3.4/100,000) had a diagnosis of annular pancreas. When compared with the control group, patients with annular pancreas were more likely to have a history of alcohol use, smoking, acute pancreatitis, chronic pancreatitis, gastritis, duodenitis, jaundice, and gastrointestinal outlet obstruction.

Conclusions:

This is the largest study evaluating the epidemiology of annular pancreas. We found the estimated prevalence rate of annular pancreas to be 3.4/100,000 in those who had abdominal imaging. Annular pancreas was more likely to be diagnosed in patients with symptoms pertaining to acute or chronic pancreatitis, biliary, and gastric outlet obstruction.
End-of-Life Care in Taiwan: Single-Center Retrospective Study of Modes of Death*
Authors: Wu En-Ting , Wang Ching-Chia , Huang Shu-Chien , Chen Chieh-Ho , Jou Shiann-Tarng , Chen Yih-Charng , Wu Mei-Hwan , Lu Frank Leigh
Published: March 2021

OBJECTIVES:

Medical advances and the National Health Insurance coverage in Taiwan mean that mortality in the PICU is low. This study describes change in modes of death and end-of-life care in a single center, 2011–2017.

SETTING:

Multidisciplinary PICU in a tertiary referral Children’s Hospital in Taiwan.

PATIENTS:

There were 316 deaths in PICU patients.

INTERVENTIONS:

Palliative care consultation in the PICU service occurred after the 2013 “Hospice Palliative Care Act” revision.

MEASUREMENTS AND MAIN RESULTS:

In the whole cohort, 22 of 316 patients (7%) were determined as “death by neurologic criteria”. There were 94 of 316 patients (30%) who had an event needing cardiopulmonary resuscitation within 24 hours of death: 17 of these patients (17/94; 18%) died after failed cardiopulmonary resuscitation without a do-not-resuscitate order, and the other 77 of 94 patients (82%) had a do-not-resuscitate order after cardiopulmonary resuscitation. Overall, there were 200 of 316 patients (63%) who had a do-not-resuscitate order and were entered into the palliative program: 169 of 200 (85%) died after life-sustaining treatment was limited, and the other 31 of 200 (15%) died after life-sustaining treatment was withdrawn. From 2011 to 2017, the time-trend in end-of-life care showed the following associations: 1) a decrease in PICU mortality utilization rate, from 22% to 7% (p < 0.001); 2) a decrease in use of catecholamine infusions after do-not-resuscitate consent, from 87% to 47% (p = 0.001), in patients having limitation in life-sustaining treatment; and 3) an increase in withdrawal of life-sustaining treatment, from 4% to 31% (p < 0.001).

CONCLUSIONS:

In our practice in a single PICU-center in Taiwan, we have seen that the integration of a palliative care consultation service, developed after the revision of a national “Palliative Care Act,” was associated with increased willingness to accept withdrawal of life-sustaining treatment and a lowered PICU care intensity at the end-of-life.
Mucosal immunity to severe acute respiratory syndrome coronavirus 2 infection
Authors: Fröberg Janeri , Diavatopoulos Dimitri A.
Published: March 2021

Purpose of review

Despite its crucial role in protection against viral infections, mucosal immunity has been largely understudied in the context of coronavirus disease 2019 (COVID-19). This review outlines the current evidence about the role of mucosal immune responses in the clearance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, as well as potential mucosal mechanisms of protection against (re-)infection.

Recent findings

The angiotensin-converting enzyme 2 cellular entry receptor for SARS-CoV-2 is most highly expressed in the upper respiratory tract and most SARS-CoV-2 shedding occurs from the upper respiratory tract. Viral shedding peaks early during infection around the onset of symptoms, before dropping rapidly in most individuals within 7 days of symptom onset, suggesting mucosal inhibition of viral infection. Serum and mucosal immunoglobulin G and immunoglobulin M responses were found to be strongly correlated in infected patients, whereas correlations were much weaker for immunoglobulin A (IgA). Mucosal IgA responses have been detected in infected cases in the absence of serum antibody responses, with mucosal antibody levels correlating strongly with virus neutralization. Bulk and single-cell RNA sequencing analysis of nasopharyngeal swabs and bronchoalveolar lavage samples of COVID-19 patients revealed the induction of mucosal chemokine and cytokine genes, complement pathways, Janus Kinase/Signal Transducer and Activator of Transcription signaling and cytotoxic T cells.

Although most clinical studies focus on antibodies and cellular immunity in peripheral blood, mucosal immune responses in the respiratory tract play a key role in the early restriction of viral replication and the clearance of SARS-CoV-2. Identification of mucosal biomarkers associated with viral clearance will allow monitoring of infection-induced immunity. Further studies are needed to understand how the systemic immunological endpoints measured in vaccination studies translate to mucosal protection against SARS-CoV-2 infection.
The returned traveler with neurologic manifestations: could my patient have a parasite?
Authors: Coyle Christina M.
Published: March 2021

Purpose of review

The present review focuses on parasitic infections of the central nervous system (CNS) that can affect the international traveler.

Recent findings

The epidemiology of imported parasitic infections is changing and clinicians are treating increasing numbers of returned travelers with parasitic infections in the CNS with which they are not familiar.

The epidemiology, life cycle, clinical manifestations, diagnosis, and treatment of parasites that affect the CNS will be discussed.
Inpatient Versus Outpatient Operative Management of Isolated Facial Fractures
Authors: Ali Barkat , Choi EunHo Eunice , Barlas Venus , Morrell Nathan T.
Published: March 2021

Background:

Patients with isolated facial fractures requiring operative fixation can be managed on an inpatient or outpatient basis. The goal of this study was to compare the safety of each approach using a large multi-institutional database.

Methods:

The American College of Surgeons’ National Surgical Quality Improvement Project was reviewed for facial fractures between 2005 and 2018. Groups were identified using inpatient and outpatient status as designated in the database. Patients who required additional procedures, concurrent procedures, or other emergency procedures were excluded. Descriptive statistics were used for group comparisons and logistic regression models were used to identify risk factors for complications.

Results:

We identified 4240 patients who underwent operative fixation of isolated facial fractures. The majority of these cases (67.9%) were done on an outpatient basis. Compared to those in the outpatient group, patients in the inpatient group were older, had more medical comorbidities, had higher wound class, and had higher American Society of Anesthesiologists class. Complication (5.9% versus 2.3%), reoperation (4.3% versus 1.7%), and readmission (5.7% versus 2.5%) rates were all higher in the inpatient group (P < 0.01). By logistic regression analysis, the odds ratios for complications, reoperation, and readmission were higher in the inpatient group. After adjusting for imbalanced preoperative patient characteristics, the increased risk of complications [odds ratio (OR) = 1.728, confidence interval (CI) 1.146–2.606, P = 0.01] and the increased risk of reoperation (OR = 2.302, CI 1.435–3.692, P = 0.01) in the inpatient group persisted, while the risk of readmission (OR = 1.684, CI 0.981–2.891, P = 0.06) no longer showed statistical significance between the inpatient and outpatient groups.

Conclusions:

Inpatient operative management of isolated facial fractures is associated with an increased risk of complications and a 2-fold increased risk of reoperation, though no increased risk of readmission.
Frontal Sinus Fractures: A Review on Etiology and Management Emphasizing Minimally Invasive and Endoscopic Techniques
Authors: Langlie Jake , Kim Minji , Thaller Seth R.
Published: March 2021

In spite of a long and tortuous history of the acute management of frontal sinus fractures, current optimal management remains steeped in controversy. These fractures are frequently produced by excessive forces and are often accompanied with other injuries. However, disruption of the nasofrontal duct persists as essential to maintain proper sinus function and should guide current management. Although there has never been any distinct procedure defining optimal outcomes, proper treatment is contingent on precise diagnosis culled from a complete history, physical examination, and imaging studies. This is further augmented by the surgeon's intraoperative findings. Reconstruction will ultimately rest on the degree of disruption of the anterior and posterior sinus walls, as well as the status and function of the nasofrontal ducts. For these reasons, current management continues to be challenging and evolving. Thus, this review will discuss the etiology and clinical presentation of frontal sinus fractures, the current complications arising in the subject, and the evolution of treatment options towards a more conservative and endoscopic approach to care.
A Composite Tissue Flap for Double-Eyelid Blepharoplasty in Asian Patients: A Retrospective Study
Authors: Fu Xiujun , Zhou Xianyu , Sun Di , Gu Chuan
Published: March 2021

Double-eyelid blepharoplasty, the procedure to create supratarsal crease, has been one of the most popular cosmetic operations in Asia for many years. This study aimed to assess the effectiveness and safety of a surgical procedure using a composite tissue flap for double-eyelid blepharoplasty. A surgical technique was introduced and patients having blepharoplasty with this technique from January 2017 to August 2019 were retrospectively studied. In this technique, a composite tissue flap consisted of the posterior septum and levator aponeurosis was formed and fixed with orbicularis oculi muscle and tarsus. The cosmetic outcomes, patient satisfaction, and complications from the documented medical records were analyzed. Eighty female and 1 male patients had blepharoplasty with the proposed technique and were followed up from 6 months to 42 months. Six patients were found to have mild blepharoptosis. As for cosmetic outcomes, 71patients were graded as good, 7 patients were graded as fair, and only 1 patient was graded as poor. Those patients who were not graded as good had visible scarring, shallow eyelid crease, or asymmetry. The overall patient satisfaction was as high as 95.1%. Mild hematoma formation occurred in 3 patients and no infection or blepharoptosis was observed. One patient complained of asymmetry and 2 patients complained of unilateral crease fading as the complications. The technique is effective to develop durable and natural-looking double eyelids with minimal complications. It could also be an option for mild ptotic patients who ask for double-eyelid blepharoplasty.
Ideal Nasal Radix Position in Fluctuating Facial Asymmetry
Authors: Hsu Fang-Yu , Yen Cheng-I , Chang Chun-Shin , Hsiao Yen-Chang
Published: March 2021

Background:

Augmentation rhinoplasty had become increasingly popular among Asians. Failure to recognize nasal deviation before surgery may engender unsatisfactory outcomes because the deviation becomes prominently visible after surgery due to the central position of the nose. Ideal nasal radix positioning has yet to be addressed. The head position affects facial asymmetry judgements; however, its effect on rhinoplasty has never been studied. This study determined the ideal nasal radix position in facial fluctuating asymmetry and investigated the effects of the natural head position (NHP) on nasal deviation perceptions.

Methods:

A survey was conducted to compare different head and nasal radix horizontal positions using images of patients who underwent augmentation rhinoplasty. Images were retouched using editing software to adjust the head and nasal radix positions. The survey was performed using questionnaires involving 3 plastic surgeons and 3 laypersons, who were asked to determine the presence of nasal deviation and select the ideal nasal radix position among the retouched images.

Results:

Twenty patients who underwent primary rhinoplasty were included in this study. The recognition of nasal deviation was significantly higher in the NHP than in the compensatory head position. The surgeons and the laypersons considered the midsagittal line the most appropriate position of the nasal radix.

Conclusions:

Facial analysis for augmentation rhinoplasty should be performed with the patient's head in the NHP to prevent nasal deviation masking. The preferred nasal radix position in facial fluctuating asymmetry is the midsagittal line.

Level of Evidence: Level V, descriptive study.
An Integrated Approach to the Management of Meningoencephalocoeles
Authors: Roumeliotis Grayson , Wiberg Akira , Thomas Gregory , Magdum Shailendra , Jayamohan Jayaratnam , Wall Steven , Johnson David
Published: March 2021

Meningoencephalocoeles are congenital herniations of meningeal and cerebral tissues through a cranial defect. They occur most commonly in South-East Asia, and are relatively rare amongst European ancestry populations, with an estimated prevalence of 1/40,000 live births. The treatment of congenital meningoencephalocoeles is primarily surgical and are best managed by dedicated multi-disciplinary craniofacial teams. The authors performed a retrospective case review of all primary meningoencephalocoeles managed in the Oxford University Hospitals NHS Foundation Trust between 1986 and 2012. Twenty-nine cases (13 frontal, 9 occipital, 2 parietal, and 5 basal) were included in this study. The median age at presentation was 11 months (range 0–60 years). Twenty-five cases presented with an external mass; 3 with recurrent meningitis and 1 with otorrhoea. Twenty-six cases underwent surgery, and 17 of these were managed by an integrated approach between 2 or more surgical specialties. Twenty out of 26 operations were performed via a transcranial approach. The authors describe a particularly complex case in order to highlight the challenges associated with management of meningoencephalocoeles, the surgical technique employed, and the importance of a multidisciplinary surgical approach. This is the largest reported case series of meningoencephalocoeles managed in a single hospital in the United Kingdom. Designated craniofacial units with access to multidisciplinary surgical specialties provide a safe and optimal setting for the management of meningoencephalocoeles.
Application of Proximal Splenic Vein Embolization to Interrupt Complicated Large Splenorenal Shunts in Adult Living Donor Liver Transplantation
Authors: Kang Woo-Hyoung , Moon Deok-Bog , Ko Gi-Young , Gwon Dong-Il , Yoon Young-In , Cho Hwui-Dong , Lee Sung-Gyu
Published: March 2021

Objective:

The aim of the present study is to evaluate efficacy and safety of proximal splenic vein embolization (PSVE) for liver transplant recipients having complicated large splenorenal shunts (SRS).

Background:

In adult living donor liver transplantation for a patient who has large splenorenal shunts (SRS), their interruption is utmost important to maintain adequate portal flow by avoidance of portal flow steal through the preexisting SRS. We effectively managed most of the recipients with surgical ligation and/or additional radiologic embolization using by intraoperative cine-portogram. However, when complete interruption is not achieved in a few recipients having complicated large SRS, it may leave a chance of lethal portal flow steal in the recipient afterward.

Methods:

PSVE was performed in 13 patients between April 2014 and November 2017. We performed a retrospective analysis of preoperative images, postoperative graft and recipient outcomes, and presence of isolated portal hypertension.

Results:

Ten patients underwent PSVE as an additional secondary method because of portal steal syndrome through the remaining SRS after surgical interruption and/or embolization, and 3 patients underwent PSVE only as a primary method of SRS interruption. In all 13 patients, portal steal on the final intraoperative cine-portogram completely disappeared after PSVE. All patients recovered with satisfactory regeneration of the partial liver graft without the reappearance of portosystemic collaterals, and there were no procedure-related complications.

Conclusions:

PSVE is an effective and safe procedure to secure adequate portal flow without portal steal for patients with complicated large SRS arising from multiple sites of the splenic vein or escaping to multiple terminal ends.
How Hospitals Can Save Lives and Themselves
Authors: Litvak Eugene , Keshavjee Shaf , Gewertz Bruce L. , Fineberg Harvey V.
Published: March 2021

COVID-19 has strained hospital capacity, detracted from patient care, and reduced hospital income. This article lays out a tested strategy that surgical and hospital leaders can use to overcome clinical and financial strain, emphasizing the experience at 2 leading North American medical centers. By classifying the time and resource needs of surgical patients and smoothing the flow of surgical admissions over all days of the week, hospitals can dramatically improve hospital efficiency, the quality of care and timely access to care for emergent and urgent surgeries. Through and beyond the time of COVID, smoothing the flow of surgical patients is a key means to restore hospital vitality and improve the care of all patients.
Genetic Variants Associated With Alzheimer Disease in the 22 Arab Countries
Authors: Al-Thani Hissa F. , Ahmad Muneera N. , Younes Salma , Zayed Hatem
Published: March 2021

Background and Aims:

Alzheimer disease (AD) is a progressive and complex neurodegenerative disease. Approximately 70% of AD risk is attributed to genetic risk factors, including variants in amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) genes. Several studies have revealed a considerable number of candidate loci and genes for AD among different ethnic populations. However, the outcomes of these studies have been inconsistent. In this study, we aimed to investigate the spectrum of variants that are associated with the onset and development of AD among 22 Arab countries.

Methodology:

We systematically searched 4 literature databases (Science Direct, Scopus, PubMed, and Web of Science) from the date of inception until July 2020 using various search terms to obtain all the reported genetic data on Arab AD cases.

Results:

In total, 18 studies were included, comprising a total of 2173 individuals, of whom 888 were clinically diagnosed AD patients and were genetically tested for genes and variants associated with AD. A total of 27 variants in 8 genes were found to be associated with AD. Of these variants, 17 were unique to the Arab population and 10 were shared with other ethnic groups.

Conclusions:

There is a dearth of studies on the genetics of AD in the Arab world. There seems to be distinctive genetic and clinical susceptibility profiles for Arab patients with AD.
Factors Affecting Ophthalmology Resident Choice to Pursue Neuro-Ophthalmology Fellowship Training
Authors: Solomon Alexander M. , Patel Vivek R. , Francis Courtney E.
Published: March 2021

Background:

The number of ophthalmology-trained residents applying to neuro-ophthalmology fellowships has not increased despite a trend toward seeking fellowship training after residency. This study sought to identify factors affecting the choice to pursue or not pursue neuro-ophthalmology fellowship training by graduating ophthalmology residents and recently graduated neuro-ophthalmology fellows.

Methods:

An anonymous survey was sent to Association of University Professors of Ophthalmology residency directors to distribute to post-graduate Year 4 (PGY4) ophthalmology residents graduating in either 2018 or 2019. A second anonymous survey was distributed via the North American Neuro-Ophthalmology Society (NANOS) Young Neuro-Ophthalmologists listserv to ophthalmology-trained neuro-ophthalmology fellows. A total of 147 respondents, including 96 PGY4 ophthalmology residents not going into neuro-ophthalmology and 51 practicing neuro-ophthalmologists are included.

Results:

The most common reasons for residents to choose to not pursue further training in neuro-ophthalmology included a stronger interest in other fields, types of patients seen, no intraocular surgery, and the assumption that it is a nonsurgical discipline. The leading factors influencing graduated, ophthalmology-trained fellows to choose neuro-ophthalmology included interest in the clinical diseases treated, interaction with other specialty fields, and a supportive NANOS culture. Interestingly, despite perceptions of graduating residents, two-thirds of the neuro-ophthalmologists surveyed perform surgery. There were no differences between the 2 groups with respect to the degree of exposure to neuro-ophthalmology in medical school, presence of a dedicated neuro-ophthalmology rotation in residency, or timing of the rotation.

Conclusions:

There are a variety of factors influencing decisions regarding pursuing neuro-ophthalmology fellowship among ophthalmology residents. The perceived lack of surgical opportunities in neuro-ophthalmology is a deterrent for many. However, a significant number of neuro-ophthalmologists continue to perform surgery, including intraocular surgery. Repeated exposure later in residency may provide an opportunity to reconsider the field and to re-emphasize opportunities to remain surgically involved as a neuro-ophthalmologist. Exposure to the practice patterns of recently graduated neuro-ophthalmologists offers residents in training excellent exposure to the contemporary practice of neuro-ophthalmology. Hence, ensuring trainees receive a balanced exposure to practicing neuro-ophthalmologists across the spectrum of seniority and scope of practice may promote greater interest among ophthalmology residents to pursue a career in neuro-ophthalmology.
Healthy diets, lifestyle changes and wellbeing during and after lockdown: Longitudinal evidence from the West Midlands
Authors: van Rens Thijs , Hanson Petra , Oyebode Oyinlola , Walasek Lukasz , Barber Thomas M. , Mujcic Redzo , Al-Khudairy Lena
Published: March 2021

Background

‘Lockdowns’ to control the spread of COVID-19 in the UK have affected many aspects of life, with concerns that they may have adversely affected diets. We aimed to examine (i) the effect of living in lockdown on fruit and vegetable consumption; (ii) whether any population subgroup was particularly adversely affected; (iii) the barriers and facilitators to a healthy diet in lockdown; and (iv) the effect of lockdown on secondary outcomes such as weight and mental wellbeing.

Methods

We conducted a mixed-method longitudinal study, involving an online survey of 1003 adults in the West Midlands, UK, 494 of whom were surveyed at two different points in time. Our first time point (T0: May 2020) was during stringent COVID-19 lockdown and the second (T1: September 2020) during a period of more relaxed restrictions. The survey included detailed quantitative questions about fruit and vegetable consumption; questions on physical activity, socio-demographic characteristics, BMI and wellbeing; and qualitative data collection about the reasons behind reported changes.

Results

We find no evidence for respondents decreasing their fruit and vegetable consumption during lockdown compared to afterwards. If anything, consumption of fruit and vegetables increased by about half a portion daily among women, particularly among those who normally have a long commute. These findings combined with a significant increase in physical activity, suggest that behaviours were healthier during lockdown, consistent with higher self-reported health compared with afterwards. However, there was a marked deterioration in wellbeing during lockdown, and on average participants self-reported being heavier during this period as well. Our qualitative data suggested that an abundance of resources supported higher fruit and vegetable consumption during lockdown, for instance, participants had more time, while access issues were one barrier to consumption.

Conclusions

Our results are reassuring for those concerned that lockdowns may have adversely affect diets. They may point to the impact of commuting on diet, particularly for women, and intervening to reduce commuting times may be one way to improve population diets. Our study adds longitudinal evidence to a growing body of literature on the adverse effect of lockdown on mental health.
Simultaneous evaluation of antibodies that inhibit SARS-CoV-2 RBD variants with a novel competitive multiplex assay
Authors: Lopez Ester , Haycroft Ebene R. , Adair Amy , Mordant Francesca L. , O’Neill Matthew T. , Pymm Phillip , Redmond Samuel , Gherardin Nicholas A. , Wheatley Adam K. , Juno Jennifer. A. , Selva Kevin J. , Davis Samantha , Harty Leigh , Purcell Damian F.J. , Subbarao Kanta , Godfrey Dale I. , Kent Stephen J. , Tham Wai-Hong , Chung Amy W.
Published: March 2021

The SARS-CoV-2 Receptor Binding Domain (RBD) is both the principal target of neutralizing antibodies, and one of the most rapidly evolving domains, which can result in the emergence of immune escape mutations limiting the effectiveness of vaccines and antibody therapeutics. To facilitate surveillance, we developed a rapid, high-throughput, multiplex assay able to assess the inhibitory response of antibodies to 24 RBD natural variants simultaneously. We demonstrate that immune escape can occur through two mechanisms, antibodies that fail to recognize mutations, along with antibodies that have reduced inhibitory capacity due to enhanced variant RBD-ACE2 affinity. A competitive approach where antibodies simultaneously compete with ACE2 for binding to the RBD may therefore more accurately reflect the physiological dynamics of infection. We describe the enhanced affinity of RBD variants N439K, S477N, Q493L, S494P and N501Y to the ACE2 receptor, and demonstrate the ability of this assay to bridge a major gap for SARS-CoV-2 research; informing selection of complementary monoclonal antibody candidates and the rapid identification of immune escape to emerging RBD variants following vaccination or natural infection.
The 501Y.V2 SARS-CoV-2 variant has an intermediate viral load between the 501Y.V1 and the historical variants in nasopharyngeal samples from newly diagnosed COVID-19 patients
Authors: Teyssou Elisa , Soulie Cathia , Visseaux Benoit , Lambert-Niclot Sidonie , Ferre Valentine , Marot Stéphane , Jary Aude , Sayon Sophie , Zafilaza Karen , Leducq Valentin , Schnuriger Aurélie , Abdi Basma , Wirden Marc , Houhou-Fidouh Nadhira , Charpentier Charlotte , Morand-Joubert Laurence , Burrel Sonia , Descamps Diane , Calvez Vincent , Geneviève Marcelin Anne
Published: March 2021

The 501Y.V2 and the 501Y.V1 SARS-CoV-2 variants emerged and spread rapidly into the world. We analysed the viral load of 643 nasopharyngeal samples of COVID-19 patients at diagnosis and found that the 501Y.V1 and the 501Y.V2 variants presented a viral load three to ten times and two times higher than the historical variants, respectively.

Highlights

Viral load in COVID-19 patient nasopharyngeal samples was different between variants.

The 501Y.V2 variant had a viral load 2 times higher than the historical variants

The 501Y.V2 variant had a viral load slightly lower than the 501Y.V1

The 501Y.V1 variant had a viral load 3-10 times higher than the historical variants
Hyperglycemia in Acute COVID-19 is Characterized by Adipose Tissue Dysfunction and Insulin Resistance
Authors: Reiterer Moritz , Rajan Mangala , Gómez-Banoy Nicolás , Lau Jennifer D. , Gomez-Escobar Luis G. , Gilani Ankit , Alvarez-Mulett Sergio , Sholle Evan T. , Chandar Vasuretha , Bram Yaron , Hoffman Katherine , Rubio-Navarro Alfonso , Uhl Skyler , Shukla Alpana P. , Goyal Parag , tenOever Benjamin R. , Alonso Laura C. , Schwartz Robert E. , Schenck Edward J. , Safford Monika M. , Lo James C.
Published: March 2021

COVID-19 has proven to be a metabolic disease resulting in adverse outcomes in individuals with diabetes or obesity. Patients infected with SARS-CoV-2 and hyperglycemia suffer from longer hospital stays, higher risk of developing acute respiratory distress syndrome (ARDS), and increased mortality compared to those who do not develop hyperglycemia. Nevertheless, the pathophysiological mechanism(s) of hyperglycemia in COVID-19 remains poorly characterized. Here we show that insulin resistance rather than pancreatic beta cell failure is the prevalent cause of hyperglycemia in COVID-19 patients with ARDS, independent of glucocorticoid treatment. A screen of protein hormones that regulate glucose homeostasis reveals that the insulin sensitizing adipokine adiponectin is reduced in hyperglycemic COVID-19 patients. Hamsters infected with SARS-CoV-2 also have diminished expression of adiponectin. Together these data suggest that adipose tissue dysfunction may be a driver of insulin resistance and adverse outcomes in acute COVID-19.
Genomic profiling defines variable clonal relatedness between invasive breast cancer and primary ductal carcinoma in situ
Authors: Lips Esther H. , Kumar Tapsi , Megalios Anargyros , Visser Lindy L. , Sheinman Michael , Fortunato Angelo , Shah Vandna , Hoogstraat Marlous , Sei Emi , Mallo Diego , Roman-Escorza Maria , Ahmed Ahmed A. , Xu Mingchu , Brugman Wim , Clements Karen , Davies Helen R. , Fu Liping , Grigoriadis Anita , Hardman Timothy M. , King Lorraine M. , Krete Marielle , Kristel Petra , Maaker Michiel de , Maley Carlo C. , Marks Jeffrey R. , Menegaz Brian , Mulder Lennart , Nieboer Frank , Nowinski Salpie , Pinder Sarah , Quist Jelmar , Salinas-Souza Carolina , Schaapveld Michael , Schmidt Marjanka K. , Shaaban Abeer M. , Shami Rana , Sridharan Mathini , Zhang John , Stobart Hilary , Collyar Deborah , Nik-Zainal Serena , Wessels Lodewyk F.A. , Hwang E. Shelley , Navin Nicholas N. , Futreal Andrew , Thompson Alastair , Wesseling Jelle , Sawyer Elinor J.
Published: March 2021

Pure ductal carcinoma in situ (DCIS) is being diagnosed more frequently through breast screening programmes and is associated with an increased risk of developing invasive breast cancer. We assessed the clonal relatedness of 143 cases of pure DCIS and their subsequent events using a combination of whole exome, targeted and copy number sequencing, supplemented by single cell analysis. Unexpectedly, 18% of all invasive events after DCIS were clonally unrelated to the primary DCIS. Single cell sequencing of selected pairs confirmed our findings. In contrast, synchronous DCIS and invasive disease (n=44) were almost always (93%) clonally related. This challenges the dogma that almost all invasive events after DCIS represent invasive transformation of the initial DCIS and suggests that DCIS could be an independent risk factor for developing invasive disease as well as a precursor lesion. Our findings support a paradigm shift that confirms a more complex role for DCIS than previously recognized, and that the future management of DCIS should take into account both the precursor and risk factor implications of this diagnosis.
Acute Brain Ischemia, Infarction and Hemorrhage in Subjects Dying with or Without Autopsy-Proven Acute Pneumonia
Authors: Beach Thomas G. , Sue Lucia I. , Intorcia Anthony J. , Glass Michael J. , Walker Jessica E. , Arce Richard , Nelson Courtney M. , Serrano Geidy E.
Published: March 2021

Stroke is one of the most serious complications of Covid-19 disease but it is still unclear whether stroke is more common with Covid-19 pneumonia as compared to non-Covid-19 pneumonia. We investigated the concurrence rate of autopsy-confirmed acute brain ischemia, acute brain infarction and acute brain hemorrhage with autopsy-proven acute non-Covid pneumonia in consecutive autopsies in the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND), a longitudinal clinicopathological study of normal aging and neurodegenerative diseases. Of 691 subjects with a mean age of 83.4 years, acute pneumonia was histopathologically diagnosed in 343 (49.6%); the concurrence rates for histopathologically-confirmed acute ischemia, acute infarction or subacute infarction was 14% and did not differ between pneumonia and non-pneumonia groups while the rates of acute brain hemorrhage were 1.4% and 2.0% of those with or without acute pneumonia, respectively. In comparison, in reviews of Covid-19 publications, reported clinically-determined rates of acute brain infarction range from 0.5% to 20% while rates of acute brain hemorrhage range from 0.13% to 2%. In reviews of Covid-19 autopsy studies, concurrence rates for both acute brain infarction and acute brain hemorrhage average about 10%. Covid-19 pneumonia and non-Covid-19 pneumonia may have similar risks tor concurrent acute brain infarction and acute brain hemorrhage when pneumonia is severe enough to cause death. Additionally, acute brain ischemia, infarction or hemorrhage may not be more common in subjects dying of acute pneumonia than in subjects dying without acute pneumonia.
Endogenous interferon-beta but not interferon-alpha or interferon-lambda levels in nasal mucosa predict clinical outcome in critical COVID-19 patients independent of viral load
Authors: Menezes Soraya Maria , Braz Marcos , Llorens-Rico Veronica , Wauters Joost , Van Weyenbergh Johan
Published: March 2021

Although the subject of intensive preclinical and clinical research, controversy on the protective vs. deleterious effect of interferon (IFN) in COVID-19 remains. Some apparently conflicting results are likely due to the intricacy of IFN subtypes (type I: IFN-alpha/beta, type III: IFN-lambda), timing and mode of administration (nebulized/subcutaneous) and clinical groups targeted (asymptomatic/mild, moderate, severe/critical COVID-19). Within the COntAGIouS (COvid-19 Advanced Genetic and Immunologic Sampling) clinical trial, we investigated endogenous type I and type III IFNs in nasal mucosa as possible predictors of clinical outcome in critical patients, as well as their correlation to SARS-CoV-2 viral load, using nCounter technology. We found that endogenous IFN-beta expression in the nasal mucosa predicts clinical outcome, independent of viral replication or Apache II score, and should be considered as a prognostic tool in a precision medicine approach of IFN therapy in COVID-19 clinical management.
The fMRI signature of acute catatonic state and its response to benzodiazepines
Authors: Parekh Pravesh , Gozi Anirban , Reddi Venkata Senthil Kumar , Saini Jitender , John John P.
Published: March 2021

We report for the first time, functional MRI markers of the acute retarded catatonic state and its response to benzodiazepines.

In this cross-sectional MRI study, we have compared the resting state whole-brain, within-network and seed (left precentral gyrus)-to-voxel connectivity, as well as cortical complexity between a sample of patients in acute retarded catatonic state (n = 15) and a demographically-matched healthy control sample (n = 15). Additionally, we examined whether the above variables were different between responders (n = 9) and non-responders (n = 6) to lorazepam.

Acute retarded catatonia was characterized by reduced functional connectivity, most robustly within the sensorimotor network, diffuse long-range hyperconnectivity, and seed (left precentral gyrus)-to-voxel hyperconnectivity in the frontoparietal and cerebellar regions. The lorazepam responders showed long-range as well as seed-to-voxel functional hyperconnectivity in comparison to the non-responders. Seed (left precentral gyrus)-to-voxel connectivity was positively correlated to the catatonia motor ratings. The catatonia sample showed a cluster of reduced vertex-wise cortical complexity in the right insular cortex and contiguous areas.

We have identified neuroimaging markers that characterize the acute retarded catatonic state and predict treatment response. We discuss how these novel findings have important translational implications for understanding the pathophysiology of catatonia and for predicting treatment response to benzodiazepines.
Impact of a Population-based Systems Approach on Evidence-based Care for Medicaid-insured Pregnant and Postpartum Women: A Quasi-Experimental Study
Authors: Roman Lee Anne , Raffo Jennifer E. , Strutz Kelly L. , Luo Zhehui , Johnson Melinda , VanderMeulen Peggy , Henning Susan , Baker Dianna , Titcombe Claire , Meghea Cristian I.
Published: March 2021

Introduction

Evidence-based enhanced prenatal/postnatal care (EPC) programs for Medicaid-insured women have significant positive effects on care and health outcomes. However, EPC enrollment rates are typically low, enrolling less than 30% of eligible women. This study investigated the effects of a population-based systems approach on timely EPC participation and other health care utilization.

Methods

This quasi-experimental, population-based, difference-in-difference study used linked birth certificates, Medicaid claims, and EPC data from complete statewide Medicaid birth cohorts retrieved from 2009-2017 and analyzed in 2019-20. System strategies included cross-agency leadership, clinical-community linked practices, Community Health Worker care, mental health coordination, and patient empowerment. Outcomes included EPC participation and early enrollment, prenatal care adequacy, emergency department contact, and postpartum care.

Results

Prenatal EPC (7.4 absolute percentage points; 95% CI: 6.3—8.5) and first trimester EPC, (12.4; 95% CI: 10.2—14.5) increased among women served by practices that co-located EPC resources, relative to the comparator group. First trimester EPC improved in the county (17.9; 95% CI: 15.7—20.0); ED decreased in the practices (−11.1; 95% CI: -12.3— -9.9) and postpartum care improved (7.1; 95% CI: 6— 8.2) in the county. EPC participation for Black women served by the practices improved (4.4; 95% CI: 2.2—6.6), as well as early EPC (12.3; 95% CI: 9.0—15.6) and postpartum visits (10.4; 95% CI: 8.3—12.4).

Conclusions

A population systems approach improved EPC participation and service utilization for Medicaid-insured women in a county population, for those in practices that co-located EPC resources, and for Black women.
Human IgG and IgA responses to COVID-19 mRNA vaccines
Authors: Campillo-Luna Julian , Wisnewski Adam V , Redlich Carrie A
Published: March 2021

SARS-CoV-2 spike antigen-specific IgG and IgA elicited by infection mediate viral neutralization and are likely an important component of natural immunity, however, limited information exists on vaccine induced responses. We measured COVID-19 mRNA vaccine induced IgG and IgA in serum serially, up to 80 days post vaccination in 4 subjects. Spike antigen-specific IgG levels rose exponentially and plateaued 21 days after the initial vaccine dose. After the second vaccine dose IgG levels increased further, reaching a maximum approximately 7-10 days later, and remained elevated (average of 78% peak levels) during the additional 20-50 day follow up period. COVID-19 mRNA vaccination elicited spike antigen-specific IgA with similar kinetics of induction and time to peak levels, but more rapid decline in serum levels following both the 1st and 2nd vaccine doses (<23% peak levels within 80 days of the initial shot). The data demonstrate COVID-19 mRNA vaccines effectively induce spike antigen specific IgG and IgA and highlight marked differences in their persistence in serum.
COVID-19 antibody seroprevalence in Duhok, Kurdistan Region, Iraq: A population-based study
Authors: Hussein Nawfal R , Balatay Amer A , Naqid Ibrahim A , Jamal Shakir A , Rasheed Narin A , Ahmed Alind N , Salih Reving S , Mahdi Ahmed S , Mansour Sabeeha A , Mahdi Shaveen , Ibrahim Nashwan , Musa Dildar H , Saleem Zana SM.
Published: March 2021

Objective

This population-based study aimed to evaluate the seroprevalence of antibodies to SARS-CoV-2 in Duhok City, Kurdistan Region of Iraq.

Methods

We analyzed the national COVID-19 database that contains data regarding COVID-19 testing, management, and clinical outcomes in Duhok. For this study, different subdistricts within each district of Duhok were considered distinct clusters. Blood samples were collected from and questionnaires were administered to eligible and consenting participants who were members of different families from the subdistricts. Immunoassays were conducted to detect antibodies against SARS-CoV-2, and the associations between certain variables were investigated.

Results

The average number cases of COVID-19 before November 2020 was 23141 ± 4364, which was significantly higher than the average number of cases between November 2020 and February 2021 (3737 ± 2634; P = 0.001). A total of 743 individuals agreed to participate and were enrolled in the study. Among the participants, 465/743 (62.58%) were found to have antibodies against severe acute respiratory syndrome coronavirus 2. Among the participants with antibodies, 262/465 (56.34%) denied having any history of COVID-19-related symptoms. The most common symptom was fever (81.77%), followed by myalgia (81.28%). We found that antibody levels increased steadily with age (Pearson correlation coefficient = 0.117; P = 0.012). A significant association was found between antibody levels and the presence of symptoms (P = 0.023; odds ratio = 1.0023; 95% confidence interval = 1.0002-1.0061).

Conclusions

A significant reduction in the number of COVID-19 cases was observed. This might be due to the high prevalence of SARS-CoV-2 antibodies in Duhok. However, infection-prevention measures should be followed as it remains unclear whether acquired immunity is protective against reinfection. It expected that the infection rates during the next wave will not be as high as the first wave due to the high infection rate in the society.