bluuebunny/crossref_metadata_2025 huggingface dataset:
Early Transient Hypoglycemia and Test Performance in At-Risk Newborns
Authors: ElHassan Nahed O. , Schaefer Eric W. , Gonzalez Basilia , Nienaber Thomas , Brion Luc P. , Kaiser Jeffrey R.
Published: July 2021

Objective This study aimed to evaluate if early (within the first 3 hours after birth) transient neonatal hypoglycemia (TNH) is associated with poor academic performance in infants at-risk for hypoglycemia.

Study Design This was a retrospective cohort study of at risk-infants (late preterm infants, small and large for gestational age infants, and infants of diabetic mothers [IDMs]) who were born in 1998 and 1999 at the University of Arkansas for Medical Sciences and had ≥1 recorded glucose concentration. The outcome measure was proficiency on 4th grade literacy and mathematics achievement tests. Three glucose concentration cutoffs for defining hypoglycemia (<35, <40, and <45 mg/dL) were investigated. Logistic regression models were developed to examine the association between early TNH and achievement test proficiency based on perinatal factors.

Results Among 726 infants, 472 had one, 233 had two, and 21 had three risk factor(s). Early TNH (glucose concentration <35, <40, and <45 mg/dL) was observed in 6.3, 11.6, and 20.5% of the study cohort, respectively. Irrespective of the cutoff used, the frequency of early TNH (number of patients with early TNH in a risk category divided by the total number of patients in that category) was significantly greater among infants with multiple risk factors. After controlling for perinatal factors, early TNH (cutoffs <35 and <40 mg/dL) was significantly associated with decreased probability of proficiency in literacy but not mathematics. Despite that early TNH was more common in IDMs and infants with three risk factors, the category or number of risk factors did not impact academic proficiency.

Conclusion Early TNH (<35 and <40 mg/dL) was associated with lower adjusted probability of proficiency on 4th grade literacy achievement tests in at-risk infants. The impact of early TNH on academic performance was similar irrespective of category or number of risk factors.

Key Points
Vena Cava Atresia and Deep Vein Thrombosis: A Case Report and Systematic Review
Authors: Castro V. Alende , Díaz-Peromingo Jose Antonio
Published: July 2021

Congenital anomalies of the vena cava often go unnoticed, and their incidental finding is frequent in imaging tests performed for another cause in asymptomatic patients. However, an association with the development of thromboembolic disease has been described, mainly in young patients.

We report the case of a young woman with deep vein thrombosis associated with vena cava atresia.

We conducted a search of the PubMed/Medline database. The search identified 17 articles, of which 5 were selected for extraction and data analysis. Twelve studies were excluded because they failed to match the main criteria.

We identified six new cases of deep vein thrombosis associated with vena cava abnormalities, with a mean age of 42.5 years; 83.3% were male. Regarding clinical manifestations, all patients presented as deep vein thrombosis, one case of recurrence, and another case associated with the kidney and inferior vena cava abnormalities with leg thrombosis syndrome. Only one patient had a target triggering factor (cholecystectomy postoperative). The thrombophilia study was negative in all cases and none of the patients died. Treatment included enoxaparin and vitamin K antagonists.

This is the first study to report on a systematic review of vena cava atresia associated with deep vein thrombosis in Spain. It shows that in this region, the disease affects young population—even in the absence of risk factors—and is linked to a low mortality. The most frequent presentation form was deep vein thrombosis. Therefore, congenital abnormalities of the vena cava should be suspected in young patients with thromboembolic disease, due to their implications regarding to the duration of anticoagulant treatment, as well as their possible association with other prothrombotic factors.
Trataka Kriya in Individuals with Digital Eye Strain: A Pre–Post Experimental Design
Authors: Kumar K.U. Dhanesh , Shetty Sparsha , Amin Hrishikesh , Rashmitha A. P. , Rani P. Shilna
Published: July 2021

Introduction Digital eye strain is the physical discomfort felt after 2 or more hours in front of a digital screen, including cell phones. Digital eye strain is otherwise known as computer vision syndrome. Trataka is to look at or to gaze—it is a preliminary step for meditation that involves staring at a single point such as a small object, black dot, or candle flame.

Objective This study aimed to analyze the effect of trataka kriya in the management of digital eye strain.

Materials and Methods Thirty participants of the age group 18 to 40 years were recruited in the study. The study design was a pre–post experiment. A convenient sampling technique was used to recruit the participants. The study included participants who use laptops or smartphones for a minimum of 2 hours daily and also participants having eye strain, dry eyes, burning sensation in the eyes, headache, and eye fatigue. They performed trataka kriya exercises once a day on alternative days for 1 month. Outcome measures was a computer vision syndrome questionnaire to assess the visual fatigue experienced by the study participants and the Schrimer test to find out whether the eye produces enough tears to keep it moist.

Statistical Analysis and Results Statistical analysis was done using SPSS version 16.0. To compare the computer vision syndrome questionnaire and Schrimer test before and after interventions paired t-test was used. A p-value of less than 0.05 is considered significant for the study.

Conclusion The study concludes that there was an improvement in the subjects with digital eye strain after performing trataka kriya. The clinical implication of the study is that this method can be used as one of the nonpharmacological interventions for digital eye strain.
Outcomes of Cardiopulmonary Resuscitation in the Pediatric Intensive Care of a Tertiary Center
Authors: Al-Eyadhy Ayman , Almazyad Mohammed , Hasan Gamal , AlKhudhayri Nawaf , AlSaeed Abdullah F. , Habib Mohammed , Alhaboob Ali A. N. , AlAyed Mohammed , AlSehibani Yazeed , Alsohime Fahad , Alabdulhafid Majed , Temsah Mohamad-Hani
Published: July 2021

Understanding the factors affecting survival and modifying the preventable factors may improve patient outcomes following cardiopulmonary resuscitation (CPR). The aim of this study was to assess the prevalence and outcomes of cardiac arrest and CPR events in a tertiary pediatric intensive care unit (PICU). Outcomes of interest were the return of spontaneous circulation (ROSC) lasting more than 20 minutes, survival for 24 hours post-CPR, and survival to hospital discharge. We analyzed data from the PICU CPR registry from January 1, 2011 to January 1, 2018. All patients who underwent at least 2 minutes of CPR in the PICU were included. CPR was administered in 65 PICU instances, with a prevalence of 1.85%. The mean patient age was 32.7 months. ROSC occurred in 38 (58.5%) patients, 30 (46.2%) achieved 24-hour survival, and 21 (32.3%) survived to hospital discharge. Younger age (p < 0.018), respiratory cause (p < 0.001), bradycardia (p < 0.018), and short duration of CPR (p < 0.001) were associated with better outcomes, while sodium bicarbonate, norepinephrine, and vasopressin were associated with worse outcome (p < 0.009). The off-hour CPR had no impact on the outcome. The patients' cumulative predicted survival declined by an average of 8.7% for an additional 1 minute duration of CPR (p = 0.001). The study concludes that the duration of CPR, therefore, remains one of the crucial factors determining CPR outcomes and needs to be considered in parallel with the guideline emphasis on CPR quality. The lower survival rate post-ROSC needs careful consideration during parental counseling. Better anticipation and prevention of CPR remain ongoing challenges.
Tea or Thrush?: A Case of Nonaccidental Oral Injury in an Infant
Authors: Jan Meryam , Dully Kathleen , Kostecki Carissa , Alexander Randell C.
Published: July 2021

A 5-month-old girl child patient presented to the emergency department for oral thrush and poor feeding but instead demonstrated concern for abuse after physical exam, as findings were consistent with oral injury. Correct identification of the oral findings as traumatic necessitated navigating language and cultural issues before the mechanism of injury and abuse determination could be made. Exploring the involvement of other caregivers was a crucial piece for investigation of the clinical scenario. The incidence of child abuse and pediatric oral injuries concerning for abuse were reviewed in this case report.
Transient Hyperammonemic Encephalopathy in a Child with Relapsed Acute Lymphoblastic Leukemia and Severe Tumor Lysis Syndrome
Authors: Dubinski Ilja , Feuchtinger Tobias , Maier Esther , Tacke Moritz , Hoffmann Florian
Published: July 2021

Idiopathic hyperammonemia (IHA) is a severe condition, which has been reported in intensive chemotherapy and bone marrow transplantation. This case elucidates the diagnostic dilemma in children undergoing initiation of chemotherapy and developing severe disorders of qualitative and quantitative consciousness in the presence of hyperammonemia (HA) and lactic acidosis. The role of mitoxantrone as a causative agent for IHA in children is elusive. Children undergoing chemotherapy are often in a poor general condition, and the clinical presentation of HA is heterogeneous. This case should be a reminder for clinicians to check for HA in children with tumor lysis syndrome and acute neurological deterioration.
Pulmonary Embolism in a Critically Ill Infant with Univentricular Parallel Circulation
Authors: Shoya Kazuhiro , Maeda Jun , Nagamine Hiroki , Shimotakahara Akihiro , Yoshimura Yukihiro , Saito Osamu
Published: July 2021

A 3-month-old infant patient with hypoplastic left heart syndrome diagnosed in the prenatal period required long-term intensive care for refractory chylothorax and chylous ascites after undergoing bilateral pulmonary artery banding at age 6 days. Weaning from mechanical ventilation was difficult due to massive edema, and a central venous catheter was required because enteral feeding was hampered by the refractory chyle leakage, for which surgery was ineffective. On the evening after central venous catheter replacement was performed, his respiratory condition suddenly deteriorated; cardiac ultrasound revealed that the left pulmonary arterial blood flow had decreased, and enhanced computed tomography demonstrated a left pulmonary embolism (PE), which was identified as the cause of a sudden decrease in the pulmonary blood flow. The patient died due to refractory septic shock at age 5 months. PEs in children, especially patients with cyanotic congenital heart disease, are difficult to diagnose because of their atypical presentation. Current diagnostic criteria are based on adult guidelines, and a few factors in the criteria, such as tachycardia and hypoxia, are difficult to apply for pediatric cyanotic patients with intracardiac or extracardiac right-to-left shunt. In fact, those criteria have lower specificities in children. In conclusion, the present case suggested that a sudden decrease in the pulmonary blood flow can aid the physicians in diagnosing PE in patients with cyanotic congenital heart disease. We need more pediatric cases and evidence of PE in children to make a PE guideline, which is specific to pediatric patients including cyanotic congenital heart disease.
A Case Series of Unusual or Infrequent Locations of Breast Cancer Metastases
Authors: Liew Amanda Ling Fung , Yu Ern Yu , Chotai Niketa
Published: July 2021

Breast cancer metastasis to unusual locations may present as a diagnostic challenge. Recognizing the different manifestations of metastatic breast disease can help to guide patient treatment and assist in disease prognosis. The purpose of this article is to illustrate the imaging findings of some of the unusual or infrequent locations of breast metastases through a series of interesting cases and to revisit this uncommon clinical issue.
Acute effects of an injury preventive warmup programme on unanticipated jump‐landing‐task performance in adult football players: A crossover trial
Authors: Friebe David , Giesche Florian , Niederer Daniel , Ashigbi Evans Y. K. , Groneberg David A. , Banzer Winfried
Published: July 2021

In football, unpredictable events (e.g. unexpected landings) seem to play a crucial role in the mechanism of non‐contact knee injuries. This study investigated the effects of a single bout of an injury preventive warmup protocol on biomechanical landing stability and decision‐making quality during preplanned and unanticipated jump‐landings. A crossover study on 18 male amateur football players was performed. The participants completed a standard (ergometer) and an injury‐preventive warmup protocol (Prevent injury and Enhance Performance (PEP)) on two different test days. After each protocol, participants performed countermovement jumps with preplanned (landing side displayed before takeoff) and unanticipated (landing side shown after takeoff) single‐leg landings on a force plate. Outcomes were landing stability (height and time of the maximum vertical ground reaction force (pGRF), centre of pressure (CoP), the number of standing errors (ground contact with free leg)) and decision‐making quality (landing error (wrong foot) count). Carry‐over and crossover‐tests were performed to find potential between‐condition‐differences. No carry‐over effects occurred (p > .05). The PEP led to a reduced CoP trace length (−18.4 ± 32.2%, p = .021) and earlier occurrence of pGRF (−4.72 ± 6.78%, p = .017) in the preplanned condition. No significant between‐treatment‐differences occurred within the unanticipated landings and decision‐making quality (p > .05). The primarily neuromuscular warmup protocol affects landing stability in the preplanned condition. However, it does not seem to better prepare football players for unpredictable events than a standard warmup.

Trial registration: German Clinical Trials Register identifier: DRKS00016942.

Highlights

Adapting movements rapidly to unanticipated external stimuli (e.g. unexpected landings) is crutial to prevent injuries in football

It is unclear wether popular neuromuscular injury preventive warmup programmes (e.g. Prevent injury and Enhance Performance (PEP)) adaquatly prepare athletes for these situations

Our study shows that the PEP warm up programme has acute effects on anticipated landing stability, but no influence on unanticipated landings or decision making quality

Classic neuromuscular warm up programmes may not be the optimal choice to prepare athletes properly for the upcoming motor‐cognitive demands in a football match
Progress in Microdermal Grafting for Color Regeneration of White Scars
Authors: Tsao Su-Ben , Jong Lih-Ren , Su Yue-Chiu , Kuo Yur-Ren
Published: July 2021

Background

Microdermal grafting with knife-cut, partially de-epithelialized skin can regenerate color in white (hypopigmented) scars. However, the scalp has more melanocytes, and dermabrasion can preserve more melanocytes than knife cutting during partial de-epithelialization.

Objectives

The aim of this study was to evaluate the color regeneration results and complications of various microdermal grafting procedures for white scar color regeneration.

Methods

Two refinements to an existing microdermal grafting technique for treating white scars were described: dermabrasion, rather than knife cutting, was used to partially de-epithelialize skin, and melanocyte donor sites were harvested from the scalp, rather than from skin. A review was performed of 65 cases in which various combinations of these refinements were used to treat scars on the face and forearms.

Results

Sixty-five patients (36 forearms; 29 faces) were treated, 40 receiving 1 session, 23 receiving 2 sessions, and 2 receiving 3 sessions of treatment. The follow-up was 6.5 months (range, 4-16 months). The use of both technique refinements produced approximately 15% better color generation than the original procedure after 1 session of treatment and approximately 20% better than the original procedure after 2 sessions. Histologic immunostaining showed that the dermabrasion method preserved more melanocytes around the epidermal-dermal region, and that the scalp has richer melanocytes than skin. The complication rate was reduced.

Conclusions

The use of the scalp as the donor site and partial de-epithelialization by dermabrasion can be safely incorporated into a previously developed microdermal grafting procedure for better color regeneration of white scars.

Level of Evidence: 4
An integrated computational pipeline for designing high-affinity nanobodies with expanded genetic codes
Authors: Padhi Aditya K , Kumar Ashutosh , Haruna Ken-ichi , Sato Haruna , Tamura Hiroko , Nagatoishi Satoru , Tsumoto Kouhei , Yamaguchi Atushi , Iraha Fumie , Takahashi Mihoko , Sakamoto Kensaku , Zhang Kam Y J
Published: July 2021

Protein engineering and design principles employing the 20 standard amino acids have been extensively used to achieve stable protein scaffolds and deliver their specific activities. Although this confers some advantages, it often restricts the sequence, chemical space, and ultimately the functional diversity of proteins. Moreover, although site-specific incorporation of non-natural amino acids (nnAAs) has been proven to be a valuable strategy in protein engineering and therapeutics development, its utility in the affinity-maturation of nanobodies is not fully explored. Besides, current experimental methods do not routinely employ nnAAs due to their enormous library size and infinite combinations. To address this, we have developed an integrated computational pipeline employing structure-based protein design methodologies, molecular dynamics simulations and free energy calculations, for the binding affinity prediction of an nnAA-incorporated nanobody toward its target and selection of potent binders. We show that by incorporating halogenated tyrosines, the affinity of 9G8 nanobody can be improved toward epidermal growth factor receptor (EGFR), a crucial cancer target. Surface plasmon resonance (SPR) assays showed that the binding of several 3-chloro-l-tyrosine (3MY)-incorporated nanobodies were improved up to 6-fold into a picomolar range, and the computationally estimated binding affinities shared a Pearson’s r of 0.87 with SPR results. The improved affinity was found to be due to enhanced van der Waals interactions of key 3MY-proximate nanobody residues with EGFR, and an overall increase in the nanobody’s structural stability. In conclusion, we show that our method can facilitate screening large libraries and predict potent site-specific nnAA-incorporated nanobody binders against crucial disease-targets.
Recent omics-based computational methods for COVID-19 drug discovery and repurposing
Authors: Tayara Hilal , Abdelbaky Ibrahim , To Chong Kil
Published: July 2021

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the main reason for the increasing number of deaths worldwide. Although strict quarantine measures were followed in many countries, the disease situation is still intractable. Thus, it is needed to utilize all possible means to confront this pandemic. Therefore, researchers are in a race against the time to produce potential treatments to cure or reduce the increasing infections of COVID-19. Computational methods are widely proving rapid successes in biological related problems, including diagnosis and treatment of diseases. Many efforts in recent months utilized Artificial Intelligence (AI) techniques in the context of fighting the spread of COVID-19. Providing periodic reviews and discussions of recent efforts saves the time of researchers and helps to link their endeavors for a faster and efficient confrontation of the pandemic. In this review, we discuss the recent promising studies that used Omics-based data and utilized AI algorithms and other computational tools to achieve this goal. We review the established datasets and the developed methods that were basically directed to new or repurposed drugs, vaccinations and diagnosis. The tools and methods varied depending on the level of details in the available information such as structures, sequences or metabolic data.
O5 Dose mean opening pressure predominantly assess internal anal sphincter function
Authors: Byrne C M , Sharma A , Kiff E S , Telford K J
Published: July 2021

Introduction

We have suggested that mean Opening Pressure (Op) recorded during Anal Acoustic Reflectometry (AAR) predominantly represents IAS function however, the extent remains unknown. The aim was to investigate this by excluding the external anal sphincter during general anaesthetic (GA) with confirmed neuromuscular blockade (NMB).

Method

Patients undergoing elective abdominal surgery requiring GA+NMB were approached. Patients had pre-operative (awake) and during GA + NMB (asleep) AAR measurements performed. The rectoanal inhibitory reflex (RAIR) was assessed permitting the Op value to also be recorded when the IAS was inhibited. Op was recorded at prerectal distension and then after 100 mls of air was inflated within a balloon in the rectum (post-rectal distension).

Result

19 patients were included. The values of Op (cmH20) and the reductions observed during the RAIR when awake/asleep are as follows:

Awake Op: prerectal distension (64.94) and post-rectal distension (35.35) therefore mean change 29.59 cmH2O i.e. 44.6% reduction

Asleep Op: prerectal distension (37.64) and post-rectal distension (15.55) therefore mean change 22.1 i.e. 55.3% reduction

The contribution of the IAS to Op is calculated as follows: (Mean change Op awake x 100)/% reduction in RAIR asleep = IAS contribution awake (29.59cmH20 x 100)/55.3 = 53.51cmH20 Total mean Op awake—IAS contribution awake = EAS contribution awake 64.94cmH20–53.51cmH20 (82.4%) = 11.43cmH20 (17.6%)

Conclusion

The IAS accounts for 82.4% of Op at rest and it remains our hypothesis that Op primarily represents IAS function.

Take-home Message

Opening pressure primarily represents internal anal sphincter function.
O7 Toll-like receptor 3 mediates osteoblastic phenotype switch in calcific aortic valve disease
Authors: Gollmann-Tepeköylü C , Graber M , Pölzl L , Hirsch J , Nägele F , Naschberger A , Kirchmair E , Degenhart G , Demetz E , Lobenwein D , Lener D , Fuchs C , Feuchtner G , Hackl H , Meyer D , Grimm M , Tancevski I , Holfeld J
Published: July 2021

Introduction

Calcific aortic valve disease (CAVD) is caused by an osteoblastic phenotype switch of valvular interstitial cells (VICs), the predominant cell type in heart valves. However, the trigger for the phenotype switch remains unknown. Toll-like receptor 3 (TLR3) is part of the innate immune system activated by viral and endogenous RNA released from injured cells. We hypothesized that mechanical strain leads to TLR3 activation leading to an osteoblastic phenotype switch of VICs with subsequent initiation of CAVD.

Methods

Aortic valves were obtained from patients undergoing aortic valve replacement or from explanted hearts. VICs were isolated and treated with TLR3 agonist poly (I: C) or a TLR3/dsRNA complex inhibitor. Osteoblastic gene expression was evaluated via RNA sequencing. Cells were challenged with osteoblastic medium and analyzed for alkaline phosphatase activity and calcific nodule formation. Zebrafish were treated with TLR3/dsRNA complex inhibitor. A Flexcell system was used to apply mechanical strain to VICs. Aortic valve morphology and function of aged wild-type (WT) and TLR3-/- mice were analyzed via transthoracic echocardiography, microCT and histological evaluation. To confirm results in a second model, experiments were repeated in ApoE-/- and ApoE-/-/TLR3-/- mice.

Results

Aortic valves and VICs showed abundant TLR3 expression. Mechanical stimulation of VICs resulted in TLR3 activation. Stimulation of TLR3 lead to expression of TNF-a, IL-6, IFN-y, IL-10, Runx2 and BMP2 and, caused a phenotype switch towards osteoblasts as revealed by RNA sequencing and resulted in enhanced calcific nodule production. Mice showed age-dependent TLR3 expression. Aortic valves as well as VICs derived from CAVD patients showed increased TLR3 expression compared to healthy control valves and VICs. TLR3 Inhibition resulted in prevention of osteogenic phenotype switch in conditioned VICs. Zebrafish exhibited decreased calcification after TLR3 inhibition. Aged WT mice showed significantly increased mean gradients and mean velocity in transthoracic echocardiographs. MicroCT and histological analyses revealed thickened valve leaflets and commissural atherosclerotic plaques. These changes were missing completely in age-matched TLR3-/- mice. ApoE-/- mice under high fat diet exhibited clear signs of CAVD with decreased aortic valve opening diameters and increased valve leaflet thickness. However, these findings were completely missing in ApoE-/-/TLR3-/- mice.

Conclusion

TLR3 stimulation leads to an osteoblastic phenotype switch of VICs, whereas inhibition of TLR3 prevents from osteoblastic activity. TLR3 expression is increased in aortic valves from CAVD patients. TLR3-/- mice show no phenotype of CAVD. TLR3 could become an effective target for the pharmacological prevention of CAVD.
O8 Tracking wound infection with smartphone technology (twist): a randomised controlled trial in emergency surgery patients
Authors: McLean K A , Mountain K E , Shaw C A , Drake T M , Ots Riinu , Knight Stephen R , Fairfield Cameron J , Sgrò Alessandro , Skipworth Richard J E , Wigmore Stephen J , Potter Mark A , Harrison Ewen M ,   TWIST collaborators
Published: July 2021

Introduction

Surgical site infections (SSI) complicate 2%–10% of general surgery cases, and represent a significant burden on acute healthcare services. We aim to investigate if a smartphone-delivered wound assessment tool results in earlier treatment.

Method

This parallel, single-blinded randomised control trial enrolled adult emergency abdominal surgery patients in two tertiary hospitals (ClinicalTrials.gov number, NCT02704897). Patients were randomised (1:1 ratio) between standard postoperative care and additional access to a smartphone-delivered wound assessment tool for 30-days postoperatively. Patients routinely submitted wound questionnaires and photos for surgical review at postoperative days 3, 7, and 15. The primary outcome measure was time-to-diagnosis of SSI (CDC definition) within 30 postoperative days.

Result

492 patients undergoing emergency surgery were randomised (smartphone intervention = 223; standard care = 269). There was no significant difference (P = 0.513) in the 30-day SSI rate between trial arms: 21 (9.4%) in smartphone vs 20 (7.4%) in standard care. While the mean time-to-diagnosis of SSI was 9.3 days (SD = 6.3) in the smartphone group, and 11.8 days (SD = 6.7) in the control group, this did not demonstrate a significant difference for the primary outcome (P = 0.255). However, patients in the smartphone group had 3.7-fold higher odds to be diagnosed in first 7 postoperative days (95% CI: 1.02 to 13.51, P = 0.043).

Conclusion

Digital patient-driven postoperative wound follow-up can be feasibly delivered in a broad cohort of emergency surgery patients. This can facilitate triage of patients to the appropriate level of assessment required, allowing diagnosis of SSI earlier in the postoperative period.

Take-home Message

Digital patient-driven postoperative wound follow-up can be feasibly delivered in a broad cohort of emergency surgery patients. This can facilitate triage of patients to the appropriate level of assessment required, allowing diagnosis of SSI earlier in the postoperative period.
O9 M1 macrophages evoke an increase in PIGR expression in MDA-MB468 breast cancer cells through interlukin-1β
Authors: Asanprakit W , Lobo D N , Eremin O , Bennett A J
Published: July 2021

Introduction

The polymeric immunoglobulin receptor (PIGR) is a transmembrane protein, which transports polymeric immunoglobulin (pIg) across the epithelial cells. High expression of PIGR in breast cancer has been reported to associate with increased 5-year survival rate. In this study, the factors in tumour microenvironment which affected PIGR expression in breast cancer cell lines, were investigated.

Method

M1, M2 macrophage conditioned media (CM) and recombinant human cytokines were used to determine factors which increased PIGR expression in breast cancer cells. The level of PIGR expression in the cells and secreted PIGR free secretory component (SC) were evaluated by real time quantitative polymerase chain reaction and Western blotting.

Results

M1 macrophage CM induced a striking dose dependent increase in PIGR mRNA expression in MDA-MB468 cells, up to 20-fold in 100% CM. Interferon gamma (IFNγ) and interleukin (IL)-1β also increased PIGR expression in MDA-MB468 cells. However, IL-1β was demonstrated to increase in M1 macrophages, while IFNγ was not. The role of IL-1β secreted from M1 macrophages in increasing expression of PIGR was confirmed by IL-1 receptor blockade, indicating that IL-1β was the M1 macrophage cytokine that enhanced PIGR expression in breast cancer cells.

Conclusions

IL-1β was the M1 macrophage cytokine which enhanced PIGR expression in breast cancer cells. IFNγ was also shown to increase PIGR expression in the present study. These imply that elevated PIGR expression in breast cancer in vivo may reflect the polarization state of tumour associated immune cells.

Take-home Message

IL-1β secreted from M1 macrophage enhances PIGR expression in breast cancer cells. The elevated PIGR expression in breast cancer in vivo may reflect the polarization state of tumour associated immune cells.
O17 Multidisciplinary decision-making strategies may reduce the need for surgery in complex colonic polyps—a systematic review
Authors: Parker J , Gupta S , Torkington J , Dolwani S
Published: July 2021

Introduction

The recognition of complex colonic polyps is increasing. Management varies considerably and the impact of this on clinical outcomes is unclear. The aim of this systematic review was to assess the impact of group decision-making strategies and defined selection criteria on the treatment outcomes of complex colonic polyps.

Method

A systematic literature review identified studies reporting complex polyp treatment outcomes and describing their decision-making strategies. Databases searched included PubMed, Web of Science, CINAHL and Scopus. Articles were identified by two blinded reviewers using defined inclusion criteria. The review protocol was registered on PROSPERO and performed in line with PRISMA guidelines.

Results

There were 303 identified articles describing treatment outcomes of complex colonic polyps. Only 9 of these fully described the decision-making strategy and met the inclusion criteria. The median adverse event, unsuspected malignancy and secondary surgery rates were 7.7%, 3.8% and 14.4% respectively. Grouping of articles into a hierarchy of decision-making strategies demonstrated a sequential reduction in secondary surgery rates with improving strategies. The secondary surgery rate was significantly lower in studies using group decision-making and defined selection criteria. There was no significant difference in comparisons of adverse event or unsuspected malignancy rates.

Conclusions

There is limited reporting of decision-making strategies in studies describing complex polyp treatment outcomes. The use of group decision-making and defined selection criteria may reduce the need for surgery in complex colonic polyps. This has implications of cost effectiveness for healthcare systems and benefits to patient quality of life.
O18 Activated leukocyte cell adhesion molecule (ALCAM) and its intracellular linkers in assessing the outcome of patients with breast cancer
Authors: Yang Y M , Sanders A J , Davies E , Mansel R E , Jiang W G
Published: July 2021

Introduction

ALCAM (also known as CD166) is a membrane integral protein and said to have a role in predicting the clinical outcome of patients with breast cancer, but the pattern of the prediction value is inconsistent. ALCAM confers cell-cell adhesion via heterotypic and homotypic interactions and linked to cytoskeleton via the ERM protein family (Ezrin, Moesin, Radixin and EHM2), particularly ezrin. The present study explored if the ALCAM and its ERM linkers may assist in refining the prognostic value of ALCAM.

Method

Gene transcripts of ACLAM and the ERM family members were quantitatively analysed in an existing breast cancer cohort collected freshly after surgery. The relationship between ALCAM and patient’s survival (follow-up 10 years) were stratified by the ALCAM linkers. Statistical methods were Kaplan-Meier’s survival method, ROC and logistic regression.

Result

ALCAM significantly correlated with four ERM family members (P < 0.005). Patients with high levels of ALCAM transcripts had significantly long overall survival. Further stratification by the epithelial rich Ezrin and endothelial rich Moesin identified subgroup of patients with good prognosis. Multivariant analysis indicates that the combined power of ALCAM and ERM family serves as an independent prognostic factor (P = 0.003) together with the other two factors, namely the Nottingham Prognostic Index and Nodal status (P = 0.02). A similar prediction power for disease free survival was seen with ALCAM and ERM combination.

Conclusion

ALCAM and its intracellular cytoskeletal linker molecules, the ERM family, together forms a significant prognostic factor to the clinical outcome of patients with breast cancer.

Take-home Message

ALCAM stratified by the ERM family have prognostic value in breast cancer
O24 Predictive and prognostic roles of polymeric immunoglobuilin receptor in breast cancer
Authors: Asanprakit W , Zaitoun A M , Lobo D N , Eremin O , Bennett A J
Published: July 2021

Introduction

Neoadjuvant chemotherapy (NAC) is used with increasing frequency as the primary treatment for breast cancer. Pathological complete response (pCR) which contributes to survival benefit is achieved in only 25–30% of patients with little benefit and significant morbidity in the remainder. Therefore, predicting the patients who are likely to achieve a pCR before commencing NAC is desirable. A pilot study using next generation RNA sequencing of 10 large and locally advanced breast cancer biopsy specimens demonstrated that the expression of polymeric immunoglobulin receptor (PIGR) was significantly increased in breast cancers with pCR. The predictive and prognostic roles of PIGR in breast cancer were expanded in the present study.

Method

PIGR mRNA expression was determined by RNA in situ hybridization assay in formalin-fixed paraffin-embedded (FFPE) specimens of pre-treatment breast cancer core biopsy from 46 women with breast cancer who received NAC. The expression of PIGR and its associations with pCR and overall survival was examined.

Results

PIGR mRNA expression was lower in breast cancer compared with normal breast tissue (median H score: 0 vs. 120, P < 0.0001). There was no statistically significant difference in the proportion of pCR in PIGR positive compared with PIGR negative tumours (22.2% vs. 32.1%, P = 0.466). Five-year overall survival of the patients with PIGR positive and negative tumours was 88.9% and 78.3%, respectively. However, overall survival was not significantly different (P = 0.406).

Conclusions

The expression of PIGR did not appear to be associated with pCR after NAC and did not correlate with overall survival in breast cancer patients.

Take-home Message

The expression of PIGR did not appear to be associated with pCR after NAC and did not correlate with overall survival in breast cancer patients.
O29 Aberrant expression of BMP8A and the BMPRs involves in the progression of breast cancer
Authors: Sui L J , Sanders A , Jiang W G , Ye L
Published: July 2021

Introduction

Role of Bone morphogenetic protein 8A (BMP8A) and BMP receptors (BMPRs) in the tumourigenesis and progression of breast cancer remains elusive. Present study aims to investigate the expression of BMP8A and related BMPRs in breast cancer and their clinical implication.

Method

Expression of BMP8A and BMPRs was analysed using the RNA sequencing data of the TCGA breast cancer cohort. Findings were further validated in a meta gene array dataset (E-MDTA6703, n = 2302). STRING dataset was applied to explore the predicted receptors of BMP8A. Clinical relevance of deregulated BMP8A and BMPRs in breast cancer was assessed using both ANOVA and Kaplan-Meier tests. Correlation with markers of proliferation and invasion was evaluated using Spearman test.

Result

Analysis of datasets revealed that BMP8A and BMPR1B were highly expressed in breast cancer while ACVRL1, ACVR1, BMPR1A, ACVR1C, TGFBR2, TGFBR3, BMPR2 and ACVR2A were lower-expressed compared with normal controls. Expressions of BMPR1B, BMPR1A, BMPR2, ACVR2A and ACVR2B were highly correlated with BMP8A in the breast cancers. Overall survival in the group with higher BMP8A expression was shorter(median= 122.3 months), P = 0.012 compared with lower-expressed group(median = 215.2 months). No significant difference was observed in BMP8A and BMPRs in tumours according to their staging and lymph node involvement. Positive correlations were found between BMP8A and tumour proliferation, EMT, angiogenic markers.

Conclusion

BMP8A is increased in breast cancer and correlates with poor prognosis. The highly correlated BMPRs might be involved in the signal transduction of BMP8A to co-regulate BMP responsive genes and cellular functions which is yet to be investigated.

Take-home Message

BMP8A is increased in breast cancer and correlates with poor prognosis.
O31 Central venous access in ventilated COVID-19 patients: a vascular surgery perspective
Authors: Liu P , Lui D , Cheema S M , Hussain S T , Husain T , Malina M
Published: July 2021

Introduction

The number of patients on intensive care units (ICU) increased manifold during the initial COVID-19 surge and medical staff were relocated to help compensate. The need for central venous catheters (CVCs) increased accordingly and comprised a significant workload under challenging circumstances. Several models were proposed to manage the lines. We assigned a vascular team of vascular surgeons and interventional radiologists for CVCs in ICU. We report on the workload, outcomes and lessons learned.

Method

50 consecutive ventilated COVID-19 patients in ICU (median age 63 years, 80% male) who had a CVC inserted by the vascular team from March to May 2020 were assessed. Median follow up was 18 days (range 14– 29 days) after ICU admission.

Result

166 CVCs (80 VasCaths) were inserted. Femoral access was preferred. Each patient required a median of 3 lines (IQR 2–4). CVCs were exchanged after median 7 days (IQR 4–9) for thrombosis (35%), infection (24%) or prophylactically (41%). Our learning curve included the establishment of an online referral pathway, CVC teams of two operators, extended disposable CVC kits and ICU based ultrasound scanners. Additional staffing and retraining were avoided. There were no technical complications.

Conclusion

Ventilated COVID-19 patients require multiple CVCs which is a challenging workload during a pandemic. Vascular surgeons and interventional radiologists with endovascular skills are well positioned to perform central venous cannulation to alleviate the burden on critical care teams. Our lessons learned can help to provide a safe and efficient model amidst the ongoing national outbreaks.

Take-home Message

With the postponement of many elective vascular procedures during the pandemic crisis, the involvement of vascular surgeons in a dedicated Lines team is an important way that they can contribute given their proficiency with wires and cannulation equipment, as well as familiarity in femoral triangle and jugular anatomy. The retraining of staff and additional on-call rotas can then be avoided.
O32 COVID-19 mortality after vascular procedures during the initial UK surge: moving forward with elective vascular work
Authors: Liu P , Cheema S M , Adeoye I , Theivacumar N S , Hussain S T , Malina M
Published: July 2021

Introduction

Following the initial COVID-19 surge in the United Kingdom, there was a national incentive for elective vascular surgery to be restricted to clean sites in order to reduce perioperative cross infection and subsequent mortality. We assessed the risk of dying from perioperatively acquired COVID-19 during the peak of the London outbreak.

Materials and Methods

43 consecutive patients who had vascular (n = 48) procedures in March and April 2020 at a regional hub serving five London hospitals were analysed. The patients were screened for COVID-19 in the 30-day postoperative period and the main outcome measure was mortality from COVID-19. A comparison was then made with patients who underwent minimally invasive procedures from our integrated interventional radiology department. Median follow-up was 41 days (IQR 8–58 days).

Result

Three patients (7%) in the vascular group (median age 61 years, all diabetic, two male) died from COVID-19, all of whom tested positive postoperatively. Two others became positive but recovered. In comparison, two patients (2%) in the interventional radiology group died from COVID-19, however one was positive prior to their procedure.

Conclusion

Only urgent vascular cases should be performed during a COVID-19 surge, with elective work delayed or continued at clean sites. However, with growing waiting lists for elective surgery currently, further restrictions may not be a viable long-term solution. Resumption of care at hot sites should be considered, if resources allow for it and if safety measures can be implemented. The advantages of minimally invasive surgery may inherently reduce risk as well.

Take-home Message

Only urgent vascular cases should be performed during a peak outbreak of COVID-19, however we cannot continue to postpone elective procedures indefinitely or restrict all cases to solely clean sites. The resumption of care at hot sites encompasses a fine balance of risks versus benefits.
O33 Outcomes of patients undergoing emergency surgery during the first phase of national lockdown in the United Kingdom due to COVID-19 pandemic: experience at a district general hospital
Authors: Luo W , Limb R , Aslam A , Kattimani R , Karthikappallil D , Paramasivan A , Waseem M
Published: July 2021

Introduction

This study aimed to assess the impact of the COVID-19 pandemic on emergency operations during the first phase of lockdown in the United Kingdom, compared to the equivalent population in the same calendar period in 2019.

Method

We retrospectively reviewed patients undergoing surgery in emergency theatres at our district general hospital between March 23rd and May 11th in 2019 and 2020. Data collected included demographics, National Confidential Enquiry into Patient Outcome and Death (NCEPOD) category and procedure. The primary outcome was 90-day post-operative mortality; secondary outcomes included time to intervention and length of inpatient stay.

Result

132 patients (2020) versus 141 (2019) patients were included with no significant difference in age (P = 0.676), sex (P = 0.230), or overall 90-day postoperative mortality (P = 0.196). Notably, time to intervention was faster for NCEPOD code 3 patients in 2020 than 2019 (P = 0.027). Time to intervention in 2020 was longer for those dying within 90 days post-operatively compared to survivors (P = 0.02). There was no difference in length of stay between years, both overall and when comparing subgroups by NCEPOD category or procedures (fractured neck of femur (P = 0.776), laparoscopies (P = 0.866), laparotomies (P = 0.252)), except for upper limb trauma (P = 0.007).

Conclusion

This study is amongst the first describing the general case mix in emergency theatres in the UK. Patient pre-operative characteristics and demographics did not change. Our data confirms patient prioritisation according to NCEPOD recommendations and streamlining of surgical services, with no difference in overall mortality, time to intervention or length of stay compared to 2019.

Take-home Message

At this district general hospital, patients were appropriately prioritised, and our results show adaptation of hospital practice to emerging national guidelines during the first phase of lockdown. A national validation audit assessing morbidity and mortality outcomes for all NCEPOD patients may be facilitate further understanding of risks posed to patients requiring urgent surgery during these unprecedented times.
O34 Colorectal cancer resections during COVID-19: to do or not to do?
Authors: Barter R , Kalaiselvan R
Published: July 2021

Introduction

Ascertaining the practice of colorectal cancer (CRC) resections during the COVID-19 pandemic in England and Wales.

Method

A list of all colorectal multi-disciplinary teams (MDTs) was obtained from the National Bowel Cancer Audit (NBOCA) database. A survey was designed using Google Forms and emailed to at least one consultant colorectal surgeon of each MDT. One response per MDT was used in the analysis. All responses were anonymous. Study duration was from 15th April 2020 to 30th June 2020.

Result

Sixty-eight of the 150 MDTs enlisted on the NBOCA database in England and Wales responded. 86.6% were performing CRC resections and 86% were screening patients pre-operatively for COVID-19. 84.9% were using full Personal Protective Equipment (PPE—FFP3 and eye protection) in all cases whereas 12.3% were using PPE only in suspected cases. 44.4% had resorted to open resections due to risk of laparoscopy being an aerosol generating procedure. 13.7% attributed post-operative complications to COVID-19 and 4 centres reported death due to COVID-19 related complications. 40% of MDTs used short course radiotherapy in rectal cancer patients where resections were postponed either by patient or by the team. 55% responded to feeling uncomfortable/very uncomfortable to cancel cancer resections while 31.7% were equivocal and others comfortable not to operate during the pandemic.

Conclusion

This survey demonstrates a snapshot of practice during the peak of the COVID-19 pandemic. The majority of the centres continued to perform CRC resections safely where possible. There has been obvious disruption to services and change to normal practice.

Take-home Message

COVID-19 led to an unprecedented situation where safe guidance had to be implemented at short notice to enable safe surgical practice. This survey aimed to establish how colorectal MDTs in England and Wales were adapting their colorectal cancer resection practice in light of new guidance amidst the first wave of the pandemic.