bluuebunny/crossref_metadata_2025 huggingface dataset:
Disruption of targeted muscle reinnervation due to heterotopic ossification in an amputated lower extremity
Authors: Anderson Spencer R , Gupta Nishtha , Johnson Elise A , Johnson Ron Michael
Published: May 2022

A patient in his late 40s presented after 1-year following below knee amputation and targeted muscle reinnervation (TMR) with new prosthesis intolerance and pinpoint pain, suspicious for neuroma. X-ray confirmed fibular heterotopic ossification (HO). Operative revision identified HO encompassing a TMR construct with a large neuroma requiring excision and neuroplasty revision. Now approximately 1-year post procedure, the patient remains active, pain-free and ambulating with a prosthetic. Amputated extremities can be at risk for development of HO. Although described in literature, the pathophysiology and timeline for HO development is not well understood. Preventative measures for HO have been described, yet results remain variable. The gold standard for existing HO remains to be operative excision. Due to the unpredictable nature and debilitating presentation, risk of HO should be incorporated into patient–physician discussions. Additionally, new prosthetic intolerance absent of prior trauma should raise suspicion for possible HO development.
Characterisation of the vascular anterior surface of type 1 macular neovascularisation after anti-VEGF therapy
Authors: Corvi Federico , Bacci Tommaso , Corradetti Giulia , Staurenghi Giovanni , Sarraf David , Freund K. Bailey , Sadda SriniVas
Published: May 2022

Background

To evaluate whether the status of vasculature at the top of type 1 macular neovascularisation (MNV) could function as mediator of the observed protective effect against the development of complete retinal pigment epithelial and outer retinal atrophy (cRORA).

Methods

In consecutive treatment-naïve patients, the vasculature at the anterior surface of the MNV was isolated using a slab designed to extract the most superficial vascular portion of the MNV lesion showing a choriocapillaris (CC)-like structure which we termed the ‘neo-CC’. The ratio between the neo-CC area (isolated using this custom slab) and the MNV area (isolated using the standard outer retina-CC slab) at baseline and at last follow-up was evaluated.

Results

Forty-four eyes from 44 patients were included. 20 showed cRORA by the final follow-up (median 23 months), whereas 24 did not progress to atrophy (median 23.5 months). The proportion of MNV with neo-CC at the anterior surface was significantly lower in eyes which progressed to cRORA compared with those which did not. The multivariate regression showed that a lower proportion of neo-CC coverage over the MNV was associated with an increased odds for cRORA development.

Conclusions

More extensive coverage of neo-CC is associated with a lower likelihood of development of macular atrophy in eyes receiving antivascular endothelial growth factor therapy, suggesting the protective effect of a type 1 MNV may be mediated by the development of a neo-CC and may provide insights into the biological significance of MNV as a response mechanism in eyes with age-related macular degeneration.
Quantitative evaluation of retinal and choroidal vascularity and retrobulbar blood flow in patients with myopic anisometropia by CDI and OCTA
Authors: Liu Fang , Niu Lingling , Guo Jie , Jian Weijun , Shang Jianmin , Zhao Jing , Xue Kang , Zhou Xingtao
Published: May 2022

Aims

To investigate the association between the myopic severity and retinal microvascular density, choroidal vascularity and retrobulbar blood flow in adult anisomyopes.

Methods

This study comprised 90 eyes of 45 myopic anisomyopes who were recruited for Colour Doppler imaging (CDI) and optical coherence tomography angiography (OCTA). The superficial vessel density (SVD), deep vessel density (DVD), choroidal thickness (ChT) and choroidal vascularity, including total choroidal area (TCA), luminal area (LA), stromal area (SA) and Choroidal Vascularity Index (CVI), were measured using OCTA. Moreover, the Pulsatile Index, peak systolic velocity (PSV) and end diastolic velocity (EDV) of posterior ciliary artery (PCA), central retinal artery (CRA) and ophthalmic artery (OA) were quantified by CDI, and all parameters were compared between two eyes and the correlations among parameters were analysed.

Results

The mean difference of spherical equivalent (SE) and axial lengths (AL) between eyes were −6.00±2.94 D and 2.48±1.31 mm, respectively. The SVD, DVD, ChT, TCA, LA, SA and CVI were significantly lower in more myopic eyes compared with the contralateral eyes. In more myopic eyes, CDI parameters of CRA and PSV and EDV of PCA were also significantly lower. After adjusting for age and sex, the binocular asymmetry in LA and ChT was independent risk factor affecting interocular difference in both AL and SE.

Conclusion

Retinal microvascular density, choroidal vascularity and retrobulbar blood flow were simultaneously lower in adult myopic anisomyopes with more myopic eyes and disturbed choroid circulation was related to the severity of myopia. Further longitudinal study was helped to identify the effect of choroidal parameters for myopic progression.
Validation of the RCOphth and UKEGS glaucoma risk stratification tool ‘GLAUC-STRAT-fast’
Authors: Konstantakopoulou Evgenia , Kastner Alan , Gazzard Gus , Jayaram Hari
Published: May 2022

Background/aims

The aim of this study was to validate the Glaucoma Risk Stratification Tool (GLAUC-STRAT-fast) currently recommended by the Royal College of Ophthalmologists for the risk stratification of patients with glaucoma in the UK National Health Service Hospital Eye Service.

Methods

GLAUC-STRAT fast was applied to the LiGHT trial participants by risk-stratifying the worse eye of each patient at baseline and after 3 years of treatment. Metrics of disease severity or treatment intensity used for the validation were: increased number of monitoring visits or treatment escalations; needing a trabeculectomy; a reduction of >2 dB in visual field mean deviation (VF MD) during the monitoring period; identification of rapid VF loss on total (TD) and/or pattern deviation (PD). The proportion of eyes within each baseline stratum for each of the above markers was compared against the other strata, using a χ2test for proportions.

Results

There was an association between the baseline stratification and the number of treatment escalations needed to maintain the eye-specific target intraocular pressure (p=0.001), the number of visits needed throughout the 3-year follow-up period (p=0.001), the need for trabeculectomy (p<0.001) and absolute loss of MD over the course of the monitoring period (p<0.001). The rate of VF progression was not associated with baseline risk stratification for TD or PD progression (p≥0.007, with Bonferroni correction).

Conclusion

The GLAUC-STRAT fast tool is a useful tool for risk stratifying eyes with ocular hypertension or open angle glaucoma. Further research is needed to confirm and validate its applicability to more advanced glaucomas and generalisability to clinical use.

Trial registration number

The LiGHT trial is registered at controlled-trials.com (ISRCTN32038223).
Association between vision impairment and depression: a 9-year, longitudinal, nationwide, population-based cohort study in South Korea
Authors: Seong Hyo Jin , Kim Jiwon , Yook Tae Mi , Lee Deokjong , Chung Eun Jee
Published: May 2022

Background/Aims

Vision impairment (VI) increases the risk of various comorbidities, including depression. However, the relationship between depression and VI is unclear, and existing findings are inconsistent. We therefore investigated the risk of depression in adults before and after their registration as visually impaired.

Methods

In this longitudinal, nationwide, retrospective cohort study, 131 434 patients (aged ≥18 years) with newly registered VI during 2005–2013 were evaluated using the Korean National Health Insurance Service database. Using 1:1 propensity score matching, randomly selected patients (control group) were compared with patients with VI (patient group) according to age, sex, residential area and household income. Each patient was tracked from 3 years before and 5 years after registration. The risk of depression before and after VI registration was evaluated using a conditional logistic regression model.

Results

The risk of depression gradually increased from 3 years before registration (OR, 1.186; 95% CI 1.089 to 1.290), then peaked at the time of registration (OR, 1.925; 95% CI 1.788 to 2.073), and then gradually decreased until 5 years after registration (OR, 1.128; 95% CI 1.046 to 1.216). Male patients, those with severe VI and those aged 18–29 years had a higher risk of depression.

Conclusions

Patients with VI had an increased risk of depression from 3 years before to 5 years after registration. Significant risk factors included severity, male sex and younger age. Thus, public mental health services are necessary to provide appropriate support and interventions to people before and after registration as visually impaired.
Cardiovascular morbidity and all-cause mortality in patients with retinal vein occlusion: a Danish nationwide cohort study
Authors: Frederiksen Katrine Hartmund , Stokholm Lonny , Frederiksen Peter Hartmund , Jørgensen Christina Mørup , Möller Sören , Kawasaki Ryo , Peto Tunde , Grauslund Jakob
Published: May 2022

Background/aims

Associations between retinal vein occlusion (RVO) and subsequent cardiovascular disease (CVD) or mortality have not been evaluated in a recent cohort, after novel therapeutic options have increased referrals for treatment of the condition. We aimed to evaluate overall and subtype-stratified risk of CVD and all-cause mortality following RVO and assess any alterations after the introduction of angiostatic therapy in Denmark in 2011.

Methods

This nationwide, registry-based cohort study from 1998 to 2018 evaluated 4 194 781 individuals. Hazard ratios (HRs) were reported for RVO as an overall measure and subclassified as branch and central RVO.

Results

Patients with RVO (n=15 665) were median 71.8 years old at the time of exposure and 50.7% were women. RVO associated with incident CVD (adjusted HR 1.13, 95% CI 1.09 to 1.17) but not mortality (adjusted HR 1.00, 95% CI 0.97 to 1.03). Almost similar risks of CVD were found for patients with branch and central RVO (adjusted HRs 1.14, 95% CI 1.03 to 1.25, and 1.12, 95% CI 1.00 to 1.25, respectively), but only patients with central RVO exhibited increased mortality (adjusted HR 1.12, 95% CI 1.04 to 1.21). Risk of CVD, especially non-ischaemic, was higher for patients diagnosed after 2011 (adjusted HRs 1.24, 95% CI 1.15 to 1.33 vs 1.06, 95% CI 1.01 to 1.12).

Conclusion

In a cohort of the Danish population aged 40 years or more, patients with RVO had a 13% increased risk of incident CVD compared with unexposed individuals. Risk of CVD was increased after 2011, when intravitreal angiostatic treatment was introduced and referral practices altered.
Dapagliflozin protects neural and vascular dysfunction of the retina in diabetes
Authors: Luo Qianyi , Leley Sameer P , Bello Erika , Dhami Hurshdeep , Mathew Deepa , Bhatwadekar Ashay Dilip
Published: May 2022

Introduction

Dapagliflozin, a sodium-glucose transporter inhibitor, effectively reduces blood glucose and is indicated for individuals with kidney diseases and cardiovascular disorders. In this study, we further expand the therapeutic benefit of dapagliflozin in the neural and vascular retina, with the potential to effectively manage diabetic retinopathy (DR), the most common complication of diabetes.

Research design and methods

Db/db mice, an animal model of type 2 diabetes, were treated with dapagliflozin orally, and the electroretinogram (ERG) response and acellular capillary numbers were assessed. Messenger RNA levels of inflammatory cytokines were studied using real-time quantitative (q)PCR. We assessed endothelial cell migration in a scratch wound assay and retinal glucose uptake using human retinal endothelial cells.

Results

The dapagliflozin treatment improved the ERG b-wave amplitude and decreased acellular capillary numbers. The scratch wound assay demonstrated a reduction in wound closure after dapagliflozin treatment. Retinal glucose uptake reduced after dapagliflozin treatment compared with the respective controls.

Conclusions

Our studies suggest that dapagliflozin treatment effectively corrects neural and vascular dysfunction of the retina in diabetes. This effect is mediated by a decrease in inflammation and improved glycemic control. In addition, dapagliflozin exhibits decreased wound healing and glucose uptake, which could benefit the retina. Thus, dapagliflozin could be helpful in the management of DR, with multimodal therapeutic effects.
COVID-19 and liver cancer: lost patients and larger tumours
Authors: Geh Daniel , Watson Robyn , Sen Gourab , French Jeremy J , Hammond John , Turner Paul , Hoare Tim , Anderson Kirsty , McNeil Michael , McPherson Stuart , Masson Steven , Dyson Jessica , Donnelly Mhairi , MacDougal Louise , Patel Preya , Hudson Mark , Anstee Quentin M , White Steven , Robinson Stuart , Pandanaboyana Sanjay , Walker Lucy , McCain Misti , Bury Yvonne , Raman Shreya , Burt Alastair , Parkinson Daniel , Haugk Beate , Darne Antony , Wadd Nick , Asghar Syed , Mariappan Lavanya , Margetts Jane , Stenberg Benjamin , Scott John , Littler Peter , Manas Derek M , Reeves Helen L
Published: May 2022

Background

Northern England has been experiencing a persistent rise in the number of primary liver cancers, largely driven by an increasing incidence of hepatocellular carcinoma (HCC) secondary to alcohol-related liver disease and non-alcoholic fatty liver disease. Here we review the effect of the COVID-19 pandemic on primary liver cancer services and patients in our region.

Objective

To assess the impact of the COVID-19 pandemic on patients with newly diagnosed liver cancer in our region.

Design

We prospectively audited our service for the first year of the pandemic (March 2020–February 2021), comparing mode of presentation, disease stage, treatments and outcomes to a retrospective observational consecutive cohort immediately prepandemic (March 2019–February 2020).

Results

We observed a marked decrease in HCC referrals compared with previous years, falling from 190 confirmed new cases to 120 (37%). Symptomatic became the the most common mode of presentation, with fewer tumours detected by surveillance or incidentally (% surveillance/incidental/symptomatic; 34/42/24 prepandemic vs 27/33/40 in the pandemic, p=0.013). HCC tumour size was larger in the pandemic year (60±4.6 mm vs 48±2.6 mm, p=0.017), with a higher incidence of spontaneous tumour haemorrhage. The number of new cases of intrahepatic cholangiocarcinoma (ICC) fell only slightly, with symptomatic presentation typical. Patients received treatment appropriate for their cancer stage, with waiting times shorter for patients with HCC and unchanged for patients with ICC. Survival was associated with stage both before and during the pandemic. 9% acquired COVID-19 infection.

Conclusion

The pandemic-associated reduction in referred patients in our region was attributed to the disruption of routine healthcare. For those referred, treatments and survival were appropriate for their stage at presentation. Non-referred or missing patients are expected to present with more advanced disease, with poorer outcomes. While protective measures are necessary during the pandemic, we recommend routine healthcare services continue, with patients encouraged to engage.
Prevalence, severity, duration and resolution of cholestasis after acute liver failure
Authors: Warming Scott , Michel Claire , Serpa Neto Ary , Kishore Kartik , Marhoon Nada , Holmes Natasha , Bellomo Rinaldo , Testro Adam , Sinclair Marie , Gow Paul , Warrillow Stephen
Published: May 2022

Objective

Persistent cholestasis may follow acute liver failure (ALF), but its course remains unknown. We aimed to describe the prevalence, onset, severity, duration and resolution of post-ALF cholestasis.

Design

Cohort of 127 adult patients with ALF at a liver transplantation centre identified using electronic databases. We obtained laboratory data every 6 hours for the first week, daily until day 30 and weekly, when documented, until day 180.

Results

Median age was 40.7 (IQR 31.0–52.4) years, median peak alanine aminotransferase level was 5494 (2521–8819) U/L and 87 (68.5%) cases had paracetamol toxicity. Overall, 12.6% underwent transplantation (3.4% for paracetamol vs 32.5% for non-paracetamol; p<0.001). Ninety-day mortality was 20.7% for paracetamol versus 30.0% for non-paracetamol patients. All non-transplanted survivors reached a bilirubin level>50 µmol/L, which peaked 3.5 (1.0–10.1) days after admission at 169.0 (80.0–302.0) µmol/L. At hospital discharge, 18.8% of patients had normal bilirubin levels and, at a median follow-up time from admission to last measurement of 16 (10-30) days, 46.9% had normal levels. Similarly, there was an increase in alkaline phosphatase (ALP) (207.0 (148.0–292.5) U/L) and gamma-glutamyl transferase (GGT) (336.0 (209.5–554.5) U/L) peaking at 4.5 days, with normalised values in 40.3% and 8.3% at hospital discharge.

Conclusion

Post-ALF cholestasis is ubiquitous. Bilirubin, ALP and GGT peak at 3 to 5 days and, return to baseline in the minority of patients at median follow-up of 16 days. These data inform clinical expectations of the natural course of this condition.
Flash glucose monitoring: the story so far and the journey ahead
Authors: Crabtree Thomas Simon James , Choudhary Pratik , Kar Partha , Wilmot Emma G
Published: May 2022

Just a few years ago FreeStyle Libre (FSL) was a rarely encountered device, used only by a select few people with type 1 diabetes who could afford to self-fund it. This small disc has a small cannula under the skin which allows for interstitial glucose measurements and remains in situ for 14 days. Over the last 4 years the number of people with access to this life-changing technology on the National Health Service (NHS) has increased rapidly. Although there were barriers to implementing access and encouraging uptake of this technology, including systems, healthcare professionals and the users themselves, innovative interventions from NHS England and diabetes organisations ensured those who stood to gain the most benefit were not impeded in their access, with a particular emphasis on enabling FSL use in those who are often the hardest to reach. This article reviews the impact of FSL on type 1 diabetes care in England, the key events to date and the lessons learnt that can be applied in the future for newer diabetes technologies.
Approaching healthcare delivery through a new lens: a crowdsourcing challenge to identify health-related social innovations to increase universal health coverage in Nigeria
Authors: Ekwunife Obinna Ikechukwu , Onubogu Chinyere Ukamaka , Aribodor Ogechukwu Benedicta , Anigbogu Kingsley Chike , Ogwaluonye Uchenna Chukwunonso , Ekwunife Chinyelu Angela , Okunna Chinyere Stella , Nwaorgu Obioma
Published: May 2022

Background

Nigeria, the most populous country in Africa, is faced with several health challenges including neglected tropical diseases, non-communicable diseases and emerging infectious diseases. Unfortunately, the country has a weak health system to tackle these health challenges. Creative solutions for solving these systemic health challenges through social innovations are therefore needed in Nigeria. Hence, Social Innovation in Health Initiative (SIHI) Nigeria conducted a pilot crowdsourcing challenge to identify social innovation solutions in Anambra State, Nigeria.

Method

A crowdsourcing approach was used to identify social innovations in healthcare delivery that has been applied in Nigeria for a minimum of 1 year. The six-stage process of the crowdsourcing challenge contest included: (1) selection of challenge focus, (2) organising community steering group, (3) engaging the community to contribute, (4) receiving and evaluating contributions, (5) recognising finalists and (6) sharing solutions. The crowdsourcing challenge was hosted by SIHI Nigeria, based at the Nnamdi Azikiwe University, Awka, Nigeria.

Result

Seventeen innovations were received in the crowdsourcing challenge. Five of the innovations were eligible based on criteria developed and were sent to the panel of experts for review. Following the review of the average score and case study research, the panel of experts selected top three innovations, which included a digital health solution, a mobile clinic and a community-based health insurance programme.

Conclusion

Top three social innovations were identified in the crowdsourcing challenge. These innovations could be refined and scaled up to increase universal health coverage in Nigeria by subjecting them to further research.
Thoracic spinal anaesthesia for abdominal surgery in a humanitarian military field hospital: a prospective observational study
Authors: Aissaoui Younes , Bahi M , El Khader A , El Barni R , Belhadj A
Published: May 2022

Background

Providing safe and effective anaesthesia in the context of humanitarian medicine is always a challenging situation. Spinal anaesthesia, and in particular its thoracic approach, represents a promising technique for such a limited-resource environment. This prospective observational study investigated the feasibility of thoracic spinal anaesthesia (TSA) for abdominal surgery in a field-deployed military hospital.

Materials and methods

We included adults scheduled for elective open cholecystectomy in a field hospital. Patients received TSA at the T9–T10 level. The primary outcomes were the feasibility of surgery under TSA and the haemodynamic/respiratory stability of this anaesthetic technique. The secondary outcomes included patient satisfaction and surgeon comfort regarding the anaesthesia technique and postoperative events (nausea and vomiting, urinary retention, postdural puncture headache).

Results

Surgery was performed successfully in 61 patients under TSA (90% female, 53±13 years old). Intraoperative pain scores were low, with a median Numeric Rating Scale score of 0 (IQR 0–2). Surgeon and patient satisfaction scores were excellent. The haemodynamic and respiratory parameters remained stable throughout the surgery. The incidence of postoperative events was low (nausea/vomiting=8%). None of our patients presented with postdural puncture headache or urinary retention.

Conclusion

TSA could be an effective anaesthetic technique for abdominal surgery in the context of a field hospital or austere environment.
Non-invasive ventilation for acute hypoxaemic respiratory failure: a propensity-matched cohort study
Authors: Jayasimhan Dilip , Martynoga Robert Adam , Fairweather Sarah M , Chang Catherina L
Published: May 2022

Background

Non-invasive ventilation (NIV), although effective in treating hypercapnic respiratory failure, has not demonstrated the same efficacy in treating acute hypoxaemic respiratory failure. We aimed to examine the effect of NIV use on ventilator-free days in patients with acute hypoxaemic respiratory failure admitted to the intensive care unit (ICU).

Methods

We conducted a retrospective study of patients admitted to the ICU with acute hypoxaemic respiratory failure at Waikato Hospital, New Zealand, from 1 January 2009 to 31 December 2018. Patients treated with NIV as the initial oxygenation strategy were compared with controls treated with early intubation. The two groups were matched using a propensity score based on baseline characteristics. The primary outcome was the number of ventilator-free days at day 28. The secondary outcomes were ICU and hospital length of stay and in-hospital mortality.

Results

Out of 175 eligible patients, 79 each out of the NIV and early intubation groups were matched using a propensity score. Early NIV was associated with significantly higher median ventilator-free days than early intubation (17 days vs 23 days, p=0.013). There was no significant difference in median ICU length of stay (112.5 hours vs 117.7 hours), hospital length of stay (14 days vs 14 days) or in-hospital mortality (31.6% vs 37.9%) between the NIV and the early intubation group.

Conclusion

Compared with early intubation, NIV use was associated with more ventilator-free days in patients with hypoxaemic respiratory failure. However, this did not translate into a shorter length of stay or reduced mortality based on our single-centre experience.
Functional status recovery trajectories in hospitalised older adults with pneumonia
Authors: Park Chan Mi , Dhawan Ravi , Lie Jessica J , Sison Stephanie M , Kim Wonsock , Lee Eun Sik , Kim Jong Hun , Kim Dae Hyun
Published: May 2022

Background and objectives

Pneumonia is associated with significant mortality and morbidity in older adults. We investigated changes in functional status over 6 months after pneumonia hospitalisation by frailty status.

Methods and measurements

This single-centre prospective cohort study enrolled 201 patients (mean age 79.4, 37.3% women) who were hospitalised with pneumonia. A deficit-accumulation frailty index (range: 0–1; robust <0.15, pre-frail 0.15–0.24, mild-to-moderately frail 0.25–0.44, severely frail ≥0.45) was calculated on admission. Functional status, defined as self-reported ability to perform 21 activities and physical tasks independently, was measured by telephone at 1, 3 and 6 months after discharge. Group-based trajectory model was used to identify functional trajectories. We examined the probability of each trajectory based on frailty levels.

Results

On admission, 51 (25.4%) were robust, 43 (21.4%) pre-frail, 40 (20.0%) mild-to-moderately frail and 67 (33.3%) severely frail patients. Four trajectories were identified: excellent (14.4%), good (25.4%), poor (28.9%) and very poor (31.3%). The trajectory was more strongly correlated with frailty level on admission than pneumonia severity. The most common trajectory was excellent trajectory (59.9%) in robust patients, good trajectory (74.4%) in pre-frail patients, poor trajectory (85.0%) in mild-to-moderately frail patients and very poor trajectory (89.6%) in severely frail patients. The risk of poor or very poor trajectory from robust to severely frail patients was 11.8%, 25.6%, 92.5% and 100%, respectively.

Conclusions

Frailty was a strong determinant of lack of functional recovery over 6 months after pneumonia hospitalisation in older adults. Our results call for hospital-based and post-acute care interventions for frail patients.
Modelling the potential spread of virus during soccer matches
Authors: Knudsen Nikolas Sten , Thomasen Manuel Mounir Demetry , Andersen Thomas Bull
Published: May 2022

Objective

In the present study, we model the potential spread of virus during soccer matches.

Methods

Tracking data from 14 elite soccer matches was used. One player in each match was designated as a virus carrier (called ‘infected player’) for the purpose of the study. The exposure score (measured in seconds) was calculated as time spent closer than 1.5 m from the infected player or time spent in an exponentially declining zone, where the infected player was positioned earlier.

Results

The results revealed that, on average, each player was exposed for 87.8 s per match.

Conclusion

Potential spread of virus during soccer matches was modelled and it revealed that the exposure to a virus during soccer matches is limited.
Major variation in hepatocellular carcinoma treatment and outcomes in England: a retrospective cohort study
Authors: Beecroft Sue , O’Connell Matthew , Nassar Ayman , Noon Katie , Pollock Kevin G , Palmer Dan , Cross Timothy J S
Published: May 2022

Objective

Hepatocellular carcinoma (HCC) is increasingly incident in England, while survival remains poor with regional disparities. We aimed to explore the differences in HCC treatment across different geographical regions and to examine the impact on cancer survival.

Methods

Incident HCC cases and treatment were identified from the English Hospital Episode Statistics (2016–2017) and then a subset by National Health Service (NHS) regions. Treatment was grouped into curative, palliative and untreated. Median survival was estimated to date of death in the national statistics.

Results

The median observed survival was 8.6 months (95% CI 7.5 to 9.9) across all 2160 HCC cases, 52.1 months (CI 50.5, not reached) in 449 (20.8%) treated with curative intent, 21.0 months (CI 18.5 to 24.5) after other cancer-specific treatment in 449 (20.8%), and 2.3 months (CI 2.1 to 2.6) in 1262 (58.4%) untreated. Across NHS regions, <50% of cases received treatment (30.4%–49.6%), while between 14.2% and 27.7% had curative treatment. The 3-year survival was similar (23.5%–29.7%), except in the London region (40.0%).

Conclusion

Majority of HCC cases in England are untreated and survival remains low, with variation in outcomes in regions with similar incident rates. A deeper exploration of regional treatments and screening practice is required to improve early detection and survival.
Development and validation of the scale for measuring biopsychosocial approach of family physicians to their patients
Authors: Makivić Irena , Klemenc-Ketiš Zalika
Published: May 2022

Objective

While other models focus more on disease and pathophysiology, the biopsychosocial approach emphasises the importance of human health and disease in their fullest contexts. If we are to gain an insight into physical and psychological health needs, and address them quickly and adequately, it is important that we recognise them already at the family practice stage. An approach that assesses needs at patient level could also be seen as patient-centred care, which is one of the key elements of high-quality care. To the best of our knowledge, no scale for measuring the biopsychosocial approach of family physicians has yet been developed.

Design

The aim of this study was to develop and validate a scale that measures the biopsychosocial approach of family physicians to their patients through the Delphi and validation process.

Setting

The scale was developed through the Delphi study and validated by means of significant statistical methods. Pearson’s correlation coefficient, Cronbach’s alpha, the intracorrelation coefficient, the Spearman-Brown coefficient and exploratory factor analysis were applied.

Participants

Five family physicians took part in a brainstorming process and 24 family medicine experts took part in the Delphi study. For the first part of the validation process, there were 31 family medicine trainees in the first group and 32 in the second group. For the last part of the validation process, 164 family physicians completed the scale.

Result

Through the Delphi study, 39 final items covering three areas within the biopsychosocial approach were identified. Construct validity was high, with positive linear correlation and good face validity. The intraclass correlation coefficient for test–retest reliability was 0.862. The Spearman-Brown coefficient was the highest (0.931) on an even and odd division. Factor rotation showed that three factors on 35 items explained 39.5% of variances. The final internal consistency on 35 items was 0.911.

Conclusion

The developed scale measures the biopsychosocial dimension of family physicians’ work with high Cronbach’s alpha measures and good validity.
Tacrolimus-binding protein FKBP8 directs myosin light chain kinase-dependent barrier regulation and is a potential therapeutic target in Crohn’s disease
Authors: Zuo Li , Kuo Wei-Ting , Cao Feng , Chanez-Paredes Sandra D , Zeve Daniel , Mannam Prabhath , Jean-François Léa , Day Anne , Vallen Graham W , Sweat Yan Y , Shashikanth Nitesh , Breault David T , Turner Jerrold R
Published: May 2022

Objective

Intestinal barrier loss is a Crohn’s disease (CD) risk factor. This may be related to increased expression and enzymatic activation of myosin light chain kinase 1 (MLCK1), which increases intestinal paracellular permeability and correlates with CD severity. Moreover, preclinical studies have shown that MLCK1 recruitment to cell junctions is required for tumour necrosis factor (TNF)-induced barrier loss as well as experimental inflammatory bowel disease progression. We sought to define mechanisms of MLCK1 recruitment and to target this process pharmacologically.

Design

Protein interactions between FK506 binding protein 8 (FKBP8) and MLCK1 were assessed in vitro. Transgenic and knockout intestinal epithelial cell lines, human intestinal organoids, and mice were used as preclinical models. Discoveries were validated in biopsies from patients with CD and control subjects.

Results

MLCK1 interacted specifically with the tacrolimus-binding FKBP8 PPI domain. Knockout or dominant negative FKBP8 expression prevented TNF-induced MLCK1 recruitment and barrier loss in vitro. MLCK1-FKBP8 binding was blocked by tacrolimus, which reversed TNF-induced MLCK1-FKBP8 interactions, MLCK1 recruitment and barrier loss in vitro and in vivo. Biopsies of patient with CD demonstrated increased numbers of MLCK1-FKBP8 interactions at intercellular junctions relative to control subjects.

Conclusion

Binding to FKBP8, which can be blocked by tacrolimus, is required for MLCK1 recruitment to intercellular junctions and downstream events leading to immune-mediated barrier loss. The observed increases in MLCK1 activity, MLCK1 localisation at cell junctions and perijunctional MLCK1-FKBP8 interactions in CD suggest that targeting this process may be therapeutic in human disease. These new insights into mechanisms of disease-associated barrier loss provide a critical foundation for therapeutic exploitation of FKBP8-MLCK1 interactions.
Hepatic p63 regulates glucose metabolism by repressing SIRT1
Authors: Gonzalez-Rellan Maria J , Novoa Eva , da Silva Lima Natalia , Rodriguez Amaia , Veyrat-Durebex Christelle , Seoane Samuel , Porteiro Begoña , Fondevila Marcos F , Fernandez Uxia , Varela-Rey Marta , Senra Ana , Iglesias Cristina , Escudero Adriana , Fidalgo Miguel , Guallar Diana , Perez-Fernandez Roman , Prevot Vincent , Schwaninger Markus , López Miguel , Dieguez Carlos , Coppari Roberto , Frühbeck Gema , Nogueiras Ruben
Published: May 2022

Objective

p63 is a transcription factor within the p53 protein family that has key roles in development, differentiation and prevention of senescence, but its metabolic actions remain largely unknown. Herein, we investigated the physiological role of p63 in glucose metabolism.

Design

We used cell lines and mouse models to genetically manipulate p63 in hepatocytes. We also measured p63 in the liver of patients with obesity with or without type 2 diabetes (T2D).

Results

We show that hepatic p63 expression is reduced on fasting. Mice lacking the specific isoform TAp63 in the liver (p63LKO) display higher postprandial and pyruvate-induced glucose excursions. These mice have elevated SIRT1 levels, while SIRT1 knockdown in p63LKO mice normalises glycaemia. Overexpression of TAp63 in wild-type mice reduces postprandial, pyruvate-induced blood glucose and SIRT1 levels. Studies carried out in hepatocyte cell lines show that TAp63 regulates SIRT1 promoter by repressing its transcriptional activation. TAp63 also mediates the inhibitory effect of insulin on hepatic glucose production, as silencing TAp63 impairs insulin sensitivity. Finally, protein levels of TAp63 are reduced in obese persons with T2D and are negatively correlated with fasting glucose and homeostasis model assessment index.

Conclusions.

These results demonstrate that p63 physiologically regulates glucose homeostasis.
Recent advances in clinical practice: management of inflammatory bowel disease during the COVID-19 pandemic
Authors: Lin Simeng , Lau Louis HS , Chanchlani Neil , Kennedy Nicholas A , Ng Siew C
Published: May 2022

The COVID-19 pandemic has raised considerable concerns that patients with inflammatory bowel disease (IBD), particularly those treated with immunosuppressive therapies, may have an increased risk of SARS-CoV-2 acquisition, develop worse outcomes following COVID-19, and have suboptimal vaccine response compared with the general population. In this review, we summarise data on the risk of COVID-19 and associated outcomes, and latest guidance on SARS-CoV-2 vaccines in patients with IBD. Emerging evidence suggests that commonly used medications for IBD, such as corticosteroids but not biologicals, were associated with adverse outcomes to COVID-19. There has been no increased risk of de novo, or delayed, IBD diagnoses, however, an overall decrease in endoscopy procedures has led to a rise in the number of missed endoscopic-detected cancers during the pandemic. The impact of IBD medication on vaccine response has been a research priority recently. Data suggest that patients with IBD treated with antitumour necrosis factor (TNF) medications had attenuated humoral responses to SARS-CoV-2 vaccines, and more rapid antibody decay, compared with non-anti-TNF-treated patients. Reassuringly, rates of breakthrough infections and hospitalisations in all patients who received vaccines, irrespective of IBD treatment, remained low. International guidelines recommend that all patients with IBD treated with immunosuppressive therapies should receive, at any point during their treatment cycle, three primary doses of SARS-CoV-2 vaccines with a further booster dose as soon as possible. Future research should focus on our understanding of the rate of antibody decay in biological-treated patients, which patients require additional doses of SARS-CoV-2 vaccine, the long-term risks of COVID-19 on IBD disease course and activity, and the potential risk of long COVID-19 in patients with IBD.
British Society of Gastroenterology (BSG) and British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) joint consensus guidelines on the diagnosis and management of eosinophilic oesophagitis in children and adults
Authors: Dhar Anjan , Haboubi Hasan N , Attwood Stephen E , Auth Marcus K H , Dunn Jason M , Sweis Rami , Morris Danielle , Epstein Jenny , Novelli Marco R , Hunter Hannah , Cordell Amanda , Hall Sharon , Hayat Jamal O , Kapur Kapil , Moore Andrew Robert , Read Carol , Sami Sarmed S , Turner Paul J , Trudgill Nigel J
Published: May 2022

Background

Eosinophilic oesophagitis (EoE) is an increasingly common cause of dysphagia in both children and adults, as well as one of the most prevalent oesophageal diseases with a significant impact on physical health and quality of life. We have provided a single comprehensive guideline for both paediatric and adult gastroenterologists on current best practice for the evaluation and management of EoE.

Methods

The Oesophageal Section of the British Society of Gastroenterology was commissioned by the Clinical Standards Service Committee to develop these guidelines. The Guideline Development Group included adult and paediatric gastroenterologists, surgeons, dietitians, allergists, pathologists and patient representatives. The Population, Intervention, Comparator and Outcomes process was used to generate questions for a systematic review of the evidence. Published evidence was reviewed and updated to June 2021. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system was used to assess the evidence and make recommendations. Two rounds of voting were held to assess the level of agreement and the strength of recommendations, with 80% consensus required for acceptance.

Results

Fifty-seven statements on EoE presentation, diagnosis, investigation, management and complications were produced with further statements created on areas for future research.

Conclusions

These comprehensive adult and paediatric guidelines of the British Society of Gastroenterology and British Society of Paediatric Gastroenterology, Hepatology and Nutrition are based on evidence and expert consensus from a multidisciplinary group of healthcare professionals, including patient advocates and patient support groups, to help clinicians with the management patients with EoE and its complications.
Longitudinal changes of thoracic aortic diameters in the general population aged 55 years or older
Authors: Thijssen Carlijn G E , Mutluer Ferit O , van der Toorn Janine E , Bons Lidia R , Gökalp Arjen L , Takkenberg Johanna JM , Mokhles Mostafa M , van Kimmenade Roland R J , Vernooij Meike W , van der Lugt Aad , Budde Ricardo P J , Roos-Hesselink Jolien W , Kavousi Maryam , Bos Daniel
Published: May 2022

Objective

Longitudinal data on age-related changes in the diameters of the thoracic aorta are scarce. To better understand normal variation and to identify factors influencing this process, we aimed to report male-female-specific and age-specific aortic growth rate in the ageing general population and identify factors associated with growth rate.

Methods

From the prospective population-based Rotterdam Study, 943 participants (52.0% females, median age at baseline 65 years (62–68)) underwent serial non-enhanced cardiac CT. We measured the diameters of the ascending (AA) and descending aorta (DA) at two time points and expressed absolute and relative differences. Linear mixed effects analysis was performed to identify determinants associated with change in aortic diameters.

Results

Mean AA diameter at baseline was 37.3±3.6 mm in male population and 34.7±3.2 mm in female population, mean DA diameter was 29.6±2.3 in male population and 26.9±2.2 mm in female population. The median absolute change in diameters during follow-up (mean scan interval 14.1±0.3 years) was 1 mm (0–2) for both the AA and DA. Absolute change per decade in AA diameter was significantly larger in males than in females (0.72 mm/decade (0.00–1.43) vs 0.70 mm/decade (0.00–1.41), p=0.006), as well as absolute change in AD diameter (0.71 mm/decade (0.00–1.42) vs 0.69 mm/decade (0.00–1.36), p=0.008). There was no significant difference between male and female population in relative change of their aortic diameters during follow-up. Age, male sex, higher body mass index (BMI) and higher diastolic blood pressure (DBP) showed a statistically significant independent association with increase in AA and DA diameters over time.

Conclusions

Some degree of increase in thoracic aortic diameters is typical in both men and women of an aging population. Factors associated with this change in thoracic aortic diameters were sex, age, BMI and DBP.
Fractional flow reserve versus angiography alone in guiding myocardial revascularisation: a systematic review and meta-analysis of randomised trials
Authors: Elbadawi Ayman , Sedhom Ramy , Dang Alexander T , Gad Mohamed M , Rahman Faisal , Brilakis Emmanouil S , Elgendy Islam Y , Jneid Hani
Published: May 2022

Background

Randomised trials evaluating the efficacy and safety of fractional flow reserve (FFR)-guided versus angiography-guided revascularisation among patients with obstructive coronary artery disease (CAD) have yielded mixed results.

Aims

To examine the comparative efficacy and safety of FFR-guided versus angiography-guided revascularisation among patients with obstructive CAD.

Methods

An electronic search of MEDLINE, SCOPUS and Cochrane databases without language restrictions was performed through November 2021 for randomised controlled trials that evaluated the outcomes of FFR-guided versus angiography-guided revascularisation. The primary outcome was major adverse cardiac events (MACE). Data were pooled using a random-effects model.

Results

The final analysis included seven trials with 5094 patients. The weighted mean follow-up duration was 38 months. Compared with angiography guidance, FFR guidance was associated with fewer number of stents during revascularisation (standardised mean difference=−0.80; 95% CI −1.33 to −0.27), but no difference in total hospital cost. There was no difference between FFR-guided and angiography-guided revascularisation in long-term MACE (13.6% vs 13.9%; risk ratio (RR) 0.97, 95% CI 0.85 to 1.11). Meta-regression analyses did not reveal any evidence of effect modification for MACE with acute coronary syndrome (p=0.36), proportion of three-vessel disease (p=0.88) or left main disease (p=0.50). There were no differences between FFR-guided and angiography-guided revascularisation in the outcomes all-cause mortality (RR 1.16, 95% CI 0.80 to 1.68), cardiovascular mortality (RR 1.27, 95% CI 0.50 to 3.26), repeat revascularisation (RR 0.99, 95% CI 0.81 to 1.21), recurrent myocardial infarction (RR 0.92, 95% CI 0.74 to 1.14) or stent thrombosis (RR 0.61, 95% CI 0.31 to 1.21).

Conclusion

Among patients with obstructive CAD, FFR-guided revascularisation did not reduce the risk of long-term adverse cardiac events or the individual outcomes. However, FFR-guided revascularisation was associated with fewer number of stents.

PROSPERO registration number

CRD42021291596.
Perioperative outcomes and readmissions following cardiac operations in kidney transplant recipients
Authors: Madrigal Josef , Richardson Shannon , Hadaya Joseph , Verma Arjun , Tran Zachary , Sanaiha Yas , Benharash Peyman
Published: May 2022

Objective

Although kidney transplant (KTx) recipients are at significant risk for cardiovascular disease, outcomes following cardiac operations have been examined in limited series. The present study thus aimed to assess the impact of KTx on in-hospital perioperative outcomes and readmissions in a nationally representative cohort.

Methods

All adults undergoing elective coronary artery bypass grafting, valve repair/replacement or a combination thereof were identified from the 2010–2018 Nationwide Readmissions Database. Patients were stratified by history of KTx. Transplant-capable centres were defined as hospitals performing at least one KTx annually. To perform risk-adjustment in assessing outcomes, multivariable regression models were developed.

Results

Of an estimated 1 407 351 patients included for analysis, 0.2% (n=2849) were KTx recipients. Compared with the general cardiac surgical population, patients with prior KTx experienced higher adjusted odds of in-hospital mortality (adjusted OR (AOR) 2.44, 95% CI 1.72 to 3.47, p<0.001) and perioperative complication (AOR 1.67, 95% CI 1.44 to 1.94, p<0.001). Additionally, KTx was independently associated with greater readmission rates within 30 days (AOR 1.96, 95% CI 1.65 to 2.34, p<0.001) with kidney injury contributing significantly to the burden of rehospitalisation (4.6 vs 1.8%, p=0.005). In a subpopulation comprised of only KTx recipients, treatment at a transplant-capable centre reduced odds of kidney injury with non-transplant hospitals as reference (AOR 0.65, 95% CI 0.43 to 0.98, p=0.037).

Conclusions

Kidney transplant recipients undergoing cardiac operations encounter significant risks compared with the general surgical population. Referral to transplant-capable centres should be explored to improve outcomes and to preserve allograft function in this population.