bluuebunny/crossref_metadata_2025 huggingface dataset:
O078 Is there a role for SLNB in women with breast cancer >70 years old? A retrospective institutional review
Authors: Daly G , Hamza E , Dowling G , Kearney J , Downey E , Naz T , Calpin G , Butt A , Power C , Hill A
Published: May 2023

Introduction

The Choosing Wisely guidelines were published to de-escalate surgical staging of the axilla in women >70 years of age with early invasive breast cancer. They advised against performing a sentinel lymph node biopsy (SLNB) in clinically node negative, ER+, HER2- breast cancer. Despite these guidelines, some surgeons continue to perform SLNB for adjuvant chemo/radiotherapy guidance in this cohort.

Methods

A retrospective review of 347 women >70 years of age with invasive breast cancer, who underwent a SLNB between 2014 and 2022 in a single institution was performed using the Beaumont Breast Cancer Database. Data was collected on patient and tumour characteristics, subsequent management and overall survival (OS).

Results

Of 347 patients included, 91(26.22%) had a positive SLNB. 49 (14.1%) patients received chemotherapy. Of the 66 patients >80 years old, 1 received chemotherapy (1.5%). Total of 13/128(10.15%) patients (aged 75-79) and 35/153(22.9%) of patients (aged 70-74) received chemotherapy. Of 272 ER+/HER2- patients, Oncotype DX was performed in 102 patients (37.5%). From those, 17 patients had a high (>25) score (16.7%) and 10 received chemotherapy (58.8%). The remaining 86 had a low score (84.3%) and 4 received chemotherapy (4.7%).

Conclusion

Sentinel lymph node biopsy had little influence in guiding management decisions and adjuvant therapy in patients over 80 in this study. However, we found that SLNB still had a role in patients aged 70-80 and should be used selectively in this cohort. Ongoing prospective trials will expand the increasing role of Oncotype Dx and axillary US as a replacement for SLNB.
O092 SRC intervention for treating breast cancer
Authors: Abdulhadi A , Irakleidis F , Al Omran S , Derguti V , Welch H
Published: May 2023

Introduction

The non-receptor tyrosine kinase SRC interacts with multiple signalling pathways and has important roles in tumourigenesis. Thus far, SRC intervention for treating breast cancer remains inconclusive. To investigate the underlying molecular mechanisms affecting responses we generated breast cancer cells resistant to the SRC-inhibitor, Bosutinib (BOS).

Methods

BOS-Resistant (BOS-R) cell lines: ER+ (MCF-7, ZR-75-30) and ER- (Hs578T, MDA-MB-231) were developed by cultivation in increasing concentrations of BOS (0.1-10uM); protein expression changes were determined by Western Blot and densitometry. Dose-responses to [BOS] were assessed by IC50, mitochondrial and LDH assays.

Results

BOS sensitivity did not correlate with sub-type: MCF-7, ZR-75-30, Hs578T were inhibited significantly (p<0.05) by 5uM BOS and above (IC50=6uM, 6.4uM, 5.5uM respectively) while MDA-MB-231 tolerated >8.5uM BOS (IC50 7.6uM). Sustained growth of ZR-75-30BOS-R and Hs578TBOS-R was achieved in 5uM, MCF-7BOS-R in 7.5uM and MDA-MB-231BOS-R in 10uM BOS (proliferation rates similar to MDA-MB-231). Densitometry comparisons showed increased levels of SRC/SFK (SRC Family Kinases) in all BOS-R cells (range: 12%-57%). In contrast, expression of CSK (C-terminal SRC Kinase) was reduced by >34% (MCF-7BOS-R, MDA-MB-231BOS-R) or lost (ZR-75-30BOS-R, Hs578TBOS-R). Expression of FAK (Focal Adhesion Kinase) increased in all BOS-R cells (range 25%-50%). Furthermore, differential expression of SRC/SFK and alternative SRC-transcripts distinguished five ER+ from four ER- cell lines.

Conclusion

Regulation of SRC/SFK and their interactions are highly complex. We show resistance to BOS is, in part, associated with increased expressions of SRC/SFK and FAK.
O104 Effect of a surgical adjuvant on IL-6 and IL-10 levels produced by human dermal fibroblasts using an in vitro wound healing model
Authors: O'Callaghan S , Foley C , Redmond H
Published: May 2023

Introduction

Interleukin-6 (IL-6) and Interleukin-10 (IL-10) are members of the cytokine family demonstrating pro-inflammatory and anti-inflammatory properties respectively. Disruption in the balance of inflammation postoperatively leads to wound complications and cancer recurrence. Surgical adjuvants including 1,4,5-oxathiazinane-4,4-dioxide (OTD) can reduce inflammation while also demonstrating cytotoxic effects on cancer cells. Thus, we evaluated the effect of OTD on Human Dermal Fibroblasts (HDFs) and subsequent IL-6 and IL-10 levels.

Methods

Five concentrations of OTD were applied to HDF cells over time to assess migration and wound closure. Leica Las X software and a light microscope were used to obtain photographs at nine timepoints. After 30 hours cell media was removed and levels of IL-6 and IL-10 were measured. Migration and wound closure were assessed using percentage area of the wound gap, determined using ImageJ.

Results

OTD application demonstrated a dose-dependent arrest in fibroblast migration, greatest at 3-6 hours. This is represented by greater percentage area relative to control (15%Area – 6hrs) for concentrations 0.75mM (19%Area – 6hrs), 1mM (25%Area – 6hrs) and 1.25mM (30.5%Area - 6hrs). Percentage area was greater for 1mM and 1.25mM at 3hrs relative to 0hrs indicating gap widening, however for 0.75mM %Area was reduced. This correlated with IL-6 and IL-10 levels which were raised at 30hrs for 1mM and 1.25mM but not 0.75mM.

Conclusion

Lower concentrations of OTD do not demonstrate a negative effect on fibroblast migration, IL-6 and IL-10 levels despite previously demonstrated cytotoxic effects on cancer cells. Thus, OTD is a potential surgical adjuvant in cancer treatment.
O124 Synchronous colorectal and liver resections for colorectal cancer – use of the National Consultant Information Programme (NCIP) to highlight colorectal surgical practice in England
Authors: Galla A , Booth M , Young L , Bogovac M , Williams N , Maxwell-Armstrong C
Published: May 2023

Introduction

The NCIP tool uses HES data collected from Trusts to understand the spread and variation of a range of surgical procedures. This work uses the tool to understand the current practice of synchronous colorectal and liver resection in England and how Covid-19 affected practice.

Methods

Pseudonymised data was extracted from NCIP dashboards by NHS England Improvement data analysts. The various metrics looked at included surgical approach, number of cases, length of stay (LOS), incidence of stoma maturation and readmission, and mortality.

Results

523 elective patients over 17+ years – 244 cases between April 2018-March 2020 and 279 cases between April 2020-March 2022. Most primary tumours were colonic (407), with fewer rectosigmoid (47) and rectal cancers (69). 81.26% of procedures were performed open. 57 centres undertook synchronous colorectal and liver resections, 68.42% of total providers did <10 cases in the 4-year data period. Average LOS was 14 days. Mean stoma rate was 35% in units performing >20 cases (range 21%-58%). 14.90% of patients were readmitted within 30 days. The 90-day mortality was 1.53%.

Conclusion

There was no impact of the Covid pandemic on current practice, possibly due to reluctance to give chemotherapy in this patient group. There was a significant variation observed at provider level for each procedure sub-group. Data suggests stoma creation within episode is a contributor to higher average LOS, readmission rate and mortality rate. In addition, significant variation observed in stoma formation between units, and a significant number of units are performing a small number of procedures.
O130 Transarterial chemoembolization in rectal cancer: a systematic review
Authors: Kler A , Najran A , Choan M S , Fok M , Vimalachandran D
Published: May 2023

Background

Locally advanced rectal cancer (LARC) is typically treated with neoadjuvant chemoradiotherapy. Response can be unpredictable, with 8-20% of patients achieving complete pathological response, whilst 20-30% have no response or progression. Transarterial chemoembolisation (TACE) is established as a non-surgical option to treat colorectal liver metastases by delivering chemotherapy and an embolic agent via its primary arterial supply. This allows for reduction in systemic toxicity whilst delivering higher doses to tumours. There have been trials of TACE in LARC, but its role as a therapeutic modality is still unknown. Therefore, this review aims to assess existing evidence of TACE in LARC and whether it warrants further investigation as a treatment.

Methods

A systematic literature search was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Databases searched included PubMed, Scopus and Web of Science. Risk of bias was assessed using the Newcastle-Ottawa scale. The assessed outcomes included complete pathological response, objective response rate, complications, recurrence, disease-free and overall survival.

Results

Five reports were considered for inclusion. Minimal complications and adverse events were noted. Improved pathological complete response or objective response rates were noted in four out of five studies when compared to systemic neoadjuvant regimes. One study showed TACE reduced the risk of distant recurrence. Significant heterogeneity and bias were noted in all studies.

Conclusion

TACE is a safe modality, but its superiority over conventional treatment has yet to be demonstrated. Current literature is of inadequate quality but warrants further investigation in preclinical and clinical settings.
O141 The patterns of metastatic disease and survival in patients with pancreatic neuroendocrine tumours: a retrospective observational study
Authors: Wong T , Buddle E , Jaffer R , Adiamah A , Murugan V , Wong Z , Lobo D N
Published: May 2023

Background

The 5-year survival of patients with pancreatic neuroendocrine tumours (pNET) without metastatic spread can be as high as 93% and as low as 24% in cases with distant metastases, influenced by the resectability of the tumour and adjuvant therapies. This study examined the patterns of metastasis and survival outcomes of patients with pNET.

Methods

This retrospective observational study at a regional hepatopancreaticobiliary centre, used electronic healthcare records to identify all patients with confirmed pNET referred to the multidisciplinary team between 2010 and 2019. Demographic characteristics of the patients were compared using chi-squared testing, and the patterns of metastatic disease defined on radiological imaging. The 5-year survival outcomes were determined using Kaplan-Meier survival estimates, stratified by the presence (and location) or absence of metastatic disease.

Results

In total 96 [50 (52.1%) female] patients with pNET were identified. Of the female patients, 46% were older than 70-years compared with 24% of the males (p=0.016). Metastatic disease was present in 48% of patients at presentation. The commonest sites of metastases was the liver (50%) distant lymph node metastases (32%) and multisite metastases (13%). The corresponding 5-year survivals were 58%, 50% and 39%.

Conclusion

pNET is a unique type of pancreatic cancer with better overall survival compared with other pancreatic cancers. Survival is influenced by the patterns of metastatic disease with worse overall survival in those with multisite metastases.
O145 A systematic review of quality of life instruments in acute and chronic pancreatitis: a consensus-based standards for the selection of health measurement instruments (COSMIN) approach
Authors: Jakaityte I
Published: May 2023

Introduction

A systematic review was conducted to identify and evaluate the methodological quality of the QoL instruments used for patients with acute or chronic pancreatitis.

Methods

Prospective studies that evaluated quality of life (QoL) in acute or chronic pancreatitis were identified from systematic review of MEDLINE, EMBASE, and Web of Science until 5th August 2021 (PROSPERO: CRD42021274743). Characteristics of QoL instruments were extracted, and their methodological quality assessed using COSMIN guidelines and GRADE approach. A narrative synthesis was conducted, with recommendations for instrument use based on COSMIN criteria regarding internal consistency and content validity (evaluated according to WHO QoL domains: physical health, psychological health, social relationships, level of independence, environment, and personal values).

Results

From 3850 records screened, 43 QoL instruments were identified across 131 studies included, involving 20,331 patients. The majority (69.8%, n=30) were designed to assess general health-related-QoL, with 7 (16.3%) specific to abdominal pathologies, and 6 (14.0%) specific to chronic pancreatitis. Approximately half of the instruments (51.1%, n=22) demonstrated sufficient content validity (incorporating ≥3 WHO QoL domains). However, only a minority incorporated public and patient involvement (33.3%, n=15) or had undergone validation (22.3%, n=10). Only the “Gastrointestinal Quality of Life Index” met the criteria to be recommended based on COSMIN methodological assessment.

Conclusion

There is significant heterogeneity in instruments used to assess QoL after pancreatitis, with almost all studies incorporating instruments with either insufficient methodological quality or construct validity. Robust, validated, and relevant instruments are needed to better understand and determine appropriate interventions to improve these patients’ QoL.
O150 The risk of hepatic pseudoaneurysm after liver trauma in relation to the severity of liver injury: a meta-analysis and meta-regression analysis
Authors: Saji A P , Hajibandeh S , Hajibandeh S , Alessandri G , Duncan T , Kumar N , O’Reilly D
Published: May 2023

Introduction

A systematic review and meta-analysis was conducted to determine the risk of hepatic pseudoaneurysm after liver trauma in relation to the severity of liver injury.

Methods

We performed a systematic review and meta-analysis in compliance with PRISMA statement standards. A search of electronic information sources was conducted to identify all studies reporting the incidence of hepatic pseudoaneurysm after liver trauma. The JBI assessment tool was used to assess the risk of bias. Random-effects models were applied to calculate pooled outcome data.

Results

A total of 2030 patients from six studies were included. Based on the American Association for the Surgery of Trauma classification system, 21% had grade I injury; 33% grade II injury; 28% grade III injury; 12% grade IV injury; 5% grade V injury. The pooled risk of hepatic pseudoaneurysm was 1.8% (95% CI 1.1-2.5%). The risk was 0.4% (0-1.2%) in patients with grade I injury, 0.7% (0-1.7%) in patients with grade II injury; 1.5% (0.4-2.7%) in patients with grade III injury; 4.6% (1.4-7.7%) in patients with grade IV injury; 10.6% (1.8-22.9%) in patients with grade V injury. The average time between liver injury and detection of hepatic pseudoaneurysm was 6 days (1-10).

Conclusion

The risk of hepatic pseudoaneurysm after liver trauma increases as the severity of liver injury increases. Hepatic pseudoaneurysms are rare after grade I or grade II injuries, and increasingly common after grades III, IV and V injuries. We do not hesitate to recommend routine surveillance imaging in patients with grade III to V injuries.
P05 Developing an open-access knowledge exchange platform for breast surgeons
Authors: Robinson A , Reveendran D , Oates E , Shaheen A , Bennett J , Ng A
Published: May 2023

Introduction

Compiling information for best practice and exams is time-consuming. Furthermore, having this on-demand is not always feasible. A group of breast surgery trainees sought to develop a resource that could easily be accessed from a computer or mobile device, and that consolidated all relevant literature. The aim of this survey was to assess the needs for such a resource and inform its design.

Methods

An online survey was sent to current breast trainees and consultants working in the North East, Northwest and Yorkshire. Oncology trainees in the Northeast were also canvassed. Questions included demographics;, stage of training and qualifications;, online resources used;, potential gains and needs from a resource and preferred learning methods (visual, auditory, kinesthetic, note-making).

Results

A total of 33 participants completed the survey:24 breast surgeons and 9 oncologists. 60% of the respondents were in higher training (ST5-ST7). The most commonly used resources by breast trainees were ABS (87.5%), NICE guidance (75%) and iBreastbook (45.8%)., Oncology trainees commonly reported using NICE guidance (77.8%), ESMO (77.8%) and NCCN (55.6%). The majority of the respondents identified as visual learners (N=20, 60.6%). 93.9% of respondents would like to have access to recent papers on the online resource, 90% would like access to consolidated guidance.

Conclusion

Based on the pilot survey results, we have developed an online learning resource (Best of Breast Resource) that addresses these needs. This has been released and is being collaboratively iterated with participants with the aim to release it more widely in the breast community.
P07 Single centre experience of the balloon occlusion microcatheter for prostate artery embolisation (PAE)
Authors: Kilic Y , Hesketh R , Walkden M , Munneke G , Hines J , Von Stempel C
Published: May 2023

Introduction

Prostate artery embolization (PAE) is an effective in patients with benign prostatic hyperplasia (BPH) particularly. Balloon occlusion PAE (bPAE) is novel procedural adaption to the standard technique using a 2.2fr microcatheter with a compliant silicone balloon.

Methods

Retrospective single centre study of the first experience of balloon occlusion microcatheter for PAE in the UK. All patients undergoing PAE in the last 18 months were identified and those who had bPAE were included.

Results

22 patients were included in the study mean age 72 (11 IQR, 67.25-78.2). Median prostate volume was 121g (86.75 IQR, 57.5- 144.25). Median IPSS, Qmax and PVR at base line were 19 (5.25 IQR, 16-21.25), 7.4 ml/s (4.27 IQR, 5-9.35), 188 mls (255 IQR, 42.5 - 298) respectively. Four patients had long term catheters pre-procedure. Patients were embolised with 45-150 µm Contour PVA particles (n=8) or 250 µm Embozene microspheres (n = 14) (Boston Scientific, MA, USA). At 3 months post bPAE, MRI demonstrated prostate volume reduction of 31% (37.5± IQR, 11-48.5) with a further infarct of a median of 5ml (9.6 IQR, 0.95-10.6). IPSS reduction of 11 points (8.5 IQR, 7-15.5), Qmax of 11.6 ml/s (13.4 IQR, 4.8-18.2) and PVR of 98 mls (161 IQR, 19-180).

Conclusion

Balloon occlusion PAE is effective in reducing lower urinary tract symptoms. It effectively reversed the penile and rectal shunts in 8/22 cases with no cases of non-target embolization.
P14 Postoperative calcium monitoring is not necessary in hemi-thyroidectomy patients
Authors: Youssef F , Alasttal S , Fouad M , Ahmad M , Charakopoulou A , Tunstall L , Carvell J , Chadwick D , Christakis I
Published: May 2023

Introduction

There is no standardised practice for the management of calcium post-operatively. Hemithyroidectomies pose a smaller risk for PH, compared to total thyroidectomies. The aim of the study was to establish if routine testing of serum calcium was needed in patients undergoing hemithyroidectomy operations.

Methods

We have included patients that had hemithyroidectomy between 2017 -2021. Patients operated on between 04/2017-03/2019 had post-operative blood test for serum calcium (Group A) while patients operated on between 04/2019-10/2021 did not have any testing (Group B).

Results

178 patients were included in the analysis (70 In group A and 108 in group B). Baseline chrematistics (age p= 0.815, sex p=0.0324, indication of surgery, ASA grade p=0.086) were not statistically different between groups. The percentage of malignancy on histology did not statistically differ (23% for group 1 and 36% for group 2, p=0.069). Group A patients were found to have borderline low adjusted calcium level (<2.2 mmol/l) in 6% of the cases (lowest level of recorded calcium was 2.13 mmol/l). The mean adj. calcium for Group A pts was 2.34 (SD:0.1). There were no patients in Group A or group B who developed clinical symptoms of hypocalcemia. The length of stay (LOS) did not statistically differ (mean LOS:1.3 days for group 1 (SD:1.4) and 1.3 days (SD:1.6) for group 2, p=0.981).

Conclusion

Hemithyroidectomy patients do not develop clinically relevant hypocalcaemia, hence do not require routine post-operative serum calcium measurement. This could be a cost-saving and quality-improvement initiative for Units performing thyroid surgery.
Pathological and perioperative outcomes of extracorporeal versus intracorporeal anastomosis in laparoscopic transverse colon cancer resection: retrospective multicentre study
Authors: Zhong Hao , Cai Zhenghao , Lu Junyang , Yang Yingchi , Xu Qing , Wang Nan , He Liang , Hu Xiyue , Fingerhut Abraham , Zheng Minhua , Lu Aiguo , Liu Zheng , Xiao Yi , Feng Bo
Published: May 2023

Background

The aim of this study was to compare the pathological and perioperative outcomes of extracorporeal versus intracorporeal anastomosis after laparoscopic transverse colon cancer resection.

Methods

In this retrospective study, patients from seven institutions in China who underwent laparoscopic resection of transverse colon cancer between 2019 and 2021 were selected and included. Either extended right hemicolectomy or transverse colectomy/extended left hemicolectomy was performed. The clinical characteristics and the pathological and perioperative outcomes were compared between patients undergoing extracorporeal or intracorporeal anastomosis. Resection margin lengths were measured on formalin-fixed specimens and an inadequate margin was defined as less than 4.2 cm between the division and the tumour. The outcome of interest was the prevalence of specimens with an inadequate margin. Length of incision, bowel function recovery, hospital stay, early postoperative pain (first day after surgery), 30-day complications, and nodal harvest were investigated as secondary outcomes.

Results

Of 411 patients treated during the study interval, 370 patients with transverse colon cancer were included (23.2 per cent treated with intracorporeal anastomosis and 76.8 per cent treated with extracorporeal anastomosis). The prevalence of specimens with inadequate margins was lower in the intracorporeal anastomosis group compared with the extracorporeal anastomosis group in patients undergoing extended right hemicolectomy (P = 0.045) and in patients undergoing transverse colectomy/extended left hemicolectomy (P = 0.030). In multivariate analysis, extracorporeal anastomosis (OR 2.94 (95 per cent c.i. 1.33 to 6.49), P = 0.008) and transverse colectomy/extended left hemicolectomy (OR 1.75 (95 per cent c.i. 1.03 to 2.96), P = 0.038) were independent risk factors for specimens with an inadequate margin. Intracorporeal anastomosis was associated with a shorter incision length (P < 0.001), an earlier recovery of bowel function (P = 0.035), a shorter postoperative hospital stay (P = 0.042), less early postoperative pain (P < 0.001), a longer specimen length (P = 0.042), a longer resection margin (P = 0.007), and a greater lymph node harvest (P = 0.036). There was no statistically significant difference in 30-day complications.

Conclusion

Patients with transverse colon cancer have better perioperative outcomes, fewer margins of less than 4.2 cm, and larger lymph node harvests when the anastomosis is performed intracorporeally. Further studies are needed to confirm these findings.

Registration number

NCT05061199 (www.clinicaltrials.gov).
Cortical representation of speech temporal information through high gamma-band activity and its temporal modulation
Authors: Tamura Shunsuke , Hirano Yoji
Published: May 2023

Numerous studies have investigated low-frequency (theta-band) and high-frequency (gamma-band) neural activities that are phase-locked to temporal structures, including the temporal envelope and fine structure (TFS) of speech signals. Nonetheless, the neural mechanisms underlying the interaction between envelope and TFS processing remain elusive. Here we examined high gamma-band activities and their low-frequency amplitude modulations while listening to monotone speech (MS) with a fundamental frequency (F0) of 80 Hz and non-speech sounds with similar temporal characteristics to MS, namely an amplitude-modulated click train (AMC). Additionally, we utilized noise-vocoded speech (NVS) to evaluate the impact of eliminating the TFS from MS on the high gamma-band activity. We observed discernible high gamma-band activity at the same frequency as F0 of MS and the train frequency of AMC (80 Hz). Furthermore, source localization analysis revealed that the high gamma-band activities exhibited left hemisphere dominance in both MS and AMC conditions. Finally, high gamma-band activities exhibited amplitude-modulation at the same rate as the stimulus envelope of MS and AMC (5 Hz), though such modulation was not observed in NVS. Our findings indicate that the high gamma-band activity in the left hemisphere is pivotal in the interaction of envelope and TFS information processing, regardless of the nature of the stimulus being speech or non-speech.
Gyrification of the medial and lateral orbitofrontal cortex in first-degree relatives of patients with obsessive-compulsive disorder
Authors: Tomiyama Hirofumi , Murayama Keitaro , Nemoto Kiyotaka , Kato Kenta , Matsuo Akira , Ohno Aikana , Kang Mingi , Togao Osamu , Ishigami Kousei , Nakao Tomohiro
Published: May 2023

Gyrification patterns reflect early neurodevelopment and could be highly heritable. While some discrepant results have been reported, the most consistent finding was that patients with obsessive-compulsive disorder showed altered gyrification patterns in the orbitofrontal cortex. Nevertheless, no study has investigated the alterations in gyrification in unaffected first-degree relatives of patients with obsessive-compulsive disorder. We measured local gyrification by the FreeSurfer software in 23 unaffected first-degree relatives of patients with obsessive-compulsive disorder and 52 healthy control participants. We explored differences in the local gyrification index using vertex-wise whole-brain analysis and a region of interest-based approach in the medial and lateral orbitofrontal cortex. There was no significant difference in the local gyrification index between the 2 groups in the vertex-wise whole-brain analysis. Region of interest analyses showed that, compared with healthy controls, first-degree relatives showed significantly reduced local gyrification index in the left medial and lateral orbitofrontal cortex. A negative correlation was observed between the reduced local gyrification index in lateral orbitofrontal cortex and the subclinical anxiety scores of first-degree relatives. Our results showed that first-degree relatives of patients with obsessive-compulsive disorder had an altered local gyrification index in the orbitofrontal cortex. Especially, reduced local gyrification index in lateral orbitofrontal cortex associated with subclinical anxiety symptom could be a potential neurodevelopmental marker for the illness onset.
Defining the reporting threshold for a cybersecurity incident under the NIS Directive and the NIS 2 Directive
Authors: Schmitz-Berndt Sandra
Published: May 2023

The NIS Directive and sector-specific cybersecurity regulations require the reporting of (security) incidents to supervisory authorities. Following the risk-based approach adopted in the NIS Directive, the NIS 2 Directive enlists as a basic security element the reporting of significant incidents that (i) have caused or (ii) are capable to cause harm, as well as (iii) notifying the service recipients of cyber threats. Although during the interinstitutional negotiations between the European Commission, the European Parliament, and the Council of the European there was consensus that the NIS Directive’s reporting framework needs to be reformed, views on the determination of what needs to be reported varied. This paper outlines and analyses the different concepts of a report-worthy significant incident that have been proposed during the legislative procedure for the NIS 2 Directive from a legal and policy perspective. Irrespective of further motives that may inhibit reporting, legal compliance is difficult to achieve where legal requirements are vague. In that regard, the difficulties to determine the reporting thresholds in the past and in the future are addressed. In consideration of the increased attack surface and threat scenario, it is argued that incidents where no harm has materialized should not be treated any different than incidents that have actually resulted in harm in order to acquire the envisaged full picture of the threat landscape and create value for business and society.
The evolution of antibiotic resistance in an incurable and ultimately fatal infection
Authors: Woods Robert J , Barbosa Camilo , Koepping Laura , Raygoza Juan A , Mwangi Michael , Read Andrew F
Published: May 2023

Background and objectives

The processes by which pathogens evolve within a host dictate the efficacy of treatment strategies designed to slow antibiotic resistance evolution and influence population-wide resistance levels. The aim of this study is to describe the underlying genetic and phenotypic changes leading to antibiotic resistance within a patient who died as resistance evolved to available antibiotics. We assess whether robust patterns of collateral sensitivity and response to combinations existed that might have been leveraged to improve therapy.

Methodology

We used whole-genome sequencing of nine isolates taken from this patient over 279 days of a chronic infection with Enterobacter hormaechei, and systematically measured changes in resistance against five of the most relevant drugs considered for treatment.

Results

The entirety of the genetic change is consistent with de novo mutations and plasmid loss events, without acquisition of foreign genetic material via horizontal gene transfer. The nine isolates fall into three genetically distinct lineages, with early evolutionary trajectories being supplanted by previously unobserved multi-step evolutionary trajectories. Importantly, although the population evolved resistance to all the antibiotics used to treat the infection, no single isolate was resistant to all antibiotics. Evidence of collateral sensitivity and response to combinations therapy revealed inconsistent patterns across this diversifying population.

Conclusions

Translating antibiotic resistance management strategies from theoretical and laboratory data to clinical situations, such as this, will require managing diverse population with unpredictable resistance trajectories.
Rapid, accurate publication and dissemination of clinical trial results: benefits and challenges
Authors: Zannad Faiez , Crea Filippo , Keaney John , Spencer Stuart , Hill Joseph A , Pfeffer Marc A , Pocock Stuart , Raderschadt Emma , Ross Joseph S , Sacks Chana A , Van Spall Harriette G C , Winslow Ron , Jessup Mariell
Published: May 2023

Large-scale clinical trials are essential in cardiology and require rapid, accurate publication, and dissemination. Whereas conference presentations, press releases, and social media disseminate information quickly and often receive considerable coverage by mainstream and healthcare media, they lack detail, may emphasize selected data, and can be open to misinterpretation. Preprint servers speed access to research manuscripts while awaiting acceptance for publication by a journal, but these articles are not formally peer-reviewed and sometimes overstate the findings. Publication of trial results in a major journal is very demanding but the use of existing checklists can help accelerate the process. In case of rejection, procedures such as easing formatting requirements and possibly carrying over peer-review to other journals could speed resubmission. Secondary publications can help maximize benefits from clinical trials; publications of secondary endpoints and subgroup analyses further define treatment effects and the patient populations most likely to benefit. These rely on data access, and although data sharing is becoming more common, many challenges remain. Beyond publication in medical journals, there is a need for wider knowledge dissemination to maximize impact on clinical practice. This might be facilitated through plain language summary publications. Social media, websites, mainstream news outlets, and other publications, although not peer-reviewed, are important sources of medical information for both the public and for clinicians. This underscores the importance of ensuring that the information is understandable, accessible, balanced, and trustworthy. This report is based on discussions held on December 2021, at the 18th Global Cardiovascular Clinical Trialists meeting, involving a panel of editors of some of the top medical journals, as well as members of the lay press, industry, and clinical trialists.
Association of healthy dietary patterns and cardiorespiratory fitness in the community
Authors: Mi Michael Y , Gajjar Priya , Walker Maura E , Miller Patricia , Xanthakis Vanessa , Murthy Venkatesh L , Larson Martin G , Vasan Ramachandran S , Shah Ravi V , Lewis Gregory D , Nayor Matthew
Published: May 2023

Aims

To evaluate the associations of dietary indices and quantitative cardiorespiratory fitness (CRF) measures in a large, community-based sample harnessing metabolomic profiling to interrogate shared biology.

Methods and results

Framingham Heart Study (FHS) participants underwent maximum effort cardiopulmonary exercise tests for CRF quantification (via peak VO2) and completed semi-quantitative food frequency questionnaires. Dietary quality was assessed by the Alternative Healthy Eating Index (AHEI) and Mediterranean-style Diet Score (MDS), and fasting blood concentrations of 201 metabolites were quantified. In 2380 FHS participants (54 ± 9 years, 54% female, body mass index 28 ± 5 kg/m2), 1 SD higher AHEI and MDS were associated with 5.2% (1.2 mL/kg/min, 95% CI 4.3–6.0%, P < 0.0001) and 4.5% (1.0 mL/kg/min, 95% CI 3.6–5.3%, P < 0.0001) greater peak VO2 in linear models adjusted for age, sex, total daily energy intake, cardiovascular risk factors, and physical activity. In participants with metabolite profiling (N = 1154), 24 metabolites were concordantly associated with both dietary indices and peak VO2 in multivariable-adjusted linear models (FDR < 5%). Metabolites that were associated with lower CRF and poorer dietary quality included C6 and C7 carnitines, C16:0 ceramide, and dimethylguanidino valeric acid, and metabolites that were positively associated with higher CRF and favourable dietary quality included C38:7 phosphatidylcholine plasmalogen and C38:7 and C40:7 phosphatidylethanolamine plasmalogens.

Conclusion

Higher diet quality is associated with greater CRF cross-sectionally in a middle-aged community-dwelling sample, and metabolites highlight potential shared favourable effects on cardiometabolic health.
Protecting and promoting the rights of the ‘reserve army of labour’: a policy analysis of structural determinants of migrant worker health in Pakistan and Qatar
Authors: Hawkes Sarah , Evagora-Campbell Mireille , Zahidie Aysha , Rabbani Fauziah , Buse Kent
Published: May 2023

Labour migrants who travel overseas for employment can face deep health inequities driven in large part by upstream social and structural determinants of health. We sought to study the ‘labour migrant health ecosystem’ between one sending country (Pakistan) and one host country (Qatar), with a focus on how the ecosystem realizes the rights of labour migrants when addressing the social and structural determinants (e.g. housing, employment law, etc.) of health. Study objectives were to (1) undertake an in-depth review of policies addressing the structural and social determinants of the health of labour migrants in both Pakistan and Qatar, analysing the extent to which these policies align with global guidance, are equity-focused and have clear accountability mechanisms in place, and (2) explore national stakeholder perspectives on priority setting for labour migrant health. We used a mixed methods approach, combining policy content analysis and interviews with stakeholders in both countries. We found a wide range of guidance from the multilateral system on addressing structural determinants of the health of labour migrants. However, policy responses in Pakistan and Qatar contained a limited number of these recommended interventions and had low implementation potential and minimal reference to gender, equity and rights. Key national stakeholders had few political incentives to act and lacked inter-country coordination mechanisms required for an effective and cohesive response to labour migrant health issues. Effectively addressing such determinants to achieve health equity for labour migrants will depend on a shift in governments’ attitudes towards migrants—from a reserve army of transient, replaceable economic resources to rights-holding members of society deserving of equality, dignity and respect.
On-pump beating-heart technique for managing a ruptured left coronary artery aneurysm
Authors: Hiromoto Atsushi , Sakamoto Shun-Ichiro , Suzuki Kenji , Ishii Yosuke
Published: May 2023

We present the case of an 86-year-old woman with a ruptured left coronary artery aneurysm associated with coronary-pulmonary artery fistula. She was transferred to our hospital with complaints of chest discomfort. Echocardiography revealed cardiac tamponade, and subsequently, a bloody pericardial effusion was drained. Coronary angiography and computed tomography revealed a ruptured left coronary artery aneurysm originating from a branch of the proximal left anterior descending artery and a coronary-pulmonary artery fistula. In the emergency operation, under cardiopulmonary bypass, the inlet and outlet vessels were ligated, and the aneurysm was closed without arresting the heart. By utilizing cardiopulmonary bypass, the pulmonary trunk was easily decompressed, and dissection around the aneurysm and identification of the inlet and outlet vessels was facilitated without cardiac arrest. Thus, to conclude, an on-pump beating-heart technique should be considered in such cases.
Outcomes of the arterial switch for transposition during infancy using a standardized approach over 30 years
Authors: Drury Nigel E , Mussa Shafi , Stickley John , Stumper Oliver , Crucean Adrian , Dhillon Rami , Seale Anna N , Botha Phil , Khan Natasha E , Barron David J , Brawn William J , Jones Timothy J ,   Collaborators†, Miller Paul A , Chikermane Ashish , Desai Tarak , Mehta Chetan , Bhole Vinay K , Chaudhari Milind P , Harris Michael , McGuirk Simon P
Published: May 2023

OBJECTIVES

The aim of this study was to describe the early and late outcomes of the arterial switch for transposition.

METHODS

A single-centre retrospective cohort study was conducted to assess the early and late outcomes of arterial switch performed during infancy using a standardized institutional approach between 1988 and 2018, compared by morphological groups.

RESULTS

A total of 749 consecutive patients undergoing arterial switch during infancy were included, 464 (61.9%) with intact septum, 163 (21.8%) with isolated ventricular septal defect and 122 (16.3%) with complex transposition with associated lesions, including 67 (8.9%) with Taussig–Bing anomaly. There were 34 early deaths [4.5%, 95% confidence interval (CI) 3.1–6.1] with only 10 (2.6%) early deaths since 2000. Complex morphology (odds ratio 11.44, 95% CI 4.76–27.43) and intramural coronary artery (odds ratio 5.17, 95% CI 1.61–15.91) were identified as the most important risk factors for 90-day mortality. Overall survival was 92.7% (95% CI 90.8–94.6) at 5 years and 91.9% (95% CI 89.9–94.1) at 20 years; in hospital survivors, there were 15 (2.1%) late deaths during a median follow-up of 13.7 years. Cumulative incidence of surgical or catheter reintervention was 16.0% (95% CI 14.5–17.5) at 5 years and 22.7% (95% CI 21.0–24.0) at 20 years; early and late reinterventions were more common in the complex group, with no difference between the other groups.

CONCLUSIONS

Using a standardized approach, the arterial switch can be performed with low early mortality, moderate rates of reintervention and excellent long-term survival. Concomitant lesions were the most important risk factor for early death and were associated with increased risk of late reintervention.
Asymmetric time-varying dependence and variable structure dependence measurement and analysis of EUA and CER
Authors: Yang Xing , Ye Yi-ting , Li Jia-wen , Mi Jun-long
Published: May 2023

This paper analyzed the time-varying dependence and structural dependence between EU allowances (EUAs) and certified emission reductions (CERs) by using price fluctuation data from 2008 to 2021 on EU ETS. It was found that (1) there was a strong nonlinear spillover relationship between EUAs and CERs. From 14 March 2008 to 16 March 2012, the time-varying dependence values of EUAs and CERs were mostly between 0.6 and 1 and the mean coefficient of dependence was 0.86, showing a strong interdependence. From 17 March 2012 to 2 January 2017, the correlation between them was mostly below 0.6 and the mean coefficient of dependence fell to 0.25. This indicates that the dependency between EUA futures and CER futures was very low at this stage. However, in general, the mean value of dependence was above 0.55, that is, there was a dependency between them. (2) From 14 March 2008 to 2 January 2017, there were 12 structural mutation points in EUA and CER yield sequences. After four mutation points, the dependence coefficient increased and the structural dependence enhanced. Meanwhile, after eight mutation points, the dependence coefficient decreased and the structural dependence weakened. The overall level remained above 0.6, showing the existence of structural dependence. (3) Abrupt changes in EUA and CER prices were closely related to the promulgation of major policies and unpredictable emergencies. The former caused carbon prices to fluctuate slightly. When the period of change was short and the recovery was rapid, it caused sharp fluctuations in carbon prices. When the duration of change was long, and the recovery was slow, it yielded impacts that extend far beyond the publication of important information.
Bacterial Vaginosis and Spontaneous Clearance of Chlamydia trachomatis in the Longitudinal Study of Vaginal Flora
Authors: Brown Sarah E , Tuddenham Susan , Shardell Michelle D , Klebanoff Mark A , Ghanem Khalil G , Brotman Rebecca M
Published: May 2023

Background

Up to 26% of urogenital Chlamydia trachomatis infections spontaneously resolve between detection and treatment. Mechanisms governing natural resolution are unknown. We examined whether bacterial vaginosis (BV) was associated with greater chlamydia persistence versus spontaneous clearance in a large, longitudinal study.

Methods

Between 1999 and 2003, the Longitudinal Study of Vaginal Flora followed reproductive-age women quarterly for 1 year. Baseline chlamydia screening and treatment were initiated after ligase chain reaction testing became available midstudy, and unscreened endocervical samples were tested after study completion. Chlamydia clearance and persistence were defined between consecutive visits without chlamydia-active antibiotics (n = 320 persistence/n = 310 clearance). Associations between Nugent score (0–3, no BV; 4–10, intermediate/BV), Amsel-BV, and chlamydia persistence versus clearance were modeled with alternating and conditional logistic regression.

Results

Of chlamydia cases, 48% spontaneously cleared by the next visit (310/630). Nugent-intermediate/BV was associated with higher odds of chlamydia persistence (adjusted odds ratio [aOR] = 1.89; 95% confidence interval [CI], 1.30–2.74), and the findings were similar for Amsel-BV (aOR 1.39; 95% CI, .99–1.96). The association between Nugent-intermediate/BV and chlamydia persistence was stronger in a within-participant analysis of 67 participants with both clearance/persistence intervals (aOR = 4.77; 95% CI, 1.39–16.35). BV symptoms did not affect any results.

Conclusions

BV is associated with greater chlamydia persistence. Optimizing the vaginal microbiome may promote chlamydia clearance.
Lipopolysaccharide and Glycolipoprotein Coordinately Triggered Necroptosis Contributes to the Pathogenesis of Leptospira Infection in Mice
Authors: Du Lin , Wu Yunqiang , Pan Yuqing , Wang Lingxia , Zhang Haiwei , Li Jiayin , Liu Ya’nan , Zhang Haibing , He Ping
Published: May 2023

Leptospirosis is a recurring but neglected zoonotic disease caused by pathogenic Leptospira. The explicit underlying mechanism of necroptosis and its role in Leptospira infection have not yet been elucidated. Here we reported that leptospiral pathogen-associated molecular patterns, lipopolysaccharide, and glycolipoprotein activate the necroptotic RIPK1-RIPK3-MLKL cascade through the TLR4 signaling pathway in mouse macrophages. Using the murine acute leptospirosis model, we reveal that abolition of necroptosis exhibited significantly improved outcomes in acute phases, with enhanced eradication of Leptospira from liver, mild clinical symptoms, and decreased cytokine production. RIPK3 was also found to exert a necroptosis-independent function in CXCL1 production and neutrophil recruitment, with the consequence of improved Leptospira control. These findings improve our understanding of the mechanism of Leptospira-macrophage interactions, indicating potential therapeutic values by targeting necroptosis signaling pathways.
The Sympathetic Nervous System Is Necessary for Development of CD4+ T-Cell Memory Following Staphylococcus aureus Infection
Authors: Reel Jessica M , Abbadi Jumana , Bueno A Jesse , Cizio Katarazyna , Pippin Richard , Doyle D Annie , Mortan Laura , Bose Jeffrey L , Cox Maureen A
Published: May 2023

Lymph nodes and spleens are innervated by sympathetic nerve fibers that enter alongside arteries. Despite discovery of these nerve fibers nearly 40 years ago, the role of these nerves during response to infection remains poorly defined. We have found that chemical depletion of sympathetic nerve fibers compromises the ability of mice to develop protective immune memory to a Staphylococcus aureus infection. Innate control of the primary infection was not impacted by sympathectomy. Germinal center formation is also compromised in nerve-depleted animals; however, protective antibody responses are still generated. Interestingly, protective CD4+ T-cell memory fails to form in the absence of sympathetic nerves after S aureus infection.