bluuebunny/crossref_metadata_2025 huggingface dataset:
The identification of a novel orally available ferroptosis inducer for the treatment of clear cell renal carcinoma
Authors: Koh Mei Yee
Published: August 2023

Background

Background: Clear cell renal cell carcinoma (ccRCC), the most common form of kidney cancer, is typically initiated by inactivation of the von Hippel Lindau (VHL) gene resulting in constitutive activation of the hypoxia inducible factors, HIF-1α and HIF-2α. HIF-2α is a central driver of kidney cancer progression and is a well validated therapeutic target for ccRCC. Additionally, VHL loss and HIF activation promote lipid accumulation that increases the sensitivity of ccRCC cells to ferroptosis, a form of cell death characterized by iron dependent lipid peroxidation. However, classical inducers of ferroptosis, which induce ferroptosis in vitro, show limited activity in vivo due to possible redundancies in the extracellular space, suggesting a need for novel molecular targets for the induction of ferroptosis in vivo for therapeutic benefit.

Methods

Method: We performed a high-throughput screen to identify small molecule inhibitors of HIF-2α and performed additional validation and structure activity relationship studies to identify compounds with improved potency of HIF-2α inhibition. The molecular target of these inhibitors was determined by mass spectrometry using the Drug Affinity Responsive Target Stability (DARTS) assay, and target validation was confirmed using siRNA knockdown and NMR. In vivo anti-tumor efficacy was verified using syngeneic RENCA cells injected into Balb/C mice. Exposure to KD061 was verified using LC-MS/MS detection of KD061 in the plasma and tumors of treated mice.

Results

Results: We identified a novel molecule, KD061, which decreases levels of HIF-1/2α and induces ferroptosis in vivo through oral administration by targeting Iron Sulfur Cluster Assembly 2 (ISCA2). ISCA2 is a component of the late mitochondrial Iron Sulfur Cluster (L-ISC) assembly complex and ISCA2 inhibition either pharmacologically or using siRNA triggers the iron starvation response, resulting in iron/metals overload and death via ferroptosis. Cell death induced by KD061 was decreased by re-expression of VHL, suggesting synthetic lethality in the context of VHL loss. ISCA2 inhibition also decreased HIF-2α protein levels by blocking iron-responsive element (IRE)-dependent translation, and at higher concentrations, also decreased HIF-1α translation through unknown mechanisms. Treatment of tumor-bearing RENCA-Balb/C mice with KD061 significantly reduced tumor growth in vivo, decreased HIF-α levels and increased lipid peroxidation, suggesting increased ferroptosis in vivo. Treatment with KD061 was well tolerated at the therapeutic dose with no detectable effects on blood chemistry and blood counts.

Conclusions

Conclusions: Here, we describe the first orally available inducer of ferroptosis with anti-tumor efficacy in vivo. The targeting of ISCA2 using KD061 is a promising therapeutic strategy to inhibit HIF-1/2α and to induce ferroptosis in pVHL deficient cells.

CDMRP DOD Funding: yes
NRG-GU012: randomized phase II stereotactic ablative radiation therapy (SABR) for metastatic unresected renal cell carcinoma (RCC) receiving immunotherapy (SAMURAI)
Authors: McKay Rana
Published: August 2023

Background

Background: It is estimated that a significant number of patients presenting with metastatic RCC are either ineligible, not recommended for, or refuse surgery. There remains no well-established method for addressing the primary tumor in such patients. Stereotactic ablative radiotherapy (SABR) is a highly effective modality for the treatment of the primary tumor in RCC. Our study seeks to evaluate SABR as an alternative approach to treat the primary tumor in patients with metastatic RCC receiving immunotherapy, who are not recommended for surgery, or who decline surgery. The primary objective of the study is to determine whether the addition of SABR to the primary tumor in combination with immunotherapy improves outcomes compared to immunotherapy alone in patients with metastatic, unresected, renal cell carcinoma (RCC). The primary endpoint is nephrectomy and radiographic progression-free survival (nrPFS) with progression determined as per iRECIST criteria. Patients are eligible if they are not recommended for upfront surgery, have a primary tumor treatable with SABR, and are candidates for immunotherapy. Immunotherapy is physician’s choice and will include either two different immunotherapy regimens (IO-IO) or immunotherapy in combination with a VEGF inhibitor (IO-VEGF).

Methods

240 patients will be randomized in a 2:1 ratio favoring SABR plus immunotherapy (n=160) as compared to standard of care immunotherapy alone (n=80). The sample size will provide 90% power at a one-sided alpha level of 0.05 to detect a hazard ratio for nrPFS of 0.61, i.e., a 40% reduction in the rate of events. One-year PFS in the nivolumab plus ipilmumab arm was 50% (n=550, intermediate/poor risk population). Checkmate 9ER (Choueiri 2021) showed a one-year PFS rate in patients receiving nivolumab plus Cabozantinib (n=323) of 45-58% (intermediate/poor risk population). We have therefore estimated a one-year nrPFS rate of 50% in the control (immunotherapy alone) arm for SAMURAI. We expect nephrectomies to contribute only a small fraction to the total nrPRS events. To detect a hazard ratio of 0.62, which corresponds under exponential distribution assumptions to an absolute 15% improvement in one-year nrPFS from 50% in the control group to 65% in the experimental arm (SABR plus immunotherapy), a total sample size of 240 patients will be enrolled. This design will provide 90% power, based on a one-sided logrank test at the 0.05 alpha level, with three years of accrual and two further years of follow-up. The expected number of nrPFS events is E=175. The calculations allow for a 10% non-eligible/early dropout rate. The trial is currently open and accruing through the NRG oncology cooperative group (NCT05327686).
Policing in England and Wales and the purpose of this book
Authors: Boon Bryan
Published: August 2023

This chapter provides an overview of policing in England and Wales. The Metropolitan Police Act 1829 and its practical consequences became the template for policing throughout England and Wales. Despite the changes, complexity, multicultural, and multifaceted features of social context, crime prevention, the detection and arrest of offenders and the maintenance of public order, remains at the heart of policing. The chapter highlights the importance of leadership among police sergeants and inspectors. It clarifies that this book aims to supplement and add to authorised police training manuals, textbooks, and other official instructions, referencing that it brings a mixture of theory and practice and helpful tips and a series of brief, skills-based checklists.
Delegation
Authors: Boon Bryan
Published: August 2023

This chapter explains the importance of the delegation of work within a team. It clarifies that a sergeant or inspector leader cannot do everything that needs to be done on his or her own. Thus, leaders have a responsibility to manage workloads, relieve stress, and encourage the development of individual and team competence. Moreover, delegation is expected to form part of a structured individual and team development programme. While leaders can delegate responsibility, authority, and tasks to members, they cannot delegate accountability and are ultimately accountable themselves for situations that go wrong. The chapter details the conditions to achieve a successful delegation, which includes being clear about the reasons for delegation.
Communications—modes of behaviour and transactional analysis
Authors: Boon Bryan
Published: August 2023

This chapter discusses modes of behaviour and transactional analysis under the notion of communication. The transactional analysis offers an understanding of how people adopt and modify their behaviour accordingly, which is a vital skill complementary to interpersonal and assertiveness skills. The chapter notes that transactional analysis should be used as a means to develop relationships, not damage them through calculated manipulation. A leader will develop their transactional analysis skills through constant use and critical self-analysis of their performance, which will also benefit from honest feedback from others. The chapter considers the process of transactional analysis explained within a police context.
Communications—feedback
Authors: Boon Bryan
Published: August 2023

This chapter details the concept and purpose of feedback concerning sergeant and inspector leaders. Feedback primarily involves commenting in a constructive, assertive way on the behaviours and performance of individual team members and the team as a whole. Moreover, feedback entails identifying and remarking on good progress and difficulties and tackling any obstacles to the completion of tasks and objectives. The chapter explains how a leader can use feedback skills to debrief teamwork and projects. It explains that feedback is a non-hostile method of communication and exploration, so a leader should encourage feedback to help develop themselves and the team.
Communications—briefing skills
Authors: Boon Bryan
Published: August 2023

This chapter considers briefing skills in communication under the context of policing. It discusses n large-scale briefings resulting from major policing events involving things such as the exercise of democratic rights to protest, rioting, major incidents such as a train crash or ceremonial occasions involving the monarch. A leader will know if they briefed people properly through an examination of the results of whether an operation passes off successfully, although factors other than briefings can affect outcomes. The chapter then details what a leader has to do to carry out an effective briefing. It also tackles the risk of interpretations being different when several briefings are conducted to accommodate a large number of participants.
Communications—debriefing skills
Authors: Boon Bryan
Published: August 2023

This chapter highlights the importance of a leader's debriefing skills in police operations. It explains that debriefing amounts to a feedback session and the role of leaders in the debriefing procedure. Moreover, failing to debrief any event and significant events is unwise given the loss of valuable experience and learning that may occur. Neglecting to debrief helps to maintain the status quo while debriefing opens the way to doing things differently, more economically, and better. After a debriefing session, the leader may have to take some remedial action to correct continuing operational faults. The chapter notes that critical self-analysis and constructive feedback can help leaders realise whether they did well in the debriefing session.
Leader’s team audit
Authors: Boon Bryan
Published: August 2023

(See Chapter 3, ‘Leadership and team work’)

Summary

It is essential that a newly appointed leader of an established or new team should start well and illustrate at once all the characteristics of determined, competent leadership.

When joining a team, a leader needs to...
Leader’s equality and diversity
Authors: Boon Bryan
Published: August 2023

(See Chapter 4, ‘Treating people equally and valuing diversity’)

Summary

The importance of how people are treated cannot be overemphasised. Leaders have a moral and legal responsibility to treat all people including team members, colleagues, external agencies and members of the public equally. This...
Leader’s planning
Authors: Boon Bryan
Published: August 2023

(See Chapter 5, ‘Planning’)

Summary

Planning is an integral part of a leader’s job. Without planning skills or the willingness to plan properly a leader is unlikely to be effective.

Planning involves being clear about what is to be achieved after a risk assessment,...
Leader’s delegation
Authors: Boon Bryan
Published: August 2023

(See Chapter 6, ‘Delegation’)

Summary

Being able to delegate successfully is an important leadership function. A leader who does not delegate is likely to be regarded as a poor leader. Delegation is of the greatest importance if individual and team contributions are to be...
Leader’s problem solving
Authors: Boon Bryan
Published: August 2023

(See Chapter 7, ‘Problem solving’)

Summary

Problems are a feature of everyday life whether in the workplace or socially. In the workplace when plans are laid they do not always go as anticipated and problems occur and difficulties appear regularly on an almost daily...
Preventing Cyber Crime
Authors: Staniforth Andrew
Published: August 2023

This chapter seeks to provide all police practitioners with an introduction to preventing cyber crime. The prevention of cyber crime remains the highest priority for all cyber crime investigators. This chapter seeks to guide all police practitioners through the complexities and challenges of effectively providing practical cyber crime prevention advice. Most importantly, this chapter sets out how cyber crime investigators can better protect themselves and their operational activities from all manner of cyber-related threats. There now exists a plethora of free and accessible information designed to keep all online users safe and to provide confidence and reassurance to the public, police partners and private industry; it is absolutely essential that all police officers are able to provide practical cyber crime preventative guidance and advice. It is also important for police officers to be able to readily signpost the public, partners and private businesses to trusted sources of information which will help to keep them safe online, leading to greater online protection and increased awareness of cyber crime prevention methods.
Cyber-Enabled Child Protection Offences
Authors: Staniforth Andrew
Published: August 2023

This chapter will look at the key criminal offences which relate to sexual offending against children which can be, and quite often are, cyber-enabled. They fall into two categories and are potentially damaging and dangerous in their effect. The key categories are online grooming and the proliferation of indecent images of children.
Cyber-Enabled Terrorism
Authors: Staniforth Andrew
Published: August 2023

The internet has transformed the way in which terrorist organisations operate, providing them with an easy-to-access international communications platform previously only available to states. It has enabled the concept of global jihad. Without the internet, terrorists would find it much more difficult to reach a global audience and to plan specific operations. Terrorists use the internet for the following.
Crime Scene Preservation and Management
Authors: Beaufort-Moore Deborah
Published: August 2023

This chapter explores the principles and roles within crime scene preservation and management. It mentions how failure to properly address the issues of contamination and transfer can render any potential evidence unfit for analysis or inadmissible in a court of law. Crime scenes must be preserved in order to maximise the potential for gathering any material which can corroborate or refute allegations or versions of events. The principles of crime scene preservation of protecting potential evidence are essentially the same for a dwelling burglary or a murder. The chapter elaborates on Locard's Principle of Exchange which highlights a two-way transfer principle.
Crime Scene and Evidence Recording
Authors: Beaufort-Moore Deborah
Published: August 2023

This chapter explores the process of the crime scene and evidence recording. The best way to record a crime scene investigation is for initial responders to employ scene preservation techniques and photography of the scene and potential evidence before moving. Technical photography is a key skill of a crime scene investigator (CSI) or anyone required to gather evidence for potential criminal proceedings. The chapter mentions how digital imaging technology transferred the use of photographic images for crime scene recording while referencing the usefulness of 360° photography and digital 3D virtual reconstruction of a crime scene. Additionally, sketch diagrams are a good method of recording a crime scene as they provide an aide memoire for writing reports and statements.
Exhibit Handling
Authors: Beaufort-Moore Deborah
Published: August 2023

This chapter covers the principles of exhibit handling and packaging of exhibits. It highlights how the exhibit's handling, packaging, labelling, and subsequent storage can largely affect the investigation. While items for forensic examination must be left in their original position for recovery by a crime scene investigator (CSI), circumstances arise wherein the items may be lost, destroyed or damaged if left in their original position. Thus, the items must be preserved and moved with care and consideration to the potential forensic material available. The chapter also showcases techniques for the recovery of items ensuring that potential evidential recovery is maximised while also considering health, safety, and exhibit integrity.
DNA—Deoxyribonucleic Acid
Authors: Beaufort-Moore Deborah
Published: August 2023

This chapter tackles the application of DNA technology within an investigation of a crime. It explains how samples of DNA can reliably identify individuals and technological advancement allows DNA profiles to be obtained from increasingly small samples. The evidence from a DNA profile is based on a probability match between the suspect sample and the crime scene sample, and the likelihood of anyone else having the same profile. However, one of its disadvantages is the possibility of investigators becoming overly dependent on forensic evidence. The chapter discusses the samples and the importance of the national DNA database (NDNAD) for investigations, which also considers the recovery and preservation of DNA materials.
Firearms and Ballistic Evidence
Authors: Beaufort-Moore Deborah
Published: August 2023

This chapter looks into firearms and ballistic evidence. It mentions the importance of the health and safety of all personnel who deal with firearm incidents. When dealing with firearm related incidents, the firearm and any related material such as cartridge cases, bullets, clothing and wound types can potentially provide an investigator with forensic evidence. Thus, National Ballistic Intelligence Service (NABIS) was developed in order to gather and collate information on the criminal use of firearms and also provides a ballistics examination service. The chapter then details the process of forensic examination of firearms and ballistic material and the examination to establish cause.
Glass, Paint and Soils
Authors: Beaufort-Moore Deborah
Published: August 2023

This chapter considers the evidential value of glass, paint and soils and the considerations an officer will need to make regarding their forensic viability. It explains that different investigators must recover potential evidence from different scenes, so the issue of inadvertent secondary transfer poses a risk. When recovered from crime scenes and compared with samples recovered from a suspect or victim, links can be established between them. Moreover, the retention of glass, paint and soil on surfaces depends on several factors, such as the nature of the receptor surface. The chapter then mentions how soil, paint, and glass are easily transferable which makes them susceptible to inadvertent cross-transfer.
Hair and Fibres
Authors: Beaufort-Moore Deborah
Published: August 2023

This chapter discusses the evidential value of hairs and fibre. It also examines the considerations an officer will need to make regarding the effects of the time elapsed between the commission of the offence and the recovery of items from a suspect. In a forensic capacity, head and pubic hair are the most commonly encountered hair at crime scenes and can be a valuable source of evidence. Hairs and fibres are capable of providing intelligence and potential forensic evidence to link persons to crime scenes. The chapter also mentions how police vehicles become a key area for potential secondary transfer.
Document Examination
Authors: Beaufort-Moore Deborah
Published: August 2023

This chapter looks into examinations employed in document analysis. It cites that forged or altered cheques and vehicle documents are some of the types of documents encountered in the investigation of a crime, referred to as ‘questioned documents’. Thus, questioned document examination can provide evidence in the form of fingerprints, footwear marks, indented writing, handwriting analysis, and the physical fit of a piece of paper to a pad from which it has been torn. The chapter explains the process of handwriting analysis, identifying forged handwriting, and indenting impressions. It also considers the recovery and preservation of documents to maximise potential evidence available from documents.
A History of Policing in England and Wales from 1974: A Turbulent Journey
Authors: Brain Timothy
Published: August 2023

In 1974 local
government reforms became the catalyst for the introduction of a new police
service structure, creating 43 separate forces under a new tripartite system.
The years since then represent one of the most profoundly turbulent periods of
British political, economic and social life. It was a time of great change, and
the police service was at the very centre of those changes. Today the service is
only superficially recognisable as the one which entered the final quarter of
the 20th. A History of Policing in England and Wales from 1974: The Turbulent
Years offers a detailed and descriptive chronology of the period, exploring the
key themes of order and social stability, the professionalization of the police
service, centralization, the dynamics of police community relations, and the
‘reform’ programmes of the Thatcher, Major and Blair administrations, in
particular charting the failure of the Charles Clarke drive for amalgamations in
2005/6. Written by a former chief constable involved in policing throughout much
of the period, the book vividly describes the great events of the time,
including the threat and ultimate defeat of IRA terrorism; the urban riots of
the 1980s; major crime investigations - such as the ‘Yorkshire Ripper’, the West
Case, and the Soham murders - and their lasting impact; the controversial
policing of the 1984 Miners’ Strike; and the return of terrorism to the British
mainland in 2005.
The Struggle for Stability: 1975–9
Authors: Brain Timothy
Published: August 2023

If the picture
that summed up 1974 was that of a policeman standing somewhat disconsolately in
a snowstorm, the picture that summed up the start of 1975 showed a frighteningly
young-looking 21-year-old Metropolitan Police constable, Stephen Tibble. His
official photograph, a head-and-shoulders monochrome, was typical of thousands
taken at the time of newly appointed officers. He is neat, clean-shaven, and
simply looks at the camera, relatively expressionless. In February 1975 he had
just six months’ service, and was married to his childhood sweetheart, herself
only 19. It had been his life-long ambition to be a police officer. On the
morning of 25 February he was off-duty in Hammersmith, west London, when he saw
a man escaping from three colleagues, part of an anti-burglary team that had
earlier seen a man enter a flat in Fairholme Road. They had been patient and
waited for the man to leave and, when he did (some 30 minutes later) they
stopped him, but he refused to be searched, instead nervously pulling out a wad
of Irish five-pound notes. He then made a break for it. Constable Tibble did
what most off-duty police officers would have done in such circumstances; he
helped out. He gave chase on his motorcycle. In Charleville Road he overtook the
suspect, dismounted from his bike, and held out his arms. To what must have been
the profound shock of the pursuers, the man pulled out a pistol and shot PC
Tibble three times at point-blank range, killing the young officer. Constable
Wilson, one of the pursuing officers, picked up the motorcycle and, despite the
obvious risk, continued the chase until the man was lost to sight.
Fracture: 1980–5
Authors: Brain Timothy
Published: August 2023

The morning of
Wednesday 2 April 1980 in Bristol was warm and sunny, a break after a somewhat
cold and wet start to spring. It was the first day of the school holidays, but
otherwise had nothing to distinguish it from many other spring days before or
since. The officers of ‘C’ Group at the city’s Trinity Road Police Station,
which covered the nearby inner-city area of St Paul’s, were finishing their
stint of seven days’ duty prior to two days’ leave. One probationary officer
performing cell duty that day thought nothing of the charge sergeant’s genial
instruction to set up an additional charge sheet. At home, just over three hours
later, he listened in disbelief to the 5.00 pm news headlines announcing that
three police cars had been burnt in riots in the St Paul’s area of the city. It
was the start of a long night of rioting for St Paul’s and the Avon and Somerset
force. At a critical point in the early evening the chief constable, Brian
Weigh, withdrew his officers from the area, leaving it to the rioters. In the
hours that followed a bank and shops were set on fire and looted.
Police Reform Revived: 2001–5
Authors: Brain Timothy
Published: August 2023

The only serious
issue of doubt at the 2001 general election was the size of Labour’s majority. A
dull campaign was enlivened when a man in Rhyl threw an egg at Labour deputy
leader John Prescott, who threw a punch in return, and when a member of the
public in Birmingham confronted the Prime Minister with the painful realities of
booking an appointment at some GP surgeries. The campaign was interesting,
however, for the clues it held to Labour’s second-term priorities.
Damocles Unbound: 2005–7
Authors: Brain Timothy
Published: August 2023

Charles Clarke’s
accession to office was as smooth as it could be in the circumstances. Son of a
senior civil servant, he had made his way through Highgate School and Cambridge,
becoming, like Jack Straw before him, president of the National Union of
Students. In the 1970s he was a member of the ‘broad left’ but by late 2004 that
had long been transformed into support for New Labour. He quickly set off on
what many chief constables saw as a positive course by inviting them, in
contrast to Blunkett’s ex cathedra style, to a convivial private ‘get to
know you’ (or at least, resume acquaintance) meeting at a London hotel. In his
brief speech he declared an intention to be practical and not to concentrate on
structure over getting the business done. It appeared that he was ‘a man that
you can do business with’.
A Tale of Two Winters: 2007–9
Authors: Brain Timothy
Published: August 2023

The consequences
of the events of 21 and 22 July 2005 for the Metropolitan Police and its most
senior officers began to unfold progressively throughout 2007. Although the IPCC
had completed its first investigation into the events at Stockwell in 2005, it
awaited a decision from the CPS on prosecutions before publishing its report. In
July 2006 the CPS announced that there was insufficient evidence to prosecute
any individual officer but that the Metropolitan Police would be prosecuted
under the Health and Safety Act. The inquest into Jean Charles de Menezes’ death
was then formally adjourned to allow for the completion of the prosecution
process. In May 2007 the IPCC announced that none of the front-line officers
involved would be disciplined but left the position open in the case of the
senior officers. In August the IPCC published its report into the handling by
the Metropolitan Police of the media statements that were made in the immediate
aftermath of the shooting. As it was the second report to have been commissioned
it was known as Stockwell Two, although it was the first to be published.
In this report the focus was inevitably on what the Commissioner had said and
what he had known at the time he said it.
Pathogen-induced m6A dynamics affect plant immunity
Authors: Prall Wil , Sheikh Arsheed H , Bazin Jeremie , Bigeard Jean , Almeida-Trapp Marilia , Crespi Martin , Hirt Heribert , Gregory Brian D
Published: August 2023

Posttranscriptional regulation of mRNA mediated by methylation at the N6 position of adenine (N6-methyladenosine [m6A]) has profound effects on transcriptome regulation in plants. Focused studies across eukaryotes offer glimpses into the processes governed by m6A throughout developmental and disease states. However, we lack an understanding of the dynamics and the regulatory potential of m6A during biotic stress in plants. Here, we provide a comprehensive look into the effects of m6A on both the short-term and long-term responses to pathogen signaling in Arabidopsis (Arabidopsis thaliana). We demonstrate that m6A-deficient plants are more resistant to bacterial and fungal pathogen infections and have altered immune responses. Furthermore, m6A deposition is specifically coordinated on transcripts involved in defense and immunity prior to and proceeding the pathogen signal flagellin. Consequently, the dynamic modulation of m6A on specific stress-responsive transcripts is correlated with changes in abundance and cleavage of these transcripts. Overall, we show that the m6A methylome is regulated prior to and during simulated and active pathogen stress and functions in the coordination and balancing of normal growth and pathogen responses.
Walking Exercise Sustainability Through Telehealth for Veterans With Lower-Limb Amputation: A Study Protocol
Authors: Hanlon Shawn L , Swink Laura A , Akay Rachael Brink , Fields Thomas T , Cook Paul F , Gaffney Brecca M M , Juarez-Colunga Elizabeth , Christiansen Cory L
Published: August 2023

Objective

This randomized controlled superiority trial will determine if an 18-month telehealth walking exercise self-management program produces clinically meaningful changes in walking exercise sustainability compared to attention-control education for veterans living with lower-limb amputation.

Methods

Seventy-eight participants with lower-limb amputation (traumatic or nontraumatic) aged 50 to 89 years will be enrolled. Two groups will complete 6 one-on-one intervention sessions, and 6 group sessions over an 18-month intervention period. The experimental arm will receive a self-management program focusing on increasing walking exercise and the control group will receive attention-control education specific to healthy aging. Daily walking step count (primary outcome) will be continuously monitored using an accelerometer over the 18-month study period. Secondary outcomes are designed to assess potential translation of the walking exercise intervention into conventional amputation care across the Veteran Affairs Amputation System of Care. These secondary outcomes include measures of intervention reach, efficacy, likelihood of clinical adoption, potential for clinical implementation, and ability of participants to maintain long-term exercise behavior.

Impact

The unique rehabilitation paradigm used in this study addresses the problem of chronic sedentary lifestyles following lower-limb amputation through a telehealth home-based walking exercise self-management model. The approach includes 18 months of exercise support from clinicians and peers. Trial results will provide rehabilitation knowledge necessary for implementing clinical translation of self-management interventions to sustain walking exercise for veterans living with lower-limb amputation, resulting in a healthier lifestyle.
COVID-19 surge testing in a unitary local authority in England: an observational study
Authors: Norman Grace , Akomfrah George , Mytton Oliver , Brown Ian
Published: August 2023

Background

In May 2021, due to rising case rates and the detection of a new variant of concern, increased asymptomatic ‘surge testing’ for COVID-19 was implemented in Bedford Borough.

Methods

Over 3 weeks, surge testing in higher incidence areas utilized: (i) mobile testing units, (ii) home test kit collection and drop-off and (iii) Door-to-door outreach. Testing was voluntary and supported by a communication campaign. Test results and data provided by participants were analyzed.

Results

During surge testing, 16% (n = 5018) of the target population were tested, resulting in 125 positive results (2.5%). Females, those identifying as white, and those living in the most deprived quintile (Q1) were over-represented in testing. Test positivity was relatively higher for ages 0–19 (4.0%), for minority ethnic groups (2.8%), and those not listing an ethnic group (15.1%). Test positivity was lowest for the door-to-door outreach approach (0.9%), despite collecting the most samples (2225).

Conclusions

Surge testing in Bedford reached a large number of people, was particularly successful at reaching people living in the most deprived areas, and identified cases that might have otherwise been missed. However, the testing did not reach the majority of the population, and began after new infections had begun to fall.
Effect of Intra Operative Intravenous Lidocaine Infusion on Control of Pain and Recovery of Intestinal Function Following Surgical Appendectomy
Authors: Ibrahim Ahmed Saeed Mohamed , El-Shazly Ghanim Ahmad , Abdelaal Wail Ahmed Mohamed
Published: August 2023

Background

Intravenous lidocaine infusion has been shown to facilitate postoperative recovery after major abdominal surgery. This current randomized controlled study will assess the effect of intraoperative intravenous lidocaine infusion on pain intensity, bowel function and cytokine response after surgical appendectomy.

Aim of the Work

To determine the role of intraoperative lidocaine infusion in reducing perioperative pain and analgesia requirement and enhancing the recovery of intestinal function in patients undergoing surgical Appendectomy.

Patients and Methods

The current prospective randomized double-blinded study was conducted at the surgery department, Faculty of Medicine, Ain Shams University and it included 40 patients who were undergone urgent open appendectomy and met the selection criteria. They were classified into 2 groups: Group L: patient who received IV bolus injection of lidocaine (1.5 mg/kg slowly over 10 min) 30 minutes before the skin incisions followed by a continuous IV infusion at the rate of 2 mg/kg/h via infusion pump(B-BRAUN), Group S (control): patient who received 0.9% normal saline in equal volume and in the same manner.

Results

There was statistically significant difference between the studied groups regarding time to pass flatus. Patients within lidocaine group pass flatus significantly earlier than those with control group. There is statistically non-significant difference between the studied groups regarding postoperative complications.

Conclusion

From the current study, it was concluded that perioperative IV lidocaine injection had significant effect in reduction of postoperative pain and increased the main pain free period also noticed IV lidocaine decreased opioid requirement and time to pass flatus so shorten hospital stay. Perioperative IV lidocaine had no effect on postoperative complications and IV lidocaine during incision and extubation attenuated hemodynamic response.
Comparison of Propofol versus Midazolam Infusion for Conscious Sedation during Spinal Anaesthesia in Patients Undergoing Inguinal Hernia Repair
Authors: El Kady Galal Adel Abd El-Rahim , El-Sersi Mayar Hassan , Kassem Amr Ahmed , Hussein Ahmed Yasser Mohammed
Published: August 2023

Background

The operating room is an anxiety provoking environment. Supplemental sedation with an intravenous agent is often required to allay fear and anxiety in patients subjected to spinal anaesthesia. Sedation is a valuable tool to make surgery under regional anaesthesia convenient for the patient, the anaesthetist and the surgeon. Conscious sedation is a minimally depressed level of consciousness that retains the patient’s ability to maintain his or her airway independently and continuously and to respond appropriately to physical stimulation and verbal commands, produced by pharmacologic or non-pharmacologic methods alone or in combination.

Aim of the Work

This study will be designed to compare Propofol and Midazolam with regard to their suitability as sedative agents during spinal anaesthesia in terms of onset & recovery from sedation, haemodynamic stability, dosage and side effects of both the drugs.

Patients and Methods

This Interventional clinical study (Randomized double blinded study was conducted in Ain Shams University Hospital’s operating rooms through 3 months on 50 patients. After obtaining approval from the medical ethical committee in Ain Shams University Hospital’s operating rooms, a written informed consent was obtained from every patient after explaining the procedure.

Results

Based on this study the following conclusions have been made: Cardiovascular parameters and respiration were well maintained in both the study groups, no incidence of apnea was noticed in both the study groups, pain during the injection of propofol was a side effect noticed, onset of action was faster in the propofol group, propofol group was less co-operative than midazolam group but this was clinically insignificant, midazolam group showed slower recovery than propofol group restricting and wasting the productive time of the patient, qualities such as short plasma half-life period, absence of postoperative nausea and vomiting, make propofol a better choice for sedation and thus propofol is a fast acting, safe and easily controllable sedative with rapid recovery. This offered the advantage of early patient discharge and better patient compliance.

Conclusion

When given as a sedative adjunct to spinal I, both propofol and midazolam in equisedative infusions offer good anxiolysis and good cardio respiratory stability. Propofol has the advantage of providing faster onset of sedation, a rapid clear headed recovery from the same and lesser postoperative impairment of recall while midazolam offers better intraoperative amnesia.
Glycemic Control in Postoperative Patients in ICU (Comparative Study between Euglycemic Control and Mild Hyperglycemic Control in Patients Outcome)
Authors: Mustafa Zakaria Abdelaziz , El shebiny Ahmed Ali , koraitem Ahmed farouk , Abouzeid Fawzy kamel Abdelaziz
Published: August 2023

Background

Hyperglycemia is common complication in postoperative patients admitted to intensive care units, whether a patient has a history of diabetes or not. Hyperglycemia has been associated with increased perioperative morbidity and mortality.

Objective

To compare between outcome of euglycemia and mild hyperglycemia in postoperative patients admitted to ICU. And achieving the optimal target range for blood glucose in postoperative patients.

Patients and Methods

We conducted our prospective study on 70 postoperative patients admitted to ICU with blood glucose above 180 mg/dl we managed all of them with intravenous insulin with 2 different blood glucose level targets. Group one with euglycemic control aimed blood glucose level between 110 gm/dl to 140 gm/dl. Group two with mild hyperglycemia aimed blood glucose level target between 140 gm/dl to 180 gm/dl.

Results

We found in our study that euglycemic control didn’t significantly reduce the postoperative complications and improve the patients outcome in comparison to the mild hyperglycemic group. We also found that there is a mild lower rates of complications in non diabetic patients on euglycemic control compared with those non diabetics treated with mild hypoglycemic targets.

Conclusion

In our prospective study to compare between effects of euglymic control versus mild hyperglycemia we found that there is no significant difference in patients outcomes between patients controlled at target range 110 gm/dl to 140 gm/dl in comparison to the controlled group between blood glucose range 140 gm/dl to 180 gm/dl in postoperative patients admitted to ICU However there is less complications rates in non diabetics with euglycemic control group in comparison to non diabetics in group two (mild hyperglycemia). The optimal target for blood glucose level is a wide range from 110 mg/dl up to 180 mg/dl.
Acute Kidney Injury in Polytrauma Patients in Intensive Care Unit: A Prospective Observational Study
Authors: Elsaaedy Mohammed Ismael Abd Elfattah , El Gendy Hanaa Mohamed Abdullah , Abd El Hameed Gam al Eldin Adel , Ebrahim Mahmoud Abdelrahman Seifelnasr
Published: August 2023

Background

Acute Kidney Injury (AKI) is a common complication of severe trauma patients and is associated with increased morbidity and mortality. Injury Severity Score (ISS) > 15 represents approximately 10% of all trauma patients in intensive care unit (ICU). The primary outcome of the study was to correlate between the AKI by using RIFLE criteria and the trauma severity by using ISS. While; the secondary outcomes were; identifying the incidence of AKI in polytrauma patients, the length of ICU and hospital stay and 28 days mortality.

Methods

This is a prospective observational study which was conducted during the period from May 2020 to September 2020. It Included 60 cases of polytrauma patients who have ISS>15, at Ain shams university hospitals, their ages ranged from 18-70 years. All patients’ data were recorded for: Injury Severity Score (ISS). RIFLE criteria. Length of ICU and hospital stay. 28 days mortality.

Results

There was no correlation between the incidence of AKI and the severity of the trauma by using ISS. Incidence of AKI the percentage was (45 %) among all the studied cases. According to RIFLE criteria, within this population, patients were classified as (21.7%) of the patients in the Risk stage; (18.3%) of the patients in Injury stage, and (5%) of the patients in Failure stage. There was statistically significant difference between AKI and No AKI regarding risk factors, percentages of sepsis, rhabdomyolysis, drugs, abdominal trauma and hypovolemic shock were higher in AKI patients than No AKI patients. There was no statistically significant difference between AKI patients and No AKI patients regarding mechanical ventilation, ICU stay, Hospital stay and 28 d Mortality.

Conclusion

The incidence of acute kidney injury in polytrauma patients in the intensive care unit was high and the overall mortality of our patients was as high as that reported in other studies. A better comprehension of risk factors associated with trauma-associated AKI is important, such as rhabdomyolysis, sepsis, abdominal trauma (compartment) and hypovolemic shock.
Intraperitoneal versus Intravenous Dexamethasone Effect on Postoperative Nausea and Vomiting in Patients Undergoing Laparoscopic Cholecystectomy
Authors: Ali Mohamed A , Abd El Latef Ayman A , Soliman Samar M , Anis Marco S
Published: August 2023

Background

Post-operative nausea and vomiting (PONV) is a common unwanted effect in patients undergoing laparoscopic cholecystectomy (LC). This study compared the effect of intraperitoneal versus intravenous dexamethasone for reducing PONV after laparoscopic cholecystectomy surgeries.

Aim of the Work

to compare the efficacy of intraperitoneal versus intravenous administration of dexamethasone in reducing the incidence of PONV after LC surgeries.

Patients and Methods

Ninety patients, American Society of Anesthesiologists physical status I–II, scheduled for laparoscopic cholecystectomy surgery were randomized to receive 8 mg dexamethasone intraperitoneally (IP) (n = 45) or intravenously (IV) (n = 45). The primary outcome was the PONV incidence during the first 24 h after laparoscopy. Secondary outcomes included visual analogue scale (VAS) pain scores, total analgesic consumption during the first 24 h postoperatively, the need for rescue antiemetic drugs, and the incidence of complications that may accompany these medications.

Results

The incidence of nausea in the IV group was 26.7% (12 patients) and that in the IP group was 6.7% (3 patients) in the first 24 hours post-operatively (P = 0.011). There were no significant differences in the incidence of retching or vomiting, or the need for rescue antiemetics between the 2 groups. In terms of side effects, patients in the IP group had a lower rate of side effects than those in the IV group (6.7% vs. 24.4%, P = 0.020). The mean VAS pain score and total pethidine consumption for the first 24 hours postoperatively were lower in the IP group than in the IV group. However, these differences did not reach statistical significance.

Conclusion

Intraperitoneal injection of dexamethasone at a dose of 8 mg in patients undergoing Laparoscopic Cholecystectomy surgery reduces significantly the incidence of postoperative nausea, in comparison to the intravenous route.
Value of Transthoracic Echocardiography in Predicting Short Term Major Adverse Cardiac Events after ST Elevation Myocardial Infarction in COVID 19 Era
Authors: Farouk Dina , Bastawy Islam , Rayan Mona
Published: August 2023

Background

Acute myocardial infarction remains a leading cause of morbidity and mortality worldwide. In the era of COVID 19, early risk stratification and identification of high-risk patients with ST-segment elevation myocardial infarction are of great significance in prognosis, and in guiding diagnosis and treatment decisions. Measuring left ventricular peak systolic global longitudinal strain may be a useful addition to ejection fraction using echocardiography.

Aim of the Study

Is to evaluate different parameters of echocardiography in predicting major adverse cardiac events in patients after acute ST-segment elevation myocardial infarction in the era of Covid 19.

Methods and patients

This study included 97 patients who presented with acute STsegment elevation myocardial infarction within 12 hours of onset of chest pain and managed by primary percutaneous coronary intervention, it was performed in Ain Shams university hospitals from January 2021 to June 2021. Echocardiography was used to measure ejection fraction and left ventricular strain parameters

Results

The study included 97 patients, 55 % of which presented with anterior STEMI. Out of the whole group 29 patients (21%) developed MACE at 3 months follow up. Within the whole group, the mean ejection fraction was (44.04±6.07% VS .40.07±6.52% p = 0.007) and the mean global longitudinal strain was (-12.56±3.61% VS -10.1±3.25% p=0.002). Based on CT chest finding, 33 patients were Covid 19 patients who were younger in age, included significantly more females and had significantly higher Killip score as compared to the non covid patients. Among COVID-19 patients, the mean ejection fraction was (46.11±5.29% VS 40.6±7.11% p=0.02) and the mean global longitudinal strain was (-13.17±3.35% VS 10.35±3.38% p=0.026). At 3 months follow up, 39% of the Covid patients had MACE as compared to 25% of the non covid patients P = 0.0001.

Conclusion

In the era of COVID 19, young patients with female gender who suffered from STEMI were more likely to be COVID 19 patients and were liable to develop MACE at 3 months follow up. However, their LV EF and GLS were comparable to non-COVID 19 patients

Ethical approval

this study protocol was approved by the local ethics committee with a consent was obtained from all participants.

Abbreviations

MACE: major adverse cardiac events; LV: left ventricle; GLS: global longitudinal strain; STEMI: ST elevation myocardial infarction