bluuebunny/crossref_metadata_2025 huggingface dataset:
1159 Achilles Tendon Rupture Rate – Is There a COVID-19 Pandemic Effect?
Authors: Ismail R
Published: August 2023

Aim

The COVID-19 pandemic has caused a noticeable shift in trauma injuries across the United Kingdom. Achilles tendon ruptures (ATR) – a common sports-related injury – are frequently seen in athletes who are active intermittently. This retrospective study is aimed at proving the hypothesis that restriction easing and shift in activity levels during the COVID-19 pandemic has led to a higher prevalence of ATR in comparison to pre-pandemic numbers.

Method

Our study looked at ATR cases referred to the Virtual Fracture Clinic locally. We reviewed historical cases from 2015 to 2021 to compare rates and incidences of pre-pandemic cases with those during the pandemic and after restrictions were lifted. Additionally, we developed a scoring system to quantify the level of physical activity and exercise restrictions during the pandemic. The incidence and rate of ATRs were recorded and mapped against a restriction score over the course of the pandemic.

Results

Pre-pandemic, the yearly average number of ATR referrals was 77, but was 110 in 2021 after restrictions were lifted. In addition, the number of cases in 2020 during the pandemic was 63. Furthermore, when cases were mapped against activity restrictions throughout the pandemic period (2020-2021), a clear elevation in the number of cases emerges as the restrictions ease.

Conclusions

After restrictions were lifted, yearly cases were revealed to be considerably higher than the average pre-pandemic numbers. This shows that after a period of more sedentary lifestyle during the pandemic, the risk of ATR becomes higher upon return to play, hence supporting our hypothesis.
1198 Outcomes Following Internal Bracing for Anterior Sternoclavicular Joint Instability: A Systematic Review
Authors: Kapur K , Zaki P , Chaudhury S , Tytherleigh-Strong G , Panayiotou D
Published: August 2023

Aim

There is a paucity of data regarding optimal treatment strategies for atraumatic sternoclavicular joint (SCJ) instability, as this is a relatively uncommon aetiology. Atraumatic SCJ instability may be due to capsular laxity, muscle sequencing or a combination of both.

This study aims to systematically review the literature regarding SCJ instability with isolated capsular laxity to determine whether anterior capsular surgical plication and augmentation with internal bracing can prevent further episodes of instability in a population that is refractory to non-operative management.

Method

Studies that reported functional surgical outcomes were identified using the search terms “sternoclavicular AND joint AND dislocation AND reconstruction”. Nine studies and a total of 111 patients were identified to have met the inclusion criteria.

Results

Of the 111 patients identified, 9% of patients reported residual instability. 5.4% required a reoperation due to persistent impairment of shoulder function related to SCJ instability or osteoarthritis. There were satisfactory reported outcomes in 91% of patients.

Conclusions

Internal stabilisation techniques for atraumatic sternoclavicular joint (SCJ) instability have shown to be an effective method to improve shoulder function and patient symptoms. Revision rates remained at only 5.4% with a significant improvement in functional status. Complications were rare and included haematoma formation and discharging wound site. Therefore, internal bracing techniques should be considered in patients with chronic anterior SCJ instability after a course of failed conservative treatment.
1244 Wound Dehiscence and Infection of a Total Knee Replacement Secondary to Postoperative ‘Dorsal Fin’ Intra-Articular Vertical Patella Dislocation
Authors: Redman I , Jones G
Published: August 2023

A 75-year-old man presented to our emergency department with a bleeding wound 19 days following a primary hinged left total knee replacement, performed elsewhere, for lateral tibiofemoral osteoarthritis.

Examination revealed a knee held in fixed flexion of 30°, with partial dehiscence of the wound, implant exposure and a visible patella. Radiographs revealed an abnormally raised joint line with a vertical appearance of the patella on the lateral image. The decision was made to proceed with a two-stage revision. At operation, the patella was confirmed to be vertically positioned in the trochlea groove of the femoral component and identified as the likely cause for the wound dehiscence. There was evidence of a large lateral release having been performed during the primary surgery. A joint orthoplastic wound debridement was performed, together with implant removal, and static cement spacer insertion. Following an eight-week interval of IV antibiotics, the second stage was performed. A new hinged implant was implanted, with metaphyseal sleeves and stems. A tibial tubercle osteotomy was required to address the lateral tracking patella and a gastrocnemius flap was necessary to address a distal soft tissue defect.

This case study highlights an unusual cause for wound dehiscence following total knee arthroplasty. Patella dislocation with vertical axis rotation has been described in the native knee1, but to our knowledge, this is the first report of this phenomenon following arthroplasty. This was almost certainly secondary to component malpositioning and emphasizes the significance of restoring the native joint line and correct implant rotation during knee replacement surgery.
145 Patient Experience of Bladder Outlet Surgery During Covid-19 in a District General Hospital
Authors: Maniarasu S , McNicholas D P , Mistry R
Published: August 2023

Aim

During the pandemic, bladder outlet surgeries (TURP,Urolift,Rezum) were delayed. Operations were prioritised (P2<1month, P3<3months, P4>3months). We wanted to find out patient’s experience due to this.

Method

Patients identified who had surgery and on waiting list between January 2020 and June 2021. A questionnaire was designed to identify patient's experience and whether they felt their operation was delayed, if received correspondence about delays, if aware of the waiting-list grading, if attended GP/ED with issues, if felt their outcome affected by delays, listed P-grading, duration waited for operation, and overall satisfaction.

Results

56 patients were identified. 50% delayed. In delayed sub-group, 45% did not feel their operation was delayed. 82% delayed received information from the hospital. 70% knew about the grading system in place according to clinical urgency. In delayed sub-group, 41% felt their operation would be more difficult or less likely to be successful compared to 15% in non-delayed sub-group. 43% who were delayed attended GP/ED with issues compared to 9% in non-delayed group. 84% were happy or very happy (Likert4/5) with their experience.

Conclusions

Large numbers of BOO procedures were delayed due to the pandemic. Many patients aware of the waiting list grading system and understanding of the pressures on the NHS. There was good communication between the hospital to inform patients of their delays thus most patients were happy with the service they received, despite being delayed. Delays leads to significantly higher attendances to GP/ED and patients feel their operation is more likely to be difficult or unsuccessful.
458 Primary Renal Mesenchymal Neoplasms: A Retrospective Clinicopathological Study
Authors: Chacko A , Gopinathan V , Roy S , Prashanty A , Kumar S
Published: August 2023

Aim

Mesenchymal tumors are rare primary neoplasms of the kidney with limited demographic data in literature. We sought to study the prevalence of this rare subset of tumors in adults, at our tertiary care hospital focusing on the pathological and radiological characteristics.

Method

Clinico-radiological and intra-operative details were retrospectively analyzed for adult primary renal mesenchymal neoplasms received between 2006 and 2021 and correlated with the histopathology data.

Results

Of 2164 nephrectomies performed for neoplastic conditions, 97 (4.5%) were diagnosed as renal mesenchymal tumors. There were 59 (60.8%) benign, 10 (10.3%) with intermediate biologic behavior and 28 (28.9%) malignant tumors. The mean age was similar across these categories. Hematuria was seen in 11 of 38 (29%) intermediate grade and malignant tumors and in only 6 of 59 (10%) benign tumors a difference that was statistically significant (p = 0.017). Tumors ≥ 7cm were more likely to be malignant/intermediate grade than benign (p = 0.027). Classical angiomyolipomas constituted 90% of the benign tumors. Epithelioid angiomyolipomas and solitary fibrous tumors were the common intermediate grade tumors. Undifferentiated small round cell sarcoma was the most common malignant neoplasm. Immunohistochemical and molecular studies were useful for confirmation of diagnosis, particularly in cases of intermediate/malignant tumors.

Conclusions

Mesenchymal tumors constitute 4.5% of adult primary renal tumors, are predominantly benign tumors but are malignant in 1/4 th of cases. Malignant tumors are typically larger and more often present with hematuria. Immunohistochemistry (IHC) and molecular studies play a role in the diagnosis of intermediate and malignant mesenchymal tumors.
609 Improving Patient Counselling in Patients' With PI-RADS 3 Lesions with the Use of PSA Density, A Retrospective Study in a UK District General Hospital
Authors: Maniarasu S , Elsayed M , Barker H
Published: August 2023

Introduction

NICE and EAU guidelines recommend offering prostate biopsy for patients with PI-RADS 3 lesions in a multiparametric MRI. Employing PSA density (PSAd), to further risk-stratify these patients, is a promising approach to advocate for PSA surveillance over biopsies. Here, we appraise the ability of PSAd to risk-stratify PI-RADs 3 lesions across patients who underwent a prostate biopsy.

Method

A retrospective analysis was performed on all patients who had a multiparametric MRI with PI-RADs 3 lesions over 2-year period Jan 2021 – Dec 2022. Patients were divided into two groups according to their PSAd value and whether they have neoplastic features on histopathology. The data was analysed using Chi-Square to determine the association between PSAd levels and cancer incidence in PI-RADS 3 lesions.

Results

116 patients out of 613 had PIRADS 3 reported (19%). 83 patients had biopsies (72%). 44 was positive for neoplasia (53%) and 39 was negative (47%). 44 patients in the biopsy arm had a PSAd of <0.15 (53%). Of these patients, 27 had no neoplasia (61.4%). 39 patients had PSAd >0.15 (47%) and 12 had no neoplasia (31%). PSAd < 0.15 PI-RADS 3 lesions were significantly associated with lower occurrence of prostatic malignancy on statistical analysis.

Conclusions

Out of all biopsied PIRADS 3 lesions, almost half (47%) had no neoplasia. More than half of patients with PSAd <0.15 had no neoplasia. Patients with PSAD <0.15 were statistically more likely to have no neoplasia compared to patients with PSAD >0.15. This information is useful for prebiopsy risk stratification and patient counselling.
761 Effectiveness of Chemohypothermia with Mitomycin C vs Immunotherapy with BCG in High Risk Non Muscle Invasive Bladder Cancer Patients
Authors: Hasan M Y , Nawaz U , Khan F U R
Published: August 2023

Aim

Initial data to compare the effectiveness of Chemohypothermia with Mitomycin C (MMC) and Immunotherapy with Bacillus-Calmette-Guerin (BCG) in High risk Non muscle invasive bladder cancer (NMIBC).

Method

Sixty six patients who underwent Trans-urethral resection of bladder tumor (TURBT) were divided into two equal groups; hyperthermic intravesical chemotherapy group and BCG group. Six intravesical instillation's (one per week) of 40mg of hyperthermic MMC diluted in 40ml of distill water and heated at 43 C were given to patients for 60 min with HIVEC machine. For BCG group intravesical doses of BCG, once weekly for 6 weeks were administered at concentration of 80mg diluted in 50ml of normal saline. Follow up check cystoscopy at 3 months from initial TURBT was done to check effectiveness of both treatments. Patients were also accessed for side effects during the treatment.

Results

28 patients (84.8%) had no recurrence and 5 patients (15.2%) had recurrence in chemohypethermia group while in BCG group 29(87.8%) patients had no recurrence and 4(12.2%) patients had recurrence.

3(9%) patients had bladder spasms, 1(3%) had hematuria, 3(9.1%) had Urinary tract infection (UTI) while 26(78.8%) had no adverse effect in Chemohyperthermia group. In BCG group, 1(3%) had bladder spasm, 4(12.4%) had hematuria, 5(15.2%) had UTI and 23(69.5%) had no adverse effect.

Conclusions

Chemohyperthermia is safe and efficacious treatment choice in patient suffering from NMIBC with outcomes comparable with BCG treatment and improved side effect profile.
789 Primary Ureteroscopy in the Emergency Setting: Our Experience from a District General Hospital
Authors: Moghe D , Ong K , Lunawat R
Published: August 2023

Aim

The aim of this study is to evaluate how many patients with ureteric stone disease underwent primary ureteroscopy in the emergency setting (eP-URS) and how many of them had their stone retrieved successfully. In those patients in whom eP-URS was not attempted, we assessed if a reason for not doing so was documented. In addition, we analyzed the possible factors influencing the decision to perform a primary ureteroscopy in the emergency setting.

Method

This is a retrospective observational study of patients presenting to the emergency department of our district general hospital between January and December 2022 with ureteric stone disease requiring emergency surgical intervention in the form of eP-URS or emergency stenting.

Results

Out of 160 patients presenting with ureteric stone disease, eP-URS was attempted in 35% (n = 56) of patients and in the majority of these patients (64.3%, n = 36), the stone was retrieved successfully. On the other hand, eP-URS was not attempted in 65% patients (n = 104), and a decision for emergency stenting alone was made. A reason for this was clearly documented in 46.1%(n = 48) patients: urosepsis, mucky urine, impacted stone, patient factors, obstructed infected system, while in 53.8% (n = 56) cases no reason was mentioned. In our study, the location of the stone and the presence of consultant in theatre were found to significantly influence the decision to definitive stone surgery (p-value <0.05).

Conclusions

Despite clear guidance and potential benefits of definitive treatment of ureteric stones, eP-URS is yet to become an everyday practice. Reasons for not attempting eP-URS should be clearly documented.
1119 A Scoping Review of Kidney Transplantation in Africa: How Far Have We Come?
Authors: Davis S , Zubair A , Igbokwe M , Abu M , Chiedozie C A , Sanni Q , Jesuyajolu D
Published: August 2023

Aim

Kidney transplantation is a life-saving treatment for patients with end-stage kidney disease. However, the availability of kidney transplantation in Africa has lagged behind other regions of the world, leading to significant disparities in access to care. In this study, we sought to analyse indications for transplant, demographic characteristics, and outcomes of kidney transplantation in Africa from inception till date.

Method

The Preferred Reporting Items for Systematic Reviews and Meta-Analyses were used in conducting this study. PubMed, Google Scholar, and African Journal Online were searched. Data on procedure done, graft outcomes, donor, prophylaxis given for graft, post-op complications, and survival timelines were pooled together and analysed. Thirty-three studies fully satisfied the eligibility criteria and were used in this review.

Results

The most common causes of end-stage kidney disease requiring transplant included glomerulonephritis and Nephroangiosclerosis. Overall, open nephrectomy accounted for 95% of the surgical approach used. The other approaches documented were Hand-assisted Laparoscopic Nephrectomy (3.88%), Extraperitoneal approach (0.55%), and Simultaneous Unilateral native nephrectomy (0.12%). In total, 56.3% (4221) of all donors were living donors of which 68.5% were related to the recipient (living-related donor), while 43.7% (3280) patients received transplants from cadaveric donors. The commonest surgical complication was graft rejection (39.44%). In the follow-up period, 60.49% of patients who had a kidney transplant developed hypertension.

Conclusions

In conclusion, our study not only highlights the potential for kidney transplantation to improve the lives of patients in Africa, but also the need for further research and infrastructure development to make this a more widespread and successful option.
276 Favorable Outcomes for Endovascular Aneurysm Repair with Aorto-Uni-Iliac (AUI) Stent Grafts for Treatment of Abdominal Aortic Aneurysms (AAA) by a Single Team in 8 Years at South Mersey Arterial (SMArt): A Tertiary Care Vascular Surgery Centre
Authors: Shehata R , Aslam J , Nee beng T
Published: August 2023

Background

Endovascular Aneurysm Repair (EVAR) is established procedure for management of both elective and ruptured abdominal aortic aneurysms (AAA). However, in several cases, standard EVAR with bilateral limb extension cannot be done due to complex anatomy or calcified contralateral iliac artery. In such cases AUI stent graft and Fem-Fem cross over is a feasible option. This study aims to assess the outcomes of AUI with or without fem-fem cross over performed in SMART centre over 8 years

Method

A retrospective study on patients who had repair of AAA using AUI between 2014-2022, with or without crossover. Demographic, procedural, and radiological data was collected through digital database.

The outcomes were based on mode of admission, mortality rate, complications and patency rate of the graft at 2 years.

Results

A total of 28 patients had AUI between January 2014-January 2022. Median age was 79 years (59-94) with male predominance (85%). 50% of the patients presented with ruptured AAA, 46% had elective repair and 4% of patients presented with Acute limb ischaemia.

30-day mortality was found to be 21%. Local complications included endoleak, graft infection, groin bleeding, lymph leak and wound dehiscence and general complications included a predominance of HAP and cardiac issues.

The patency rate was checked at 6 months, 1-2 years. 6-month patency of the graft was found to be 93%. Similarly, 1 and 2-year patency was also found to be 93%

Conclusions

AUI with or without Fem-Fem crossover is an acceptable alternative treatment modality for ruptured or non-ruptured AAAs despite involving an extra-anatomical bypass.
600 Long-Term Clinical Outcomes of the Abdominal Aortic Aneurysm Get Fit Trial: A Randomised Controlled Trial of Exercise to Improve Fitness in Patients with Abdominal Aortic Aneurysm
Authors: Tay T , Haque A
Published: August 2023

Aim

Improved fitness of patients on Abdominal Aortic Aneurysm (AAA) surveillance is predicted to reduce cardiovascular events and improve perioperative morbidity and mortality. The AAA GetFit Trial was a randomised control trial comparing community exercise programme (CEP) with standard care which demonstrated improved CardioPulmonary Exercise Test-related fitness in AAA patients to inform a definitive RCT. This study aims to investigate longer-term four-year clinical outcomes of these individuals.

Method

The AAA GetFit trial recruited participants from Greater Manchester's AAA Surveillance programme, and randomly assigned participants to either i)24-week CEP with choice of gym or home exercises, or ii) standard clinical care. We performed a retrospective analysis of prospective clinical outcomes from this trial over four-year follow-up reviewing whether they underwent operative repair, 30-day postoperative morbidity, cardiovascular event, and mortality with four-year followup. We defined 30-day post-operative morbidity using Clavien-Dindo classification≥3.

Results

In total,56 participants recruited, 28 were randomised to CEP group, 86% were males. Mean age at time of enrolment was 72.8(SD5.7) years. At four-year follow-up, mortality in CEP and control were both 14%(n = 4). In each group, 25%(n = 7) underwent operative repair. There was no perioperative mortality.Perioperative morbidity(n = 2) was 29% in CEP and 0% in control.Cardiovascular events(n = 9) was 7% in CEP and 25% in control.Mean diameter of aneurysm increased slower in CEPvsControl(0.84vs0.93cm).

Conclusions

The AAA GetFit trial showed significant benefits in cardiovascular fitness through community-based exercise. Although clinical outcomes thus far were similar in both groups, there is a suggestion of reduced cardiovascular events in the CEP group.
941 A Systematic Review of Surgical Intervention Criteria for Thoracic Aortic Aneurysms
Authors: Neill H , Taylor S
Published: August 2023

Aim

Elective surgical repair of thoracic aortic aneurysms (TAAs) is the only treatment that prevents dissection or rupture. Current guidelines from the American College of Cardiology/American Heart Association and the European Society of Cardiology, recommend an aortic diameter threshold of 5.5cm for surgical intervention of TAAs. Recent studies have questioned the efficacy of current guidelines as they highlighted that the majority of dissections occur before reaching the threshold. This review aims to determine if an aortic diameter of 5.5cm is an appropriate threshold for prophylactic surgical repair of non-syndromic ascending TAAs.

Method

A search of Ovid MEDLINE and Pubmed databases was performed. Search terms included “ascending thoracic aortic aneurysm”, “ATAA”, “aortic diameter” and “aortic size paradox”. Non-English papers, animal studies and case reports were excluded. Reference lists from each article were assessed for further literature which met the inclusion criteria.

Results

22 studies were included. Four themes emerged from these papers which support lowering the threshold for prophylactic surgery: quantifying the changes in aortic diameter that occur during dissection, the discovery of the aortic size paradox, the identification of a new hinge point, and the improved safety of modern surgery. Regardless of this evidence, it appears to be unjustified to lower the threshold based on relative risk calculations.

Conclusions

Despite current guidelines, the use of aortic diameter as a risk assessment tool for TAAs is inadequate. Multiple studies have shown the ineffectiveness of a 5.5cm threshold, suggesting revision of current surgical guidelines is warranted.
1233 Role of Preoperative Embolization in the Surgical Management of Carotid Body Tumors: A Systematic Review and Meta-Analysis
Authors: Kaya M G , Romagnoli S , Mandigers T J , Bissacco D , Domanin M , Settembrini Al , Trimarchi S
Published: August 2023

Aim

The role of preoperative embolization in the surgical management of carotid body tumors (CBT) remains a topic of debate. The aim of this study was to evaluate the effect of preoperative embolization on CBT resection.

Method

A systematic review and meta-analysis was conducted following the PRISMA protocol. Pubmed, Scopus and Web of Science were screened for studies published between 2010-2022. Primary outcomes investigated were intraoperative blood loss, operative time, length of hospital stay, and perioperative complications such as TIA/stroke, vascular injury and cranial nerve injury. Quality assessment of selected studies was performed using the Newcastle-Ottawa Scale (NOS). Publication bias was assessed using funnel plots and Egger’s regression test.

Results

Twenty-five studies were included in the systematic review, involving 1649 patients. Twenty-three studies were eligible for meta-analysis. The incidence of vascular injury necessitating intervention was significantly less in the preoperative embolization group (OR = 0.60; 95% CI: 0.42-0.84; P = .003). There was no statistically significant difference between the two groups with regards to intraoperative blood loss, operative time, length of hospital stay, incidence of TIA/stroke and cranial nerve injury. Subgroup analyses did not show significant difference between Shamblin I, II and III subgroups with regards to operative time.

Conclusions

This systematic review and meta-analysis found preoperative embolization to be significantly beneficial in reducing vascular injury. No statistically significant difference was found between the two groups regarding intraoperative blood loss, operative time, length of hospital stay and complications such as TIA/stroke and cranial nerve injury.
1240 Life Expectancy of Octogenarians Following EVAR
Authors: Sultana E , Seraj S , Jones S
Published: August 2023

Background

The aim of elective Abdominal Aortic Aneurysm (AAA) repair is to prevent premature death from rupture. The Endovascular Aneurysm Repair (EVAR) 2 trial showed that patients with AAA who are not fit for open repair do not benefit in terms of life-expectancy from EVAR. In our region, the average life expectancy for men is above the national average but controversy remains when offering octogenarians expensive procedures with the aim of prolonging life. This study aimed to quantify the life-expectancy following an EVAR between octogenarians and younger patients.

Method

A retrospective review was performed of the electronic notes of all patients receiving EVAR at our unit between October 2009 to October 2019. Survival post EVAR was compared between the octogenarian group and the younger patient group. A survival analysis was undertaken using the SPSS software to calculate a Kaplan-Meier curve.

Results

294 patients received EVAR between 2009-2019. Patients were between ages 45 and 89 (Median: 75); 87.4% were male. 169 patients died during follow up (n = 64 ≥80 years, n = 105 <80 years). Time of death post-EVAR in octogenarians (average age 82.91 years) ranged between 0 - 131 months, whilst those under 80 years (average age 71.77 years) ranged between 1 - 152 months. Log rank (Mantel-Cox) analysis demonstrated statistical significance (p = 0.017). Median years post-EVAR for ≥80 years was 3.02 - 4.98 and <80 years was 5.12 - 6.87.

Conclusions

Octogenarians undergoing EVAR have a shorter life-expectancy compared to those under 80 years of age. This should be considered when discussing elective options with patients and their relatives.
Correlations of receptor desensitization of gain-of-function GABRB3 variants with clinical severity
Authors: Lin Susan X N , Ahring Philip K , Keramidas Angelo , Liao Vivian W Y , Møller Rikke S , Chebib Mary , Absalom Nathan L
Published: August 2023

Genetic variants associated with developmental and epileptic encephalopathies have been identified in the GABRB3 gene that encodes the β3 subunit of GABAA receptors. Typically, variants alter receptor sensitivity to GABA resulting in either gain- or loss-of-function, which correlates with patient phenotypes. However, it is unclear how another important receptor property, desensitization, contributes to the greater clinical severity of gain-of-function variants.

Desensitization properties of 20 gain-of-function GABRB3 variant receptors were evaluated using two-electrode voltage-clamp electrophysiology. The parameters measured included current decay rates and steady-state currents. Selected variants with increased or reduced desensitization were also evaluated using whole-cell electrophysiology in transfected mammalian cell lines.

Of the 20 gain-of-function variants assessed, 13 were found to alter receptor desensitization properties. Seven variants reduced desensitization at equilibrium, which acts to worsen gain-of-function traits. Six variants accelerated current decay kinetics, which limits gain-of-function traits. All affected patients displayed severe clinical phenotypes with intellectual disability and difficult-to-treat epilepsy. Nevertheless, variants that reduced desensitization at equilibrium were associated with more severe clinical outcomes. This included younger age of first seizure onset (median 0.5 months), movement disorders (dystonia and dyskinesia), epilepsy of infancy with migrating focal seizures (EIMFS) and risk of early mortality. Variants that accelerated current decay kinetics were associated with slightly milder phenotypes with later seizure onset (median 4 months), unclassifiable developmental and epileptic encephalopathies or Lennox–Gastaut syndrome and no movement disorders.

Our study reveals that gain-of-function GABRB3 variants can increase or decrease receptor desensitization properties and that there is a correlation with the degree of disease severity. Variants that reduced the desensitization at equilibrium were clustered in the transmembrane regions that constitute the channel pore and correlated with greater disease severity, while variants that accelerated current decay were clustered in the coupling loops responsible for receptor activation and correlated with lesser severity.
Assessing the Skin and UV Neoplasia Transplant Risk Assessment Calculator in an Irish cohort of thoracic organ transplant recipients
Authors: Yoo Li Jie Helena , Bowe Stephanie , Quigley Claire , Victory Liana , Devenney Ciara , Lenane Patsy
Published: August 2023

The Skin and UV Neoplasia Transplant Risk Assessment Calculator (SUNTRAC) is a tool that can be used to decide when to first screen for skin cancer in organ transplant recipients (OTRs). The objective of this study was to assess the applicability of this tool in thoracic OTRs. Based on data from patient files, the OTRs were categorized into four risk groups according to the SUNTRAC tool. The time of the first post-transplant skin cancer in each OTR was recorded. The proportion of OTRs with post-transplant skin cancer in the low-, medium-, high- and very high-risk groups was 0%, 28.3%, 58.3% and 100%, respectively. This positive correlation suggests that SUNTRAC can be used to determine when to first screen for skin cancer in heart and lung OTRs.
PDE4D mediates impaired β-adrenergic receptor signalling in the sinoatrial node in mice with hypertensive heart disease
Authors: Dorey Tristan W , McRae Megan D , Belke Darrell D , Rose Robert A
Published: August 2023

Aims

The sympathetic nervous system increases HR by activating β-adrenergic receptors (β-ARs) and increasing cAMP in sinoatrial node (SAN) myocytes while phosphodiesterases (PDEs) degrade cAMP. Chronotropic incompetence, the inability to regulate heart rate (HR) in response to sympathetic nervous system activation, is common in hypertensive heart disease; however, the basis for this is poorly understood. The objective of this study was to determine the mechanisms leading to chronotropic incompetence in mice with angiotensin II (AngII)-induced hypertensive heart disease.

Methods and results

C57BL/6 mice were infused with saline or AngII (2.5 mg/kg/day for 3 weeks) to induce hypertensive heart disease. HR and SAN function in response to the β-AR agonist isoproterenol (ISO) were studied in vivo using telemetry and electrocardiography, in isolated atrial preparations using optical mapping, in isolated SAN myocytes using patch-clamping, and using molecular biology. AngII-infused mice had smaller increases in HR in response to physical activity and during acute ISO injection. Optical mapping of the SAN in AngII-infused mice demonstrated impaired increases in conduction velocity and altered conduction patterns in response to ISO. Spontaneous AP firing responses to ISO in isolated SAN myocytes from AngII-infused mice were impaired due to smaller increases in diastolic depolarization (DD) slope, hyperpolarization-activated current (If), and L-type Ca2+ current (ICa,L). These changes were due to increased localization of PDE4D surrounding β1- and β2-ARs in the SAN, increased SAN PDE4 activity, and reduced cAMP generation in response to ISO. Knockdown of PDE4D using a virus-delivered shRNA or inhibition of PDE4 with rolipram normalized SAN sensitivity to β-AR stimulation in AngII-infused mice.

Conclusions

AngII-induced hypertensive heart disease results in impaired HR responses to β-AR stimulation due to up-regulation of PDE4D and reduced effects of cAMP on spontaneous AP firing in SAN myocytes.
ZIF-1-mediated degradation of zinc finger proteins in the Caenorhabditis elegans germ line
Authors: Schwartz Aaron Z A , Abdu Yusuff , Nance Jeremy
Published: August 2023

Rapid and conditional protein depletion is the gold standard genetic tool for deciphering the molecular basis of developmental processes. Previously, we showed that by conditionally expressing the E3 ligase substrate adaptor ZIF-1 in Caenorhabditis elegans somatic cells, proteins tagged with the first CCCH Zn finger 1 (ZF1) domain from the germline regulator PIE-1 degrade rapidly, resulting in loss-of-function phenotypes. The described role of ZIF-1 is to clear PIE-1 and several other CCCH Zn finger proteins from early somatic cells, helping to enrich them in germline precursor cells. Here, we show that proteins tagged with the PIE-1 ZF1 domain are subsequently cleared from primordial germ cells (PGCs) in embryos and from undifferentiated germ cells in larvae and adults by ZIF-1. We harness germline ZIF-1 activity to degrade a ZF1-tagged fusion protein from PGCs and show that its depletion produces phenotypes equivalent to those of a null mutation. Our findings reveal that ZIF-1 transitions from degrading CCCH Zn finger proteins in somatic cells to clearing them from undifferentiated germ cells, and that ZIF-1 activity can be harnessed as a new genetic tool to study the early germline.
Effectiveness of the Australian MATES in Construction Suicide Prevention Program: a systematic review
Authors: Gullestrup Jorgen , King Tania , Thomas Samantha L , LaMontagne Anthony D
Published: August 2023

Suicide is a major public health issue globally. The World Health Organization has called for nations to create comprehensive national suicide prevention strategies including multisectoral collaboration, awareness raising, advocacy and capacity building. The workplace provides opportunity and structure for suicide prevention programs. However, many of these programs are poorly documented and evaluated. The MATES in Construction (MATES) program is a multimodal workplace-based suicide prevention program designed for and by the construction industry. This systematic review examined the available evidence for the effectiveness of the MATES program and is reported according to PRISMA guidelines. A literature search resulted in the inclusion of 12 peer-reviewed articles published between January 2010 and February 2023 containing primary data of evaluations of MATES. There was evidence of the effectiveness of the MATES program in improving mental health and suicide prevention literacy, helping intentions and reducing stigma. The results highlighted the importance of worker-to-worker peer approaches with workers consistently stating that supervisors were the least trusted resources for mental health and suicide concerns. Favourable results were found in relation to reduced suicide risk in the construction industry. The evidence base for MATES is limited in terms of causal inference with very few controlled evaluations and no experimental studies having been conducted to date. Improved understanding of how the program motivates volunteers, their experiences and research on the longer-term impacts of the program on the industry is required.
Finite Groups Acting on Compact Complex Parallelizable Manifolds
Authors: Golota Aleksei
Published: August 2023

We prove that the automorphism group of a compact complex parallelizable manifold is Jordan. In the course of the proof, we show that outer automorphism groups of cocompact lattices in complex Lie groups have bounded finite subgroups.
A Genetic Lab-on-Phone Test for Point-of-Care Diagnostic of Lactose Intolerance near Patient and in less than 90 Minutes
Authors: Conceição Mariana , Assunção Hugo , Doria Gonçalo , Coelho Eduardo , Clemente Carla , Gaspar César , Furtado Tiago , Yamaguchi Takumi , Santos António , Silva Mónica , Rodriguez Lidia , Rodrigues Liliana , Flores Orfeu
Published: August 2023

Background

The −13910 C/T single nucleotide polymorphism located within the MCM6 gene, an enhancer region located upstream of the lactase-phlorizin hydrolase gene, is associated with lactase persistence/non-persistence traits among the Caucasian population. The performance of a new point-of-care CE-IVD (In Vitro Diagnostic) marked isothermal lab-on-phone lactose intolerance assay, using crude samples, was assessed in comparison with Sanger sequencing using purified DNA, as reference method.

Methods

The study was conducted following a non-probability sampling using direct buccal swab (n = 63) and capillary blood (n = 43) clinical samples from a total of 63 volunteers. A 3 × 3 confusion matrix/contingency table was used to evaluate the performance of the isothermal lab-on-phone lactose intolerance assay.

Results

The isothermal lab-on-phone lactose intolerance assay successfully detected the −13910 C/T variant with a limit of detection of 5 cells/assay and demonstrated an overall accuracy of 98.41% (95% CI, 91.47%–99.96%) for buccal swab samples and 100% (95% CI, 91.19%–100%) for capillary blood, taking just 90 min from sample to result, with only 2 min hands-on.

Conclusions

The lab-on-phone pocket-sized assay displayed good performance when using direct buccal swab and capillary blood samples, enabling a low-cost, real-time, and accurate genotyping of the −13910 C/T region for the rapid diagnosis of primary lactose intolerance at point-of-care, which enables a prompt implementation of appropriate diet habits and/or intolerance therapies. To our knowledge, this is the first point-of-care genetic test for lactose intolerance to be made available on the market.
Effects of machine learning-based clinical decision support systems on decision-making, care delivery, and patient outcomes: a scoping review
Authors: Susanto Anindya Pradipta , Lyell David , Widyantoro Bambang , Berkovsky Shlomo , Magrabi Farah
Published: August 2023

Objective

This study aims to summarize the research literature evaluating machine learning (ML)-based clinical decision support (CDS) systems in healthcare settings.

Materials and methods

We conducted a review in accordance with the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta Analyses extension for Scoping Review). Four databases, including PubMed, Medline, Embase, and Scopus were searched for studies published from January 2016 to April 2021 evaluating the use of ML-based CDS in clinical settings. We extracted the study design, care setting, clinical task, CDS task, and ML method. The level of CDS autonomy was examined using a previously published 3-level classification based on the division of clinical tasks between the clinician and CDS; effects on decision-making, care delivery, and patient outcomes were summarized.

Results

Thirty-two studies evaluating the use of ML-based CDS in clinical settings were identified. All were undertaken in developed countries and largely in secondary and tertiary care settings. The most common clinical tasks supported by ML-based CDS were image recognition and interpretation (n = 12) and risk assessment (n = 9). The majority of studies examined assistive CDS (n = 23) which required clinicians to confirm or approve CDS recommendations for risk assessment in sepsis and for interpreting cancerous lesions in colonoscopy. Effects on decision-making, care delivery, and patient outcomes were mixed.

Conclusion

ML-based CDS are being evaluated in many clinical areas. There remain many opportunities to apply and evaluate effects of ML-based CDS on decision-making, care delivery, and patient outcomes, particularly in resource-constrained settings.
The association of miR-204 and mir-483 5p expression with clinicopathological features of Wilms tumor: Could this provide foresight?
Authors: Orgen Calli Aylin , Issin Gizem , Yilmaz Ismail , Ince Dilek , Tural Ersin , Guzelis Ismail , Cecen Refik Emre , Olgun Hatice Nur , Gokcay Deniz , Ozer Erdener
Published: August 2023

Background

Wilms tumor is the most common cancer of the kidney that occurs during childhood, and histologically, it mimics renal embryogenesis. With the development and improvement of up-to-date treatment protocols, the survival rates of Wilms tumor have increased. However, metastases or local relapses are still observed in 15% of patients. The search for reliable biomarkers to identify at-risk patients is ongoing to predict the variability in treatment success. Currently, the evaluation of clinical, histopathological and genetic features are common diagnostic methods; however, epigenetic features can be examined with microRNA expression analyses and might allow us to comment on the behavior of the tumor and treatment response.

Methods

In this study, we aimed to evaluate the relationship between microRNA-204 and microRNA-483-5p expression with clinicopathological data and the effect on Wilms tumor survival. For this purpose, the expression levels of RNU6B, microRNA-204 and microRNA-483-5p were evaluated in tumor and normal tissue by qreal time-polymerase chain reaction. We also investigated the relationship between microRNA expression levels with the clinicopathological and histological features of Wilms tumor.

Results and conclusion

The results of our study indicate that the relative expression levels of microRNA-204 in Wilms tumor tissues were significantly lower than that in adjacent normal tissues. By contrast, tumor tissue had a higher microRNA-483-5p expression than the corresponding normal tissues. A statistically significant difference between microRNA-204 expression level with age and the presence of anaplasia was observed. The upregulation of microRNA-483-5p was found to have a significant correlation with patients after preoperative chemotherapy and complete tumor necrosis. Taken together, our data suggest that microRNA-204 could play a critical role as a tumor suppressor, whereas microRNA-483-5p acts as an oncogene in Wilms tumor progression. More importantly, microRNA-204 might be a novel predictive biomarker for anaplastic histology and could be useful for developing therapeutic interventions targeting this marker.
On the importance of disc chemistry in the formation of protoplanetary disc rings
Authors: Nolan C A , Zhao B , Caselli P , Li Z Y
Published: August 2023

Radial substructures have now been observed in a wide range of protoplanetary discs (PPDs), from young to old systems; however, their formation is still an area of vigorous debate. Recent magnetohydrodynamic (MHD) simulations have shown that rings and gaps can form naturally in PPDs when non-ideal MHD effects are included. However, these simulations employ ad hoc approximations to the magnitudes of the magnetic diffusivities in order to facilitate ring growth. We replace the parametrization of these terms with a simple chemical network and grain distribution model to calculate the non-ideal effects in a more self-consistent way. We use a range of grain distributions to simulate grain formation for different disc conditions. Including ambipolar diffusion, we find that large grain populations (>1 $\mu$m), and those including a population of very small polyaromatic hydrocarbons (PAHs) facilitate the growth of periodic, stable rings, while intermediate-sized grains suppress ring formation. Including Ohmic diffusion removes the positive influence of PAHs, with only large grain populations still producing periodic ring and gap structures. These results relate closely to the degree of coupling between the magnetic field and the neutral disc material, quantified by the non-dimensional Elsasser number Λ (the ratio of magnetic forces to Coriolis force). For both the ambipolar-only and ambipolar-ohmic cases, if the total Elsasser number is initially of the order of unity along the disc mid-plane, ring and gap structures may develop.
The plant-unique protein DRIF1 coordinates with sorting nexin 1 to regulate membrane protein homeostasis
Authors: Zhu Ying , Zhao Qiong , Cao Wenhan , Huang Shuxian , Ji Changyang , Zhang Wenxin , Trujillo Marco , Shen Jinbo , Jiang Liwen
Published: August 2023

Membrane protein homeostasis is fine-tuned by the cellular pathways for vacuolar degradation and recycling, which ultimately facilitate plant growth and cell–environment interactions. The endosomal sorting complex required for transport (ESCRT) machinery plays important roles in regulating intraluminal vesicle (ILV) formation and membrane protein sorting to vacuoles. We previously showed that the plant-specific ESCRT component FYVE DOMAIN PROTEIN REQUIRED FOR ENDOSOMAL SORTING1 (FREE1) performs multiple functions in plants, although the underlying mechanisms remain elusive. In this study, we performed a suppressor screen of the FREE1-RNAi mutant and identified and characterized 2 suppressor of free1 (sof) mutants in Arabidopsis (Arabidopsis thaliana). These mutants, sof10 and sof641, result in a premature stop codon or a missense mutation in AT5G10370, respectively. This gene was named DEAH and RING domain-containing protein as FREE1 suppressor 1 (DRIF1). DRIF1 has a homologous gene, DRIF2, in the Arabidopsis genome with 95% identity to DRIF1. The embryos of drif1 drif2 mutants arrested at the globular stage and formed enlarged multivesicular bodies (MVBs) with an increased number of ILVs. DRIF1 is a membrane-associated protein that coordinates with retromer component sorting nexin 1 to regulate PIN-FORMED2 recycling to the plasma membrane. Altogether, our data demonstrate that DRIF1 is a unique retromer interactor that orchestrates FREE1-mediated ILV formation of MVBs and vacuolar sorting of membrane proteins for degradation in plants.
Baseline predictors of disease severity in immune checkpoint inhibitor-induced inflammatory arthritis
Authors: Cappelli Laura C , Kamal Omer , Jones Michelle , Bingham Clifton O , Shah Ami A
Published: August 2023

Objectives

The objective of this study was to determine baseline risk factors for requiring immunosuppression and having persistent arthritis in patients with immune checkpoint inhibitor–induced inflammatory arthritis (ICI–inflammatory arthritis).

Methods

Participants were adults with rheumatologist diagnosed ICI–inflammatory arthritis. The primary outcome was requirement of conventional synthetic (cs) or biologic (b) DMARDs; other outcomes were persistence of inflammatory arthritis >6 months after ICI cessation and requirement of CSs. Logistic regression models evaluated associations between clinical features and primary and secondary outcomes, with adjustment for potential confounders, as appropriate.

Results

One hundred and twenty-six patients with ICI–inflammatory arthritis were included; 53 patients (42%) required a csDMARD/bDMARD. In the univariate logistic regression analysis, higher clinical disease activity index (CDAI), tenosynovitis, longer symptom duration before first rheumatology visit and longer ICI duration were significantly associated with a higher likelihood of requiring DMARDs; in addition, there was a trend towards those treated with prior chemotherapy being less likely to need DMARDs. After adjustment, tenosynovitis, longer symptom duration and higher CDAI remained associated with requiring DMARDs, while those with prior chemotherapy were significantly less likely to require DMARDs. Combination anti-CTLA-4 (cytotoxic T-lymphocyte-associated protein-4)/PD-1 (Programmed cell death protein-1) therapy and CS use at baseline were associated with a higher risk of persistent inflammatory arthritis.

Conclusion

Higher levels of disease activity, tenosynovitis and longer symptom duration prior to rheumatology referral were associated with requiring DMARDs for ICI–inflammatory arthritis, while those treated previously with chemotherapy were less likely to require additional immunosuppression. The presence of risk factors for severe disease at baseline may indicate a role for higher initial CS dose, earlier rheumatology referral, and adoption of immunosuppression beyond CSs to improve outcomes.