Publications by authors named "Benjamin Thomas"

269 Publications

Genetics of testicular cancer: a review.

Curr Opin Urol 2022 Sep 18;32(5):481-487. Epub 2022 Jul 18.

Department of Medical Oncology, Peter MacCallum Cancer Centre.

Purpose Of Review: Testicular germ cell tumours (TGCTs) are the most common solid malignant cancer diagnosed in young males and the incidence is increasing. Understanding the genetic basis of this disease will help us to navigate the challenges of early detection, diagnosis, treatment, surveillance, and long-term outcomes for patients.

Recent Findings: TGCTs are highly heritable. Current understanding of germline risk includes the identification of one moderate-penetrance predisposition gene, checkpoint kinase 2 ( CHEK2 ), and 78 low-to-moderate-risk single nucleotide polymorphisms identified in genome-wide-associated studies, which account for 44% of familial risk. Biomarker research in TGCTs has been challenging for multiple reasons: oncogenesis is complex, actionable mutations are uncommon, clonal evolution unpredictable and tumours can be histologically and molecularly heterogeneous. Three somatic mutations have thus far been identified by DNA exome sequencing, exclusively in seminomas: KIT, KRAS and NRAS . Several genetic markers appear to be associated with risk of TGCT and treatment resistance. TP53 mutations appear to be associated with platinum resistance. MicroRNA expression may be a useful biomarker of residual disease and relapse in future.

Summary: The biology of testicular germ cells tumours is complex, and further research is needed to fully explain the high heritability of these cancers, as well as the molecular signatures which may drive their biological behaviour.
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http://dx.doi.org/10.1097/MOU.0000000000001017DOI Listing
September 2022

Development of a mathematical formula and online tool to calculate the potential maximum flap width to allow for primary anterolateral thigh donor-site closure in Caucasians.

Microsurgery 2022 Jul 12. Epub 2022 Jul 12.

Department of Hand, Plastic and Reconstructive Surgery, Burn Center, BG Trauma Center Ludwigshafen, University of Heidelberg, Heidelberg, Germany.

Background: Primary anterolateral thigh (ALT) flap donor-site closure is crucial to achieve patient satisfaction, avoid burdensome secondary surgeries, and avert poor outcomes. Only vague maximum flap width recommendations have been suggested, which fall short of acknowledging individual patient habitus and thigh morphology. Therefore, we aimed at identifying a user-friendly preoperative calculation of maximum flap width for primary closure.

Methods: A total of 429 ALT free flaps performed between 2009 and 2020 were analyzed. A total of 350 donor-sites were closed primarily (82%) and 79 (18%) were split-thickness skin-grafted (STSG). Patient demographics including sex, age, and BMI, operative details, and flap characteristics were compared to assess their impact on the outcome variable. Receiver operating characteristic (ROC) curves were plotted for all significant predictors discriminating between closure and STSG. Areas under the curve (AUCs) were calculated for each parameter combination and optimal cutoffs were determined using Youden's Index.

Results: Sex, age, BMI, and flap width alone were poor discriminators. Dividing flap width by BMI and logarithmized BMI yielded AUCs of 0.91 and 0.94, respectively. Including patient sex yielded the best fitting regression model (χ  = 251.939, p < .0001) increasing the AUC to 0.96 (95% CI: 0.93-0.98, p < .0001). The optimal cutoff value discriminated between primary closure and STSG with 90% sensitivity and 89% specificity. An online calculator of patient-individual maximum ALT width was then programmed.

Conclusions: Sex and BMI are reliable predictors of successful primary ALT donor-site closure in Caucasians. We devised a novel formula for calculating patient-individual maximum ALT widths preoperatively, predicting failure of primary closure with 90% sensitivity in our cohort, available at: https://kitteltaschenbuch.com/altwidth/calculate.htm.
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http://dx.doi.org/10.1002/micr.30934DOI Listing
July 2022

Phase 2 Study of Neoadjuvant FGFR Inhibition and Androgen Deprivation Therapy Prior to Prostatectomy.

Clin Genitourin Cancer 2022 May 18. Epub 2022 May 18.

Urology Unit, Royal Melbourne Hospital, Parkville, VIC, Australia; Department of Surgery, University of Melbourne, Royal Melbourne Hospital, VIC, Australia; Victorian Comprehensive Cancer Centre, Parkville, VIC, Australia. Electronic address:

Background: Disease recurrence is common following prostatectomy in patients with localised prostate cancer with high-risk features. Although androgen deprivation therapy increases the rates of organ-confined disease and negative surgical margins, there is no significant benefit on disease recurrence. Multiple lines of evidence suggest that (Fibroblast Growth Factor/Fibroblast Growth Factor Receptor) FGF/FGFR-signalling is important in supporting prostate epithelial cell survival in hostile conditions, including acute androgen deprivation. Given the recent availability of oral FGFR inhibitors, we investigated whether combination therapy could improve tumour response in the neo-adjuvant setting.

Methods: We conducted an open label phase II study of the combination of erdafitinib (3 months) and androgen deprivation therapy (4 months) in men with localised prostate cancer with high-risk features prior to prostatectomy using a Simon's 2 stage design. The co-primary endpoints were safety and tolerability and pathological response in the prostatectomy specimen. The effect of treatment on residual tumours was explored by global transcriptional profiling with RNA-sequencing.

Results: Nine patients were enrolled in the first stage of the trial. The treatment combination was poorly tolerated. Erdafitinib treatment was discontinued early in six patients, three of whom also required dose interruptions/reductions. Androgen deprivation therapy for 4 months was completed in all patients. The most common adverse events were hyperphosphataemia, taste disturbance, dry mouth and nail changes. No patients achieved a complete pathological response, although patients who tolerated erdafitinib for longer had smaller residual tumours, associated with reduced transcriptional signatures of epithelial cell proliferation.

Conclusions: Although there was a possible enhanced anti-tumour effect of androgen deprivation therapy in combination with erdafitnib in treatment naïve prostate cancer, the poor tolerability in this patient population prohibits the use of this combination in this setting.
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http://dx.doi.org/10.1016/j.clgc.2022.05.007DOI Listing
May 2022

Perfusion of the proximal scaphoid pole: correlation between preoperative ge-MRI and intraoperative findings.

Arch Orthop Trauma Surg 2022 Jun 1. Epub 2022 Jun 1.

Department of Hand, Plastic and Reconstructive Surgery, Burn Center, Department of Hand and Plastic Surgery of Heidelberg University, BG Trauma Center, Ludwigshafen, Germany.

Background: Gadolinium enhanced MRI (ge-MRI) is considered as gold standard for perfusion evaluation in case of scaphoid nonunion (SNU). However, its clinical value and specificity is still not clearly evaluated. This study compares preoperative ge-MRI-based perfusion assessment and intraoperative proximal pole (PP) perfusion after scaphoid reconstruction by vascularized bone grafts. In addition, the postoperative osseous consolidation (OC) was correlated to intraoperative perfusion findings.

Methods: Between 08/2010 and 01/2020, 60 of 271 patients with scaphoid nonunion received a vascularized radius bone graft for reconstruction. Medical reports were checked for intra-op perfusion findings. Consolidation rate was assessed at mean follow-up of 3 months by CT evaluation. In 50 cases (83.2%), complete medical and radiological history could be obtained. Preoperative ge-MRI was reevaluated by a blinded radiologist for advanced analysis of sensitivity and specificity.

Results: Preoperative ge-MRI (initial finding, IF) showed 23 avascular, 20 malperfused, and seven vital PP. Blinded radiological follow-up (second finding, SF) revealed 14 avascular, 28 malperfused, and 8 vital PP, with a concordance of 65.3% (n = 35). After correlation with the intra-op findings, a specificity of preoperative ge-MRI of 76.5% (IF) and 88.2 (SF), respectively, was revealed for exclusion of avitality. For detection of malperfusion, there was a sensitivity of 92.7% (IF) and 85.4% (SF), respectively. Complete OC was seen 12 weeks postoperatively in 37 (73.5%), partial OC in 9 (18.3%), and nonunion in 4 cases (8.2%) on CT-scans. Of the 41 malperfused/avascular PP, 31 (75.6%) progressed to complete and 6 (14.6%) to partial (at least 2 adjacent CT-layers of 2 mm) OC, with 4 nonunions.

Conclusion: The sensitivity and specificity of ge-MRI for detection/ exclusion of malperfusion/avitality of the PP was lower than expected. Therewith, the intraoperative assessment of PP perfusion regains a high value in decision-making for the appropriate graft. We recommend preservation of the dorsal radial vascular plexus initially until the vascularity of the proximal pole has been estimated. Patient education for all contingencies and retraction options should be obtained.
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http://dx.doi.org/10.1007/s00402-022-04480-8DOI Listing
June 2022

Accuracy of emergency medical service telephone triage of need for an ambulance response in suspected COVID-19: an observational cohort study.

BMJ Open 2022 05 16;12(5):e058628. Epub 2022 May 16.

Centre for Urgent and Emergency Care Research (CURE), Health Services Research School of Health and Related Research (ScHARR), University of Sheffield, Sheffield, UK.

Objective: To assess accuracy of emergency medical service (EMS) telephone triage in identifying patients who need an EMS response and identify factors which affect triage accuracy.

Design: Observational cohort study.

Setting: Emergency telephone triage provided by Yorkshire Ambulance Service (YAS) National Health Service (NHS) Trust.

Participants: 12 653 adults who contacted EMS telephone triage services provided by YAS between 2 April 2020 and 29 June 2020 assessed by COVID-19 telephone triage pathways were included.

Outcome: Accuracy of call handler decision to dispatch an ambulance was assessed in terms of death or need for organ support at 30 days from first contact with the telephone triage service.

Results: Callers contacting EMS dispatch services had an 11.1% (1405/12 653) risk of death or needing organ support. In total, 2000/12 653 (16%) of callers did not receive an emergency response and they had a 70/2000 (3.5%) risk of death or organ support. Ambulances were dispatched to 4230 callers (33.4%) who were not conveyed to hospital and did not deteriorate. Multivariable modelling found variables of older age (1 year increase, OR: 1.05, 95% CI: 1.04 to 1.05) and presence of pre-existing respiratory disease (OR: 1.35, 95% CI: 1.13 to 1.60) to be predictors of false positive triage.

Conclusion: Telephone triage can reduce ambulance responses but, with low specificity. A small but significant proportion of patients who do not receive an initial emergency response deteriorated. Research to improve accuracy of EMS telephone triage is needed and, due to limitations of routinely collected data, this is likely to require prospective data collection.
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http://dx.doi.org/10.1136/bmjopen-2021-058628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9114316PMC
May 2022

The prognostic role of extended preoperative hypercoagulability work-up in high-risk microsurgical free flaps: a single-center retrospective case series of patients with heterozygotic factor V Leiden thrombophilia.

BMC Surg 2022 May 14;22(1):190. Epub 2022 May 14.

Department of Hand, Plastic and Reconstructive Surgery, Burn Center, BG Trauma Center Ludwigshafen, Plastic- and Hand Surgery, University of Heidelberg, Ludwig-Guttmann-Str. 13, 67071, Ludwigshafen, Germany.

Introduction: Hypercoagulability is associated with an increased risk of microvascular complications and free flap failures. The authors present their experience and approach to diagnosing and treating patients with heterozygotic factor V Leiden (hFVL) thrombophilia undergoing free flap reconstruction.

Methods: Between November 2009 and June 2018, 23 free flap surgeries were performed in 15 hypercoagulable patients with hFVL. According to the timing of perioperative hypercoagulability work-up, they were grouped into flaps with established diagnoses prior to surgery (Group A) versus flaps with unknown diagnoses prior to surgery (Group B). Baseline characteristics and perioperative complications were compared between both groups, including revision surgeries due to microvascular thromboses, acute bleedings, hematomas, flap necroses, and reconstructive failures.

Results: HFVL mutations had been confirmed preoperatively in 14 free flap surgeries (61%, Group A), whereas in 9 free flap surgeries (39%, Group B), mutations were only diagnosed postoperatively after the occurrence of microvascular thromboses had warranted extended hypercoagulability work-up. The overall rate of intraoperative flap thromboses was 9% (n = 2), whereas the overall rate of postoperative flap thromboses was 43% (n = 10). The corresponding salvage rates were 100% (n = 2/2) for intraoperative and 40% (n = 4/10) for postoperative pedicle thromboses. A total of five free flaps were lost (22%). Upon comparison, flaps with an unconfirmed diagnosis prior to surgery were at ten times higher risk for developing total necroses (flaps lost in Group B = 4/9 versus Group A = 1/14; OR: 10.4; 95% CI 1.0, 134.7; p = 0.03).

Conclusion: Meticulous preoperative work-up of patients with any history of hypercoagulability can help reduce free flap loss rates, thus improving surgical outcomes and increasing patient safety.
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http://dx.doi.org/10.1186/s12893-022-01639-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9107705PMC
May 2022

An intervention to promote self-management, independence and self-efficacy in people with early-stage dementia: the Journeying through Dementia RCT.

Health Technol Assess 2022 05;26(24):1-152

School of Health and Related Research, University of Sheffield, Sheffield, UK.

Background: There are few effective interventions for dementia.

Aim: To determine the clinical effectiveness and cost-effectiveness of an intervention to promote self-management, independence and self-efficacy in people with early-stage dementia.

Objectives: To undertake a randomised controlled trial of the Journeying through Dementia intervention compared with usual care, conduct an internal pilot testing feasibility, assess intervention delivery fidelity and undertake a qualitative exploration of participants' experiences.

Design: A pragmatic two-arm individually randomised trial analysed by intention to treat.

Participants: A total of 480 people diagnosed with mild dementia, with capacity to make informed decisions, living in the community and not participating in other studies, and 350 supporters whom they identified, from 13 locations in England, took part.

Intervention: Those randomised to the Journeying through Dementia intervention ( = 241) were invited to take part in 12 weekly facilitated groups and four one-to-one sessions delivered in the community by secondary care staff, in addition to their usual care. The control group ( = 239) received usual care. Usual care included drug treatment, needs assessment and referral to appropriate services. Usual care at each site was recorded.

Main Outcome Measures: The primary outcome was Dementia-Related Quality of Life score at 8 months post randomisation, with higher scores representing higher quality of life. Secondary outcomes included resource use, psychological well-being, self-management, instrumental activities of daily living and health-related quality of life.

Randomisation And Blinding: Participants were randomised in a 1 : 1 ratio. Staff conducting outcome assessments were blinded.

Data Sources: Outcome measures were administered in participants' homes at baseline and at 8 and 12 months post randomisation. Interviews were conducted with participants, participating carers and interventionalists.

Results: The mean Dementia-Related Quality of Life score at 8 months was 93.3 (standard deviation 13.0) in the intervention arm ( = 191) and 91.9 (standard deviation 14.6) in the control arm ( = 197), with a difference in means of 0.9 (95% confidence interval -1.2 to 3.0;  = 0.380) after adjustment for covariates. This effect size (0.9) was less than the 4 points defined as clinically meaningful. For other outcomes, a difference was found only for Diener's Flourishing Scale (adjusted mean difference 1.2, 95% confidence interval 0.1 to 2.3), in favour of the intervention (i.e. in a positive direction). The Journeying through Dementia intervention cost £608 more than usual care (95% confidence interval £105 to £1179) and had negligible difference in quality-adjusted life-years (-0.003, 95% confidence interval -0.044 to 0.038). Therefore, the Journeying through Dementia intervention had a mean incremental cost per quality-adjusted life-year of -£202,857 (95% confidence interval -£534,733 to £483,739); however, there is considerable uncertainty around this. Assessed fidelity was good. Interviewed participants described receiving some benefit and a minority benefited greatly. However, negative aspects were also raised by a minority. Seventeen per cent of participants in the intervention arm and 15% of participants in the control arm experienced at least one serious adverse event. None of the serious adverse events were classified as related to the intervention.

Limitations: Study limitations include recruitment of an active population, delivery challenges and limitations of existing outcome measures.

Conclusions: The Journeying through Dementia programme is not clinically effective, is unlikely to be cost-effective and cannot be recommended in its existing format.

Future Work: Research should focus on the creation of new outcome measures to assess well-being in dementia and on using elements of the intervention, such as enabling enactment in the community.

Trial Registration: This trial is registered as ISRCTN17993825.

Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 26, No. 24. See the NIHR Journals Library website for further project information.
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http://dx.doi.org/10.3310/KHHA0861DOI Listing
May 2022

The utility of magnetic resonance imaging in prostate cancer diagnosis in the Australian setting.

BJUI Compass 2021 Nov 4;2(6):377-384. Epub 2021 Jun 4.

Department of Urology The Royal Melbourne Hospital Melbourne VIC Australia.

Objectives: To investigate the utility of Magnetic Resonance Imaging (MRI) for prostate cancer diagnosis in the Australian setting.

Patients And Methods: All consecutive men who underwent a prostate biopsy (transperineal or transrectal) at Royal Melbourne Hospital between July 2017 to June 2019 were included, totalling 332 patients. Data were retrospectively collected from patient records. For each individual patient, the risk of prostate cancer diagnosis at biopsy based on clinical findings was determined using the European Randomized study of Screening for Prostate Cancer (ERSPC) risk calculator, with and without incorporation of MRI findings.

Results: MRI has good diagnostic accuracy for clinically significant prostate cancer. A PI-RADS 2 or lower finding has a negative predictive value of 96% for clinically significant cancer, and a PI-RADS 3, 4 or 5 MRI scan has a sensitivity of 93%. However, MRI has a false negative rate of 6.5% overall for clinically significant prostate cancers. Pre- biopsy MRI may reduce the number of unnecessary biopsies, as up to 50.0% of negative or ISUP1 biopsies have MRI PI-RADS 2 or lower. Incorporation of MRI findings into the ERSPC calculator improved predictive performance for all prostate cancer diagnoses (AUC 0.77 vs 0.71,  = .04), but not for clinically significant cancer (AUC 0.89 vs 0.87,  = .37).

Conclusion: MRI has good sensitivity and negative predictive value for clinically significant prostate cancers. It is useful as a pre-biopsy tool and can be used to significantly reduce the number of unnecessary prostate biopsies. However, MRI does not significantly improve risk predictions for clinically significant cancers when incorporated into the ERSPC risk calculator.
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http://dx.doi.org/10.1002/bco2.99DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8988779PMC
November 2021

Accuracy of telephone triage for predicting adverse outcomes in suspected COVID-19: an observational cohort study.

BMJ Qual Saf 2022 Mar 30. Epub 2022 Mar 30.

Centre for Urgent and Emergency Care Research (CURE), Health Services Research School of Health and Related Research (ScHARR), University of Sheffield, Sheffield, UK.

Objective: To assess accuracy of telephone triage in identifying need for emergency care among those with suspected COVID-19 infection and identify factors which affect triage accuracy.

Design: Observational cohort study.

Setting: Community telephone triage provided in the UK by Yorkshire Ambulance Service NHS Trust (YAS).

Participants: 40 261 adults who contacted National Health Service (NHS) 111 telephone triage services provided by YAS between 18 March 2020 and 29 June 2020 with symptoms indicating COVID-19 infection were linked to Office for National Statistics death registrations and healthcare data collected by NHS Digital.

Outcome: Accuracy of triage disposition was assessed in terms of death or need for organ support up to 30 days from first contact.

Results: Callers had a 3% (1200/40 261) risk of serious adverse outcomes (death or organ support). Telephone triage recommended self-care or non-urgent assessment for 60% (24 335/40 261), with a 1.3% (310/24 335) risk of adverse outcomes. Telephone triage had 74.2% sensitivity (95% CI: 71.6 to 76.6%) and 61.5% specificity (95% CI: 61% to 62%) for the primary outcome. Multivariable analysis suggested respiratory comorbidities may be overappreciated, and diabetes underappreciated as predictors of deterioration. Repeat contact with triage service appears to be an important under-recognised predictor of deterioration with 2 contacts (OR 1.77, 95% CI: 1.14 to 2.75) and 3 or more contacts (OR 4.02, 95% CI: 1.68 to 9.65) associated with false negative triage.

Conclusion: Patients advised to self-care or receive non-urgent clinical assessment had a small but non-negligible risk of serious clinical deterioration. Repeat contact with telephone services needs recognition as an important predictor of subsequent adverse outcomes.
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http://dx.doi.org/10.1136/bmjqs-2021-014382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8983415PMC
March 2022

The Free Myocutaneous Tensor Fasciae Latae Flap-A Workhorse Flap for Sternal Defect Reconstruction: A Single-Center Experience.

J Pers Med 2022 Mar 9;12(3). Epub 2022 Mar 9.

Department of Hand, Plastic and Reconstructive Surgery, Burn Center, BG Trauma Center Ludwigshafen, Plastic and Hand Surgery, University of Heidelberg, Ludwig-Guttmann-Str. 13, D-67071 Ludwigshafen, Germany.

Introduction: Deep sternal wound infections (DSWI) after cardiac surgery pose a significant challenge in reconstructive surgery. In this context, free flaps represent well-established options. The objective of this study was to investigate the clinical outcome after free myocutaneous tensor fasciae latae (TFL) flap reconstruction of sternal defects, with a special focus on surgical complications and donor-site morbidity.

Methods: A retrospective chart review focused on patient demographics, operative details, and postoperative complications. Follow-up reexaminations included assessments of the range of motion and muscle strength at the donor-site. Patients completed the Quality of Life 36-item Short Form Health Survey (SF-36) as well as the Lower Extremity Functional Scale (LEFS) questionnaire and evaluated aesthetic and functional outcomes on a 6-point Likert scale. The Vancouver Scar Scale (VSS) and the Patient and Observer Scar Assessment Scales (POSAS) were used to rate scar appearance.

Results: A total of 46 patients (mean age: 67 ± 11 years) underwent sternal defect reconstruction with free TFL flaps between January 2010 and March 2021. The mean defect size was 194 ± 43 cm. The mean operation time was 387 ± 120 min with a flap ischemia time of 63 ± 16 min. Acute microvascular complications due to flap pedicle thromboses occurred in three patients (7%). All flaps could be salvaged without complete flap loss. Partial flap loss of the distal TFL portion was observed in three patients (7%). All three patients required additional reconstruction with pedicled or local flaps. Upon follow-up, the range of motion (hip joint extension/flexion ( = 0.73), abduction/adduction ( = 0.29), and internal/external rotation ( = 0.07)) and muscle strength at the donor-sites did not differ from the contralateral sides ( = 0.25). Patient assessments of aesthetic and functional outcomes, as well as the median SF-36 (physical component summary (44, range of 33 to 57)) and LEFS (54, range if 35 to 65), showed good results with respect to patient comorbidities. The median VSS (3, range of 2 to 7) and POSAS (24, range of 18 to 34) showed satisfactory scar quality and scar appearance.

Conclusion: The free TFL flap is a reliable, effective, and, therefore, valuable option for the reconstruction of extensive sternal defects in critically ill patients suffering from DSWIs. In addition, the TFL flap shows satisfactory functional and aesthetic results at the donor-site.
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http://dx.doi.org/10.3390/jpm12030427DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8951458PMC
March 2022

Identification of Independent Risk Factors for Skin Complications in a Multifactorial Logistic Regression Analysis of Simultaneous Immediate Autologous Breast Reconstruction and Skin Reduction Mastectomy in Large and Ptotic Breasts Using an Inferiorly Based Deepithelialized Dermal Breast Flap.

J Pers Med 2022 Feb 23;12(3). Epub 2022 Feb 23.

Department of Plastic Surgery and Breast Center, Spital Zollikerberg, 8125 Zollikerberg, Switzerland.

Autologous immediate breast reconstruction in large and ptotic breasts remains challenging. We aimed to identify independent risk factors for impaired wound healing and nipple necrosis after skin reducing wise pattern mastectomy in autologous reconstruction with an auxiliary deepithelialized inferiorly based dermal flap (IBDF).

Methods: This retrospective study examined patients with wise pattern mastectomy with autologous immediate breast reconstruction (IBR) between 2017 and 2019. All cases of large and ptotic breasts were included. Demographic, oncologic, reconstructive, and surgical data were compiled, and multifactorial binary logistic regression models identified independent predictors for skin complications and nipple areolar complex (NAC) necrosis.

Results: Of 591 autologous breast reconstructions, 62 (11%) met the inclusion criteria. Overall wound complication rate was 32% ( = 20, DIEP 11, thigh 9, = 0.99), including 26% minor ( = 16, non-surgically treated) and 7% major complications ( = 4, surgically treated). Complete NAC necrosis occurred in one case. Nipple sparing mastectomy (NSM) ( = 0.003), high BMI ( = 0.019), longer operation time ( = 0.044) and higher patient age ( = 0.045) were independent risk factors for skin complications. Using internal mammary artery perforators (IMAP) as recipient vessels did not result in increased complication rates ( = 0.59).

Conclusion: Higher patient age, BMI, and operation time (OT) significantly increase the risk for skin complications in combined reduction wise pattern mastectomies with autologous IBR. In this context, IBDFs help preserve the inframammary fold, providing vasculature to the T-junction and the mastectomy skin flaps. Acceptable complication rates can be achieved in large and ptotic breasts, regardless of preoperative chemotherapy or radiation. Gentle tissue handling with minimal thermal trauma preserves internal mammary artery perforators (IMAPs) as recipient vessels. In cases of flap failure and alloplastic conversion, the IBDF can serve as an autoderm, protecting the implant from exposure.
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http://dx.doi.org/10.3390/jpm12030332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8951157PMC
February 2022

[Postoperative monitoring of free muscle flaps using perforator-based adipocutaneous skin paddles: economy, quality of care and aesthetics].

Handchir Mikrochir Plast Chir 2022 Apr 14;54(2):139-148. Epub 2022 Mar 14.

BG Unfallklinik Ludwigshafen Klinik für Hand-, Plastische und Rekonstruktive Chirurgie, Mikrochirurgie, Schwerbrandverletztenzentrum, Plastische Chirurgie und Handchirurgie der Universität Heidelberg.

Introduction: Besides fasciocutaneous workhorse flaps, free muscle flaps for the reconstruction of large soft tissue defects are well-established standard microsurgical procedures. Random-pattern adipocutaneous skin paddles are often included for postoperative perfusion monitoring of the muscle flap. At our institution, both conventional broad-based and perforator-based adipocutaneous skin paddles are used. While conventional skin paddles have to be removed during a second operation, perforator-based skin paddles can be removed at the bedside by ligature. The present study aims to compare economic aspects, quality of care and aesthetic results of perforator-based versus conventional adipocutaneous skin paddles after free muscle flap transfer.

Methods: 102 patients treated between August 2014 and July 2016 were identified and included in a retrospective data analysis. Patients with perforator-based skin paddles (group A) were compared with a population of patients with conventional skin paddles (group B). Patient characteristics, procedural characteristics, economic data and aesthetic results were compared between both groups.

Results: Perforator-based skin paddles were raised in 72 patients (group A, 71 %), and conventional skin paddles were raised in the remaining 30 patients (group B, 29 %). Patient, defect, and flap characteristics were comparable in both groups. Operating times tended to be shorter in group B. Skin paddle removal was performed significantly earlier in group A (p < 0.01). Both overall and post-reconstructive length of hospital stay were significantly shorter in group A (p = 0.03; p < 0.01). Also, personnel and material resources were saved and more satisfactory aesthetic results were achieved in group A.

Conclusion: Perforator-based monitor islands can help avoid secondary operations that would otherwise be necessary to remove monitoring skin paddles. Thus, the inpatient length of stay can be reduced while sparing material and human resources.
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http://dx.doi.org/10.1055/a-1655-9135DOI Listing
April 2022

End of life care pathways in the Emergency Department and their effects on patient and health service outcomes: An integrative review.

Int Emerg Nurs 2022 Mar 28;61:101153. Epub 2022 Feb 28.

Susan Wakil School of Nursing and Midwifery, Faculty of Medicine and Health, University of Sydney, NSW 2006, Australia; Emergency Department, Wollongong Hospital, Illawarra Shoalhaven Local Health District, Crown St, Wollongong, NSW, Australia; Illawarra Health and Medical Research Institute, Building 32 University of Wollongong, Northfields Avenue, Wollongong, NSW, Australia.

Introduction: End of life (EOL) care in the Emergency Department (ED) requires focused, person-centred care to meet the needs of this vulnerable cohort of patients.

Methods: An integrative review of the literature using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was conducted. Studies were included if they were primary research relating to patients in the ED at the EOL, and/or evaluated EOL care pathways in the ED. Databases OVID Emcare, OVID Medline, and Scopus were searched from 1966-September 2021; followed by screening and appraisal. Articles were compared and data grouped into categories.

Results: Eleven research articles were included generating three categories for EOL care in ED. 1) tools/criteria to identify patients who may require EOL care in ED; 2) processes for providing EOL care, and 3) implementation methods/frameworks to support the uptake of EOL care processes.

Conclusion: There were some commonalities in the criteria used to identify patients who may be at their EOL and the interventions implemented thereafter. There was no standardised process for screening for or treating EOL care needs in the ED. Further research is required to determine the impact that EOL care pathways have on patient and health service outcomes to inform strategies for future policy development.
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http://dx.doi.org/10.1016/j.ienj.2022.101153DOI Listing
March 2022

Protocol for CAMUS Delphi Study: A Consensus on Comprehensive Reporting and Grading of Complications After Urological Surgery.

Eur Urol Focus 2022 Feb 24. Epub 2022 Feb 24.

Department of Urology, The University of Melbourne, The Royal Melbourne Hospital, Parkville, Victoria, Australia; Epworth Healthcare, Melbourne, Victoria, Australia; The Australian Medical Robotics Academy, Melbourne, Victoria, Australia; Department of Urology, University of Bern, Bern, Switzerland.

Background: Reproducible assessment of postoperative complications is essential for reliable evaluation of quality of care to enable comparison between healthcare centres and ensure transparent patient counselling. Currently, significant discrepancies exist in complication reporting and grading due to heterogeneous definitions and methodologies.

Objective: To develop a standardised and reproducible assessment of perioperative complications and overall associated morbidity, to allow for the construction of a uniform language for complication reporting and grading.

Design, Setting, And Participants: The 12-part REDCap-based Delphi survey was developed in conjunction with methodologist review and experienced urologist opinion. International urologists, anaesthetists, and intensive care unit specialists will be included. A minimum sample size of 750 participants (500 urologists and 250 critical care specialities) is targeted.

Outcome Measurements And Statistical Analysis: The survey assesses participant demographics, opinion on complication reporting and the proposed Complications After Major & Minor Urological Surgery (CAMUS) reporting recommendations, grading of intervention events using the existing Clavien-Dindo classification and the proposed CAMUS classification, and rating of various clinical scenarios. Consensus will be defined as ≥75% majority agreement. If consensus is not reached, then subsequent Delphi rounds will be performed under steering committee guidance.

Results And Limitations: Twenty-one participants completed the draft survey. The median survey completion time was 128 min (interquartile range 88-135). The survey revealed that 90% of participants believe that the current complication classification systems are useful but inaccurate, while 100% of participants believe that there is a universal demand for reporting consensus. Several amendments were made following feedback. Limitations include complexity of the proposed supplemental grades and time to completion of the survey.

Conclusions: To ensure comprehensive and comparable complication reporting and grading across centres worldwide, a conclusive uniform language for complication reporting must be created. We intend to address shortcomings of the current complication reporting and classification systems with a new CAMUS classification system developed through multidisciplinary expert consensus obtained through a Delphi survey. Ultimately, standardisation of urological complication reporting and grading may improve patient counselling and quality of care.

Patient Summary: The reporting and grading of operative complications that occur during or after an operation and associated costs provide a means to stratify quality of patient care. Current complication reporting and classification systems are not standardised and somewhat inaccurate, and thus significantly underestimate patient morbidity and surgical risk. This Delphi survey will provide the basis for the creation of a uniform complication reporting and grading system. Our new system may allow improved reporting and grading between centres, and ultimately improve patient counselling and care.
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http://dx.doi.org/10.1016/j.euf.2022.01.016DOI Listing
February 2022

Prognostic accuracy of triage tools for adults with suspected COVID-19 in a prehospital setting: an observational cohort study.

Emerg Med J 2022 Apr 9;39(4):317-324. Epub 2022 Feb 9.

Centre for Urgent and Emergency Care Research (CURE), Health Services Research School of Health and Related Research (ScHARR), The University of Sheffield, Sheffield, UK.

Background: Tools proposed to triage patient acuity in COVID-19 infection have only been validated in hospital populations. We estimated the accuracy of five risk-stratification tools recommended to predict severe illness and compared accuracy to existing clinical decision making in a prehospital setting.

Methods: An observational cohort study using linked ambulance service data for patients attended by Emergency Medical Service (EMS) crews in the Yorkshire and Humber region of England between 26 March 2020 and 25 June 2020 was conducted to assess performance of the Pandemic Respiratory Infection Emergency System Triage (PRIEST) tool, National Early Warning Score (NEWS2), WHO algorithm, CRB-65 and Pandemic Medical Early Warning Score (PMEWS) in patients with suspected COVID-19 infection. The primary outcome was death or need for organ support.

Results: Of the 7549 patients in our cohort, 17.6% (95% CI 16.8% to 18.5%) experienced the primary outcome. The NEWS2 (National Early Warning Score, version 2), PMEWS, PRIEST tool and WHO algorithm identified patients at risk of adverse outcomes with a high sensitivity (>0.95) and specificity ranging from 0.3 (NEWS2) to 0.41 (PRIEST tool). The high sensitivity of NEWS2 and PMEWS was achieved by using lower thresholds than previously recommended. On index assessment, 65% of patients were transported to hospital and EMS decision to transfer patients achieved a sensitivity of 0.84 (95% CI 0.83 to 0.85) and specificity of 0.39 (95% CI 0.39 to 0.40).

Conclusion: Use of NEWS2, PMEWS, PRIEST tool and WHO algorithm could improve sensitivity of EMS triage of patients with suspected COVID-19 infection. Use of the PRIEST tool would improve sensitivity of triage without increasing the number of patients conveyed to hospital.
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http://dx.doi.org/10.1136/emermed-2021-211934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8844966PMC
April 2022

Clinician and Patient Experience of Internet-Mediated Eye Movement Desensitisation and Reprocessing Therapy.

J Psychosoc Rehabil Ment Health 2022 Feb 3:1-12. Epub 2022 Feb 3.

School of Health and Related Research (ScHARR), University of Sheffield. Regent Court, 30 Regent Street, Sheffield, S1 4DA UK.

Many eye movement desensitization and reprocessing (EMDR) therapists moved their practice online during COVID-19. We conducted surveys and interviews to understand the implementation and acceptability of online EMDR therapy. From 17 June to 2nd August 2021 an online survey was open to EMDR therapists from the EMDR Association UK & Ireland and EMDR International Association email lists, and, through them, their clients. Questions related to determinants of implementation (for therapists) and acceptability (for clients) of online EMDR. Semi-structured interviews were conducted with a sample of therapist respondents to provide a deeper understanding of survey responses. Survey responses were received from therapists (n = 562) from five continents, and their clients (n = 148). 88% of clients responded as being extremely or very comfortable receiving EMDR therapy online. At the initial point of 'social distancing', 54% of therapists indicated strong or partial reluctance to deliver online EMDR therapy compared to 11% just over one year later. Four fifths of therapists intended to continue offering online therapy after restrictions were lifted. Free-text responses and interview data showed that deprivation and clinical severity could lead to exclusion from online EMDR. Internet connectivity could disrupt sessions, lead to cancellations, or affect the therapy process. Therapists benefited from training in online working. Online EMDR is generally acceptable to therapists and clients, with reservations about digital exclusion, case severity, poor internet connectivity and the need for training. Further research is needed to confirm that online EMDR is clinically non-inferior to in-person working.

Supplementary Information: The online version contains supplementary material available at 10.1007/s40737-022-00260-0.
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http://dx.doi.org/10.1007/s40737-022-00260-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8812350PMC
February 2022

There is a Need for a Universal Language in the Reporting and Grading of Complication and Intervention Events to Ensure Comparability and Improvement of Surgical Care.

Eur Urol 2022 05 24;81(5):440-445. Epub 2022 Jan 24.

Department of Urology, The University of Melbourne, The Royal Melbourne Hospital, Parkville, Australia; Epworth Healthcare, Melbourne, Australia; The Australian Medical Robotics Academy, Melbourne, Australia; Department of Urology, University of Bern, Bern, Switzerland. Electronic address:

To enhance the clarity and quality of complication reporting and grading for clinicians and patients, the CAMUS-Collaboration aims to develop the following: (1) a data dictionary; (2) parameters required for reporting; (3) risk-based reporting; (4) nursing and patient opinions; and (5) prospective reporting and grading of short- and long-term complications.
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http://dx.doi.org/10.1016/j.eururo.2021.12.022DOI Listing
May 2022

Combined versus Single Perforator Propeller Flaps for Reconstruction of Large Soft Tissue Defects: A Retrospective Clinical Study.

J Pers Med 2022 Jan 4;12(1). Epub 2022 Jan 4.

Department of Hand, Plastic and Reconstructive Surgery, Burn Center, BG Trauma Center Ludwigshafen, Ludwig-Guttmann-Strasse 13, 67071 Ludwigshafen, Germany.

Sufficient wound closure of large soft tissue defects remains a challenge for reconstructive surgeons. We aimed to investigate whether combined perforator propeller flaps (PPFs) are suitable to expand reconstructive options. Patients undergoing PPF reconstruction surgery between 2008 and 2021 were screened and evaluated retrospectively. Of 86 identified patients, 69 patients received one perforator propeller flap, while 17 patients underwent combined PPF reconstruction with multiple flaps. We chose major complications as our primary outcome and defined those as complications that required additional surgery. Postoperatively, 27 patients (31.4%) suffered major complications. The propeller flap size, the type of intervention as well as the operation time were not associated with a higher risk of major complications. A defect size larger than 100 cm, however, was identified as a significant risk factor for major complications among single PPFs but not among combined PPFs (OR: 2.82, 95% CI: 1.01-8.36; = 0.05 vs. OR: 0.30, 95% CI: 0.02-3.37; = 0.32). In conclusion, combined PPFs proved to be a reliable technique and should be preferred over single PPFs in the reconstruction of large soft tissue defects at the trunk and proximal lower extremity.
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http://dx.doi.org/10.3390/jpm12010041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8779697PMC
January 2022

Malignant bowel obstruction symptoms: subcutaneous bolus esomeprazole-retrospective case series.

Authors:
Benjamin Thomas

BMJ Support Palliat Care 2022 Jan 12. Epub 2022 Jan 12.

Palliative Care, Illawarra Shoalhaven Local Health District, Wollongong, New South Wales, Australia

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http://dx.doi.org/10.1136/bmjspcare-2021-003510DOI Listing
January 2022

Decentralized high-strength wastewater treatment using a compact aerobic baffled bioreactor.

J Environ Manage 2022 Mar 26;305:114281. Epub 2021 Dec 26.

Anaerobic Digestion Research and Education Center (ADREC), Biosystems and Agricultural Engineering, Michigan State University, East Lansing, MI, USA. Electronic address:

Decentralized wastewater treatment is a potential solution to the economic and sustainability issues associated with current wastewater infrastructure requirements for rural and expanding urban settings. However, wastewater produced from small-scale operations (domestic, industrial, agricultural, defense, etc.) are often found to have higher pollution concentrations than municipal wastewater and is referred to as "blackwater" in the study. A baffled bioreactor (BBR) was employed to carry out blackwater treatment. The results of this study showed the removal of organic content and inorganic nitrogen was high in all of the feed amounts tested and increased corresponding to an increase in feed amount. Microbial diversity results supported that the feed amount was the most important factor in treatment performance. The microbial community was more diverse at higher feed amounts than lower feed amounts. A non-metric multidimensional scaling (NMDS) analysis revealed that higher feed amounts enriched Verrucomicrobiaceae, unclassified Sphingomonadales, unclassified Burkholderiales in the microbial community, and facilitated the removal of total solids, total nitrogen, and NO. The energy and exergy analyses showed the consumption of 5.02 Wh/L wastewater energy with a universal exergy efficiency of 61% at the feed amount of 3750 LPD. An economic analysis further delineated the treatment cost profiles of the decentralized unit under four different energy case scenarios of electricity from the grid, propane gas engine for remote rural communities, diesel engine (I) using standard U.S. market diesel fuel costs for remote rural communities and scientific research bases, and diesel engine (II) using the fully burdened cost of diesel fuel for military contingency bases and other extreme environmental scenarios.
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http://dx.doi.org/10.1016/j.jenvman.2021.114281DOI Listing
March 2022

[Conservative treatment options for symptomatic thumb trapeziometacarpal joint osteoarthritis].

Orthopade 2022 Jan 15;51(1):2-8. Epub 2021 Dec 15.

Hand‑, Plastische und Rekonstruktive Chirurgie, Mikrochirurgie, Schwerbrandverletztenzentrum, BG Klinik Ludwigshafen, Ludwig-Guttmann-Str. 13, 67071, Ludwigshafen, Deutschland.

Background: There are numerous non-surgical treatment options for basal thumb osteoarthritis (OA).

Objectives: Aetiology, clinical appearance and diagnosis of basal thumb OA, explanation of the individual non-surgical treatment options, presentation of the current state of studies.

Material And Methods: Search for case analyses, studies, systematic reviews and meta-analyses using PubMed and LIVIVO.

Results: Intraarticular injections have no more than short-term success with the risk of infection, which should not be underestimated. Radiotherapy seems to be an effective treatment, but little research has been done on this. Physiotherapy and splinting treatment promise long-term improvement of clinical symptoms and hand function.

Conclusion: Basal thumb OA is a common and serious condition, which in the case of continuous pain should be diagnosed and treated adequately. A multi-modal therapeutic regimen with avoidance of repetitive intra-articular injections seems to provide the best long-term results.
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http://dx.doi.org/10.1007/s00132-021-04195-5DOI Listing
January 2022

Continuous monitoring of aerial density and circadian rhythms of flying insects in a semi-urban environment.

PLoS One 2021 18;16(11):e0260167. Epub 2021 Nov 18.

Department of Physics, New Jersey Institute of Technology, Newark, New Jersey, United States of America.

Although small in size, insects are a quintessential part of terrestrial ecosystems due to their large number and diversity. While captured insects can be thoroughly studied in laboratory conditions, their population dynamics and abundance in the wild remain largely unknown due to the lack of accurate methodologies to count them. Here, we present the results of a field experiment where the activity of insects has been monitored continuously over 3 months using an entomological stand-off optical sensor (ESOS). Because its near-infrared laser is imperceptible to insects, the instrument provides an unbiased and absolute measurement of the aerial density (flying insect/m3) with a temporal resolution down to the minute. Multiple clusters of insects are differentiated based on their wingbeat frequency and ratios between wing and body optical cross-sections. The collected data allowed for the study of the circadian rhythm and daily activities as well as the aerial density dynamic over the whole campaign for each cluster individually. These measurements have been compared with traps for validation of this new methodology. We believe that this new type of data can unlock many of the current limitations in the collection of entomological data, especially when studying the population dynamics of insects with large impacts on our society, such as pollinators or vectors of infectious diseases.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0260167PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8601533PMC
January 2022

Robotics in Australian urology contemporary practice and future perspectives.

ANZ J Surg 2021 11;91(11):2241-2245

Department of Urology, The University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria, Australia.

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http://dx.doi.org/10.1111/ans.17161DOI Listing
November 2021

Caseous calcification of the mitral annulus presenting with symptomatic complete heart block.

HeartRhythm Case Rep 2021 Oct 7;7(10):655-658. Epub 2021 Jul 7.

Department of Cardiology, Townsville University Hospital, Douglas, Townsville, Australia.

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http://dx.doi.org/10.1016/j.hrcr.2021.06.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8530812PMC
October 2021

Alloantigen-specific type 1 regulatory T cells suppress through CTLA-4 and PD-1 pathways and persist long-term in patients.

Sci Transl Med 2021 Oct 27;13(617):eabf5264. Epub 2021 Oct 27.

Division of Hematology, Oncology, Stem Cell Transplantation, and Regenerative Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA.

Type 1 regulatory T (Tr1) cells are inducible, interleukin (IL)-10FOXP3 regulatory T cells that can suppress graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We have optimized an in vitro protocol to generate a Tr1-enriched cell product called T-allo10, which is undergoing clinical evaluation in patients with hematological malignancies receiving a human leukocyte antigen (HLA)–mismatched allo-HSCT. Donor-derived T-allo10 cells are specific for host alloantigens, are anergic, and mediate alloantigen-specific suppression. In this study, we determined the mechanism of action of T-allo10 cells and evaluated survival of adoptively transferred Tr1 cells in patients. We showed that Tr1 cells, in contrast to the non-Tr1 population, displayed a restricted T cell receptor (TCR) repertoire, indicating alloantigen-induced clonal expansion. Tr1 cells also had a distinct transcriptome, including high expression of cytotoxic T lymphocyte–associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1). Blockade of CTLA-4 or PD-1/PD-L1 abrogated T-allo10–mediated suppression, confirming that these proteins, in addition to IL-10, play key roles in Tr1-suppressive function and that Tr1 cells represent the active component of the T-allo10 product. Furthermore, T-allo10–derived Tr1 cells were detectable in the peripheral blood of HSCT patients up to 1 year after T-allo10 transfer. Collectively, we revealed a distinct molecular phenotype, mechanisms of action, and in vivo persistence of alloantigen-specific Tr1 cells. These results further characterize Tr1 cell biology and provide essential knowledge for the design and tracking of Tr1-based cell therapies.
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http://dx.doi.org/10.1126/scitranslmed.abf5264DOI Listing
October 2021

A comparative study of peri-operative outcomes for 100 consecutive post-chemotherapy and primary robot-assisted and open retroperitoneal lymph node dissections.

World J Urol 2022 Jan 1;40(1):119-126. Epub 2021 Oct 1.

Department of Urology, Addenbrooke's Hospital, Cambridge University Hospitals, Cambridge, UK.

Purpose: To describe and compare differences in peri-operative outcomes of robot-assisted (RA-RPLND) and open (O-RPLND) retroperitoneal lymph node dissection performed by a single surgeon where chemotherapy is the standard initial treatment for Stage 2 or greater non-seminomatous germ cell tumour.

Methods: Review of a prospective database of all RA-RPLNDs (28 patients) and O-RPLNDs (72 patients) performed by a single surgeon from 2014 to 2020. Peri-operative outcomes were compared for patients having RA-RPLND to all O-RPLNDs and a matched cohort of patients having O-RPLND (20 patients). Further comparison was performed between all patients in the RA-RPLND group (21 patients) and matched O-RPLND group (18 patients) who had previous chemotherapy. RA-RPLND was performed for patients suitable for a unilateral template dissection. O-RPLND was performed prior to the introduction of RA-RPLND and for patients not suitable for RA-RPLND after its introduction.

Results: RA-RPLND showed improved peri-operative outcomes compared to the matched cohort of O-RPLND-median blood loss (50 versus 400 ml, p < 0.00001), operative duration (150 versus 195 min, p = 0.023) length-of-stay (1 versus 5 days, p < 0.00001) and anejaculation (0 versus 4, p = 0.0249). There was no statistical difference in complication rates. RA-RPLND had lower median lymph node yields although not significant (9 versus 13, p = 0.070). These improved peri-operative outcomes were also seen in the post-chemotherapy RA-RPLND versus O-RPLND analysis. There were no tumour recurrences seen in either group with median follow-up of 36 months and 60 months, respectively.

Conclusions: Post-chemotherapy RA-RPLND may have decreased blood loss, operative duration, hospital length-of-stay and anejaculation rates in selected cases and should, therefore, be considered in selected patients. Differences in oncological outcomes require longer term follow-up.
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http://dx.doi.org/10.1007/s00345-021-03832-0DOI Listing
January 2022

A review of simulation training and new 3D computer-generated synthetic organs for robotic surgery education.

J Robot Surg 2022 Aug 3;16(4):749-763. Epub 2021 Sep 3.

Department of Surgery, The University of Melbourne, Parkville, VIC, Australia.

We conducted a comprehensive review of surgical simulation models used in robotic surgery education. We present an assessment of the validity and cost-effectiveness of virtual and augmented reality simulation, animal, cadaver and synthetic organ models. Face, content, construct, concurrent and predictive validity criteria were applied to each simulation model. There are six major commercial simulation machines available for robot-assisted surgery. The validity of virtual reality (VR) simulation curricula for psychomotor assessment and skill acquisition for the early phase of robotic surgery training has been demonstrated. The widespread adoption of VR simulation has been limited by the high cost of these machines. Live animal and cadavers have been the accepted standard for robotic surgical simulation since it began in the early 2000s. Our review found that there is a lack of evidence in the literature to support the use of animal and cadaver for robotic surgery training. The effectiveness of these models as a training tool is limited by logistical, ethical, financial and infection control issues. The latest evolution in synthetic organ model training for robotic surgery has been driven by new 3D-printing technology. Validated and cost-effective high-fidelity procedural models exist for robotic surgery training in urology. The development of synthetic models for the other specialties is not as mature. Expansion into multiple surgical disciplines and the widespread adoption of synthetic organ models for robotic simulation training will require the ability to engineer scalability for mass production. This would enable a transition in robotic surgical education where digital and synthetic organ models could be used in place of live animals and cadaver training to achieve robotic surgery competency.
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http://dx.doi.org/10.1007/s11701-021-01302-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415702PMC
August 2022

A longitudinal study evaluating interim assessment of neoadjuvant chemotherapy for bladder cancer.

BJU Int 2021 Aug 21. Epub 2021 Aug 21.

Department of Urology, University Hospital of Bern, University of Bern, Bern, Switzerland.

Objectives: To evaluate the usefulness of radiological re-staging after two and four cycles of neoadjuvant chemotherapy (NAC), the impact of re-staging on further patient management, and the correlation between clinical and final pathological tumour stage at radical cystectomy (RC).

Patients And Methods: We conducted a longitudinal, single-centre, cohort study of prospectively collected consecutive patients who underwent NAC and RC for urothelial muscle-invasive bladder cancer between July 2001 and December 2017. Patients underwent repeated computed tomography scans for re-staging after two cycles of NAC and after completion of NAC before RC.

Results: Of 180 patients, 110 had ≥four cycles of NAC and had complete imaging available. In the entire cohort, further patient management was only changed in 2/180 patients (1.1%) after two cycles of NAC based on radiological findings. Patients who were stable after two cycles but then downstaged after at least four cycles of NAC had a similarly lowered risk of death (hazard ratio [HR] 0.53). Only one patient downstaged after two cycles was subsequently upstaged after four cycles. Clinical downstaging was observed in 51 patients (46%), 55 patients (50%) had no change in clinical stage and four patients (3.6%) were clinically upstaged. Patients clinically downstaged after four cycles of NAC had a lower risk of death (HR 0.49, 95% confidence interval 0.25-0.94; P = 0.033) compared to those with no change or upstaged after completion of NAC.

Conclusions: Re-staging of muscle-invasive bladder cancer after two cycles of NAC offers little additional information, rarely changes patient management, and may therefore be omitted, whereas re-staging after completion of NAC by CT is a strong predictor of overall survival.
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http://dx.doi.org/10.1111/bju.15579DOI Listing
August 2021

Pre-clinical development and molecular characterization of an engineered type 1 regulatory T-cell product suitable for immunotherapy.

Cytotherapy 2021 11 15;23(11):1017-1028. Epub 2021 Aug 15.

Division of Stem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, Center for Definitive and Curative Medicine, Stanford School of Medicine, Stanford, California, USA; Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford School of Medicine, Stanford, California, USA. Electronic address:

Background Aims: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative therapeutic approach for many hematological disorders. However, allo-HSCT is frequently accompanied by a serious side effect: graft-versus-host disease (GVHD). The clinical use of allo-HSCT is limited by the inability of current immunosuppressive regimens to adequately control GvHD without impairing the graft-versus-leukemia effect (GvL) conferred by transplanted healthy immune cells. To address this, the authors have developed an engineered type 1 regulatory T-cell product called CD4 cells. CD4 cells are obtained through lentiviral transduction, which delivers the human IL10 gene into purified polyclonal CD4 T cells. CD4 cells may provide an advantage over standard-of-care immunosuppressants because of the ability to suppress GvHD through continuous secretion of IL-10 and enhance the GvL effect in myeloid malignancies through targeted killing of malignant myeloid cells.

Methods: Here the authors established a production process aimed at current Good Manufacturing Practice (cGMP) production for CD4 cells.

Results: The authors demonstrated that the CD4 cell product maintains the suppressive and cytotoxic functions of previously described CD4 cells. In addition, RNA sequencing analysis of CD4 identified novel transcriptome changes, indicating that CD4 cells primarily upregulate cytotoxicity-related genes. These include four molecules with described roles in CD8 T and natural killer cell-mediated cytotoxicity: CD244, KLRD1, KLRC1 and FASLG. Finally, it was shown that CD4 cells upregulate IL-22, which mediates wound healing and tissue repair, particularly in the gut.

Conclusions: Collectively, these results pave the way toward clinical translation of the cGMP-optimized CD4 cell product and uncover new molecules that have a role in the clinical application of CD4 cells.
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http://dx.doi.org/10.1016/j.jcyt.2021.05.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8546780PMC
November 2021

A Comparison of Clinical Characteristics and Outcomes Between Indigenous and Non-Indigenous Patients Presenting to Townsville Hospital Emergency Department With Chest Pain.

Heart Lung Circ 2022 Feb 7;31(2):183-193. Epub 2021 Aug 7.

Department of Cardiology, Townsville University Hospital, Townsville, Qld, Australia.

Background: Indigenous Australians have a high rate of ischaemic heart disease (IHD). There is a paucity of local data for North Queensland regarding the clinical characteristics of Indigenous people who present to the emergency department (ED) with chest pain. The aim of the study is to compare the cardiovascular risk factors, social characteristics, and the clinical outcomes between Indigenous and non-Indigenous patients who presented with cardiac-related chest pain.

Methods: This is a retrospective single-centre audit. The data was collected through chart reviews of chest pain presentations to the Townsville University Hospital Emergency Department, Queensland, Australia, from January to December 2017. We categorised the patients into Indigenous and non-Indigenous groups and compared their cardiac risk factors and social characteristics. We further classified the patients into three diagnosis groups and we measured the clinical outcomes in the patients with a diagnosis of cardiac-related chest pain. We used a data linkage to the Registry of Births, Deaths and Marriages for the death outcomes. A multivariable analysis was done to determine the risk of major adverse cardiac event (MACE) for Indigenous vs non-Indigenous patients.

Results: Indigenous patients were over-represented making up 19.1% of the total cohort (compared with 11.1% of the North Queensland Indigenous population) and presented at a younger age (median age: 45 vs 52, p<0.005). Traditional cardiovascular risk factors were significantly higher in Indigenous patients. The incidence of discharge against medical advice was also higher (6.5% vs 2.7%, p<0.005). There was an underutilisation of the local chest pain pathway amongst the Indigenous group (35.8% vs 44.7%, p<0.005). In patients with a diagnosis of cardiac-related chest pain, the rate of receiving invasive coronary angiogram procedures was similar in both cohorts (44.5% vs 43.7%, p=0.836). With regards to outcomes, Indigenous patients suffered from acute coronary syndrome (ACS) at a younger median age (51 vs 64, p<0.005) and were more likely to have severe three vessel disease (17% vs 6%, p<0.005) leading to coronary bypass graft surgery (CABG) (19% vs 6%, p<0.005). When adjusted for age, gender, and comorbidities, Indigenous patients were more likely to have MACE within 1 year of their chest pain presentation, compared with non-Indigenous patients with the same diagnosis (adjusted odds ration [AOR]=2.0, 95% CI [1.1, 3.8], p=0.03).

Conclusion: In our study, Indigenous patients carried a heavier burden of cardiovascular risk factors, presented at a younger age, with more severe coronary disease and had a higher rate of CABG. We found an underutilisation of the local chest pain protocol amongst the Indigenous cohort, which suggests a need to improve support structures in the ED. In our multivariable analysis, Indigenous patients suffered from a significantly higher MACE compared to non-Indigenous patients which indicates that more collaborative efforts are needed to improve the cardiovascular health of local Aboriginal and Torres Strait Islander people.
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http://dx.doi.org/10.1016/j.hlc.2021.06.450DOI Listing
February 2022
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