bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolic Maturation Increases Susceptibility to Hypoxia-induced Damage in Human iPSC-derived Cardiomyocytes
Authors: Peters Marijn C , Maas Renee G C , van Adrichem Iris , Doevendans Pieter A M , Mercola Mark , Šarić Tomo , Buikema Jan W , van Mil Alain , Chamuleau Steven A J , Sluijter Joost P G , Hnatiuk Anna P , Neef Klaus 
Published: August 2022

Abstract
The development of new cardioprotective approaches using in vivo models of ischemic heart disease remains challenging as differences in cardiac physiology, phenotype, and disease progression between humans and animals influence model validity and prognostic value. Furthermore, economical and ethical considerations have to be taken into account, especially when using large animal models with relevance for conducting preclinical studies. The development of human-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) has opened new opportunities for in vitro studies on cardioprotective compounds. However, the immature cellular phenotype of iPSC-CMs remains a roadblock for disease modeling. Here, we show that metabolic maturation renders the susceptibility of iPSC-CMs to hypoxia further toward a clinically representative phenotype. iPSC-CMs cultured in a conventional medium did not show significant cell death after exposure to hypoxia. In contrast, metabolically matured (MM) iPSC-CMs showed inhibited mitochondrial respiration after exposure to hypoxia and increased cell death upon increased durations of hypoxia. Furthermore, we confirmed the applicability of MM iPSC-CMs for in vitro studies of hypoxic damage by validating the known cardioprotective effect of necroptosis inhibitor necrostatin-1. Our results provide important steps to improving and developing valid and predictive human in vitro models of ischemic heart disease.
Medial Elbow Exposure: Modified Taylor-Scham Versus Flexor Carpi Ulnaris–Split
Authors: Bates Taylor , Lynch Thomas B. , Achay Jennifer , Powers Robert , Sabbag Casey M. , Plucknette Benjamin F. , Wilson David 
Published: August 2022

Objective:
To compare the exposure of the coronoid process, anteromedial facet, and anterior band of the medial collateral ligament using the flexor carpi ulnaris (FCU)–splitting approach with the Taylor-Scham approach modified with an ulnar nerve transposition.

Methods:
Thirty approaches were performed on 15 fresh cadavers using a randomized cross-over design and standardized incision. Access to key anatomic landmarks was assessed, and a calibrated digital image was taken from the surgeon's best perspective of each approach. Images were analyzed using ImageJ (National Institutes of Health) software to calculate the area of osseous exposure.

Results:
All key anatomic landmarks were visualized using both approaches. The average area of exposure for the Taylor-Scham was 19.5 cm2 compared with 13.6 cm2 for the FCU-splitting (P < 0.0001). The distal extent of the FCU-splitting approach is limited by the ulnar nerve and its branches to the humeral head of the FCU.

Conclusion:
The Taylor-Scham approach provides a more extensile exposure of the anteromedial coronoid and proximal ulna than the FCU-splitting approach while avoiding cross-tensioning of the ulnar nerve.
Reconstruction of the male external genitalia in diverse disease processes: Our reconstructive algorithm, techniques, and experience
Authors: Croghan Stefanie M. , Kelly Caroline , Daniels Anne E. , Fitzgibbon Linda , Daly Pádraig J. , Cullen Ivor M. 
Published: August 2022

Abstract

Background
Male genital form and function may be rendered abnormal by a number of disease processes, with profound associated psychological and functional consequences. The aim of the study is to review our reconstructive experience with cases of genital loss or distortion due to nonmalignant diseases processes and atypical neoplasia.

Materials and methods
A retrospective review of a prospectively maintained database was performed to identify reconstructive cases performed from 2018 to 2020 under the care of a single surgeon. Male patients 18 years or older with a disease diagnosis other than squamous cell carcinoma affecting genital form were included. Disease processes, patient factors, surgical techniques, and both functional and cosmetic outcomes were reviewed.

Results
Fourteen cases were identified. The patients had a mean age of 52.2 years (range, 21–72 years). Acquired buried penis was present in 8 patients. Etiology of genital abnormality included balanitis xerotica obliterans (n = 6), excess skin loss at circumcision (n = 2), self-injection of petroleum jelly to penile shaft (n = 1), Fournier gangrene (n = 1), hidradenitis suppurativa (n = 1), extramammary Paget disease (n = 1), idiopathic lymphoedema (n = 1), and penoscrotal webbing (n = 1). Reconstructive techniques performed included penile debridement/shaft skin release, scrotectomy, suprapubic apronectomy, and division of penoscrotal webbing, in combination with split-thickness skin grafting where required. A penile implant was inserted in one patient. Reconstructive planning, techniques, and outcomes are described.

Conclusions
A variety of reconstructive techniques in andrology can be used to improve the aesthetic and functional outcomes of multiple disease processes affecting the male external genitalia.
The era of personalized treatments: Updates on immunotherapy within urothelial of bladder cancer
Authors: Wu Zhang-Song , Wu Song 
Published: August 2022

Abstract
Bladder cancer is a complex disease of the urinary system with high morbidity and mortality. Recently, the introduction of immunotherapies such as immune checkpoint inhibitors (eg, programmed cell death protein 1/programmed death-ligand 1) has proven to be a reliable means of improving survival outcomes, including patients with limited response to conventional treatment. Nevertheless, difficult questions remain in clinical practice, such as how to select appropriate patients for personalized treatment, how to predict and assess therapeutic efficacy in advance, and how to enhance the therapeutic benefits of immunotherapy treatment. These issues require urgent attention. Herein, we describe recent clinical applications of immune checkpoint inhibitors in bladder cancer therapy, examine underlying mechanisms for treatment failure in a subset of patients, and discuss potential approaches to improve their therapeutic effects.
The use of blue-light cystoscopy in the detection and surveillance of nonmuscle invasive bladder cancer
Authors: Cahill Ellen M. , Chua Kevin , Doppalapudi Sai Krishnaraya , Ghodoussipour Saum 
Published: August 2022

Abstract
Nonmuscle invasive bladder cancer is associated with a high risk of recurrence as well as progression to muscle-invasive disease. Therefore, adequate visualization and identification of malignant lesions as well as complete resection are critical. Traditional white-light cystoscopy is limited in its ability to detect bladder cancer, specifically carcinoma in situ. Blue-light cystoscopy makes use of the intravesical instillation of a heme precursor to differentiate areas of malignancy from normal tissue. A narrative review of the literature on the use of blue-light cystoscopy in bladder cancer was conducted. Blue-light cystoscopy has been shown in several randomized clinical trials to increase detection of Ta, T1, and carcinoma in situ, as well as reduce risk of recurrence at 12 months as compared with traditional white-light cystoscopy. Research into the effects of blue-light cystoscopy on risk of disease progression has produced mixed results, in part due to changing definitions of progression. However, more recent research suggests a correlation with decreased risk of progression. Whereas the use of blue-light was initially limited to rigid cystoscopy in the operating room, results from a recent randomized clinical trial showing enhanced detection of recurrent disease using blue-light in-office surveillance flexible cystoscopy have led to expanded Food and Drug Administration approval. Overall, blue-light cystoscopy offers promise as an enhancement to white-light cystoscopy for the detection of nonmuscle invasive bladder cancer and may yield additional benefits in reducing disease recurrence and progression. Further prospective research is needed to evaluate the true benefit of blue-light cystoscopy in terms of disease progression as well as the cost-effectiveness of this technique.
Hypnotherapy in management of pain in children with cancer: a case report
Authors: Choobi Anzali Babak , Muhammadi Sheida , Malkari Behnam , Goli Rasoul , Norouzrajabi Samira , Talebiazar Nasim 
Published: August 2022

Introduction and importance:
Pain is the most common symptom in cancer patients that can affect their performance and quality of life. The present study aimed to determine the effect of hypnotherapy on the intensity of pain in children with cancer.

Case presentation:
This is a case study with a single-subject research design, in which a total of 3 female children with cancer were recruited using voluntary response sampling. Classical hypnotherapy was conducted for patients in 8 treatment sessions with a 1-month postintervention follow-up. Participants completed the Oucher Pain Scale (OPS) at 5 stages including before the intervention, third, fifth, and eighth hypnotherapy sessions, and 1 month after the intervention. Data analysis was conducted using a statistical report on the recovery rate and effect size.

Clinical discussion:
The results showed that hypnotherapy had a significant effect on the intensity of pain, in the treatment and follow-up stages.

Conclusions:
It can be stated that the use of hypnotherapy has been highly effective in reducing the intensity of pain in children with cancer.
Does a Latissimus Dorsi Flap Improve Surgical Outcomes of Implant-based Breast Reconstruction following Infected Device Explantation?
Authors: Slovacek Cedar , Asaad Malke , Mitchell David , Selber Jesse C. , Clemens Mark W. , Chu Carrie K. , Mericli Alexander F. , Robb Geoffrey L. , Hanson Summer E. , Butler Charles E. 
Published: August 2022

Background:
The goal of this study was to assess whether adding a latissimus dorsi (LD) flap to a secondary implant-based reconstruction (IBR) improves outcomes following explantation of the primary device due to infection.

Methods:
We conducted a retrospective study of patients who underwent a second IBR with or without the addition of an LD flap during 2006–2019, following explantation due to infection. Surgical outcomes were collected and compared between reconstruction types.

Results:
A total of 6093 IBRs were identified during the study period. Of these, 109 underwent a second attempt at breast reconstruction with IBR alone (n = 86, 79%) or IBR/LD (n = 23, 21%) following explantation of an infected device. Rates of secondary device explantation due to a complication were similar between the two groups (26% in the IBR/LD group and 21% in the IBR group; P = 0.60). Among the patients who underwent prior radiotherapy, the IBR/LD group had lower rates of any complication (38% versus 56%; P = 0.43), infection (25% versus 44%; P = 0.39), and reconstruction failure (25% versus 44%; P = 0.39); however, differences were not statistically significant.

Conclusion:
Following a failed primary breast reconstruction due to infection, it may be appropriate to offer a secondary reconstruction. For patients with a history of radiotherapy, combining an LD flap with IBR may provide benefits over IBR alone. Although not statistically different, this outcome may have clinical significance, considering the magnitude of the effect, and may result in decreased complication rates and a higher chance of reconstructive success.
Surgical Microtia Reconstruction in Hemifacial Microsomia Patients: Current State and Future Directions
Authors: Bouhadana Gabriel , Gornitsky Jordan , Saleh Eli , Borsuk Daniel E. , Cugno Sabrina 
Published: August 2022

Background:
Hemifacial microsomia (HFM) is one of the most common congenital craniofacial disorders. Among many other features, microtia is present in the large majority of these patients. However, mainly due to the unilateral hypoplastic anatomy, microtia reconstruction among this patient population remains a reconstructive challenge for plastic surgeons. Given that no clear standards exist, an evidence-based synthesis of the literature was devised.

Methods:
A systematic search of Pubmed, Medline, and Embase was carried out, in accordance with the PRISMA guidelines. Studies discussing surgical microtia reconstruction for HFM patients were retained. Qualitative data regarding study design, challenges addressed, specific recommendations, and their respective strengths/limitations were extracted from each. Retrieved recommendations were consolidated and assigned a level of evidence grade.

Results:
Although only 11 studies were included in this review, these provided 22 main recommendations regarding the eight HFM-specific challenges identified, which were of either grade C (n = 5) or D (n = 17). Included studies addressed construct location (n = 7), the low hairline (n = 6), soft tissue construct coverage (n = 6), earlobe reconstruction (n = 6), construct projection (n = 5), anomalies of the relevant neurovascular systems (n = 2), retroauricular construct coverage (n = 2), and sizing of the construct (n = 2).

Conclusions:
Given the many persisting reconstructive challenges regarding surgical microtia reconstruction for HFM patients, the authors present a comprehensive and evidence-based consolidation of recommendations specific to these challenges. The authors hope this systematic review can appropriately guide plastic surgeons and will ultimately improve care for this patient population.
Utilization of a Chimeric Medial Femoral Condyle Free Flap for Mandibular Osteoradionecrosis
Authors: Chaiyasate Kongkrit , Gupta Rohun , John Jithin , Chaiyasate Sean , Powers Jeremy , Nguyen Alan , Issa Christopher , Hart Justin , Goldman Joshua J. , Sachanandani Neil S. 
Published: August 2022

Background:
Primary options for oromandibular reconstruction with osteocutaneous free flaps are the vascularized fibula and iliac crest. Complications of mandible reconstruction are not uncommon and include osteomyelitis, malunion, and osteoradionecrosis (ORN) after radiation therapy. The medial femoral condyle (MFC) free flap is an established salvage option for carpal reconstruction in hand surgery, frequently used for scaphoid nonunion and avascular necrosis. We hypothesize that the MFC flap can be utilized to restore blood supply and reverse the negative effects of radiotherapy in patients who require mandibular reconstruction due to ORN.

Methods:
A retrospective chart review was conducted at Beaumont Health System, Royal Oak, for patients who underwent MFC free flap reconstruction for mandibular ORN between the years 2012 and 2018. Demographic data, operative details, complications, medical comorbidities, and patient outcomes were retrospectively gathered.

Results:
A total of four patients were isolated. Four patients developed ORN after resection of squamous cell carcinoma and adjuvant radiotherapy. No patients experienced donor site deficits. Revisions after MFC reconstruction were dependent on individual aesthetics and involvement of neighboring tissue. All four patients continue to be followed with no current issues to the osseous component of the MFC flap.

Conclusion:
Utilization of the MFC periosteal flap is a viable option in selected patients to salvage nonunion/resorption of mandible reconstruction and ORN of the mandible. Our experience found that the MFC is able to provide pain resolution and healing of intraoral soft tissue defects, and may halt the progression of ORN of the mandible.
Primary Subretinal Hydatid Cyst Presenting as Leukocoria in a Child
Authors: Ozdemir Huseyin Baran , Ozdek Sengul , Ozkan Kaan , Akyurek Nalan 
Published: August 2022

Abstract

Purpose:
To describe a case of subretinal hydatid cyst presenting as leukocoria and treated with limbal vitrectomy.

Methods:
A single case report demonstrated by multimodal imaging.

Results:
An otherwise healthy 28-month-old boy was admitted to our hospital with a complaint of leukocoria and underwent combined lensectomy and vitrectomy under albendazole therapy due to vitreous space-occupying subretinal cyst. Systemic workup showed no involvement in other organs. Cyst content was adequately aspirated with a 39-gauge needle, the cyst wall was freed from surrounding attachments to the retina and the nasal choroid and was extracted through a limbal incision using a cryoprobe. Nasal retinotomy and retinectomy area was lasered and tamponaded with silicone oil. Histopathologic examination confirmed the diagnosis of hydatid cyst disease. Silicone oil was removed at postoperative 3rd month. Retina stayed attached and the patient had a fix and follow vision under contact lens and amblyopia treatment during the 21 months follow-up period.

Conclusion:
This is the youngest subretinal hydatid cyst case in the literature. Large subretinal hydatid cyst may rarely cause leukocoria in children without any involvement in other organs. Vitrectomy with limbal approach and 39G needle-assisted cyst fluid aspiration and cryo-extraction appears to be a safe and successful surgical option in such cases.
Gains in Quality of Life in Chronic Otitis Media Patients After Surgery, Adjusted for Placebo Bias
Authors: Bukurov Bojana , Haggard Mark , Spencer Helen , Arsovic Nenad , Jesic Snezana , Dudvarski Zoran 
Published: August 2022

Objective
Using a short-form specific questionnaire, we sought to quantify specific and generic benefits of surgery for chronic otitis media (COM) while adjusting for expectancy (placebo) bias.

Study Design
A prospective observational pretreatment/posttreatment study.

Setting
A national tertiary referral center.

Patients
Consecutive adult COM patients were enrolled for 1 year. Of 246 patients, 205 were recommended for surgery, and 167 were operated on the (more) affected ear.

Intervention(s)
All patients filled out two questionnaires, one specific (Chronic Otitis Media Questionaire-12) and one generic (Short Form-36) at baseline, and then again 6 and 12 months after surgery.

Main Outcome Measures
Factor-based scores of questionnaires, standardized response means (SRMs) for treatment effects, with multiple linear regression for implementing bias adjustment.

Results
All but one (generic Short Form-36 “mental” scale) of the seven considered measures gave very highly significant (p < 0.001) improvements. Unadjusted SRMs were large (1.0–2.0 standard deviation units) for audiometry, symptoms of ear discharge, reported hearing, and aggregate specific quality of life, but only moderate for the less specific activity/healthcare. The proposed bias adjustment reduced SRM magnitudes for most measures by about a third, for activity/healthcare and ear discharge by only a tenth to a fifth, and for audiometry not at all.

Conclusion
Most scores of the specific questionnaire displayed definite placebo-like biases; this demands caution in interpreting improvement after COM surgery. With bias adjustments, credible and worthwhile magnitudes of improvements remained for Chronic Otitis Media Questionnaire-12 total and subscores (0.5–1.09 standard deviation SRM), but not for generic quality of life.
COVID-19 Vaccine Uptake in Southeastern Ontario, Canada: Monitoring and Addressing Health Inequities
Authors: Carter Megan A. , Biro Suzanne , Maier Allison , Shingler Clint , Guan T. Hugh 
Published: August 2022

Context:
Implementation of a population-based COVID-19 vaccine strategy, with a tailored approach to reduce inequities in 2-dose coverage, by a mid-sized local public health agency in southeastern Ontario, Canada.

Program:
Coverage maps and crude and age-standardized coverage rates by material and social deprivation, urban/rural status, and sex were calculated biweekly and reviewed by local public health planners. In collaboration with community partners, the results guided targeted strategies to enhance uptake for marginalized populations.

Evaluation:
The largest gaps in vaccine coverage were for those living in more materially deprived areas and rural residents—coverage was lower by 10.9% (95% confidence interval: −11.8 to −10.0) and 9.3% (95% confidence interval: −10.4 to −8.1) for these groups compared with living in less deprived areas and urban residents, respectively. The gaps for all health equity indicators decreased statistically significantly over time. Targeted strategies included expanding clinic operating hours and availability of walk-in appointments, mobile clinics targeted to marginalized populations, leveraging primary care partners to provide pop-up clinics in rural and materially and socially deprived areas, and collaborating with multiple partners to coordinate communication efforts, especially in rural areas.

Discussion:
The scale and scope of monitoring and improving local vaccine uptake are unprecedented. Regular review of health equity indicators provided critical situational awareness for decision makers, allowing partners to align and tailor strategies locally and in collaboration with one another. Health care providers and pharmacies/pharmacists are key partners who require innovative support to increase uptake in marginalized groups. Continued engagement of other community partners such as schools, municipalities, and local service groups is also crucial. A “hyper local” approach is needed along with commitment from partners in all sectors and at all levels to reduce barriers to vaccination that lie further upstream for marginalized groups.
Peri-OPerative Pain Management, Education & De-escalation (POPPMED), a novel anaesthesiologist-led program, significantly reduces acute and long-term postoperative opioid requirements: a retrospective cohort study
Authors: Heldreich Charlotte , Meyer Ilonka , Dube Esther , Hu Raymond , Howard William , Holmes Natasha , Maroon Nada , Weinberg Laurence , Tan Chong O. 
Published: August 2022

Abstract

Introduction:
The opioid tolerant patient requiring surgery is highly likely to be discharged on high Oral Morphine Equivalent Daily Dosages (OMEDDs), with concomitant risk of increased morbidity and mortality.

Objectives:
We proposed that a single anaesthesiologist-led POPPMED (Peri-Operative Pain Management, Education & De-escalation) service could reduce both short and long-term postoperative patient OMEDDs.

Methods:
From April 2017, our anaesthesiologist-led POPPMED service, engaged 102 perioperative patients treated with >50mg preoperative OMEDDs. We utilized behavioural interventions; acute opioid reduction and/ or rotation; and regional, multimodal and ketamine analgesia to achieve lowest possible hospital discharge and long term OMEDDs.

Results:
Patients' preoperative OMEDDs were [median (IQR): 115mg (114mg)], and were representative of an older [age 62 (15) years], high-risk [89% ASA status 3 or 4] patient population. 46% of patients received an acute opioid rotation; 70% received ketamine infusions; and 44% regional analgesia. OMEDDs on discharge [-25mg (82mg), p=0.003] and at 6-12 months [-55mg (105mg ), p<0.0001] were significantly reduced; 84% and 87% of patients achieved OMEDD reduction on discharge and at 6-12 months. Patients with >90mg preoperative OMEDDs achieved greater reductions [discharge: 71% of patients, -52 mg (118 mg) p<0.0001; 6-12 months: 90% of patients, -90mg (115mg), p<0.0001]. On comparison with a pre-POPPMED surgical cohort, Postoperative Day 1-3 11-point Numerical Rating Scale (NRS-11) area under the curve (AUC) measurements at rest and on movement were not significantly different (largest NRS-11:hours AUC difference [median(IQR)] 22 [13], p= 0.24). Hospital length of stay was variably increased.

Conclusions:
POPPMED achieved sustained OMEDD reductions safely in an older, high-risk opioid tolerant population, with analgesia comparable to a non-POPPMED cohort, and surgery specific effects on length of stay.