bluuebunny/crossref_metadata_2025_split huggingface dataset:
Progress in the management of endometrial cancer (subtypes, immunotherapy, alterations in PIK3CA pathway): data and perspectives
Authors: Oaknin Ana , León-Castillo Alicia , Lorusso Domenica 
Published: August 2020

Purpose of reviewChanges in molecular classification together with a deeper knowledge of both immune disregulation and phosphatidylinositol-3 kinase (PI3K) pathway alterations are leading to a new endometrial cancer treatment paradigm. This review will address the cutting-edge data in this field.Recent findingsThis article will cover the updated data in endometrial cancer molecular classification and its correlation with the outcomes in randomized clinical trials (e.g., PORTEC-3). Moreover, we will review the latest data regarding checkpoint blockade molecules (CPB) in the recurrent setting and how they are changing the treatment landscape. In addition, the role of the PI3K inhibitors, their activity, and toxicity profile will be described.SummaryAs result of the incorporation of molecular classification in our daily practice, the adjuvant treatment in endometrial cancer is rapidly evolving and leading to a new paradigm. The promising data observed with CPB in the recurrent setting have led to the food and drug administration approval of pembrolizumab as monotherapy and in combination with lenvatinib. Additionally, the current outcomes achieved with PI3K inhibitor agents encourage us to continue our clinical research to identify those patients who may benefit the most.
Clinical data, limitations and perspectives on chimeric antigen receptor T-cell therapy in multiple myeloma
Authors: Beauvais David , Danhof Sophia , Hayden Patrick J. , Einsele Hermann , Yakoub-Agha Ibrahim 
Published: August 2020

Purpose of review
Despite considerable therapeutic advances over the last decade, multiple myeloma remains an incurable disease. Novel treatment strategies are urgently needed. T cells can be genetically modified to express chimeric antigen receptors (CARs) targeting defined surface antigens on tumor cells. To date, over 90 clinical trials investigating the use of CAR T cells in multiple myeloma have been registered.

Recent findings
Although two CD19-directed CAR T-cell products have been approved, CD19 surface expression on plasma cells is limited or absent and CAR T-cell therapy in multiple myeloma is less advanced. B-cell maturation antigen (BCMA)-directed CAR T cells have shown promising efficacy and safety profiles in various phase I/II clinical trials. However, almost all treated patients continue to relapse. The current focus is therefore on strategies to overcome resistance mechanisms. These include the targeting of other surface antigens, refinements in T-cell signaling and dual-targeting approaches.

Summary
CAR T-cell therapy has finally moved into routine clinical use, the first experiments having taken place over 30 years ago. A BCMA-directed product for the treatment of multiple myeloma is expected to be approved shortly. However, further refinements of both CAR T-cell constructs and treatment protocols will be required to boost persistence, overcome resistance and reduce toxicities.
CD19-directed CAR T-cell therapy in B-cell NHL
Authors: Kersten Marie José , Spanjaart Anne Mea , Thieblemont Catherine 
Published: August 2020

Purpose of review
CD19-directed chimeric antigen receptor (CAR) T-cell therapy is a valuable new treatment option for patients with relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma. The aim of this review is to give an overview of the pivotal phase I/II trials, emerging real-world evidence and ongoing trials.

Recent findings
For decades, attempts at improvement of the poor prognosis of patients with R/R large B-cell lymphoma with new treatment regimens have been disappointing. Since the first report of CD19-directed CAR-T-cell therapy in 2010, three constructs have been tested in large phase I/II trials and resulted in 30–40% durable responses. This has led to Food and Drug Administration and European Medicines Agency approval for axicabtagene ciloleucel and tisagenlecleucel and filing of the biologics license application for lisocabtagene maraleucel. Emerging real-world evidence seems to confirm the promising results. However, considerable toxicity, mainly cytokine release syndrome and neurotoxicity limits their general applicability and not all patients intended to be treated can be bridged during the manufacturing period due to kinetics of the disease. Randomized phase III clinical trials are being conducted to test anti-CD19 CAR-T-cell therapy in the second-line and several phase II trials are aiming to improve efficacy and decrease toxicity.

Summary
CD19-directed CAR-T-cell therapy has become standard of care for aggressive R/R diffuse large B-cell non-Hodgkin lymphoma (DLBCL), but challenges still remain.
The Perceptions of Cancer Patients Regarding the Causes and Preventability of Unplanned Hospital Admissions
Authors: Meisenberg Barry R. , Karpman Mitchell , Tan Jessica , Parlacoski Stephanie , Rhule Jane , Moxley John 
Published: August 2020

Objective:
The objective of this study was to determine the attitudes of oncology patients regarding the causes and preventability of unplanned hospitalizations.

Methods:
Convenience sample using a 36-question survey instrument adapted from prior studies of hospital readmissions.

Results:
A total of 95 evaluable patients answered >75% of survey items. Majorities (64%) agreed that they desired to avoid the admission, but disagreed (79%) that their own admission was preventable. Patients did not generally express lack confidence in their overall self-management abilities (only 36% agreed) or dissatisfaction with the level of home support, emotional or equipment (only 11% to 26% agreed). Patients did not complain of an inability to access their oncology care team (only 14% agreed), yet a strong majority (79%) endorsed the idea that emergency department visits represent the “quickest and easiest way to get needed care” and that the “hospital is the best place for me when I am sick” (60%). Overall, 79% indicated that their oncology care team directed them to visit the emergency department for evaluation. Most results did not differ by demographic factors.

Conclusions:
These results differ from previous results that use methods other than a direct patient survey to determine the preventability or root causes of unplanned hospital admissions/ or readmissions. Accordingly, patient support programs may not address the root causes of unplanned admissions. The use of the emergency department for unplanned care may represent local culture and institutions planning reduction efforts should include patent perceptions to plan a holistic solution.
Treatments of Periorbital Hyperpigmentation: A Systematic Review
Authors: Michelle Lauren , Pouldar Foulad Delila , Ekelem Chloe , Saedi Nazanin , Mesinkovska Natasha Atanaskova 
Published: August 2020

BACKGROUND
Periorbital hyperpigmentation (POH) is an aesthetic concern for patients. Etiologies of the condition include pigmentary, structural, vascular, and mixed causes.

OBJECTIVE
To systematically review the current literature for treatment of POH.

METHODS
A systematic literature review was performed on PubMed. Search terms included “infraorbital dark circles,” “dark circles,” “periorbital hyperpigmentation,” “idiopathic hyperchromia AND orbital,” “under-eye circles,” “ICHOR (idiopathic cutaneous hyperchromia of the orbital region),” “dark circles” AND “treatment,” and “filler” AND “dark circles.”

RESULTS
A total of 39 studies were included. Effective treatments for POH include lasers, topical creams and serums, fillers, chemical peels, carboxytherapy, plasma-rich platelet injections, blepharoplasty, and normobaric oxygen.

CONCLUSION
Soft tissue fillers and autologous fat grafting are most effective in treating dark circles due to volume loss. Blepharoplasty surgery is best when excessive skin laxity is the underlying cause. Various topical creams and chemical peels are useful in treating pigment-based POH, whereas lasers are mildly to moderately beneficial for both vascular and pigment types. Given the scarcity of high-quality evidence supporting these results, recommendations should be interpreted selectively. Additional randomized clinical trials studying POH will be helpful.
Interpolation Flaps in the Outpatient Mohs Surgery Setting: A Prospective Cohort Study of Patient Pain, Anxiety, and Satisfaction
Authors: Wong Noelle , Godinez-Puig Victoria , Makdisi Joy , Zloty David , Kossintseva Irèn 
Published: August 2020

BACKGROUND
Staged interpolation flaps (SIFs) have historically been performed under general anesthesia by specialties outside of dermatologic surgery. However, SIFs performed under local anesthesia by dermatologic surgeons have shown lower or equal complication rates.

OBJECTIVE
To date, no studies have evaluated pain, anxiety, satisfaction, and use of perioperative analgesics in patients undergoing SIFs in an outpatient setting under local anesthesia.

METHODS/MATERIALS
This is a prospective cohort study of 39 patients who received Mohs micrographic surgery and subsequent SIF repair in an outpatient setting under local anesthesia. Pain, anxiety, and satisfaction scores were recorded using 100-point validated visual analog scales. Perioperative analgesic use was quantified.

RESULTS
The defect size was ≥4 cm2 in 72% of patients; 41% had full-thickness (skin/cartilage/mucosa) defects. All pain and anxiety measures were minimal to mild. Pain scores ranged from highest (mean = 39 ± 4.1) on postoperative Day (POD) 1 to lowest (mean = 12.3 ± 2.0) on POD 7. Anxiety scores ranged from highest (mean = 42 ± 4.5) on POD 1 to lowest (mean = 18.5 ± 3.7) on POD 7. Perioperative patient satisfaction was high (mean = 95 ± 1.7). Postoperative narcotic analgesics were prescribed in 15% of patients.

CONCLUSION
Staged interpolation flaps performed under local anesthesia in the outpatient setting are well tolerated with low pain and anxiety, high patient satisfaction, and minimal analgesic use.
Incidence of gastric insufflation at high compared with low laryngeal mask cuff pressure
Authors: Hell Johannes , Pohl Holger , Spaeth Johannes , Baar Wolfgang , Buerkle Hartmut , Schumann Stefan , Schmutz Axel 
Published: August 2020

BACKGROUND
The success of ventilation with a laryngeal mask depends crucially on the seal between the mask and the periglottic tissue. Increasing the laryngeal mask's cuff volume is known to reduce oral air leakage but may lead to gastric insufflation.

OBJECTIVE
We hypothesised that a lower cuff pressure would result in less gastric insufflation. We sought to compare gastric insufflation with laryngeal mask cuff pressures of 20 cmH2O (CP20) and 60 cmH2O (CP60) during increasing peak airway pressures in a randomised controlled double-blind cross-over study. We also evaluated the incidence of gastric insufflation at the recommended peak airway pressure of 20 cmH2O or less and during both intermittent positive airway pressure and continuous positive airway pressure.

METHODS
After obtaining ethics approval and written informed consent, 184 patients ventilated via laryngeal mask received a stepwise increase in peak airway pressure from 15 to 30 cmH2O with CP20 and CP60 in turn. Gastric insufflation was determined via real-time ultrasound and measurement of the cross-sectional area of the gastric antrum. The primary endpoint was the incidence of gastric insufflation at the different laryngeal mask cuff pressures.

RESULTS
Data from 164 patients were analysed. Gastric insufflation occurred less frequently at CP20 compared with CP60 (P < 0.0001). Gastric insufflation was detected in 35% of cases with CP20 and in 48% with CP60 at a peak airway pressure of 20 cmH2O or less. Gastric insufflation occurred more often during continuous than during intermittent positive airway pressures (P < 0.01).

CONCLUSION
A laryngeal mask cuff pressure of 20 cmH2O may reduce the risk of gastric insufflation during mechanical ventilation. Surprisingly, peak airway pressure of 20 cmH2O or less may already induce significant gastric insufflation. Continuous positive airway pressure should be avoided due to an increased risk of gastric insufflation.

CLINICAL TRIAL REGISTRATION
The study was registered in the German Clinical Trials Register (DRKS00010583) https://www.drks.de.
Minimum effective volume of 0.5% ropivacaine for ultrasound-guided costoclavicular brachial plexus block
Authors: Wong Ming H. , Karmakar Manoj K. , Mok Louis Y.H. , Songthamwat Banchobporn , Samy Winnie 
Published: August 2020

BACKGROUND
Costoclavicular brachial plexus block (CC-BPB) is a relatively new regional anaesthetic technique and there are no data on the minimum effective volume 90 (MEV90) of 0.5% ropivacaine required for an ultrasound-guided CC-BPB.

OBJECTIVE
To determine the MEV90 of 0.5% ropivacaine required to produce surgical anaesthesia with an ultrasound-guided CC-BPB.

DESIGN
Prospective up-down sequential allocation study design.

SETTING
University teaching hospital in Hong Kong from March 2016 to December 2017.

PATIENTS
Forty-eight, ASA physical status I to III patients, aged 70 years or less and scheduled for elective forearm or hand surgery under an ultrasound-guided CC-BPB, were recruited.

INTERVENTION
Ultrasound-guided CC-BPB was performed with the assigned volume of 0.5% ropivacaine. The Dixon ‘up-and-down’ sequential allocation method using the biased coin design was used to determine the MEV90 of 0.5% ropivacaine. The assigned volume of ropivacaine was based on the outcome of the previous patient. After a block failure the next patient received a volume increase of 2 ml. If the block was a success, the next patient was allocated, with a probability of b = 0.11, to receive 2 ml less, or, with a probability of 1 − b = 0.89, the same volume.

MAIN OUTCOME MEASURES
A successful block was defined as a minimum score of 14 of 16 points, using a composite sensory and motor block score at 45 min after the injection. The study was stopped when 45 successful blocks were achieved. MEV90 with 95% confidence interval was calculated using the centred isotonic regression for point and interval dose response studies.

RESULTS
The MEV90 of 0.5% ropivacaine for ultrasound-guided CC-BPB was 20.9 (95% confidence interval, 20.7 to 21.8) ml. The mean ± SD time to readiness for surgery was 31.4 ± 12.60 min.

CONCLUSION
The MEV90 of 0.5% ropivacaine required to produce surgical anaesthesia with an ultrasound-guided CC-BPB is 20.9 ml.

CLINICAL TRIAL REGISTRATION
The trial was registered with the Chinese Clinical Trials Registry (www.chictr.org.cn, ChiCTR-IOR-15007515, principal investigator: Manoj Kumar Karmakar, date of registration: 4 December 2015).

CLINICAL TRIAL NUMBER AND REGISTRY URL
ChiCTR-IOR-15007515, Chinese Clinical Trials Registry (www.chictr.org.cn).
Economic Considerations for Radiation Protection in Medical Settings—Is It Time for a New Paradigm?
Authors: Demeter Sandor J. 
Published: August 2020

Abstract
The full ALARA principle includes “as low as reasonably achievable” taking social and economic factors into consideration. The International Commission on Radiological Protection advises a conventional cost benefit approach (e.g., cost per monetized averted stochastic effects or years of life saved) to consider economic factors. Given small incremental radiation dose reductions to patients, workers, or the public that may be realized in medical settings and the correspondingly small changes to theoretical stochastic effects, a conventional cost benefit approach is less than ideal. This is illustrated in the case studies presented in this paper. Alternate approaches, such as cost per unit of radiation dose averted (e.g., $/μSv averted), cancer induction/fatality probabilistic thresholds, or thresholds relative to natural background radiation may be alternate options. However, the decision regarding what is a “safe” level of radiation and what are reasonable costs to make it “safer” are driven by societal values and may vary from jurisdiction to jurisdiction.
TREATMENT OF SUBRETINAL PERFLUOROCARBON LIQUID BUBBLES COMPLICATING RETINAL DETACHMENT SURGERY USING AIR FOR DRAINAGE
Authors: Lorenzi Umberto , Mora Paolo , Luciani Enrico , Barale Pierre-Olivier , Muraine Marc 
Published: August 2020

Purpose:
The authors describe an original technique for treating multiple subretinal perfluorocarbon liquid (PFCL) bubbles complicating previous surgery for rhegmatogenous retinal detachment.

Methods:
To facilitate the induction of macular redetachment and peripheral displacement of the PFCL bubbles, we performed the subretinal injection of filtered air in addition to balanced salt solution. In this setting, the action of the PFCL in the vitreous cavity, combined with globe manipulation, allowed bubbles' displacement and full aspiration.

Results:
A 57-year-old man had a history of repeated pars plana vitrectomies for recalcitrant rhegmatogenous retinal detachment, the latter leading to multiple subretinal PFCL bubbles retained at the posterior pole. The described technique was performed 8 weeks after the last pars plana vitrectomy. A complete flattening of the macular region was obtained with visual improvement.

Conclusion:
Direct injection of air into the subretinal space may represent an effective strategy to help the surgical management of multiple retained PFCL bubbles.
THE ROLE OF CHECKPOINT INHIBITORS IN PARANEOPLASTIC ACUTE EXUDATIVE POLYMORPHOUS VITELLIFORM MACULOPATHY: REPORT OF TWO CASES
Authors: Kemels Dieter , ten Berge Josianne Carina Elvire Maria , Jacob Julie , Schauwvlieghe Pieter-Paul 
Published: August 2020

Purpose:
To report on two cases with paraneoplastic acute exudative polymorphous vitelliform maculopathy within one month after the initiation of nivolumab.

Methods:
Case report.

Results:
Two patients with metastatic mucosal melanoma were diagnosed with acute exudative polymorphous vitelliform maculopathy within one month after the initiation of the checkpoint inhibitor nivolumab. Both cases showed a neurosensory retinal detachment and subretinal hyperautofluorescent material, which persisted after discontinuation of nivolumab and treatment with local and/or systemic corticosteroids. In one case, nivolumab was introduced again in a later stage in combination with surgical reduction of the tumor, eventually leading to resolution of the subretinal lipofuscin-rich fluid.

Conclusion:
The development of paraneoplastic acute exudative polymorphous vitelliform maculopathy in melanoma patients can be triggered by treatment with nivolumab. However, achieving tumor control, which may involve continuation of nivolumab, could be the key to success.
Delivering personalized medicine in retinal care: from artificial intelligence algorithms to clinical application
Authors: Jill Hopkins J. , Keane Pearse A. , Balaskas Konstantinos 
Published: August 2020

Purpose of review
To review the current status of artificial intelligence systems in ophthalmology and highlight the steps required for clinical translation of artificial intelligence into personalized health care (PHC) in retinal disease.

Recent findings
Artificial intelligence systems for ophthalmological application have made rapid advances, but are yet to attain a state of technical maturity that allows their adoption into real-world settings. There remains an ‘artificial intelligence chasm’ in the spheres of validation, regulation, safe implementation, and demonstration of clinical impact that needs to be bridged before the full potential of artificial intelligence to deliver PHC can be realized.

Summary
Ophthalmology is currently in a stage between the demonstration of the potential of artificial intelligence and widespread deployment. Next stages include aggregating and curating datasets, training and validating artificial intelligence systems, establishing the regulatory framework, implementation and adoption with ongoing evaluation and model adjustment, and finally, meaningful human–artificial intelligence interaction with clinically validated tools that have demonstrated measurable impact on patient and healthcare system outcomes. Ophthalmologists should leverage the ability of artificial intelligence systems to glean insights from large volumes of multivariate data, and to interpret artificial intelligence recommendations in a clinical context. In doing so, the field will be well positioned to lead the transformation of health care in a personalized direction.

Video abstract

http://links.lww.com/COOP/A35.
Accelerating ophthalmic artificial intelligence research: the role of an open access data repository
Authors: Kras Ashley , Celi Leo A. , Miller John B. 
Published: August 2020

Purpose of review
Artificial intelligence has already provided multiple clinically relevant applications in ophthalmology. Yet, the explosion of nonstandardized reporting of high-performing algorithms are rendered useless without robust and streamlined implementation guidelines. The development of protocols and checklists will accelerate the translation of research publications to impact on patient care.

Recent findings
Beyond technological scepticism, we lack uniformity in analysing algorithmic performance generalizability, and benchmarking impacts across clinical settings. No regulatory guardrails have been set to minimize bias or optimize interpretability; no consensus clinical acceptability thresholds or systematized postdeployment monitoring has been set. Moreover, stakeholders with misaligned incentives deepen the landscape complexity especially when it comes to the requisite data integration and harmonization to advance the field. Therefore, despite increasing algorithmic accuracy and commoditization, the infamous ‘implementation gap’ persists. Open clinical data repositories have been shown to rapidly accelerate research, minimize redundancies and disseminate the expertise and knowledge required to overcome existing barriers. Drawing upon the longstanding success of existing governance frameworks and robust data use and sharing agreements, the ophthalmic community has tremendous opportunity in ushering artificial intelligence into medicine. By collaboratively building a powerful resource of open, anonymized multimodal ophthalmic data, the next generation of clinicians can advance data-driven eye care in unprecedented ways.

Summary
This piece demonstrates that with readily accessible data, immense progress can be achieved clinically and methodologically to realize artificial intelligence's impact on clinical care. Exponentially progressive network effects can be seen by consolidating, curating and distributing data amongst both clinicians and data scientists.
Ophthalmic manifestations of coronavirus disease 2019 and ocular side effects of investigational pharmacologic agents
Authors: Olson Daniel J. , Ghosh Arko , Zhang Alice Yang 
Published: August 2020

Purpose of review
To compile and report the ocular manifestations of coronavirus disease 2019 (COVID-19) infection and summarize the ocular side effects of investigational treatments of this disease.

Recent findings
Conjunctivitis is by far the most common ocular manifestation of COVID-19 with viral particles being isolated from tears/secretions of infected individuals. Multiple therapeutic options are being explored across a variety of medication classes with diverse ocular side effects.

Summary
Eye care professionals must exercise caution, as conjunctivitis may be the presenting or sole finding of an active COVID-19 infection. While no currently studied therapeutic agents have been found to reliably treat COVID-19, early vaccination trials are progressing and show promise. A video abstract is available for a more detailed summary.

Video abstract

http://links.lww.com/COOP/A36.