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Background and Aims: Digital single-operator cholangioscopy (DSOC) plays a critical role in directly visualizing and treating the bile duct system. Although various cholangioscopes with different external diameters are available for DSOC, certain challenging scenarios persist in which existing scopes fail to complete a thorough evaluation of the bile ducts. To overcome these limitations, we aimed to introduce and highlight the application of a novel 7F cholangioscope. Methods: In this review article we describe the novel 7F cholangioscope, provide its assembly and setup, and review cases in which the 7F cholangioscope was used for diagnostic and therapeutic guidance. Results: Four cases involving challenging biliary assessments were presented, all of which achieved technical and clinical success. No procedure-related adverse events were reported in any of these cases. Conclusions: The 7F cholangioscope can provide additional information regarding the biliary tree and guidance for treatment, overcoming the challenging assessment of small pancreatobiliary ducts and its strictures. Its potential use in cases of severe bile duct stenosis is recommended. However, further studies evaluating safety and efficacy are needed.

Purpose: Despite the call to increase the number of radiation oncologists in Latin America, the quality, similarity, and number of residency training programs are unknown. We seek to describe the current state of residency programs in radiation oncology in Latin America. Methods and Materials: Latin American Residents in Radiation Oncology performed a cross-sectional analysis of universities and training centers for radiation oncologists in Latin America. Latin American Residents in Radiation Oncology members identified and contacted current residents and specialists at each center to obtain information and documents that described their training curricula. Results: As of 2020, 13 of 23 (56.5%) Latin American countries have radiation oncology training. Seventy-three training centers were identified (59 active and 14 inactive), associated with 28 universities. On average, each active center trains 2.6 new residents per year, and in total, 156 residents are trained annually. The average length of training programs is 3.6 years. Brazil and Mexico comprise 31 (52.5%) and 7 (11.9%) of active programs, respectively, and 64 (41.8%) and 50 (32.7%) residents, respectively. Training is available in 38 cities in 13 countries, and outside Brazil and Mexico, only 13 cities in 11 countries (9 capitals and 4 noncapital cities). Individualized curriculum documents were provided by 20 (83.3%) of 24 non-Brazilian programs, while 1 standardized guideline was provided for Brazilian training programs. These demonstrated variation between subjects taught, their devoted time, outside specialty rotations, and experiences in modern techniques. Seventy-five percent include volumetric modulated arc therapy, 70% stereotactic radiosurgery, and 55% stereotactic body radiation therapy training. One-hundred percent include gynecologic brachytherapy education and

Objectives:. To evaluate the effect of high-flow oxygen implementation on the respiratory rate as a first-line ventilation support in chronic obstructive pulmonary disease patients with acute hypercapnic respiratory failure. Design:. Multicenter, prospective, analytic observational case series study. Setting:. Five ICUs in Argentina, between August 2018 and September 2019. Patients:. Patients greater than or equal to 18 years old with moderate to very severe chronic obstructive pulmonary disease, who had been admitted to the ICU with a diagnosis of hypercapnic acute respiratory failure, were entered in the study. Interventions:. High-flow oxygen therapy through nasal cannula delivered using high-velocity nasal insufflation. Measurements and Main Results:. Forty patients were studied, 62.5% severe chronic obstructive pulmonary disease. After the first hour of high-flow nasal cannula implementation, there was a significant decrease of respiratory rate compared with baseline values, with a 27% decline (29 vs 21 breaths/min; p < 0.001). Furthermore, a significant reduction of Paco2 (57 vs 52 mm Hg [7.6 vs 6.9 kPa]; p < 0.001) was observed. The high-flow nasal cannula application failed in 18% patients. In this group, the respiratory rate, pH, and Paco2 showed no significant change during the first hour in these patients. Conclusions:. High-flow oxygen therapy through nasal cannula delivered using high-velocity nasal insufflation was an effective tool for reducing respiratory rate in these chronic obstructive pulmonary disease patients with acute hypercapnic respiratory failure. Early determination and subsequent monitoring of clinical and blood gas parameters may help predict the outcome.

Omphalocele is a life-threatening abdominal wall defect without a treatment consensus due to its increased risk of complications. Discrepancies exist between a prompt or a delayed closure. In these cases, we present for the first time a conservative approach to close giant omphalocele lesions using hydrocolloid dressing.

ADAPTeR is a prospective, phase II study of nivolumab (anti-PD-1) in 15 treatment-naive patients (115 multiregion tumor samples) with metastatic clear cell renal cell carcinoma (ccRCC) aiming to understand the mechanism underpinning therapeutic response. Genomic analyses show no correlation between tumor molecular features and response, whereas ccRCC-specific human endogenous retrovirus expression indirectly correlates with clinical response. T cell receptor (TCR) analysis reveals a significantly higher number of expanded TCR clones pre-treatment in responders suggesting pre-existing immunity. Maintenance of highly similar clusters of TCRs post-treatment predict response, suggesting ongoing antigen engagement and survival of families of T cells likely recognizing the same antigens. In responders, nivolumab-bound CD8 + T cells are expanded and express GZMK/B. Our data suggest nivolumab drives both maintenance and replacement of previously expanded T cell clones, but only maintenance correlates with response. We hypothesize that maintenance and boosting of a pre-existing response is a key element of anti-PD-1 mode of action., Competing Interests: Declaration of interests L.A. is funded by the Royal Marsden Cancer Charity. E.H. and M.M. are funded by Cancer Research UK (CRUK). F.B. is funded by the Rosetrees Trust (M829). J.A. is a full-time employee of Hoffmann-La Roche AG (Basel, Switzerland). D.A.M has received consultancy fees from AstraZeneca, Thermo Fisher, and Eli Lilly. A.F. has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No. 892360. L.P. has received research funding from Pierre Fabre, and honoraria from Pfizer, Ipsen, Bristol-Myers Squibb, and EUSA Pharma. R.S. has received non-financial support from Merck and Bristol Myers Squibb; research support from Merck, Puma Biotechnology, and Roche; and advisory board fees for Bristol Myers Squibb; and personal fees from Roche for an advisory board related to a trial-research project; all related to breast cancer research projects. R.S. reports no conflict of interests related to this project. M.J.H. is a Cancer Research UK (CRUK) Clinician Scientist (RCCFEL\100099) and has received funding from CRUK, National Institute for Health Research, Rosetrees Trust, UKI NETs and NIHR University College London Hospitals Biomedical Research Center. M.J.H. is a member of the Scientific Advisory Board and Steering Committee for Achilles Therapeutics. G.K. is a scientific co-founder of and consulting for Enara Bio and a member of its scientific advisory board. G.K. receives core funding from the Francis Crick Institute (FC0010099). B.C. is supported by a CRUK Project Grant. J.L. has received research funding from Bristol-Myers Squibb, Merck, Novartis, Pfizer, Achilles Therapeutics, Roche, Nektar Therapeutics, Covance, Immunocore, Pharmacyclics, and Aveo, and served as a consultant to Achilles, AstraZeneca, Boston Biomedical, Bristol-Myers Squibb, Eisai, EUSA Pharma, GlaxoSmithKline, Ipsen, Imugene, Incyte, iOnctura, Kymab, Merck Serono, Nektar, Novartis, Pierre Fabre, Pfizer, Roche Genentech, Secarna, and Vitaccess. C.S. acknowledges grant support from Pfizer, AstraZeneca, Bristol-Myers Squibb, Roche-Ventana, Boehringer-Ingelheim, Archer Dx Inc (collaboration in minimal residual disease sequencing technologies), and Ono Pharmaceutical, is an AstraZeneca Advisory Board member and Chief Investigator for the MeRmaiD1 clinical trial, has consulted for Pfizer, Novartis, GlaxoSmithKline, MSD, Bristol-Myers Squibb, Celgene, AstraZeneca, Illumina, Genentech, Roche-Ventana, GRAIL, Medicxi, Bicycle Therapeutics, and the Sarah Cannon Research Institute, has stock options in Apogen Biotechnologies, Epic Bioscience, GRAIL, and has stock options and is co-founder of Achilles Therapeutics. Patents: C.S. holds European patents relating to assay technology to detect tumor recurrence (PCT/GB2017/053289); to targeting neoantigens (PCT/EP2016/059401), identifying patent response to immune checkpoint blockade (PCT/EP2016/071471), determining HLA LOH (PCT/GB2018/052004), predicting survival rates of patients with cancer (PCT/GB2020/050221), identifying patients who respond to cancer treatment (PCT/GB2018/051912), a US patent relating to detecting tumor mutations (PCT/US2017/28013) and both a European and US patent related to identifying insertion/deletion mutation targets (PCT/GB2018/051892). C.S. is Royal Society Napier Research Professor (RP150154). His work is supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001169), the UK Medical Research Council (FC001169), and the Wellcome Trust (FC001169). C.S. is funded by Cancer Research UK (TRACERx, PEACE and CRUK Cancer Immunotherapy Catalyst Network), Cancer Research UK Lung Cancer Center of Excellence, the Rosetrees Trust, Butterfield and Stoneygate Trusts, NovoNordisk Foundation (ID16584), Royal Society Research Professorship Enhancement Award (RP/EA/180007), the NIHR BRC at University College London Hospitals, the CRUK-UCL Center, Experimental Cancer Medicine Center and the Breast Cancer Research Foundation, USA (BCRF). His research is supported by a Stand Up To Cancer-LUNGevity-American Lung Association Lung Cancer Interception Dream Team Translational Research Grant (SU2C-AACR-DT23-17). Stand Up To Cancer is a program of the Entertainment Industry Foundation. Research grants are administered by the American Association for Cancer Research, the Scientific Partner of SU2C. C.S. also receives funding from the European Research Council (ERC) under the European Union’s Seventh Framework Program (FP7/2007-2013) Consolidator Grant (FP7-THESEUS-617844), European Commission ITN (FP7-PloidyNet 607722), an ERC Advanced Grant (PROTEUS) from the European Research Council under the European Union’s Horizon 2020 research and innovation program (835297), and Chromavision from the European Union’s Horizon 2020 research and innovation program (665233). S.A.Q. is a CRUK Senior Cancer Research Fellowship (C36463/A22246) and is funded by a CRUK Biotherapeutic Program Grant (C36463/A20764) and the Rosetrees and Stonygate Trusts (A1388) and a donation from the Khoo Teck Puat UK Foundation via the UCL Cancer Institute Research Trust (539288). S.T. is funded by Cancer Research UK (grant reference number C50947/A18176), the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC0010988), the UK Medical Research Council (FC0010988), and the Wellcome Trust (FC0010988), the National Institute for Health Research (NIHR) Biomedical Research Center at the Royal Marsden Hospital and Institute of Cancer Research (grant reference number A109), the Royal Marsden Cancer Charity, The Rosetrees Trust (grant reference number A2204), Ventana Medical Systems Inc (grant reference numbers 10467 and 10530), the National Institutes of Health (Bethesda, MD) and Melanoma Research Alliance. ST has received speaking fees from Roche, Astra Zeneca, Novartis, and Ipsen. S.T. has the following patents filed: Indel mutations as a therapeutic target and predictive biomarker PCTGB2018/051892 and PCTGB2018/051893 and Clear Cell Renal Cell Carcinoma Biomarkers P113326GB., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Little is known about the effects of NPC1 deficiency in brain development and whether these effects contribute to neurodegeneration in Niemann-Pick disease type C (NPC). Degeneration of cerebellar Purkinje cells occurs at an earlier stage and to a greater extent in NPC; therefore, we analyzed the effect of NPC1 deficiency on microglia and on climbing fiber synaptic refinement during cerebellar postnatal development using the Npc1 nmf164 mouse. Our analysis revealed that NPC1 deficiency leads to early phenotypic changes in microglia that are not associated with an innate immune response. However, the lack of NPC1 in Npc1 nmf164 mice significantly affected the early development of microglia by delaying the radial migration, increasing the proliferation and impairing the differentiation of microglia precursor cells during postnatal development. Additionally, increased phagocytic activity of differentiating microglia was observed at the end of the second postnatal week in Npc1 nmf164 mice. Moreover, significant climbing fiber synaptic refinement deficits along with an increased engulfment of climbing fiber synaptic elements by microglia were found in Npc1 nmf164 mice, suggesting that profound developmental defects in microglia and synaptic connectivity might precede and predispose Purkinje cells to early neurodegeneration in NPC., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2020. Published by The Company of Biologists Ltd.)

Three children with renal disease, hypertension, and the Cockayne syndrome were evaluated. All patients had severe hypertension; peripheral vein renin was elevated in two patients. Renal biopsy specimens from two patients were studied by light microscopy, electron microscopy, and immunofluoresence. Immunohistologic studies demonstrated deposits of immunoglobulin and complement in the vessels and glomeruli of the first patient; deposits of immunoglobulin and complement were seen in the glomeruli of the third patient. Also electron-dense deposits were seen in the glomerular basement membrane of the third patient. Circulating immune complexes were detected by the Raji cell and Clq binding techniques in this child as well. Both hypertension and renal disease are frequent complications of the Cockayne syndrome.