Guy's and St Thomas' NHS Foundation Trust

About: Guy's and St Thomas' NHS Foundation Trust is a healthcare organization based out in London, United Kingdom. It is known for research contribution in the topics: Population & Randomized controlled trial. The organization has 7686 authors who have published 9631 publications receiving 399353 citations. The organization is also known as: Guy's and St Thomas' National Health Service Foundation Trust & Guy's and St Thomas' National Health Service Trust.

Mucinous Carcinoma of the Skin, Primary, and Secondary A Clinicopathologic Study of 63 Cases With Emphasis on the Morphologic Spectrum of Primary Cutaneous Forms: Homologies With Mucinous Lesions in the Breast

Abstract: We present the largest series of mucinous carcinoma involving the skin, describing the histopathologic, immunohistochemical, electron microscopic, and cytogenetic findings. Our aim was fully to characterize the clinicopathologic spectrum and compare it with that seen in the breast. In addition, we wished to reevaluate the differential diagnostic criteria for distinguishing primary mucinous carcinomas from histologically similar neoplasms involving the skin secondarily, and study some aspects of their pathogenesis. We demonstrate that primary cutaneous mucinous carcinomas span a morphologic spectrum compatible to their mammary counterparts. Both pure and mixed types can be delineated morphologically, and some lesions have mucocele-like configurations. Most lesions seem to originate from in situ lesions that may represent, using mammary pathology terminology, ductal hyperplasia, atypical ductal hyperplasia, or ductal carcinoma in situ or a combination of the three. Inverse cell polarity appears to facilitate the progression of the changes similar to lesions in the breast. The presence of an in situ component defines the neoplasm as primary cutaneous, but its absence does not exclude the diagnosis; although for such neoplasms, full clinical assessment is essential. Mammary mucinous carcinoma involving the skin: all patients presented with lesions on chest wall, breast, axilla, and these locations can serve as clue to the breast origin. Microscopically, cutaneous lesions were of both pure and mixed type, and this correlated with the primary in the breast. Dirty necrosis was a constant histologic finding in intestine mucinous carcinomas involving the skin, and this feature may serve as a clue to an intestinal origin.

Developing in vitro expanded CD45RA+ regulatory T cells as an adoptive cell therapy for Crohn's disease

Abstract: Background and aim Thymus-derived regulatory T cells (T regs ) mediate dominant peripheral tolerance and treat experimental colitis. T regs can be expanded from patient blood and were safely used in recent phase 1 studies in graft versus host disease and type 1 diabetes. T reg cell therapy is also conceptually attractive for Crohn9s disease (CD). However, barriers exist to this approach. The stability of T regs expanded from Crohn9s blood is unknown. The potential for adoptively transferred T regs to express interleukin-17 and exacerbate Crohn9s lesions is of concern. Mucosal T cells are resistant to T reg -mediated suppression in active CD. The capacity for expanded T regs to home to gut and lymphoid tissue is unknown. Methods To define the optimum population for T reg cell therapy in CD, CD4 + CD25 + CD127 lo CD45RA + and CD4 + CD25 + CD127 lo CD45RA − T reg subsets were isolated from patients’ blood and expanded in vitro using a workflow that can be readily transferred to a good manufacturing practice background. Results T regs can be expanded from the blood of patients with CD to potential target dose within 22–24 days. Expanded CD45RA + T regs have an epigenetically stable FOXP3 locus and do not convert to a Th17 phenotype in vitro, in contrast to CD45RA − T regs . CD45RA + T regs highly express α 4 β 7 integrin, CD62L and CC motif receptor 7 (CCR7). CD45RA + T regs also home to human small bowel in a C.B-17 severe combined immune deficiency (SCID) xenotransplant model. Importantly, in vitro expansion enhances the suppressive ability of CD45RA + T regs . These cells also suppress activation of lamina propria and mesenteric lymph node lymphocytes isolated from inflamed Crohn9s mucosa. Conclusions CD4 + CD25 + CD127 lo CD45RA + T regs may be the most appropriate population from which to expand T regs for autologous T reg therapy for CD, paving the way for future clinical trials.

Intubation Practices and Adverse Peri-intubation Events in Critically Ill Patients From 29 Countries.

Abstract: Importance Tracheal intubation is one of the most commonly performed and high-risk interventions in critically ill patients. Limited information is available on adverse peri-intubation events. Objective To evaluate the incidence and nature of adverse peri-intubation events and to assess current practice of intubation in critically ill patients. Design, Setting, and Participants The International Observational Study to Understand the Impact and Best Practices of Airway Management in Critically Ill Patients (INTUBE) study was an international, multicenter, prospective cohort study involving consecutive critically ill patients undergoing tracheal intubation in the intensive care units (ICUs), emergency departments, and wards, from October 1, 2018, to July 31, 2019 (August 28, 2019, was the final follow-up) in a convenience sample of 197 sites from 29 countries across 5 continents. Exposures Tracheal intubation. Main Outcomes and Measures The primary outcome was the incidence of major adverse peri-intubation events defined as at least 1 of the following events occurring within 30 minutes from the start of the intubation procedure: cardiovascular instability (either: systolic pressure 30 minutes, new or increase need of vasopressors or fluid bolus >15 mL/kg), severe hypoxemia (peripheral oxygen saturation Results Of 3659 patients screened, 2964 (median age, 63 years; interquartile range [IQR], 49-74 years; 62.6% men) from 197 sites across 5 continents were included. The main reason for intubation was respiratory failure in 52.3% of patients, followed by neurological impairment in 30.5%, and cardiovascular instability in 9.4%. Primary outcome data were available for all patients. Among the study patients, 45.2% experienced at least 1 major adverse peri-intubation event. The predominant event was cardiovascular instability, observed in 42.6% of all patients undergoing emergency intubation, followed by severe hypoxemia (9.3%) and cardiac arrest (3.1%). Overall ICU mortality was 32.8%. Conclusions and Relevance In this observational study of intubation practices in critically ill patients from a convenience sample of 197 sites across 29 countries, major adverse peri-intubation events—in particular cardiovascular instability—were observed frequently.