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1.
Nat Commun ; 13(1): 4628, 2022 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-35941116

RESUMO

The presence of distinct stem cells that maintain the interfollicular epidermis is highly debated. Here, we report a population of keratinocytes, marked by Thy1, in the basal layer of the interfollicular epidermis. We find that epidermal cells expressing differential levels of Thy1 display distinct transcriptional signatures. Thy1+ keratinocytes do not express T cell markers, express a unique transcriptional profile, cycle significantly slower than basal epidermal progenitors and display significant expansion potential in vitro. Multicolor lineage tracing analyses and mathematical modeling reveal that Thy1+ basal keratinocytes do not compete neutrally alike interfollicular progenitors and contribute long-term to both epidermal replenishment and wound repair. Importantly, ablation of Thy1+ cells strongly impairs these processes, thus indicating the non-redundant function of Thy1+ stem cells in the epidermis. Collectively, these results reveal a distinct stem cell population that plays a critical role in epidermal homeostasis and repair.


Assuntos
Células Epidérmicas , Células-Tronco , Animais , Diferenciação Celular/fisiologia , Epiderme/metabolismo , Queratinócitos/metabolismo , Camundongos , Células-Tronco/metabolismo
2.
Int J Surg ; 67: 18-23, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30849526

RESUMO

OBJECTIVE: To determine whether clinical evaluation reporting using the IDEAL (Idea, Development, Exploration, Assessment and Long-term study) framework improves a novel double-balloon endoscopic stabilization technology. DESIGN: Observational registry 6 month study with no follow-up. Using the Prospective Development Study (PDS) format recommended by the IDEAL collaboration, we report on continued refinement and optimization of an endoscopic stabilization platform during a clinical study conducted by two clinicians from the first case onwards. Key outcomes (ability to reach cecum, inflation of balloons in the sigmoid and ascending colon, and complications) were prospectively reported for each patient sequentially. All changes to technique were highlighted, showing when they occurred and an explanation for the change. RESULTS: 30 colonoscopies were undertaken using the device from April to September 2017. Two patients were excluded from the analysis for protocol deviations. Cecum was reached in 89% of the per protocol population of patients in an average time of 13.5 ±â€¯11 min. Therapeutic zone creation was successful in 89% of patients on the right side of the intestine and 100% in those that reached the sigmoid. There were five deliberate changes in technique that occurred during the study that enabled improved device technical performance. There were no serious complications and one polyp was removed successfully using the device. Clinicians reported endoscope stability and increased visibility of the intestinal mucosa increased when using the device. CONCLUSION: The IDEAL framework provided a structured reporting of the changes made to technique. Those changes facilitated a device that is safe, has achieved stability with improved performance.


Assuntos
Colonoscopia/instrumentação , Enteroscopia de Duplo Balão/instrumentação , Melhoria de Qualidade , Ceco/cirurgia , Colo Sigmoide/cirurgia , Colonoscopia/normas , Enteroscopia de Duplo Balão/normas , Feminino , Humanos , Mucosa Intestinal/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sistema de Registros
4.
Surg Endosc ; 33(1): 315-321, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30014326

RESUMO

BACKGROUND: Flexible endoscopes ability to manipulate the intestinal environment is limited. As a result, complex endolumenal procedures are often technically demanding and result in long procedure times, impacting institutional resources. Single- and double-balloon add-on endoscopic devices have been employed throughout the GI tract to facilitate tissue control e.g., small bowel enteroscopy, with recent reports suggesting a possible colonic utility for complex procedures e.g., ESD. Our objective was to objectively analyze the efficacy of a new double-balloon device in performing ESD. METHODS: Ex vivo-12 simulated colonic lesions were created in porcine rectum using a standard 40 mm diameter template. Two categories were evaluated, standard cap technique ESD and double-balloon assisted ESD with retraction (ESD-R). Cases were performed sequentially. In vivo-Six, 40 mm lesion ESD-R's were performed in a porcine model. The primary outcomes of this study were total procedure and dissection times. RESULTS: In ex vivo studies, the median total procedure time with the double-balloon platform was significantly shorter than the traditional ESD technique (29 ± 18 vs. 57 ± 21 min, p = 0.03). In the in vivo studies, lesions were successfully removed in a mean time of 48 min, with a dissection time of 20 min with no significant complications. Balloon-clip retraction and specimen retrieval capabilities were used in all double-balloon assisted cases. After 6 cases, times were significantly shorter (ex vivo 47 vs. 17 min; in vivo 57 vs. 27 min). CONCLUSIONS: We have demonstrated the development of a unique technical ESD method facilitated by a new double-balloon device. Ex and in vivo investigation demonstrated superiority of ESD-R over the conventional ex vivo method. The DB device provided increased stability, improved visualization and tissue traction, which significantly reduced dissection time. Such an approach may increase safety, improve patient outcomes, and may prevent unnecessary surgeries for benign conditions.


Assuntos
Ressecção Endoscópica de Mucosa/métodos , Mucosa Gástrica/cirurgia , Gastroscopia/instrumentação , Animais , Dissecação/métodos , Gastroscopia/métodos , Humanos , Instrumentos Cirúrgicos , Suínos
6.
Endosc Int Open ; 6(6): E739-E744, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29876511

RESUMO

BACKGROUND AND STUDY AIMS: Complex colorectal polyps or those positioned in difficult anatomic locations are an endoscopic therapeutic challenge. Underwater endoscopic submucosal dissection (UESD) is a potential technical solution to facilitate efficient polyp removal. In addition, endoscopic tissue retraction has been confined to limited methods of varying efficacy and complexity. The aim of this study was to evaluate the efficiency of a unique UESD technique for removing complex polyps using double-balloon-assisted retraction (R). MATERIALS AND METHODS: Using fresh ex-vivo porcine rectum, 4-cm polyps were created using electrosurgery and positioned at "6 o'clock" within an established ESD model. Six resections were performed in each group. Underwater techniques were facilitated using a novel double-balloon platform (Dilumen, Lumendi, Westport, Connecticut, United States). RESULTS: UESD-R had a significantly shorter total procedural time than cap-assisted ESD and UESD alone (24 vs. 58 vs. 56 mins). UESD-R produced a dissection time on average of 5 minutes, attributed to the retraction provided. There was also a subjective significant reduction in electrosurgical smoke with the underwater techniques contributing to improved visualization. CONCLUSIONS: Here we report the first ex-vivo experience of a unique double-balloon endoscopic platform optimized for UESD with tissue traction capability. UESD-R removed complex lesions in significantly shorter time than conventional means. The combined benefits of UESD and retraction appeared to be additive when tackling complex polyps and should be studied further.

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