AIM： To search the pathophysiological mechanism of diarrhea based on daily stool weights, fecal electrolytes, osmotic gap and pH. METHODS： Seventy-six patients were included： 51 with microscopic colitis （MC） [40 ...AIM： To search the pathophysiological mechanism of diarrhea based on daily stool weights, fecal electrolytes, osmotic gap and pH. METHODS： Seventy-six patients were included： 51 with microscopic colitis （MC） [40 with lymphocytic colitis （LC）; 11 with collagenous colitis （CC）], 7 with MC without diarrhea and 18 as a control group （CG）. They collected stool for 3 d. Sodium and potassium concentration were determined by flame photometry and chloride concentration by titration method of Schales. Fecal osmotic gap was calculated from the difference of osmolarity of fecal fluid and double sum of sodium and potassium concentration. RESULTS： Fecal fluid sodium concentration was significantly increased in LC 58.11±5.38 mmol/L （P〈0.01） and CC 54.14±8.42 mmol/L （P〈0.05） than in CG 34.28±2.98 mmol/L. Potassium concentration in LC 74.65±5.29 mmol/L （P〈0.01） and CC 75.53±8.78 mmol/L （P〈0.05） was significantly less compared to CG 92.67±2.99 mmol/L. Chloride concentration in CC 36.07±7.29 mmol/L was significantly higher than in CG 24.11±2.05 mmol/L（P〈0.05）. Forty-four （86.7%） patients had a secretory diarrhea compared to fecal osmotic gap. Seven （13.3%） patients had osmotic diarrhea. CONCLUSION： Diarrhea in MC mostly belongs to thesecretory type. The major pathophysiological mechanism in LC could be explained by a decrease of active sodium absorption. In CC, decreased CI/HCO3 exchange rate and increased chloride secretion are coexistent pathways.展开更多
AIM To examine treatment decisions of gastroenterologists regarding the choice of prescribing 5-aminosalycilates(5ASA) with corticosteroids(CS) versus corticosteroids alone for patients with active ulcerative colitis(...AIM To examine treatment decisions of gastroenterologists regarding the choice of prescribing 5-aminosalycilates(5ASA) with corticosteroids(CS) versus corticosteroids alone for patients with active ulcerative colitis(UC). METHODS A cross-sectional questionnaire exploring physicians' attitude toward 5ASA + CS combination therapy vs CS alone was developed and validated. The questionnaire was distributed to gastroenterology experts in twelve countries in five continents. Respondents' agreement with stated treatment choices were assessed by standardized Likert scale. Background professional characteristics of respondents were analyzed for correlation with responses. RESULTS Six hundred and sixty-four questionnaires were distributed and 349 received(52.6% response rate). Of 340 eligible respondents, 221(65%) would continue 5ASA in a patient hospitalized for intravenous CS treatment due to a moderate-severe UC flare, while 108(32%) would stop the 5ASA(P < 0.001), and 11(3%) are undecided. Similarly, 62% would continue 5ASA in an out-patient starting oral CS. However, only 140/340(41%) would proactively start 5ASA in a hospitalized patient not receiving 5ASA before admission. Most(94%) physicians consider the safety profile of 5ASA as very good. Only 52% consider them inexpensive, 35% perceive them to be expensive and 12% are undecided. On multi-variable analysis, less years of practice and perception of a plausible additive mechanistic effect of 5ASA + CS were positively associated with the decision to continue 5ASA with CS. CONCLUSION Despite the absence of data supporting its benefit, most gastroenterologists endorse combination of 5ASA + CS for patients with active moderate-to-severe UC. Randomized controlled trials are needed to assess if 5ASA confer any benefit for these patients.展开更多
Sporadic venous malformations are genetic conditions primarily caused by somatic gain-of-function mutation of PIK3CA or TEK,an endothelial transmembrane receptor signaling through PIK3CA.Venous malformations are assoc...Sporadic venous malformations are genetic conditions primarily caused by somatic gain-of-function mutation of PIK3CA or TEK,an endothelial transmembrane receptor signaling through PIK3CA.Venous malformations are associated with pain,bleedings,thrombosis,pulmonary embolism,esthetic deformities and,in severe cases,life-threatening situations.No authorized medical treatment exists for patients with venous malformations.Here,we created a genetic mouse model of PIK3CA-related capillary venous malformations that replicates patient phenotypes.We showed that these malformations only partially signal through AKT proteins.We compared the efficacy of different drugs,including rapamycin,a mTORC1 inhibitor,miransertib,an AKT inhibitor and alpelisib,a PI3Kαinhibitor at improving the lesions seen in the mouse model.We demonstrated the effectiveness of alpelisib in preventing vascular malformations’occurrence,improving the already established ones,and prolonging survival.Considering these findings,we were authorized to treat 25 patients with alpelisib,including 7 children displaying PIK3CA(n=16)or TEK(n=9)-related capillary venous malformations resistant to usual therapies including sirolimus,debulking surgical procedures or percutaneous sclerotherapies.We assessed the volume of vascular malformations using magnetic resonance imaging(MRI)for each patient.Alpelisib demonstrated improvement in all 25 patients.Vascular malformations previously considered intractable were reduced and clinical symptoms were attenuated.MRI showed a decrease of 33.4%and 27.8%in the median volume of PIK3CA and TEK malformations respectively,over 6 months on alpelisib.In conclusion,this study supports PI3Kαinhibition as a promising therapeutic strategy in patients with PIK3CA or TEK-related capillary venous malformations.展开更多
Recently, there has been great interest in the linear polarization of photons produced by radiative electron capture (REC, the time reversed photoionization in ion-atom collisions). No such data are available for the ...Recently, there has been great interest in the linear polarization of photons produced by radiative electron capture (REC, the time reversed photoionization in ion-atom collisions). No such data are available for the high-Z regime till now. By using high efficiency by by a new generation of segmented germanium detectors that have energy as well as position resolution this field can be investigated experimentally. The展开更多
文摘AIM： To search the pathophysiological mechanism of diarrhea based on daily stool weights, fecal electrolytes, osmotic gap and pH. METHODS： Seventy-six patients were included： 51 with microscopic colitis （MC） [40 with lymphocytic colitis （LC）; 11 with collagenous colitis （CC）], 7 with MC without diarrhea and 18 as a control group （CG）. They collected stool for 3 d. Sodium and potassium concentration were determined by flame photometry and chloride concentration by titration method of Schales. Fecal osmotic gap was calculated from the difference of osmolarity of fecal fluid and double sum of sodium and potassium concentration. RESULTS： Fecal fluid sodium concentration was significantly increased in LC 58.11±5.38 mmol/L （P〈0.01） and CC 54.14±8.42 mmol/L （P〈0.05） than in CG 34.28±2.98 mmol/L. Potassium concentration in LC 74.65±5.29 mmol/L （P〈0.01） and CC 75.53±8.78 mmol/L （P〈0.05） was significantly less compared to CG 92.67±2.99 mmol/L. Chloride concentration in CC 36.07±7.29 mmol/L was significantly higher than in CG 24.11±2.05 mmol/L（P〈0.05）. Forty-four （86.7%） patients had a secretory diarrhea compared to fecal osmotic gap. Seven （13.3%） patients had osmotic diarrhea. CONCLUSION： Diarrhea in MC mostly belongs to thesecretory type. The major pathophysiological mechanism in LC could be explained by a decrease of active sodium absorption. In CC, decreased CI/HCO3 exchange rate and increased chloride secretion are coexistent pathways.
文摘AIM To examine treatment decisions of gastroenterologists regarding the choice of prescribing 5-aminosalycilates(5ASA) with corticosteroids(CS) versus corticosteroids alone for patients with active ulcerative colitis(UC). METHODS A cross-sectional questionnaire exploring physicians' attitude toward 5ASA + CS combination therapy vs CS alone was developed and validated. The questionnaire was distributed to gastroenterology experts in twelve countries in five continents. Respondents' agreement with stated treatment choices were assessed by standardized Likert scale. Background professional characteristics of respondents were analyzed for correlation with responses. RESULTS Six hundred and sixty-four questionnaires were distributed and 349 received(52.6% response rate). Of 340 eligible respondents, 221(65%) would continue 5ASA in a patient hospitalized for intravenous CS treatment due to a moderate-severe UC flare, while 108(32%) would stop the 5ASA(P < 0.001), and 11(3%) are undecided. Similarly, 62% would continue 5ASA in an out-patient starting oral CS. However, only 140/340(41%) would proactively start 5ASA in a hospitalized patient not receiving 5ASA before admission. Most(94%) physicians consider the safety profile of 5ASA as very good. Only 52% consider them inexpensive, 35% perceive them to be expensive and 12% are undecided. On multi-variable analysis, less years of practice and perception of a plausible additive mechanistic effect of 5ASA + CS were positively associated with the decision to continue 5ASA with CS. CONCLUSION Despite the absence of data supporting its benefit, most gastroenterologists endorse combination of 5ASA + CS for patients with active moderate-to-severe UC. Randomized controlled trials are needed to assess if 5ASA confer any benefit for these patients.
基金supported by the European Research Council(CoG 2020 grant number 101000948 awarded to GC)the Agence Nationale de la Recherche-Programme d’Investissements d’Avenir(ANR-18-RHUS-005 to GC)+1 种基金the Agence Nationale de la Recherche-Programme de Recherche Collaborative(19-CE14-0030-01 to GC)supported by the CLOVES SYNDROME COMMUNITY(West Kennebunk,USA),Association Syndrome de CLOVES(Nantes,France),Fondation d’entreprise IRCEM(Roubaix,France),Fonds de dotation Emmanuel BOUSSARD(Paris,France),the Fondation DAY SOLVAY(Paris,France),the Fondation TOURRE(Paris,France)to GC,the Fondation BETTENCOURT SCHUELLER(Paris,France)to GC,the Fondation Simone et Cino DEL DUCA(Paris,France),the Fondation Line RENAUD-Loulou GASTE(Paris,France,the Fondation Schlumberger pour l’Education et la Recherche(Paris,France),the Association Robert Debrépour la Recherche.
文摘Sporadic venous malformations are genetic conditions primarily caused by somatic gain-of-function mutation of PIK3CA or TEK,an endothelial transmembrane receptor signaling through PIK3CA.Venous malformations are associated with pain,bleedings,thrombosis,pulmonary embolism,esthetic deformities and,in severe cases,life-threatening situations.No authorized medical treatment exists for patients with venous malformations.Here,we created a genetic mouse model of PIK3CA-related capillary venous malformations that replicates patient phenotypes.We showed that these malformations only partially signal through AKT proteins.We compared the efficacy of different drugs,including rapamycin,a mTORC1 inhibitor,miransertib,an AKT inhibitor and alpelisib,a PI3Kαinhibitor at improving the lesions seen in the mouse model.We demonstrated the effectiveness of alpelisib in preventing vascular malformations’occurrence,improving the already established ones,and prolonging survival.Considering these findings,we were authorized to treat 25 patients with alpelisib,including 7 children displaying PIK3CA(n=16)or TEK(n=9)-related capillary venous malformations resistant to usual therapies including sirolimus,debulking surgical procedures or percutaneous sclerotherapies.We assessed the volume of vascular malformations using magnetic resonance imaging(MRI)for each patient.Alpelisib demonstrated improvement in all 25 patients.Vascular malformations previously considered intractable were reduced and clinical symptoms were attenuated.MRI showed a decrease of 33.4%and 27.8%in the median volume of PIK3CA and TEK malformations respectively,over 6 months on alpelisib.In conclusion,this study supports PI3Kαinhibition as a promising therapeutic strategy in patients with PIK3CA or TEK-related capillary venous malformations.
文摘Recently, there has been great interest in the linear polarization of photons produced by radiative electron capture (REC, the time reversed photoionization in ion-atom collisions). No such data are available for the high-Z regime till now. By using high efficiency by by a new generation of segmented germanium detectors that have energy as well as position resolution this field can be investigated experimentally. The
