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Judith Brock Andreas Schmid Thomas Karrasch Petra Pfefferle Jutta Schlegel Inga Busse Annette Hauenschild Barbara Schmidt Maria Koukou Efthymia Arapogianni Andreas Schultz Miriam Thomalla Secil Akinci Johannes Kruse Winfried Padberg Andreas Schffler Jens Albrecht 《Clinical endocrinology》2019,91(3):400-410
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Sebastian Mondaca Walid K. Chatila David Bates Jaclyn F. Hechtman Andrea Cercek Neil H. Segal Zsofia K. Stadler Anna M. Varghese Ritika Kundra Marinela Capanu Jinru Shia Nikolaus Schultz Leonard Saltz Rona Yaeger 《Clinical colorectal cancer》2019,18(1):e39-e52
Background
Treatment of advanced anal squamous cell cancer (SCC) is usually with the combination of cisplatin and 5-fluorouracil, which is associated with heterogeneous responses across patients and significant toxicity. We examined the safety and efficacy of a modified schedule, FOLFCIS (leucovorin, fluorouracil, and cisplatin), and performed an integrated clinical and genomic analysis of anal SCC.Patients and Methods
We reviewed all patients with advanced anal SCC receiving first-line FOLFCIS chemotherapy – essentially a FOLFOX (leucovorin, fluorouracil, and oxaliplatin) schedule with cisplatin substituted for oxaliplatin – in our institution between 2007 and 2017, and performed deep sequencing to identify genomic markers of response and key genomic drivers.Results
Fifty-three patients with advanced anal SCC (48 metastatic; 5 unresectable, locally advanced) received first-line FOLFCIS during this period; all were platinum-naive. The response rate was 48% (95% confidence interval [CI], 32.6%-63%). With a median follow-up of 41.6 months, progression-free survival and overall survival were 7.1 months (95% CI, 4.4-8.6 months) and 22.1 months (95% CI, 16.9-28.1 months), respectively. Among all patients with advanced anal SCC that underwent sequencing during the study period, the most frequent genomic alterations consisted of chromosome 3q amplification (51%) and mutations in PIK3CA (29%) and KMT2D (22%). No genomic alteration correlated with response to platinum-containing treatment. Although there were few cases, patients with human papillomavirus-negative anal SCC did not appear to benefit from FOLFCIS, and all harbored distinct genomic profiles with TP53, TERT promoter, and CDKN2A mutations.Conclusions
FOLFCIS appears effective and safe as first-line chemotherapy in patients with advanced anal SCC and represents an alternative treatment option for these patients. 相似文献6.
The vagal nerve as a link between the nervous and immune system in the instance of polymicrobial sepsis 总被引:5,自引:0,他引:5
Wolfram Kessler Tobias Traeger Alexandra Westerholt Friederike Neher Marlene Mikulcak Antje Müller Stefan Maier Claus-Dieter Heidecke 《Langenbeck's archives of surgery / Deutsche Gesellschaft fur Chirurgie》2006,391(2):83-87
Background The role of the vagal nerve in the autonomic nervous system is widely well known. Recently, an additional function was revealed
serving as a connector between the nervous and immune system. This connection is called the “cholinergic inflammatory pathway.”
Through stimulation of the acetylcholine receptors located upon the macrophages, the “unspecific” immune system can be directly
influenced.
Methods The vagal nerve was completely transected directly posterior to its passage through the diaphragm. The effect of complete
vagotomy was analyzed using a murine model of polymicrobial peritonitis (colon ascendens stent peritonitis, CASP). Survival
and clinical course of vagotomized or sham-operated mice were analyzed in the CASP model.
Results After CASP surgery, vagotomy led to a significantly increased mortality (64.7%) in comparison to sham-vagotomized animals
(34%). No difference in the bacterial load of various tissues (lung, liver, spleen, blood, lavage fluid, and kidney) from
septic animals with or without vagotomy was observed. Vagotomized animals reveal elevated serum cytokine levels (TNF, IL-6,
IL-10, and MCP-1) 20 h after the induction of polymicrobial peritonitis.
Conclusion The vagal nerve is therefore an important modulator of the immune system.
W. Kessler and T. Traeger contributed equally to this work
Best of Forum Papers presented at the Annual Meeting of the German Society of Surgery, 2–5 May 2006, Berlin, Germany 相似文献
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Gregory Guldner MD MS Jason Schultz BS Perry Sexton MD Corwyn Fortner BS Mark Richmond MD 《Academic emergency medicine》2003,10(2):134-139
OBJECTIVES: Physicians commonly use etomidate for adult rapid-sequence intubation (RSI), but the manufacturer does not recommend its use for children under 10 years of age due to a lack of data. The authors present their experience with etomidate for pediatric RSI in order to further develop its risk-benefit profile in this age group. METHODS: Trained abstractors reviewed the medical records for all children under 10 years old who received etomidate for RSI between July 1996 and April 2001. RESULTS: 105 children, with an average age of 3 (+/-2.9) years, received a median dose of 0.32 (+/-0.12) mg/kg of etomidate. The systolic blood pressure increased an average of 4 mm Hg (95% CI = -3.3 to 9.2); the diastolic blood pressure increased 7 mm Hg (95% CI = -3.1 to 11) within 10 minutes of receiving etomidate. The heart rate increased an average of 10 beats/min (95% CI = 4.0 to 17.4). Complications included three patients who vomited within 10 minutes of etomidate administration. There were no cases of documented myoclonus, status epilepticus, or new-onset seizures. Thirty-eight patients received corticosteroids during the hospital course, none for suspected adrenal insufficiency. Three patients died, all from severe brain injury. CONCLUSIONS: In children less than 10 years old, etomidate seems to produce minimal hemodynamic changes, and appears to have a low risk of clinically important adrenal insufficiency, myoclonus, and status epilepticus. The association between etomidate and emesis (observed in less than 3% of enrolled patients) remains unclear. For clinical situations in which minimal blood pressure changes during RSI are critical, etomidate appears to have a favorable risk-benefit profile for children under 10 years old. 相似文献
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The course of schizophrenia: Some remarks on a yet unsolved problem of retrospective data collection
Wolfram an der Heiden Bertram Krumm 《European archives of psychiatry and clinical neuroscience》1991,240(4-5):303-306
Summary The retrospective assessment of symptoms and syndromes is a basic measure in research of the longitudinal course of schizophrenia. In spite of its importance there have been few studies evaluating the standard of quality of instruments for retrospective data collection. Combining retrospectively and cross-sectionally collected data on schizophrenic symptomatology in a cohort study over a period of 5 years revealed a significant underestimation of symptoms when assessed in retrospect. The need for studies on the validity of instruments for the retrospective assessment of symptoms is stressed. 相似文献
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