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Tero Sievänen Tia-Marje Korhonen Tiina Jokela Maarit Ahtiainen Laura Lahtinen Teijo Kuopio Anna Lepistö Elina Sillanpää Jukka-Pekka Mecklin Toni T. Seppälä Eija K. Laakkonen 《International journal of cancer. Journal international du cancer》2023,152(5):932-944
Circulating microRNAs (c-miRs) are small noncoding RNA molecules that migrate throughout the body and regulate gene expression. Global c-miR expression patterns (c-miRnomes) change with sporadic carcinogenesis and have predictive potential in early detection of cancers. However, there are no studies that have assessed whether c-miRnomes display similar potential in carriers of inherited pathogenic mismatch-repair gene variants (path_MMR), known as Lynch syndrome (LS), who are predisposed to highly increased cancer risk. Using high-throughput sequencing and bioinformatic approaches, we conducted an exploratory analysis to characterize systemic c-miRnomes of path_MMR carriers, sporadic rectal cancer patients and non-LS controls. We showed for the first time that cancer-free path_MMR carriers have a systemic c-miRnome of 40 differentially expressed c-miRs that can distinguish them from non-LS controls. The systemic c-miRnome of cancer-free path_MMR carriers also resembles the systemic c-miRnomes of cancer patients with or without path_MMR. Our pathway analysis linked the found differentially expressed c-miRs to carcinogenesis. A total of 508 putative target genes were identified for 32 out of 40 differentially expressed c-miRs, and 238 of them were enriched in cancer-related pathways. The most enriched c-miR-target genes include well-known oncogenes and tumor suppressor genes such as BCL2, AKT3, PIK3CA, KRAS, NRAS, CDKN1A and PIK3R1. Taken together, our findings suggest that LS and sporadic carcinogenesis share common biological pathways and alterations in these pathways can produce a c-miR signature which can track potential oncogenic stress in cancer-free path_MMR carriers. Therefore, c-miRs hold potential in monitoring the LS risk stratification patterns during clinical surveillance or cancer management. 相似文献
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Nicolas Penel Sylvie Bonvalot Marie-Cécile Le Deley Antoine Italiano Camille Tlemsani Diane Pannier Clémence Leguillette Jean-Emmanuel Kurtz Maud Toulmonde Julien Thery Daniel Orbach Pascale Dubray-Longeras Benjamin Verret François Bertucci Cécile Guillemet Lucie Laroche Armelle Dufresne Jean-Yves Blay Axel Le Cesne 《International journal of cancer. Journal international du cancer》2023,153(2):407-416
The aim of this study is to evaluate the prevalence, determinants and prognostic value of pain at diagnosis in patients with desmoid-type fibromatosis (DF). We selected patients from the ALTITUDES cohort (NCT02867033), managed by surgery, active surveillance or systemic treatments, with pain assessment at diagnosis. Patients were invited to fill QLQ-C30 questionnaire and Hospital Anxiety Depression Scale. Determinants were identified using logistic models. Prognostic value on event-free survival (EFS) was evaluated using the Cox model. Overall, 382 patients were included in the current study (median age: 40.2 years; 117 men). The prevalence of pain was 36%, without significant difference according to first-line treatment (P = .18). In the multivariate analysis, pain was significantly associated with tumor size >50 mm (P = .013) and tumor site (P < .001); pain was more frequent in the neck and shoulder locations (odds ratio: 3.05 [1.27-7.29]). Pain at baseline was significantly associated with poor quality of life (P < .001), depression (P = .02), lower performance status (P = .03) and functional impairment (P = .001); we also observed a nonsignificant association with anxiety (P = .10). In the univariate analysis, baseline pain was associated with poor EFS; the 3-year EFS was 54% in patients with pain compared to 72% in those without pain. After adjustment for sex, age, size and line of treatment, pain was still associated with poor EFS (hazard ratio: 1.82 [1.23-2.68], P = .003). One third of recently diagnosed patients with DF experienced pain, especially those with larger tumors and neck/shoulder locations. Pain was associated with unfavorable EFS after adjustment for the confounders. 相似文献
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《Journal of pediatric surgery》2023,58(7):1258-1262
BackgroundIt is well known that small bowel length is a dominant prognostic indicator in patients with short bowel syndrome (SBS). The relative importance of jejunum, ileum, and colon is less well defined in children with SBS. Here we review the outcome of children with SBS with respect to the type of remnant intestine.MethodsA retrospective review of 51 children with SBS was conducted at a single institution. The duration of parenteral nutrition use was the main outcome variable. The length of the remaining intestine as well as the type of intestine were recorded for each patient. Kaplan–Meier analyses were conducted to compare the subgroups.ResultsChildren with greater than 10% expected small bowel length or more than 30 cm of small bowel achieved enteral autonomy faster than those with less. The presence of ileocecal valve enhanced the ability to wean from parenteral nutrition. The presence of ileum significantly enhanced the ability to wean from parenteral nutrition. Patients with the entire colon also achieved enteral autonomy sooner than those with partial colon.ConclusionsThe preservation of ileum and colon is important in patients with SBS. Approaches to preserve or lengthen ileum and colon may be beneficial for these patients.Level of evidenceIV. 相似文献
5.
《Neuro-Chirurgie》2023,69(1):101397
BackgroundWe previously described a procedure for eliciting deep spatial discrimination of individual segments in the healthy lumbar spine of normal subjects: the percutaneous mechanical provocation (PMP) test. Our goal was to devise a method for accurate identification of the spinal level of pathology in chronic low back pain (CLBP). In the present study, we validated the PMP test, using a subgroup of CLBP patients with isthmic spondylolisthesis (IS). Because there is clinical consensus that IS back pain originates in the slipped segment/disc, the level of pathology can be directly compared to the result of the PMP test. The test is agnostic with respect to the underlying pathological mechanism, and therefore might be useful in identifying the involved segment(s) irrespective of the painful structure.MethodsIn 37 patients with confirmed IS (slippage 3–15 mm), we compared sensitivity between the PMP test, the widely used provocative discography test and the discoblock test.ResultsThe PMP test reliably identified the slip level in patients with IS, with sensitivity of 92%. Accepting the slipped disc as the origin of pain in IS, the sensitivity of the provocative discography and discoblock tests were 49% and 35%, respectively: i.e., too low to be contributive in clinical practice.ConclusionsThe PMP test reliably identified the origin of localized pain in IS as the slip level, but should be used with care in CLBP patients in selecting discogenic pain patients for fusion surgery, since the specificity of the test is not known and it may be positive for any origin of localized pain. 相似文献
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M. Eikemo I. M. Meier G. E. Løseth M. Trøstheim N. Ørstavik E. N. Jensen E. L. Garland C. Berna G. Ernst S. Leknes 《Anaesthesia》2023,78(9):1102-1111
Exposure to opioid analgesics due to surgery increases the risk of new persistent opioid use. A mechanistic hypothesis for opioids' abuse liability rests on the belief that, in addition to pain relief, acute opioid treatment improves well-being (e.g. via euphoria) and relieves anxiety. However, opioids do not consistently improve mood in laboratory studies of healthy non-opioid users. This observational study determined how two commonly used opioid analgesics affected patients' subjective well-being in standard clinical practice. Day surgery patients rated how good and how anxious they felt before and after an open-label infusion of remifentanil (n = 159) or oxycodone (n = 110) in the operating theatre before general anaesthesia. One minute after drug injection, patients reported feeling intoxicated (> 6/10 points). Anxiety was reduced after opioids, but this anxiolytic effect was modest (remifentanil Cohen's d = 0.21; oxycodone d = 0.31). There was moderate to strong evidence against a concurrent improvement in well-being (Bayes factors > 6). After remifentanil, ratings of ‘feeling good’ were significantly reduced from pre-drug ratings (d = 0.28). After oxycodone, one in three participants felt better than pre-drug. Exploratory ordered logistic regressions revealed a link between previous opioid exposure and opioid effects on well-being, as only 14 of the 80 opioid-naïve patients reported feeling better after opioid injection. The odds of improved well-being ratings after opioids were higher in patients with previous opioid exposure and highest in patients with > 2 weeks previous opioid use (adjusted OR = 4.4). These data suggest that opioid-induced improvement of well-being is infrequent in opioid-naïve patients. We speculate that peri-operative exposure could increase risk of persistent use by rendering subsequent positive opioid effects on well-being more likely. 相似文献
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《Enfermedades infecciosas y microbiología clínica》2022,40(6):310-316
The aim of this study was to assess the effect of lipodystrophy (LD) associated to metabolic syndrome (MS) on oxidative stress and inflammation in a cohort of 243 HIV-infected patients with MS, all of them under three different antiretroviral regimens. We collected immunovirological, biochemical and metabolic data, as well as anthropometric measurements. In addition, cardiovascular risk was also assessed by means of Atherogenic Index of Plasma (API) and Framingham Risk Score. The MS-LD patient set was characterized by a lower initial lymphocyte CD4 count and CD4/CD8 ratio and a higher initial viral load than the group without LD. We also found worse lipidic and glycaemic profiles (with lower HDL-cholesterol and higher triglyceride and glucose levels) in the MS-LD group. BMI, systolic blood pressure and Framingham score were significantly increased compared to MS-Non LD. In addition, patients with MS and LD had significantly higher levels of carbonylated proteins, lipid peroxidation, IL-6 and IL-8, as well as a significant decrease in the levels of leptin, adiponectin and antioxidant activities of catalase, super oxide dismutase and glutathione associated enzymes. In MS-LD HIV-1 patients, a significant negative correlation was found between Framingham Risk Score and the antioxidant biomarkers, however a positive association was found between API and protein-C reactive and carbonylated proteins. Segregating by ART, the above-mentioned conditions were worse within the MS-LD group whose treatment contained protease inhibitors, such as lopinavir. In conclusion, HIV-1 infected patients treated for at least six months, especially with regimens including PIs, showed a worsening of inflammatory process and oxidative stress. 相似文献
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《Enfermedades infecciosas y microbiología clínica》2022,40(8):436-440
IntroductionDientamoeba (D.) fragilis is a common intestinal protozoan with an unresolved clinical significance. The association between D. fragilis and the etiology of gastrointestinal symptoms in children is unclear. Metronidazole is often used for treatment. The aims of this study are to clarify the clinical relevance of D. fragilis in children with gastrointestinal symptoms, and to determine the clinical and microbiological efficacy of metronidazole in D. fragilis-infected children with gastrointestinal complaints.MethodsA prospective case–control study was performed from October 2017 to February 2019. A total of 106 individuals aged 1–17 were included. Out of the 106; 59 showed gastrointestinal symptoms (case group), and 47 were without gastrointestinal symptoms (control group). We excluded 2 patients from the case group. D. fragilis was diagnosed by real-time PCR in stool samples. A 10-day course of oral Metronidazole was prescribed in D. fragilis positive children with GI symptoms. Clinical data before and after the treatment as well as peripheral eosinophilia in previous blood samples, were recorded.ResultsOf the 104 participants, D. fragilis was found in 17 (29.8%) children from the case group, whereas in the control group the parasite was detected in 11 patients (23.4%) with an odds ratio (OR) of 1.39 (IC 95% 0.53–3.75, p = 0.46). The most prevalent clinical manifestation was abdominal pain (46/57, 80.7%). Seventeen cases with a positive PCR received anti-parasitic treatment according to the established protocol, although during the collection period we received only 11 stool samples to perform the post-treatment follow-up. The PCR of the D. fragilis remained positive in 3 patients (3/11, 27.27%). Despite achieving the eradication of the parasite, 4/8 patients (50%) continued with digestive symptoms.ConclusionsAccording to our study there were no differences between the D. fragilis infection in children with or without gastrointestinal symptoms. No relation was found between the clinical and microbiological responses after said D. fragilis treatment. Therefore, we conclude that it is not justified to look specifically for D fragilis in pediatric patients with abdominal symptoms. 相似文献