55,623 research outputs found
The UN-SUSTAINABLE Match in HCV Recipients. Evidences from the Italian D-MELD Study on Balancing Donor-Recipient Risk Factors
No full textThe UN-SUSTAINABLE Match in HCV Recipients. Evidences from the Italian D-MELD Study on Balancing Donor-Recipient Risk Factor
All repair and reconstruction. Techniques from the SANTI study group
No full textBackground: Combining an anterior cruciate ligament (ACL) reconstruction with an anterolateral ligament (ALL) reconstruction results in significant advantages including reduced graft rupture rates, a lower risk of reoperation for secondary meniscectomy, improved knee stability, and higher rates of return to preinjury levels of sport. Indications: The previously reported indications for combined ACL and ALL reconstruction are as follows: ACL reconstruction revision; high-grade pivot shift test; long-term ACL rupture; young patients; pivoting activities; concomitant medial meniscus repair, and, specifically, regarding the ALL repair, it must be an acute surgery (within 15 days from injury). Technique Description: Several modern techniques have been described to repair and reconstruct the ALL. This technical note details a number of these techniques performed by the Scientific Anterior Cruciate Ligament Network International (SANTI) Study Group. Results: First, we describe a combined ACL reconstruction and double-bundle ALL reconstruction using hamstring autograft. Secondly, we describe a single-bundle ALL reconstruction using gracilis autograft. Thirdly, we describe an ALL reconstruction technique using a knotless soft anchor, which provides shallow fixation and prevents tunnel convergence. Finally, we describe a technique for ALL repair. Conclusion: Several techniques have been described to repair and reconstruct the ALL, all offering significant advantages over an isolated ACL reconstruction. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication
Robust automated detection of microstructural white matter degeneration in Alzheimer’s disease using machine learning classification of multicenter DTI data
No full textDiffusion tensor imaging (DTI) based assessment of white matter fiber tract integrity can support the diagnosis of Alzheimer’s disease (AD). The use of DTI as a biomarker, however, depends on its applicability in a multicenter setting accounting for effects of different MRI scanners. We applied multivariate machine learning (ML) to a large multicenter sample from the recently created framework of the European DTI study on Dementia (EDSD). We hypothesized that ML approaches may amend effects of multicenter acquisition. We included a sample of 137 patients with clinically probable AD (MMSE 20.6±5.3) and 143 healthy elderly controls, scanned in nine different scanners. For diagnostic classification we used the DTI indices fractional anisotropy (FA) and mean diffusivity (MD) and, for comparison, gray matter and white matter density maps from anatomical MRI. Data were classified using a Support Vector Machine (SVM) and a Naïve Bayes (NB) classifier. We used two cross-validation approaches, (i) test and training samples randomly drawn from the entire data set (pooled cross-validation) and (ii) data from each scanner as test set, and the data from the remaining scanners as training set (scanner-specific cross-validation). In the pooled cross-validation, SVM achieved an accuracy of 80% for FA and 83% for MD. Accuracies for NB were significantly lower, ranging between 68% and 75%. Removing variance components arising from scanners using principal component analysis did not significantly change the classification results for both classifiers. For the scanner-specific cross-validation, the classification accuracy was reduced for both SVM and NB. After mean correction, classification accuracy reached a level comparable to the results obtained from the pooled cross-validation. Our findings support the notion that machine learning classification allows robust classification of DTI data sets arising from multiple scanners, even if a new data set comes from a scanner that was not part of the training sample
Effectiveness of brief schema group therapy for borderline personality disorder symptoms : a randomized pilot study
No full textBackground and objectives Schema group therapy is a potentially cost-effective treatment for borderline personality disorder (BPD). We piloted the feasibility and effectiveness of a 20-session schema group therapy without individual therapy among psychiatric BPD outpatients in a randomized pilot study registered as a clinical trial (ISRCTN76381242). Methods Altogether 42 psychiatric outpatients diagnosed with BPD were randomized 2:1 to a 20-session weekly schema group therapy plus treatment as usual (TAU) (n = 28) vs. a control group with TAU alone (n = 14). The primary outcome was decline of BPD symptoms in the short Borderline Symptom List (BSL-23) score. Secondary outcomes were decline in symptoms of anxiety, depression, alcohol use, and improvement in functioning and schema modes. Two external experts evaluated validity of the intervention based on videotaped sessions. Results Overall, 23 schema group therapy patients (82%) and 12 controls (86%) completed their treatment. Treatment validity good or very good. However, no significant differences emerged in the primary outcome mean BSL-23 decline (6.95 [SE 5.91] in group schema therapy vs. 12.55 [4.85] in TAU) or in any of the secondary outcome measures. Limitations Despite randomization, the TAU subgroup had non-significantly higher baseline scores in most measures. Small sample size predisposing to type II errors; reliance on self-reported outcomes. Conclusions Schema group therapy was feasible for psychiatric outpatients with BPD. However, in this small pilot study we did not find it more effective than TAU. Effectiveness of this short intervention remains open.Peer reviewe
Preferential MGMT hypermethylation in SDH-deficient wild-type GIST
No full textAIMS: Wild-type gastrointestinal stromal tumours (wtGIST) are frequently caused by inherited pathogenic variants, or somatic alterations in the succinate dehydrogenase subunit genes (SDHx). Succinate dehydrogenase is a key enzyme in the citric acid cycle. SDH deficiency caused by SDHx inactivation leads to an accumulation of succinate, which inhibits DNA and histone demethylase enzymes, resulting in global hypermethylation. Epigenetic silencing of the DNA repair gene MGMT has proven utility as a positive predictor of the therapeutic efficacy of the alklyating drug temozolomide (TMZ) in tumours such as glioblastoma multiforme. The aim of this study was to examine MGMT promoter methylation status in a large cohort of GIST. METHODS: MGMT methylation analysis was performed on 65 tumour samples including 47 wtGIST (33 SDH-deficient wtGIST and 11 SDH preserved wtGIST) and 21 tyrosine kinase (TK) mutant GIST. RESULTS: MGMT promoter methylation was detected in 8 cases of SDH-deficient (dSDH) GIST but in none of the 14 SDH preserved wild-type GIST or 21 TK mutant GIST samples analysed. Mean MGMT methylation was significantly higher (p 0.0449) and MGMT expression significantly lower (p<0.0001) in dSDH wtGIST compared with TK mutant or SDH preserved GIST. No correlation was identified between SDHx subunit gene mutations or SDHC epimutation status and mean MGMT methylation levels. CONCLUSION: MGMT promoter hypermethylation occurs exclusively in a subset of dSDH wtGIST. Data from this study support testing of tumour MGMT promoter methylation in patients with dSDH wtGIST to identify those patients who may benefit from most from TMZ therapy
Pyruvate carboxylation enables growth of SDH-deficient cells by supporting aspartate biosynthesis
No full textSuccinate dehydrogenase (SDH) is a heterotetrameric nuclear-encoded complex responsible for the oxidation of succinate to fumarate in the tricarboxylic acid cycle. Loss-of-function mutations in any of the SDH genes are associated with cancer formation. However, the impact of SDH loss on cell metabolism and the mechanisms enabling growth of SDH-defective cells are largely unknown. Here, we generated Sdhb-ablated kidney mouse cells and used comparative metabolomics and stable-isotope-labelling approaches to identify nutritional requirements and metabolic adaptations to SDH loss. We found that lack of SDH activity commits cells to consume extracellular pyruvate, which sustains Warburg-like bioenergetic features. We further demonstrated that pyruvate carboxylation diverts glucose-derived carbons into aspartate biosynthesis, thus sustaining cell growth. By identifying pyruvate carboxylase as essential for the proliferation and tumorigenic capacity of SDH-deficient cells, this study revealed a metabolic vulnerability for potential future treatment of SDH-associated malignancies
Pulse oximetry adoption and oxygen orders at paediatric admission over 7 years in Kenya: a multihospital retrospective cohort study
No full textObjectives To characterise adoption and explore specific clinical and patient factors that might influence pulse oximetry and oxygen use in low-income and middle-income countries (LMICs) over time; to highlight useful considerations for entities working on programmes to improve access to pulse oximetry and oxygen.
Design A multihospital retrospective cohort study.
Settings All admissions (n=132 737) to paediatric wards of 18 purposely selected public hospitals in Kenya that joined a Clinical Information Network (CIN) between March 2014 and December 2020.
Outcomes Pulse oximetry use and oxygen prescription on admission; we performed growth-curve modelling to investigate the association of patient factors with study outcomes over time while adjusting for hospital factors.
Results Overall, pulse oximetry was used in 48.8% (64 722/132 737) of all admission cases. Use rose on average with each month of participation in the CIN (OR: 1.11, 95% CI 1.05 to 1.18) but patterns of adoption were highly variable across hospitals suggesting important factors at hospital level influence use of pulse oximetry. Of those with pulse oximetry measurement, 7% (4510/64 722) had hypoxaemia (SpO2 <90%). Across the same period, 8.6% (11 428/132 737) had oxygen prescribed but in 87%, pulse oximetry was either not done or the hypoxaemia threshold (SpO2 <90%) was not met. Lower chest-wall indrawing and other respiratory symptoms were associated with pulse oximetry use at admission and were also associated with oxygen prescription in the absence of pulse oximetry or hypoxaemia.
Conclusion The adoption of pulse oximetry recommended in international guidelines for assessing children with severe illness has been slow and erratic, reflecting system and organisational weaknesses. Most oxygen orders at admission seem driven by clinical and situational factors other than the presence of hypoxaemia. Programmes aiming to implement pulse oximetry and oxygen systems will likely need a long-term vision to promote adoption, guideline development and adherence and continuously examine impact
Natural history of hypertension subtypes in young and middle-age adults.
No full textBACKGROUND:
The evolution of hypertension (HT) subtypes in young-to-middle-age subjects is unclear.
METHODS:
We did a prospective study in 1,141 participants aged 18-45 years from the HARVEST study screened for stage 1 HT, and 101 nonhypertensive subjects of control during a median follow-up of 72.9 months.
RESULTS:
At baseline, 13.8% of the subjects were classified as having isolated systolic HT (ISH), 24.8% as having isolated diastolic HT (IDH), and 61.4% as having systolic-diastolic HT (SDH). All hypertensive groups developed sustained HT (clinic blood pressure > or =140/90 mm Hg from two consecutive visits occurring at least after > or =6 months of observation) more frequently than nonhypertensive subjects (P or =135/85 mm Hg, n = 798), odds ratios were 5.1 (95%CI 3.1-8.2), 5.6 (95%CI 3.2-9.8), and 3.3 (95%CI 1.7-6.3), respectively. In the fully adjusted logistic model, the risk of ambulatory HT was smaller for the ISH than the IDH (P = 0.049) or SDH (P = 0.053) individuals.
CONCLUSIONS:
The present results indicate that young-to-middle-age subjects with ISH have a smaller risk of developing ambulatory HT than either subjects with SDH or IDH. Whether antihypertensive treatment can be postponed for long periods of time in young subjects with mild elevations of clinic systolic BP and low global cardiovascular risk should be examined in further studies
a European multicenter comparative cohort study
No full textFunding Information: AR received personal fees from Maat Pharma, IML received personal fees from MSD, and Gilead. AA received personal fees from Lilly Foundation, and grants from Grifols and Fisher & Paykel. CEL received personal fees from Bayer, Merck, Aerogen, Biomérieux, ThermoFisher Brahms, and Carmat. SN received personal fees from MSD, Bio-Rad, BioMérieux, Gilead, Fisher and Paykel, and Pfizer. All other authors declare no competing interests. Funding Information: This study was supported in part by a grant from the French government through the « Programme Investissement d’Avenir» (I-SITE ULNE) managed by the Agence Nationale de la Recherche (coVAPid project). Prof. Ignacio Martin-Loeches has been supported by SFI (Science Foundation Ireland), Grant Number 20/COV/0038. The funders of the study had no role in the study design, data collection, analysis, or interpretation, writing of the report, or decision to submit for publication. Publisher Copyright: © 2022, The Author(s).Background: Recent multicenter studies identified COVID-19 as a risk factor for invasive pulmonary aspergillosis (IPA). However, no large multicenter study has compared the incidence of IPA between COVID-19 and influenza patients. Objectives: To determine the incidence of putative IPA in critically ill SARS-CoV-2 patients, compared with influenza patients. Methods: This study was a planned ancillary analysis of the coVAPid multicenter retrospective European cohort. Consecutive adult patients requiring invasive mechanical ventilation for > 48 h for SARS-CoV-2 pneumonia or influenza pneumonia were included. The 28-day cumulative incidence of putative IPA, based on Blot definition, was the primary outcome. IPA incidence was estimated using the Kalbfleisch and Prentice method, considering extubation (dead or alive) within 28 days as competing event. Results: A total of 1047 patients were included (566 in the SARS-CoV-2 group and 481 in the influenza group). The incidence of putative IPA was lower in SARS-CoV-2 pneumonia group (14, 2.5%) than in influenza pneumonia group (29, 6%), adjusted cause-specific hazard ratio (cHR) 3.29 (95% CI 1.53–7.02, p = 0.0006). When putative IPA and Aspergillus respiratory tract colonization were combined, the incidence was also significantly lower in the SARS-CoV-2 group, as compared to influenza group (4.1% vs. 10.2%), adjusted cHR 3.21 (95% CI 1.88–5.46, p < 0.0001). In the whole study population, putative IPA was associated with significant increase in 28-day mortality rate, and length of ICU stay, compared with colonized patients, or those with no IPA or Aspergillus colonization. Conclusions: Overall, the incidence of putative IPA was low. Its incidence was significantly lower in patients with SARS-CoV-2 pneumonia than in those with influenza pneumonia. Clinical trial registration The study was registered at ClinicalTrials.gov, number NCT04359693.publishersversionpublishe
Antifungal susceptibility profiles of Candida isolates from a prospective survey of invasive fungal infections in Italian intensive care units
No full textThe antifungal susceptibility pattern of 302 Candida isolates collected during an Italian survey on invasive fungal infections in an intensive care setting was investigated. The results were correlated with some epidemiological data and compared with the antifungal profiles obtained in a previous survey. No resistance to echinocandins was detected. The overall resistance levels to fluconazole, posaconazole and voriconazole were 12.6, 6.0 and 7.1 %, respectively. Candida tropicalis and Candida parapsilosis accounted for more than half of all the fluconazole resistant isolates. Reduced susceptibility to fluconazole is not uncommon among isolates (12.3 %) and appears to be increasing, particularly among C. parapsilosis isolates, which showed an increase in resistant isolates from 2 % in the 1990s to 25.8 % in the present study. Routine antifungal susceptibility testing of this species is therefore recommended
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