Continuous spinal anesthesia (CSA) has not been widely used for postoperative analgesia, mainly to avoid complications from the subarachnoid injection. Recently, the introduction of low caliber CSA ...catheters (Spinocath(®)), has allowed to decrease anesthetics doses and volumes with good analgesia and reduced complications. The aim of this present study was to compare two concentrations of levobupivacaine administered through CSA for postoperative pain management after major orthopedic surgery. Secondary outcomes were adverse events associated with CSA.
Thirty-two patients were randomized to receive sufentanil 1 mcg/h plus levobupivacaine 0.125%-1 ml/h (Group A0.125) or 0.0625%-2 ml/h (Group B0.0625) for postoperative analgesia through CSA catheter, connected to the elastomeric pump over 48 h. The quality of analgesia was assessed based on pain intensity by Visual Analogic Scale (VAS). Sensory and motor function, hemodynamic, and respiratory parameters were recorded for 96 h after surgery, after which the catheter was removed. In addition, joint mobility was assessed, and any side effects were noted.
VAS score was ≤30 mm in 25 patients. Three patients in Group A0.125 and 4 in Group B0.0625 (NS), received a rescue dose of levobupivacaine. Median VAS in Group A0.125 was lower than in Group B0.0625 on T1 h (8 ± 11 vs 16 ± 11; P < 0.05), and on T4 h (11 ± 8 vs 18 ± 1; P < 0.05). All patients remained hemodynamically stable. There were no significant differences between groups for postoperative joints mobility.
Levobupivacaine at a dose of 1.25 mg/h administered by CSA provides good quality analgesia independent of concentration and solution volume in patients undergoing total knee and hip replacement.
Hip fractures represent one of the most important causes of morbidity and mortality in elderly people. Anxiety and depression affect their quality of life and increase pain severity, and have adverse ...effects on functional recovery. Recent World Health Organization guidelines emphasize that therapeutic regimes need to be individualized and combined with psychological support. This study was launched with the primary endpoint of assessing if and to what extent client-centered therapy affects the perception of pain, reduces anxiety and depression, and increases the quality of life of elderly patients with hip fracture.
Forty patients were admitted to the Orthopedic and Trauma Surgery ward for hip fracture. Patients were randomly divided into two subgroups: (1) case (group C), had to receive patient-centered counseling throughout the hospitalization; and (2) control (group NC), receiving the analgesic treatment without receiving counseling. Short Form-36-item Health Survey Questionnaire, State-Trait Anxiety Inventory, and Hamilton Rating Scale for Depression scores were recorded before any treatment, at discharge, and after 30 days. Pain levels were evaluated by means of Visual Analog Scale every 12 hours during the hospitalization from the day of surgery until day 5.
The hierarchical clustering analysis identified before any treatment were two clusters based on different physical functioning perceptions and role limitations, which were due to physical and emotional problems. Counseling did have a positive impact on quality of life on all patients, but in a more relevant way if patients were low functioning upon admittance to the ward. Anxiety and depression decreased in patients undergoing counseling, and their pain levels were lower than among patients not receiving it.
This study reveals that hip fracture patients can be clustered on the basis of Short Form-36 baseline scores. Counseling affects the evolution of mental and physical status in these patients, and the major benefit is reported in patients whose quality of life perception is worse after the trauma. Decreasing anxiety and depression levels, as well as more satisfying pain management, assessed by means of specific tests, confirm the effectiveness of counseling in elderly patients with hip fracture.
To investigate functional connectivity of the visual resting-state network (V-RSN) in normal-sighted relapsing-remitting multiple sclerosis (RRMS) patients with and without previous optic neuritis ...(ON).
Thirty normal-sighted RRMS patients, 16 without (nON-MS) and 14 with (ON-MS) previous ON, and 15 age- and sex-matched healthy controls (HCs) underwent a neuro-ophthalmologic evaluation, including automated perimetry and retinal nerve fiber layer (RNFL) measurement, as well as an MRI protocol, including structural and resting-state fMRI (RS-fMRI) sequences. Functional connectivity of the V-RSN was evaluated by independent component analysis (ICA). Regional gray matter atrophy was assessed by voxel-based morphometry (VBM). A correlation analysis was performed between RS-fMRI results and clinical, neuro-ophthalmologic, and structural MRI variables.
Compared to HCs, patients with RRMS showed a reduced functional connectivity in the peristriate visual cortex, bilaterally. Compared to nON-MS, ON-MS patients revealed a region of stronger functional connectivity in the extrastriate cortex, at the level of right lateral middle occipital gyrus, as well as a region of reduced functional connectivity at the level of right inferior peristriate cortex. These latter changes correlated with the number of previous ON. All detected V-RSN changes did not colocalize with regional gray matter atrophy.
Normal-sighted RRMS patients show a significant functional disconnection in the V-RSN. RRMS patients recovered from a previous ON show a complex reorganization of the V-RSN, including an increased functional connectivity at the level of extrastriate visual areas.
Hepatocellular carcinoma (HCC) risk stratification in individuals with dysmetabolism is a major unmet need. Genetic predisposition contributes to non-alcoholic fatty liver disease (NAFLD). We aimed ...to exploit robust polygenic risk scores (PRS) that can be evaluated in the clinic to gain insight into the causal relationship between NAFLD and HCC, and to improve HCC risk stratification.
We examined at-risk individuals (NAFLD cohort, n = 2,566; 226 with HCC; and a replication cohort of 427 German patients with NAFLD) and the general population (UK Biobank UKBB cohort, n = 364,048; 202 with HCC). Variants in PNPLA3-TM6SF2-GCKR-MBOAT7 were combined in a hepatic fat PRS (PRS-HFC), and then adjusted for HSD17B13 (PRS-5).
In the NAFLD cohort, the adjusted impact of genetic risk variants on HCC was proportional to the predisposition to fatty liver (p = 0.002) with some heterogeneity in the effect. PRS predicted HCC more robustly than single variants (p <10-13). The association between PRS and HCC was mainly mediated through severe fibrosis, but was independent of fibrosis in clinically relevant subgroups, and was also observed in those without severe fibrosis (p <0.05). In the UKBB cohort, PRS predicted HCC independently of classical risk factors and cirrhosis (p <10-7). In the NAFLD cohort, we identified high PRS cut-offs (≥0.532/0.495 for PRS-HFC/PRS-5) that in the UKBB cohort detected HCC with ~90% specificity but limited sensitivity; PRS predicted HCC both in individuals with (p <10-5) and without cirrhosis (p <0.05).
Our results are consistent with a causal relationship between hepatic fat and HCC. PRS improved the accuracy of HCC detection and may help stratify HCC risk in individuals with dysmetabolism, including those without severe liver fibrosis. Further studies are needed to validate our findings.
By analyzing variations in genes that contribute to fatty liver disease, we developed two risk scores to help predict liver cancer in individuals with obesity-related metabolic complications. These risk scores can be easily tested in the clinic. We showed that the risk scores helped to identify the risk of liver cancer both in high-risk individuals and in the general population.
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•Genetic predisposition to liver fat accumulation predisposes to cirrhosis and HCC.•Hepatic fat promotes carcinogenesis, partly via fibrosis.•Polygenic risk scores may improve HCC risk stratification during dysmetabolism.
Transradial access (TRA) decreased bleeding after coronary interventions compared with femoral access (FA). However, no large study focused on arterial access–related outcomes in patients with acute ...coronary syndromes, although procedure-related bleeding significantly impaired prognosis. The aim was to evaluate access site–related outcomes of patients who underwent an invasive coronary procedure in the PRESTO-ACS Study. The cumulative primary study end point was death or reinfarction during hospitalization and at 1-year follow-up. Secondary end points were in-hospital bleeding and a net clinical outcome (combination of the primary end point and bleeding). Of 1,170 patients studied, 863 underwent a percutaneous coronary procedure using FA, and 307, using TRA. Compared with FA, TRA was associated with higher glycoprotein IIb/IIIa inhibitor use (52% vs 34%; p <0.0001). The in-hospital primary end point was similar between TRA (2.6%) and FA (2.9%; p = 0.79). However, TRA was associated with a significant decrease in bleeding (0.7% vs 2.4%; p = 0.05) and a nonsignificant decrease in net clinical outcome (3.3% vs 4.6%; p = 0.30). At 1-year follow-up, the TRA group had a statistically significant decrease in death or reinfarction (4.9% vs 8.3%; p = 0.05), bleeding (0.7% vs 2.7%; p = 0.03), and net clinical outcome (5.5% vs 9.9%; p = 0.02). In conclusion, in patients with non–ST-elevation acute coronary syndromes, use of TRA was associated with lower bleeding complications and identified patients with better long-term outcomes.
The causes of death within 1 year of hospital admission in patients with non–ST-segment elevation acute coronary syndromes are ill defined, particularly in patients aged ≥75 years. From January 2008 ...through May 2010, we enrolled 645 patients aged ≥75 years with non–ST-segment elevation acute coronary syndromes: 313 in a randomized trial comparing an early aggressive versus an initially conservative approach, and 332, excluded from the trial for specific reasons, in a parallel registry. Each death occurring during 1 year of follow-up was adjudicated by an independent committee. The mean age was 82 years in both study cohorts, and 53% were men. By the end of the follow-up period (median 369 days, interquartile range 345 to 391), 120 patients (18.6%) had died. The mortality was significantly greater in the registry (23.8% vs 13.1%, p = 0.001). The deaths were classified as cardiac in 94% of the cases during the index admission and 68% of the cases during the follow-up period. Eighty-six percent of the cardiac deaths were of ischemic origin. In a multivariate logistic regression model that included the variables present on admission in the whole study population, the ejection fraction (hazard ratio 0.95, 95% confidence interval 0.94 to 0.97; p <0.001), hemoglobin level (hazard ratio 0.85, 95% confidence interval 0.76 to 0.94; p = 0.001), older age (hazard ratio 1.05, 95% confidence interval 1.01 to 1.10, p = 0.010), and creatinine clearance (hazard ratio 0.99, 95% confidence interval 0.97 to 0.99; p = 0.030) were the independent predictors of all-cause death at 1 year. In conclusion, within 1 year after admission for non–ST-segment elevation acute coronary syndromes, most deaths in patients aged ≥75 years have a cardiac origin, mostly owing to myocardial ischemia.
It is debated if acromegalic patients have an increased risk to develop malignancies. The aim of the present study was to assess the standardized incidence ratios (SIRs) of different types of cancer ...in acromegaly on a large series of acromegalic patients managed in the somatostatin analogs era. It was evaluated the incidence of cancer in an Italian nationwide multicenter cohort study of 1512 acromegalic patients, 624 men and 888 women, mean age at diagnosis 45 ± 13 years, followed up for a mean of 10 years (12573 person-years) in respect to the general Italian population. Cancer was diagnosed in 124 patients, 72 women and 52 men. The SIRs for all cancers was significantly increased compared to the general Italian population (expected: 88, SIR 1.41; 95% CI, 1.18-1.68,
< 0.001). In the whole series, we found a significantly increased incidence of colorectal cancer (SIR 1.67; 95% CI, 1.07-2.58,
= 0.022), kidney cancer (SIR 2.87; 95% CI, 1.55-5.34,
< 0.001) and thyroid cancer (SIR 3.99; 95% CI, 2.32-6.87,
< 0.001). The exclusion of 11 cancers occurring before diagnosis of acromegaly (all in women) did not change remarkably the study outcome. In multivariate analysis, the factors significantly associated with an increased risk of malignancy were age and family history of cancer, with a non-significant trend for the estimated duration of acromegaly before diagnosis. In conclusion, we found evidence that acromegaly in Italy is associated with a moderate increase in cancer risk.
Non-alcoholic fatty liver disease (NAFLD) is the leading cause of liver disorders and has a strong heritable component. The aim of this study was to identify new loci that contribute to severe NAFLD ...by examining rare variants.
We performed whole-exome sequencing in individuals with NAFLD and advanced fibrosis or hepatocellular carcinoma (n = 301) and examined the enrichment of likely pathogenic rare variants vs. the general population. This was followed by validation at the gene level.
In patients with severe NAFLD, we observed an enrichment of the p.P426L variant (rs143545741 C>T; odds ratio OR 5.26, 95% CI 2.1-12.6; p = 0.003) of autophagy-related 7 (ATG7), which we characterized as a loss-of-function, vs. the general population, and an enrichment in rare variants affecting the catalytic domain (OR 13.9; 95% CI 1.9-612; p = 0.002). In the UK Biobank cohort, loss-of-function ATG7 variants increased the risk of cirrhosis and hepatocellular carcinoma (OR 3.30; 95% CI 1.1-7.5 and OR 12.30, 95% CI 2.6-36, respectively; p <0.001 for both). The low-frequency loss-of-function p.V471A variant (rs36117895 T>C) was also associated with severe NAFLD in the clinical cohort (OR 1.7; 95% CI 1.2-2.5; p = 0.003), predisposed to hepatocellular ballooning (p = 0.007) evolving to fibrosis in the Liver biopsy cohort (n = 2,268), and was associated with liver injury in the UK Biobank (aspartate aminotransferase levels, p <0.001), with a larger effect in severely obese individuals in whom it was linked to hepatocellular carcinoma (p = 0.009). ATG7 protein localized to periportal hepatocytes, particularly in the presence of ballooning. In the Liver Transcriptomic cohort (n = 125), ATG7 expression correlated with suppression of the TNFα pathway, which was conversely upregulated in p.V471A carriers.
We identified rare and low-frequency ATG7 loss-of-function variants that promote NAFLD progression by impairing autophagy and facilitating ballooning and inflammation.
We found that rare mutations in a gene called autophagy-related 7 (ATG7) increase the risk of developing severe liver disease in individuals with dysmetabolism. These mutations cause an alteration in protein function and impairment of self-renewal of cellular content, leading to liver damage and inflammation.
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•NAFLD is the leading cause of liver disorders and has a strong heritable component.•Rare loss-of-function ATG7 gene mutations increase the risk of severe liver disease in patients with NAFLD.•ATG7 mutations cause altered protein function and impairment of autophagy, leading to hepatocellular ballooning and inflammation.•The most frequent variant is responsible for a meaningful fraction of predisposition to ballooning and hepatocellular carcinoma.