9 research outputs found
Diverticulitis with abscess formation: Outcomes of non-operative management and nomogram for predicting emergency surgery: The Diplicab Study Collaborative Group.
No full text20.500.12530/87909To assess short- and long-term outcomes from non-surgical management of diverticulitis with abscess formation and to develop a nomogram to predict emergency surgery. This nationwide retrospective cohort study was performed in 29 Spanish referral centers, including patients with a first episode of a diverticular abscess (modified Hinchey Ib-II) from 2015 to 2019. Emergency surgery, complications, and recurrent episodes were analyzed. Regression analysis was used to assess risk factors, and a nomogram for emergency surgery was designed. Overall, 1,395 patients were included (1,078 Hinchey Ib and 317 Hinchey II). Most (1,184, 84.9%) patients were treated with antibiotics without percutaneous drainage, and 194 (13.90%) patients required emergency surgery during admission. Percutaneous drainage (208 patients) was associated with a lower risk of emergency surgery in patients with abscesses of ≥5 cm (19.9% vs 29.3%, P = .035; odds ratio 0.59 [0.37-0.96]). The multivariate analysis showed that immunosuppression treatment, C-reactive protein (odds ratio: 1.003; 1.001-1.005), free pneumoperitoneum (odds ratio: 3.01; 2.04-4.44), Hinchey II (odds ratio: 2.15; 1.42-3.26), abscess size 3 to 4.9 cm (odds ratio: 1.87; 1.06-3.29), abscess size ≥5 cm (odds ratio: 3.62; 2.08-6.32), and use of morphine (odds ratio: 3.68; 2.29-5.92) were associated with emergency surgery. A nomogram was developed with an area under the receiver operating characteristic curve of 0.81 (95% confidence interval: 0.77-0.85). Percutaneous drainage must be considered in abscesses ≥5 cm to reduce emergency surgery rates; however, there are insufficient data to recommend it in smaller abscesses. The use of the nomogram could help the surgeon develop a targeted approach
Global variation in postoperative mortality and complications after cancer surgery : a multicentre, prospective cohort study in 82 countries
No full textBackground 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov, NCT03471494. Findings Between April 1, 2018, and jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3.72, 95% CI 1.70-8.16) and for colorectal cancer in low-income or lower-middle-income countries (4.59, 2.39-8.80) and upper-middle-income countries (2.06,1.11-3.83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6.15, 3.26-11.59) and upper-middle-income countries (3.89, 2- 08-7- 29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.Peer reviewe
Guanosine protects against reperfusion injury in rat brain after ischemic stroke
No full textAfter ischemic stroke, early thrombolytic therapy to reestablish tissue perfusion improves outcome but triggers a cascade of deleterious cellular and molecular events. Using a collaborative approach, our groups examined the effects of guanosine (Guo) in response to ischemic reperfusion injury in vitro and in vivo. In a transient middle cerebral artery occlusion (MCAO) in rats, Guo significantly reduced infarct volume in a dose-dependent manner when given systemically either immediately before or 30 min, but not 60 min, after the onset of the 5.5-hr reperfusion period. In a separate experiment, Guo significantly reduced infarct volume after 24 hr of reperfusion when administered 5 min before reperfusion. Western blot analysis did not reveal any significant changes either in endoplasmic reticulum (ER) stress proteins (GRP 78 and 94) or HSP 70 or in levels of m-calpain. In vitro oxygen and glucose deprivation (OGD) significantly increased production of both reactive oxygen species (ROS) and interleukin-8 (IL-8) in the primary astrocytes. Guo did not alter ROS or IL-8 production when given to the astrocytes before OGD. However, Guo when added to the cells prior to or 30 min after reperfusion significantly reduced IL-8 release but not ROS formation. Our study revealed a dose- and time-dependent protective effect of Guo on reperfusion injury in vitro and vivo. The mechanisms by which Guo exerts its effect are independent of unfolded proteins in ER or the level of intracellular calcium or ROS formation. However, the effect may be induced, at least partially, by inhibiting IL-8, a marker of reperfusion-triggered proinflammatory events. © 2012 Wiley Periodicals, Inc.
Nearly 80% of strokes are caused by occlusion of the middle cerebral artery (MCA) by a thrombus. Thus, effective stroke therapies require recanalization of occluded cerebral blood vessels. During cerebral ischemia, cerebral blood flow (CBF) is reduced by the occlusion of blood vessels that supply vital oxygen to brain tissues. Reperfusion strategies (i.e., early intravenous thrombolytic therapy) to reestablish tissue perfusion in order to reduce neurological deficits and improve functional outcome have been the most effective therapies (The National Institute of Neurological Disorders and Stroke, 1995; Hacke et al., 2008; Fisher, 2011). However, reperfusion of ischemic brain tissue can also have harmful consequences, including breakdown of the blood–brain barrier, which can lead to cerebral edema and/or brain hemorrhage as well as neurovascular injury and neuronal death. In the acute phase of reperfusion injury (within the first 6 hr), reperfusion after ischemia causes oxidative stress, which is the result of overproduction of reactive oxygen species (ROS) in mitochondria. This, in turn, triggers many cellular and molecular events, including protein oxidation, lipid peroxidation, and DNA damage, which can induce cell death (Sugawara and Chan, 2003; Saito et al., 2005; Jung et al., 2010). Reperfusion injury also recruits large numbers of inflammatory cells and causes other cellular and molecular cascades (Kidwell et al., 2000; Li et al., 2000; Warach and Latour, 2004). The complications resulting from reperfusion injury reduce the effectiveness of thrombolytic therapy, hence the narrow therapeutic window (within 4–6 hr following stroke onset) of many thrombolytics on the market today. This has led to a search for strategies to protect the brain against such injuries or at least to limit these effects. Ultimately, the development of neuroprotective drugs with multiple effects on the ischemic cascade will impede the tissue and cellular consequences of the vascular occlusion and its removal (Endres et al, 2008; Fisher, 2011).
The purine nucleoside guanosine (Guo) has been shown to exist extracellularly and, like adenosine, to be an intercellular messenger demonstrating a plethora of both trophic and neuroprotective effects in vitro and in vivo (Rathbone et al., 1999, 2008; Ciccarelli et al., 2001; Traversa et al., 2002; Di Iorio et al., 2002, 2004; Pettifer et al., 2004, 2007; Moretto et al., 2005, 2009; Jiang et al., 2007, 2008a, b; Tavares et al., 2008; Su et al., 2009; Torres et al., 2010). Interestingly, after focal stroke in rats, Guo is elevated within 2 hr and remains high for 7 days (Uemura et al., 1991). This led to the investigation of the effects of exogenously administered Guo in stroke models, specifically, protection against combined oxygen and glucose deprivation (OGD) in vitro (Chang et al., 2008) and protection against stroke in an ex vivo model (Moretto et al., 2005, 2009), as well as in an in vivo rodent model of permanent ischemic stroke by MCA occlusion (MCAO; Rathbone et al., 2011).
In the present study, our groups collaborated in examining the neuroprotective effects of Guo in response to reperfusion injury using two different in vivo rat models of transient MCAO. We examined the effect of Guo not only on infarct size but also on molecular chaperones such as glucose-regulated proteins (GRP 78 and GRP 94) and the cytosolic heat-inducible protein HSP 70. Their induction has been shown to increase when protein synthesis is interrupted following ischemia, and unfolded proteins accumulate in the lumen of the endoplasmic reticulum (ER) as a result of changes in oxidative status and calcium homeostasis. In addition, the widespread overactivation of glutamate receptors in response to focal ischemia can produce a sudden increase in intracellular calcium concentrations, resulting in activation of the cysteine protease m-calpain (Siman and Noszek, 1988; Choi, 1995). Sustained calpain activation can result in cellular apoptosis (Sareen et al., 2007), and inhibition of calpain has been shown to provide neuroprotection in a model of focal ischemia (Hong et al., 1994). Therefore, we investigated the effect of Guo on m-calpain after transient cerebral ischemia. We also examined whether Guo has any effect on ROS formation and the inflammatory events in primary cultured astrocytes after induction of OGD in a model of in vitro reperfusion–ischemia
Repeated centralized multidisciplinary team assessment of resectability, clinical behavior, and outcomes in 1086 Finnish metastatic colorectal cancer patients (RAXO) : A nationwide prospective intervention study
No full textBackground: Resection of colorectal cancer (CRC) metastases provides good survival but is probably underused in real-world practice. Methods: A prospective Finnish nationwide study enrolled treatable metastatic CRC patients. The intervention was the assessment of resectability upfront and twice during first-line therapy by the multidisciplinary team (MDT) at Helsinki tertiary referral centre. The primary outcome was resection rates and survival. Findings: In 2012-2018, 1086 patients were included. Median follow-up was 58 months. Multiple metastatic sites were present in 500 (46%) patients at baseline and in 820 (76%) during disease trajectory. In MDT assessments, 447 (41%) were classified as resectable, 310 (29%) upfront and 137 (18%) after conversion therapy. Sixhundred and ninety curative intent resections or local ablative therapies (LAT) were performed in 399 patients (89% of 447 resectable). Multiple metastasectomies for multisite or later developing metastases were performed in 148 (37%) patients. Overall, 414 liver, 112 lung, 57 peritoneal, and 107 other metastasectomies were performed. Median OS was 80.4 months in R0/1-resected (HR 0.15; CI95% 0.12-0.19), 39.1 months in R2-resected/LAT (0.39; 0.29-0.53) patients, and 20.8 months in patients treated with "systemic therapy alone" (reference), with 5-year OS rates of 66%, 40%, and 6%, respectively. Interpretation: Repeated centralized MDT assessment in real-world metastatic CRC patients generates high resectability (41%) and resection rates (37%) with impressive survival, even when multisite metastases are present or develop later. (C) 2021 The Author(s). Published by Elsevier Ltd.Peer reviewe
Characteristics of Coupling Capacitance Between Signal-Ground TSVs Considering MOS Effect in Silicon Interposers
No full textAlong with extensive applications of through-silicon vias (TSVs) in 3-D systems, such as digital, logic, and memory modules, the accurate modeling of coupling capacitance between the TSVs is becoming indispensable to the signal integrity analysis of the system design. In this paper, the static characteristics of potential, electric field, and charges between signal-ground TSVs in a floating substrate are investigated, and accordingly, the effect of MOS capacitance on the coupling capacitance between signal and ground TSVs is accurately modeled and analyzed for both static and high-frequency situations. Furthermore, the impact of substrate admittance on the capacitance-voltage dependence is explored. Parametric studies are performed to study the effects of different physical and material parameters on the coupling capacitance, which include TSV radius, liner thickness, doping concentration, amount of oxide charges, and work function of TSV filling materials. Based on the proposed model, the nonlinear effect of the coupling capacitance on transient noise is examined and explained.National Basic Research Program of China [2015CB0572]; Importation and Development of High-Caliber Talents Project of Beijing Municipal Institutions, Great Wall Scholar [CITTCD20150320]; National Natural Science Foundation of China [61176102]; Collaborative Project of the National Center for Advanced Packaging, ChinaSCI(E)[email protected]; [email protected]; [email protected]; [email protected]
Telomere length change in a multidomain lifestyle intervention to prevent cognitive decline:a randomized clinical trial
No full textAbstract
Background: Shorter leukocyte telomere length (LTL) is associated with aging and dementia. Impact of lifestyle changes on LTL, and relation to cognition and genetic susceptibility for dementia, has not been investigated in randomized controlled trials (RCTs).
Methods: Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability is a 2-year RCT enrolling 1260 participants at risk for dementia from the general population, aged 60–77 years, randomly assigned (1:1) to multidomain lifestyle intervention or control group. The primary outcome was cognitive change (Neuropsychological Test Battery z-score). Relative LTL was measured using quantitative real-time polymerase chain reaction (trial registration: NCT01041989).
Results: This exploratory LTL substudy included 756 participants (377 intervention, 379 control) with baseline and 24-month LTL measurements. The mean annual LTL change (SD) was −0.016 (0.19) in the intervention group and −0.023 (0.17) in the control group. Between-group difference was nonsignificant (unstandardized β-coefficient 0.007, 95% CI −0.015 to 0.030). Interaction analyses indicated better LTL maintenance among apolipoprotein E (APOE)-ε4 carriers versus noncarriers: 0.054 (95% CI 0.007 to 0.102); younger versus older participants: −0.005 (95% CI −0.010 to −0.001); and those with more versus less healthy lifestyle changes: 0.047 (95% CI 0.005 to 0.089). Cognitive intervention benefits were more pronounced among participants with better LTL maintenance for executive functioning (0.227, 95% CI 0.057 to 0.396) and long-term memory (0.257, 95% CI 0.024 to 0.489), with a similar trend for Neuropsychological Test Battery total score (0.127, 95% CI −0.011 to 0.264).
Conclusions: This is the first large RCT showing that a multidomain lifestyle intervention facilitated LTL maintenance among subgroups of older people at risk for dementia, including APOE-ε4 carriers. LTL maintenance was associated with more pronounced cognitive intervention benefits.
Clinical Trials Registration Number: NCT0104198
Alcohol consumption and gastric cancer risk - A pooled analysis within the StoP Project Consortium
No full textAn association between heavy alcohol drinking and gastric cancer risk has been recently reported, but the issue is still open to discussion and quantification. We investigated the role of alcohol drinking on gastric cancer risk in the “Stomach cancer Pooling (StoP) Project,” a consortium of epidemiological studies. A total of 9,669 cases and 25,336 controls from 20 studies from Europe, Asia and North America were included. We estimated summary odds‐ratios (ORs) and the corresponding 95% confidence intervals (CIs) by pooling study‐specific ORs using random‐effects meta‐regression models. Compared with abstainers, drinkers of up to 4 drinks/day of alcohol had no increase in gastric cancer risk, while the ORs were 1.26 (95% CI, 1.08–1.48) for heavy (>4 to 6 drinks/day) and 1.48 (95% CI 1.29–1.70) for very heavy (>6 drinks/day) drinkers. The risk for drinkers of >4 drinks/day was higher in never smokers (OR 1.87, 95% CI 1.35–2.58) as compared with current smokers (OR 1.14, 95% CI 0.93–1.40). Somewhat stronger associations emerged with heavy drinking in cardia (OR 1.61, 95% CI 1.11–2.34) than in non‐cardia (OR 1.28, 95% CI 1.13–1.45) gastric cancers, and in intestinal‐type (OR 1.54, 95% CI 1.20–1.97) than in diffuse‐type (OR 1.29, 95% CI 1.05–1.58) cancers. The association was similar in strata of H. pylori infected (OR = 1.52, 95% CI 1.16–2.00) and noninfected subjects (OR = 1.69, 95% CI 0.95–3.01). Our collaborative pooled‐analysis provides definite, more precise quantitative evidence than previously available of an association between heavy alcohol drinking and gastric cancer risk.Associazione Italiana per la Ricerca sul Cancro (AIRC), Project no. 16715 (Investigator Grant); Fondazione Italiana per la Ricerca sul Cancro (FIRC); Italian Ministry of Health (Young Researchers) to S.B.; GR-2011–02347943; General Directorate of European and International Relations; FIRC (M.R. received a fellowship); Fundação para a Ciência e a Tecnologia (B.P. received a grant); SFRH/BPD/75918/2011; European Cancer Prevention (ECP) Organizatio
Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy
No full textBackground
The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy.
Methods
In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation.
Results
Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89·6 per cent) compared with that in countries with a middle (753 of 1242, 60·6 per cent; odds ratio (OR) 0·17, 95 per cent c.i. 0·14 to 0·21, P < 0·001) or low (363 of 860, 42·2 per cent; OR 0·08, 0·07 to 0·10, P < 0·001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high‐HDI countries (risk difference −9·4 (95 per cent c.i. −11·9 to −6·9) per cent; P < 0·001), but the relationship was reversed in low‐HDI countries (+12·1 (+7·0 to +17·3) per cent; P < 0·001). In multivariable models, checklist use was associated with a lower 30‐day perioperative mortality (OR 0·60, 0·50 to 0·73; P < 0·001). The greatest absolute benefit was seen for emergency surgery in low‐ and middle‐HDI countries.
Conclusion
Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low‐HDI countries was half that in high‐HDI countries
Evidence for large-scale gene-by-smoking interaction effects on pulmonary function.
No full textBACKGROUND: Smoking is the strongest environmental risk factor for reduced pulmonary function. The genetic component of various pulmonary traits has also been demonstrated, and at least 26 loci have been reproducibly associated with either FEV1 (forced expiratory volume in 1 second) or FEV1/FVC (FEV1/forced vital capacity). Although the main effects of smoking and genetic loci are well established, the question of potential gene-by-smoking interaction effect remains unanswered. The aim of the present study was to assess, using a genetic risk score approach, whether the effect of these 26 loci on pulmonary function is influenced by smoking. METHODS: We evaluated the interaction between smoking exposure, considered as either ever vs never or pack-years, and a 26-single nucleotide polymorphisms (SNPs) genetic risk score in relation to FEV1 or FEV1/FVC in 50 047 participants of European ancestry from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) and SpiroMeta consortia. RESULTS: We identified an interaction (βint = -0.036, 95% confidence interval, -0.040 to -0.032, P = 0.00057) between an unweighted 26 SNP genetic risk score and smoking status (ever/never) on the FEV1/FVC ratio. In interpreting this interaction, we showed that the genetic risk of falling below the FEV 1: /FVC threshold used to diagnose chronic obstructive pulmonary disease is higher among ever smokers than among never smokers. A replication analysis in two independent datasets, although not statistically significant, showed a similar trend in the interaction effect. CONCLUSIONS: This study highlights the benefit of using genetic risk scores for identifying interactions missed when studying individual SNPs and shows, for the first time, that persons with the highest genetic risk for low FEV1/FVC may be more susceptible to the deleterious effects of smoking
