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5% vs. 0.0%, p = 0.041). Discharge to home was less common in myosteatotic patients than in non-myosteatotic patients (47.7% vs. 76.9%, p  less then  0.001) and also in sarcopenic patients than in non-sarcopenic patients (62.7% vs. 75.5%, p = 0.013). Myosteatotic patients had decreased overall survival according to a Kaplan-Meier analysis (p = 0.002) and in the multivariable-adjusted Cox model (HR = 1.6, p = 0.034). CONCLUSIONS Sarcopenia increases the pneumonia and cardiorespiratory complication rates. Sarcopenia and myosteatosis predicts the need for institutional care after colorectal cancer surgery. Sarcopenia and myosteatosis seem to be negative factors for colorectal cancer patients' survival. Myosteatosis is an independent risk factor for poor overall 5-year survival. BACKGROUND Locally recurrent rectal cancer (LRRC) is a complex problem requiring multidisciplinary consultation and specialized surgical care. Given the paucity of published longer-term survival data, skepticism persists regarding the benefit of major extirpative surgery. We investigated ultra-long-term (~15 years) outcomes following radical resection of LRRC and sought relevant clinicopathologic prognostic variables. METHODS A cohort of 52 consecutive patients who underwent resection of LRRC at our institution between 1997 and 2005 were followed with serial exams and imaging up to the point of death, or 30/06/2019. RESULTS Median follow-up time was 16.5 years (9.9-18.3) for patients who were alive at last follow-up; only one patient was lost to follow-up, at 9.9 years. For the entire cohort of 52 patients, disease-specific survival (DSS) at 5, 10, and 15 years following salvage surgery was 41%, 33%, and 31%, respectively. All patients who had distant metastatic disease at the time of LRRC resection (n = 6) subsequently died of cancer, at a median of 21 months (4-46). In those without distant metastases at time of salvage surgery (n = 46), DSS at 5, 10, and 15 years was 47%, 38%, and 35%, respectively, median 60 months. Negative resection margin (R0) was independently predictive of superior outcomes. In patients with M0 disease who had R0 resection (n = 37), DSS at 5, 10 and 15 years was 58%, 47%, and 44%, respectively, median 73 months. No patient developed re-recurrence after 5.5 years. CONCLUSIONS This study demonstrates exceptionally durable long-term cancer-free survival following salvage surgery for LRRC, indicating that cure is possible. BACKGROUND Rectal gastrointestinal stromal tumours (GISTs) are rare tumours. Variability in the management may influence outcome, but there is a lack of understanding regarding contemporary variance in care. A multicenter, international, retrospective cohort study was performed to elucidate characteristics and outcomes of rectal GIST in European practice, with particular reference to surgical approach. METHODS All rectal GIST patients diagnosed between 2009 and 2018 were identified from five European databases. Recurrence free survival (RFS) and overall survival (OS) were estimated using Kaplan-Meier method. Possible confounders were identified using Cox regression analyses. RESULTS From 210 patients, 155 patients had surgery. The three main types of surgery were local tumour resection (LTR, n = 46), low anterior resection (LAR, n = 31) and abdomino-perineal resection (APR, n = 32). Most patients received neoadjuvant (65%) and/or adjuvant imatinib therapy (66%). Local recurrence rate after surgery was 15% and overall recurrence rate 28%. No significant differences were found in terms of RFS nor OS between LTR, LAR and APR. However, locally resected tumours were smaller, while LAR and APR patients more often received perioperative imatinib. General hospitals treated smaller GISTs, offered imatinib less frequently, and had a higher tumour rupture rate. In the multivariate analysis in the group having LTR, APR or LAR, the only significant prognostic factor for local recurrence was higher age (HR 1.06, CI 1.00-1.12, p = 0.048). CONCLUSIONS In European clinical practice for rectal GIST, LTR, LAR and APR have comparable local control. Multimodal approach is higher and tumour rupture less frequent in specialist centres compared to general hospitals. This study investigated the clinicopathological relationship between cognitive dysfunction and Lewy body-related pathology (LRP), and the role of Alzheimer's disease neuropathologic change (ADNC) in affecting this relationship in the Chinese population. A total of 127 brains with antemortem cognition assessment were collected. The postmortem neuropathological classification of LRP and staging of ADNC were evaluated. Pairwise correlation and ordered logistic regression analysis showed that LRP had a moderate correlation with Global Everyday Cognition scores. The proportion of the people with intermediate and high levels of comorbid ADNC increased with the deterioration of LRP. The fit of the cognition prediction model improved when we incorporated both LRP and ADNC into the model compared with LRP alone. Our study indicated that comorbid ADNC can variably present in patients with Lewy body disease. A combination of LRP and concurrent ADNC improves the prediction of cognitive dysfunction compared with LRP alone. These findings may suggest the potential benefit of combined therapeutic approaches targeting concurrent pathological pathways for the Lewy body diseases in the Chinese population. Higher levels of body fat have shown adverse effects on multiple aspects of health, including cognitive and neuroanatomical changes. We tested the relationships of body fat levels and cholesterol to longitudinal age trajectories of subcortical gray matter volume (SCV), hippocampal volume (HCV), and episodic memory. Body fat was indexed by a concerted factor of BMI, visceral adipose tissue, percentage body fat, and total fat mass and was included in the analyses as a cross-sectional measure. We hypothesized that higher level of body fat would be related to steeper age trajectories of SCV, HCV, and memory. The sample consisted of 581 participants (20-83 years) with 942 magnetic resonance imaging and 945 memory examinations. Using generalized additive mixed models, a negative effect of body fat was found on SCV, HCV, and memory. Age and body fat interacted in their association with brain volume change. The results suggest that among cognitively healthy adults, there is a negative effect of higher body fat on SCV, HCV, and memory decline, an effect that increased with age for the neuroanatomical volumes. The etiology and pathogenesis of Parkinson's disease (PD) are tightly linked to the gain-of-function of α-synuclein. However, gradual accumulation of α-synuclein aggregates in dopaminergic neurons of substantia nigra pars compacta (SNpc) leads to the depletion of the functional pool of soluble α-synuclein, and therefore, creates loss-of-function conditions, particularly in presynaptic terminals of these neurons. Studies of how this late-onset depletion of a protein involved in many important steps of neurotransmission contributes to PD progression and particularly, to worsening the nigrostriatal pathology at late stages of the disease are limited and obtained data, are controversial. Recently, we produced a mouse line for conditional knockout of the gene encoding α-synuclein, and here we used its tamoxifen-inducible pan-neuronal inactivation to study consequences of the adult-onset (from the age of 6 months) and late-onset (from the age of 12 months) α-synuclein depletion to the nigrostriatal system. No signio already existing pathology. Cognitive impairments and circadian rhythm disorders are the main clinical manifestations of Alzheimer's disease (AD). Orexin has been reported as abnormally elevated in the cerebrospinal fluid of AD patients, accompanied with cognitive impairments. Our recent research revealed that suvorexant, a dual orexin receptor antagonist, could improve behavioral circadian rhythm disorders in 9-month-old APP/PS1 mice. Here we further observed whether suvorexant could ameliorate the cognitive decline in APP/PS1 mice by using behavioral tests, and investigated the possible mechanisms by in vivo electrophysiological recording, western blot, and immunochemistry. The results showed that suvorexant treatment effectively ameliorated the cognitive impairments, alleviated in vivo hippocampal long-term potentiation suppression, restored the circadian phosphorylated CREB expression in the hippocampus, and reduced amyloid-β protein deposition in the hippocampus and cortex in APP/PS1 mice. These results indicate that the neuroprotective effects of suvorexant against AD are involved in the reduction of amyloid-β plaques, improvement of synaptic plasticity, and circadian expression of phosphorylated CREB, suggesting that suvorexant could be beneficial to the prevention and treatment of AD. Enhanced processing following a warning cue is thought to be mediated by a phasic alerting response involving the locus coeruleus-noradrenergic (LC-NA) system. We examined the effect of aging on phasic alerting using pupil dilation as a marker of LC-NA activity in conjunction with a novel assessment of task-evoked pupil dilation. While both young and older adults displayed behavioral and pupillary alerting effects, reflected in decreased RT and increased pupillary response under high (tone) versus low (no tone) alerting conditions, older adults displayed a weaker pupillary response that benefited more from the alerting tone. The strong association between dilation and speed displayed by older adults in both alerting conditions was reduced in young adults in the high alerting condition, suggesting that in young (but not older) adults the tone conferred relatively little behavioral benefit beyond that provided by the alerting effect elicited by the target. These findings suggest a functioning but deficient LC-NA alerting system in older adults, and help reconcile previous results concerning the effects of aging on phasic alerting. INTRODUCTION To the best of our knowledge, no pediatric paper has been published regarding specifically how to set the HolmiumYAG laser for multiple urologic applications. Santacruzamate A molecular weight OBJECTIVE To provide insight into the laser parameters for pediatric applications. STUDY DESIGN We describe the principle and the settings of the laser. RESULTS The HolmiumYAG laser can produce four different biological effects (1) fragmentation of stones in small fragments that can be retrieved with grasping instruments, thereby increasing the immediate stone-free outcome. For fragmentation lithotripsy, the laser has to be set with a high energy, low frequency and short pulse duration; (2) dusting which produces fine dust that can spontaneously evacuate, avoiding the use of basket retrieval. The dusting setting requires low energy, high frequency and long pulse duration; (3) incision of posterior urethral valves or ureterocele when all settings are maximized high energy, high frequency and long pulse duration; (4) coagulation of urothelial tumors using high frequency, long pulse duration and slightly lower energy than required for incision. DISCUSSION Both dusting by painting and fragmentation with retrieval for ureteroscopic laser lithotripsy are effective. Although dusting tends to be associated with shorter operative times and a lower risk of ureteral trauma, this approach has a potential risk of recurrent stone formation from dust failing to pass. In contrast, fragmentation with extraction may provide for a more immediate postoperative stone-free result. Altering the pulse energy, frequency, width and modulation can help to optimize lithotripsy efficiency. Lower pulse energy settings result in smaller fragments, less retropulsion and reduce fiber tip degradation. A shallow depth of penetration in water and tissue allows precise energy application and provides a margin of safety. CONCLUSION An understanding of Ho-YAG laser settings will permit the pediatric surgeon to make a better use of the device for different urological applications.

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