Cerebral autoregulation after subarachnoid hemorrhage: comparison of three methods

In patients after subarachnoid hemorrhage (SAH) failure of cerebral autoregulation is associated with delayed cerebral ischemia (DCI). Various methods of assessing autoregulation are available, but their predictive values remain unknown. We characterize the relationship between different indices of autoregulation. Patients with SAH within 5 days were included in a prospective study. The relationship between three indices of autoregulation was analyzed: two indices calculated using spontaneous blood pressure fluctuations, Sxa (based on transcranial Doppler) and TOxa (based on near-infrared spectroscopy); and transient hyperemic response test (THRT) where a brief compression of the common carotid artery is used. The predictive value of indices was assessed using data from the first 5 days. Overall there was only moderate correlation between indices. However, both Sxa and TOxa showed good accuracy in predicting impaired autoregulation evidenced by a negative THRT (area under the curve (AUC): 0.788, 95% CI: 0.723 to 0.854 and AUC: 0.827, 95% CI: 0.769 to 0.885, respectively). All indices proved accurate in predicting DCI when 0- to 5-day data were used (AUC: 0.801, 95% CI: 0.660 to 0.942; AUC: 0.857, 95% CI: 0.731 to 0.984, AUC: 0.796, 95% CI: 0.658 to 0.934 for THRT, Sxa, and TOxa, respectively). Combining all three indices had 100% specificity for predicting DCI. While multiple colinearities exist between the assessed methods, multimodal monitoring of cerebral autoregulation can aid in predicting DCI.     

Oncologic Effectiveness and Safety of Bursectomy in Patients with Advanced Gastric Cancer: A Systematic Review and Updated Meta-Analysis

ABSTRACT

Purpose/Aim: In the past few decades some researchers have questioned whether bursectomy for gastric cancer is essential from an oncological point of view and no consistent recommendations have been proposed. The aim of this systematic review with meta-analysis is to investigate the oncologic effectiveness and safety of bursectomy for the treatment of advanced gastric cancer patients. Materials and Methods: We planned and performed this systematic review and meta-analysis in accordance with Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement and Cochrane Handbook for Systematic Reviews of Intervention. Results: Overall, four studies with a total of 1,340 patients met inclusion criteria. The pooled hazard ratio for overall survival between the bursectomy versus nonbursectomy groups was [HR = 0.85, 95% CI 0.66–1.11, p =.252]. Interestingly, the pooled HR between the two groups in serosa-positive cases subgroup, showed a significant improvement of overall survival rate in favor of bursectomy [HR = 0.72, 95% CI 0.73–0.99, p <.05]. Conclusions: Bursectomy represents a surgical procedure that might be able to improve overall survival in serosa positive gastric cancer patients. However, a definitive conclusion could not be made because of the studies’ methodological limitations. This meta-analysis points to the urgent need of high quality, large-scaled, clinical trials with short- as well as long-term evaluation comparing bursectomy with non bursectomy procedures, in a controlled randomized manner, helping future researches and establishing a modern and tailored approach to gastric cancer.     

Hypercontrols in genotype-phenotype analysis reveal ancestral haplotypes associated with essential hypertension

The angiotensinogen gene locus has been associated with essential hypertension in most populations analyzed to date. Increased plasma angiotensinogen levels have been proposed as an underlying cause of essential hypertension in whites; however, differences in the genetic regulation of plasma angiotensinogen levels have also been reported for other populations. The aim of this study was to analyze the relationship between angiotensinogen gene polymorphisms and haplotypes with plasma angiotensinogen levels and the risk of essential hypertension in the Mexican population. We genotyped 9 angiotensinogen gene polymorphisms in 706 individuals. Four polymorphisms, A-6, C4072, C6309, and G12775, were associated with increased risk, and the strongest association was found for the C6309 allele (χ(2)=23.9; P=0.0000009), which resulted in an odds ratio of 3.0 (95% CI: 1.8-4.9; P=0.000006) in the recessive model. Two polymorphisms, A-20C (P=0.003) and C3389T (P=0.0001), were associated with increased plasma angiotensinogen levels but did not show association with essential hypertension. The haplotypes H1 (χ(2)=8.1; P=0.004) and H5 (χ(2)=5.1; P=0.02) were associated with essential hypertension. Using phylogenetic analysis, we found that haplotypes 1 and 5 are the human ancestral haplotypes. Our results suggest that the positive association between angiotensinogen gene polymorphisms and haplotypes with essential hypertension is not simply explained by an increase in plasma angiotensinogen concentration. Complex interactions between risk alleles suggest that these haplotypes act as "superalleles."     

Can sexual bother after radical prostatectomy be predicted preoperatively? Findings from a prospective national study of the relation between sexual function,activity and bother

What's known on the subject? and What does the study add? Sexual function is often impaired after radical prostatectomy resulting in reduced sexual activity and sexual bother. The main focus in the literature concerning sexual adverse effects has been on erectile dysfunction and impairment of sexual function rather than the actual sexual bother it causes, although the sexual bother is most important to the individual patient's quality of life. The relation between these measures, and in particular preoperative prediction of postoperative sexual bother, has only been studied in a limited way and with varying results. Some studies have found good mental health, low levels of preoperative sexual bother, and higher education to be associated with absence of postoperative sexual bother, but another study could not identify any preoperative predictors of postoperative sexual bother. Severe sexual bother after radical prostatectomy was reported by 64% to 95% of patients 3 years after operation, and the prevalence was associated with the level of pretreatment sexual bother and peroperative nerve preservation. On the other hand, others have reported that only 43% of men have sexual bother 2 years after radical prostatectomy. However, none of these studies stratified patients according to their preoperative sexual activity and most of them were American. It has been shown that American findings concerning sexual bother may not always be valid for non‐American patients due to differing sex role expectations, thus warranting the need for more non‐American studies. This study has shown that two‐thirds of patients experienced sexual bother 1 year after radical prostatectomy. We have identified patients with increased risk of experiencing overall sexual bother postoperatively: those who report preoperative sexual bother, those who are sexually active before radical prostatectomy, and those who display neurotic personality traits. Another important finding is that the proportion of patients who experienced bother relevant to having impaired postoperative sexual function was significantly higher among preoperatively sexually active patients than those who had been inactive. This study adds knowledge that patients' preoperative sexual activity, sexual bother and personality should be taken into account to be able to give individualized information about the risk of experiencing sexual bother after radical prostatectomy. Study Type – Therapy (outcomes research) Level of Evidence 2c

OBJECTIVE

• ? To explore the prevalence and prediction of overall sexual bother (SB) 1 year after radical prostatectomy (RP) in relation to preoperative sexual activity and postoperative sexual function.

PATIENTS AND METHODS

• ? This prospective national study included 453 men who completed the sexual domain of the Expanded Prostate Cancer Index Composite before and 1 year after RP.
• ? Preoperatively the patients were classified as sexually active or inactive based on frequency of intercourse during the previous 4 weeks.
• ? The prevalence of 1‐year SB and the proportion of bothered patients with impaired sexual function were calculated.
• ? Preoperative factors significantly associated with postoperative SB on univariate analysis (P < 0.05) were included in multivariate regression analysis, post‐prostatectomy SB being the dependent variable.

RESULTS

• ? The prevalence of SB increased from 18% preoperatively to 66% at 1 year after RP with a larger proportion of change in the active than the inactive group (59% vs 25%).
• ? The proportion of men reporting postoperative SB related to their impaired sexual function 1 year after RP was significantly higher in the preoperatively sexually active group (83%) compared with the inactive group (63%).
• ? In multivariate analysis preoperative SB, sexual activity and nervousness (neuroticism) significantly predicted postoperative SB with odds ratios of 3.71, 2.11 and 1.57, respectively.

CONCLUSION

• ? Sexual activity and SB the last month before prostatectomy and neuroticism identify men at risk of developing SB 1 year postoperatively. Assessment of preoperative sexual activity and SB should be a part of preoperative counselling.

     

Modulation of the natural killer cell KIR repertoire by cytomegalovirus infection

Patients carrying activating killer cell immunoglobulin‐like receptor (KIR) genes are significantly protected from CMV‐associated complications after solid organ or hematopoietic stem cell transplantation. Whether previous infection with CMV affects NK‐cell function in healthy donors is unknown. We studied the KIR repertoire and alterations of KIR expression after in vitro exposure to CMV in 54 healthy donors. The expression of neither activating nor inhibitory KIRs was different at baseline between 23 seropositive and 31 seronegative donors. However, after co‐culture of NK cells with CMV‐infected fibroblast cells, expression of the inhibitory receptors KIR2DL1 and KIR2DL3 and the activating receptor KIR3DS1 significantly increased in CMV‐seropositive donors. In CMV‐seronegative donors, changes were subtle and restricted to the subset of NK cells expressing NK‐cell group antigen 2C (NKG2C). Expansion of inhibitory KIRs occurred exclusively in donors carrying the cognate HLA class I ligands, whereas the presence of the putative ligand HLA‐Bw4 was not necessary for the expansion of KIR3DS1‐expressing NK cells. Our data show that previous infection with CMV does not alter the resting NK‐cell receptor repertoire, but appears to modify how NK cells respond to re‐exposure to CMV in vitro.     

Foveal regeneration after resolution of cystoid macular edema without and with internal limiting membrane detachment: presumed role of glial cells for foveal structure stabilization

AIM: To document with spectral-domain optical coherence tomography the morphological regeneration of the fovea after resolution of cystoid macular edema (CME) without and with internal limiting membrane (ILM) detachment and to discuss the presumed role of the glial scaffold for foveal structure stabilization. METHODS: A retrospective case series of 38 eyes of 35 patients is described. Of these, 17 eyes of 16 patients displayed foveal regeneration after resolution of CME, and 6 eyes of 6 patients displayed CME with ILM detachment. Eleven eyes of 9 patients displayed other kinds of foveal and retinal disorders associated with ILM detachment. RESULTS: The pattern of edematous cyst distribution, with or without a large cyst in the foveola and preferred location of cysts in the inner nuclear layer or Henle fiber layer (HFL), may vary between different eyes with CME or in one eye during different CME episodes. Large cysts in the foveola may be associated with a tractional elevation of the inner foveal layers and the formation of a foveoschisis in the HFL. Edematous cysts are usually not formed in the ganglion cell layer. Eyes with CME and ILM detachment display a schisis between the detached ILM and nerve fiber layer (NFL) which is traversed by Müller cell trunks. ILM detachment was also found in single eyes with myopic traction maculopathy, macular pucker, full-thickness macular holes, outer lamellar holes, and glaucomatous parapapillary retinoschisis, and in 3 eyes with Müller cell sheen dystrophy (MCSD). As observed in eyes with MCSD, cellophane maculopathy, and macular pucker, respectively, fundus light reflections can be caused by different highly reflective membranes or layers: the thickened and tightened ILM which may or may not be detached from the NFL, the NFL, or idiopathic epiretinal membranes. In eyes with short single or multiple CME episodes, the central fovea regenerated either completely, which included the disappearance of irregularities of the photoreceptor layer lines and the reformation of a fovea externa, or with remaining irregularities of the photoreceptor layer lines. CONCLUSION: The examples of a complete regeneration of the foveal morphology after transient CME show that the fovea may withstand even large tractional deformations and has a conspicuous capacity of structural regeneration as long as no cell degeneration occurs. It is suggested that the regenerative capacity depends on the integrity of the threedimensional glial scaffold for foveal structure stabilization composed of Müller cell and astrocyte processes. The glial scaffold may also maintain the retinal structure after loss of most retinal neurons as in late-stage MCSD.     

Sentinel lymph node status as most important prognostic factor in patients with high-risk cutaneous melanomas (tumour thickness >4.00 mm): outcome analysis from a single institution

Purpose

Sentinel lymph node biopsy (SLNB) is considered the most powerful prognostic indicator of survival in patients with cutaneous melanoma of intermediate thickness (1–4?mm). The use of SLNB in patients with melanoma with a tumour thickness >4.0?mm is still controversial. The purpose of the current study was to determine the prognostic value of SLNB in patients with thick cutaneous melanomas (tumour thickness >4.0?mm) in terms of progression-free survival (PFS) and overall survival (OS).

Methods

A retrospective single-centre study was performed at the Department of Dermatology and Allergy, University of Bonn, and the Department of Nuclear Medicine, University of Bonn, based on data collected between September 2000 and January 2010. A total of 142 patients with cutaneous melanoma of thickness >4.00?mm were identified, and 63 of these patients underwent SLNB.

Results

Of the 63 patients in whom SLNB was performed, 25 (39.7?%) had a positive SLN. Ulceration was more frequent in SLN-positive patients (44?%) than in SLN-negative patients (18.4?%). The mean follow-up time for the 63 patients was 50.7?months. Positive SLN status predicted a significantly reduced life expectancy in the analyses of PFS and OS. In SLN-positive patients 5-year OS was 76?% and in SLN-negative patients was 84.2?% (p?=?0.048). Patients with a combination of ulcerated tumour and positive SLN had the worst prognosis.

Conclusion

On the basis of our follow-up data, SLNB has to be recommended in patients with a tumour thickness >4.00?mm after exclusion of lymph node macrometastases or distant metastases. SLN status is the most significant prognostic factor in this group of patients.