Impaired lymph node stromal cell function during the earliest phases of rheumatoid arthritis.

BACKGROUND: Systemic autoimmunity can be present years before clinical onset of rheumatoid arthritis (RA). Adaptive immunity is initiated in lymphoid tissue where lymph node stromal cells (LNSCs) regulate immune responses through their intimate connection with leucocytes. We postulate that malfunctioning of LNSCs creates a microenvironment in which normal immune responses are not properly controlled, possibly leading to autoimmune disease. In this study we established an experimental model for studying the functional capacities of human LNSCs during RA development. METHODS: Twenty-four patients with RA, 23 individuals positive for autoantibodies but without clinical disease (RA risk group) and 14 seronegative healthy control subjects underwent ultrasound-guided inguinal lymph node (LN) biopsy. Human LNSCs were isolated and expanded in vitro for functional analyses. In analogous co-cultures consisting of LNSCs and peripheral blood mononuclear cells, αCD3/αCD28-induced T-cell proliferation was measured using carboxyfluorescein diacetate succinimidyl ester dilution. RESULTS: Fibroblast-like cells expanded from the LN biopsy comprised of fibroblastic reticular cells (gp38+CD31-) and double-negative (gp38-CD31-) cells. Cultured LNSCs stably expressed characteristic adhesion molecules and cytokines. Basal expression of C-X-C motif chemokine ligand 12 (CXCL12) was lower in LNSCs from RA risk individuals than in those from healthy control subjects. Key LN chemokines C-C motif chemokine ligand (CCL19), CCL21 and CXCL13 were induced in LNSCs upon stimulation with tumour necrosis factor-α and lymphotoxin α1β2, but to a lesser extent in LNSCs from patients with RA. The effect of human LNSCs on T-cell proliferation was ratio-dependent and altered in RA LNSCs. CONCLUSIONS: Overall, we developed an experimental model to facilitate research on the role of LNSCs during the earliest phases of RA. Using this innovative model, we show, for the first time to our knowledge, that the LN stromal environment is changed during the earliest phases of RA, probably contributing to deregulated immune responses early in disease pathogenesis

Coiling and clipping of middle cerebral artery aneurysms: a systematic review on clinical and imaging outcome

There is an ongoing debate on the preferred treatment of middle cerebral artery (MCA) aneurysms. The purpose of this study was to assess the clinical and imaging outcomes comparing conventional coiling and clipping of unruptured and ruptured MCA aneurysms. We searched the electronic databases PubMed, EMBASE, and Cochrane from January 1990 to May 2014. 51 studies were included in the analysis. Favorable outcome was reported in 97.0% and 77.1%, and in 97.2% and 72.8% of patients after coiling and clipping of unruptured and ruptured aneurysms, respectively. Death rates were 1.1% and 8.4% after coiling and 0.3% and 14.7% after clipping of unruptured and ruptured aneurysms, respectively. Initial adequate occlusion was obtained in 89.6% and 92.1% after coiling of unruptured and ruptured aneurysms, respectively. Only three studies on clipping reported on aneurysm occlusion during follow-up. Both coiling and clipping are procedures with low mortality and morbidity rates and, although it may seem that coiling is better for ruptured aneurysms and clipping for unruptured aneurysms, no firm conclusions can be drawn due to the variation in study design and lack of standardized reporting on MCA aneurysm treatments. Standardized observational studies from prospectively kept databases are needed to allow stronger conclusions to be drawn on what is the best treatment for MCA aneurysms. Comparable with aneurysms in other locations, a multidisciplinary approach is therefore recommended with selection of treatment modality based on the clinical condition of the patient and the morphological aspects of the aneurys

High-Dose Nadroparin Following Endovascular Aneurysm Treatment Benefits Outcome After Aneurysmal Subarachnoid Hemorrhage

BACKGROUND: Delayed cerebral ischemia (DCI) is one of the major causes of delayed morbidity and mortality in patients with aneurysmal subarachnoid hemorrhage (aSAH). OBJECTIVE: To evaluate the effect of high-dose nadroparin treatment following endovascular aneurysm treatment on the occurrence of DCI and clinical outcome. METHODS: Medical records of 158 adult patients with an aSAH were retrospectively analyzed. Those patients treated endovascularly for their ruptured aneurysm were included in this study. They received either high-dose (twice daily 5700 AxaIE) or low-dose (once daily 2850 AxaIE) nadroparin treatment after occlusion of the aneurysm. Medical charts were reviewed and imaging was scored by 2 independent neuroradiologists. Data with respect to in-hospital complications, peri-procedural complications, discharge location, and mortality were collected. RESULTS: Ninety-three patients had received high-dose nadroparin, and 65 patients prophylactic low-dose nadroparin. There was no significant difference in clinical DCI occurrence between patients treated with high-dose (34%) and low-dose (31%) nadroparin. More patients were discharged to home in patients who received high-dose nadroparin (40%) compared to low-dose (17%; odds ratio [OR] 3.13, 95% confidence interval [95% CI]: 1.36-7.24). Furthermore, mortality was lower in the high-dose group (5%) compared to the low-dose group (23%; OR 0.19, 95% CI: 0.07-0.55), also after adjusting for neurological status on admission (OR 0.21, 95% CI: 0.07-0.63). CONCLUSION: Patients who were treated with high-dose nadroparin after endovascular treatment for aneurysmal SAH were more often discharged to home and showed lower mortality. High-dose nadroparin did not, however, show a decrease in the occurrence of clinical DCI after aSAH. A randomized controlled trial seems warranted

Predicting the need for abdominal hemorrhage control in major pelvic fracture patients: the importance of quantifying the amount of free fluid

In our institution, the computed tomographic (CT) scan has largely replaced the ultrasound for the rapid detection of intraperitoneal free fluid (FF) and abdominal injuries in severely injured patients.We hypothesized that in major pelvic fracture patients, quantifying the size of FF on CT improves the predictive value for the need for abdominal hemorrhage control (AHC). The CT scans of major pelvic fracture (pelvic ring disruption) patients (January 1, 2004, to June 31, 2012) were reviewed for the presence of FF (small, moderate, or large amount) and abdominal injuries. AHC was defined as requiring a surgical intervention for active abdominal bleeding or angiographic embolization for an abdominal arterial injury.Positive predictive value (PPV) and negative predictive value (NPV) (95% confidence interval [CI]) were calculated for all patients and in a subgroup of patients with a high risk for significant hemorrhage (base deficit ≥ 6 mEq/L). Overall, 160 patients were included in the study. Of the 62 FF patients, 26 required AHC (PPV, 42%, 95% CI, 30-55%). Of the 98 patients without FF, none required AHC (NPV, 100%; 95% CI, 95-100%). For a moderate-to-large amount of FF, the PPV and NPV in all patients were 81% (95% CI, 60-93%) and 96% (95% CI, 91-99%), respectively.In the subgroup of 49 high-risk patients (31%), 17 of 26 FF patients required AHC (PPV, 65%; 95% CI, 44-82%), and none of the 23 patients without FF required AHC (NPV, 100%; 95% CI, 82-100%). For a moderate-to-large amount, the PPV and NPV in high-risk patients were 93% (95% CI, 64-100%) and 89% (95% CI, 72-96%), respectively. In major pelvic fracture patients, the predictive value of FF on CT for the need for AHC is closely related to the amount present. A moderate-to-large amount of FF is highly predictive for the presence of abdominal bleeding that requires hemorrhage control. Therapeutic study, level IV; prognostic study, level II

Management of pelvic ring fracture patients with a pelvic "blush" on early computed tomography

BACKGROUND: The sliding computed tomographic (CT) scanner in our trauma resuscitation room can be used early in the assessment of pelvic ring fracture patients. We determined the association between the presence of a pelvic blush on CT scan and the need for pelvic hemorrhage control (PHC). We hypothesized that many pelvic blushes found early in the resuscitation phase can be safely managed without intervention. METHODS: Contrast-enhanced CT scans of pelvic ring fracture (pelvic ring disruption) patients admitted from January 1, 2004, to June 31, 2012, were reviewed for the presence of a pelvic blush. PHC was defined as requiring a surgical or radiologic intervention for pelvic bleeding. A subanalysis was performed in "isolated" pelvic fracture/ blush patients (absence of a major nonpelvic bleeding source). RESULTS: Overall, 68(42%) of 162 pelvic ring fracture patients and 53 (40%) of 134 isolated pelvic fracture patients had a pelvic blush. Of those 32 (47%) and 27 (51%) patients, respectively, required PHC. In the absence of a pelvic blush, 87 (93%) of 94 of all and 77 (95%) of 81 of isolated pelvic fracture patients did not require PHC. Of all patients with a pelvic blush and of isolated pelvic blush, those with PHC had a higher Injury Severity Score (ISS) (p = 0.01 and p = 0.05), base deficit (p = 0.03 and p = 0.01), as well as 24-hour and any packed red blood cells requirement (p <0.001 and p = 0.05; p <0.001 and p = 0.02). In isolated pelvic blush patients, there was a trend toward a higher hospital and hemorrhage-related mortality in patients with PHC (p = 0.06 and p = 0.06). CONCLUSION: In pelvic ring fracture patients, a pelvic blush on early contrast-enhanced CT is a frequent finding. Many patients with (particularly isolated) pelvic blushes have stable vital signs and can be managed without surgical or radiologic PHC. The need for an intervention for a pelvic blush seems to be determined by the presence of clinical signs of ongoing bleeding. Copyright (C) 2014 by Lippincott Williams & Wilkin

Acute Pulmonary Embolism: Effect of a Computer-assisted Detection Prototype on Diagnosis-An Observer Study

Purpose: To assess the effect of a computer-assisted detection (CAD) prototype on observer performance for detection of acute pulmonary embolism (PE) with computed tomographic (CT) pulmonary angiography. Materials and Methods: In this institutional review board-approved retrospective study, six observers with varying experience evaluated 158 PE-negative and 51 PE-positive CT pulmonary angiographic studies (mean age, 57 years; 111 women, 98 men) obtained consecutively during nights and weekends. Observers were asked to determine the presence of PE and to rank their diagnostic confi dence without CAD and subsequently with CAD within a single reading session. Reading time was separately measured for both readings. Reader data were compared with an independent standard established by two readers, with a third in case of discordant results. Statistical evaluation was performed on a per-patient basis by using logistic regression for repeated measurements and Pearson correlation. Results: With CAD, there was a signifi cant increase in readers' sensitivity (P = .014) without loss of specifi city (P = .853) on a per-patient basis. CAD assisted the readers in correcting an initial false-negative diagnosis in 15 cases, with the most proximal embolus at the segmental level in four cases and at the subsegmental level in 11 cases. In eight cases, readers accepted false-positive CAD candidate lesions on scans negative for PE, and in one case, a reader dismissed a true-positive fi nding. Reading time was extended by a mean of 22 seconds with the use of CAD. Conclusion: At the expense of increased reading time, CAD has the potential to increase reader sensitivity for detecting segmental and subsegmental PE without signifi cant loss of specifi city. (C) RSNA, 201

Blood pressure and the risk of rebleeding and delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage

Introduction and objective: Blood pressure is presumably related to rebleeding and delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (aSAH) and could serve as a target to improve outcome. We assessed the associations between blood pressure and rebleeding or DCI in aSAH-patients. Materials and methods: In this observational study in 1167 aSAH-patients admitted to the intensive care unit (ICU), adjusted hazard ratio's (aHR) were calculated for the time-dependent association of blood pressure and rebleeding or DCI. The aHRs were presented graphically, relative to a reference mean arterial pressure (MAP) of 100 mmHg and systolic blood pressure (sBP) of 150 mmHg. Results: A MAP below 100 mmHg in the 6, 3 and 1 h before each moment in time was associated with a decreased risk of rebleeding (e.g. within 6 h preceding rebleeding: MAP = 80 mmHg: aHR 0.30 (95% confidence interval (CI) 0.11–0.80)). A MAP below 60 mmHg in the 24 h before each moment in time was associated with an increased risk of DCI (e.g. MAP = 50 mmHg: aHR 2.59 (95% CI 1.12–5.96)). Conclusions: Our results suggest that a MAP below 100 mmHg is associated with decreased risk of rebleeding, and a MAP below 60 mmHg with increased risk of DCI