Search

PURPOSE:We studied the current management trends for extraperitoneal bladder injuries and evaluated the use of operative repair versus catheter drainage, and the associated complications with each approach. MATERIALS AND METHODS:We prospectively collected data on bladder trauma from 20 level 1 trauma centers across the United States from 2013 to 2018. We excluded patients with intraperitoneal bladder injury and those who died within 24 hours of hospital arrival. We separated patients with extraperitoneal bladder injuries into 2 groups (catheter drainage vs operative repair) based on their initial management within the first 4 days and compared the rates of bladder injury related complications among them. Regression analyses were used to identify potential predictors of complications. RESULTS:From 323 bladder injuries we included 157 patients with extraperitoneal bladder injuries. Concomitant injuries occurred in 139 (88%) patients with pelvic fracture seen in 79%. Sixty-seven patients (43%) initially underwent operative repair for their extraperitoneal bladder injuries. The 3 most common reasons for operative repair were severity of injury or bladder neck injury (40%), injury found during laparotomy (39%) and concern for pelvic hardware contamination (28%). Significant complications were identified in 23% and 19% of the catheter drainage and operative repair groups, respectively (p=0.55). The only statistically significant predictor for complications was bladder neck or urethral injury (RR 2.69, 95% 1.21-5.97, p=0.01). CONCLUSIONS:In this large multi-institutional cohort, 43% of patients underwent surgical repair for initial management of extraperitoneal bladder injuries. We found no significant difference in complications between the initial management strategies of catheter drainage and operative repair. The most significant predictor for complications was concomitant urethral or bladder neck injury.

ObjectiveIntravenous acetaminophen/paracetamol (APAP) is well documented to cause hypotension. Since the patients receiving intravenous APAP are usually critically ill, any severe hemodynamic changes, as with those associated with APAP, can be life-threatening. The mechanism underlying this dangerous iatrogenic effect of APAP was unknown. Approach and Results: Here, we show that intravenous APAP caused transient hypotension in rats, which was attenuated by the Kv7 channel blocker, linopirdine. APAP metabolite N-acetyl-p-benzoquinone imine caused vasodilatation of rat mesenteric arteries ex vivo. This vasodilatation was sensitive to linopirdine and also the calcitonin gene-related peptide antagonist, BIBN 4096. Further investigation revealed N-acetyl-p-benzoquinone imine stimulates calcitonin gene-related peptide release from perivascular nerves, causing a cAMP-dependent activation of Kv7 channels. We also show that N-acetyl-p-benzoquinone imine enhances Kv7.4 and Kv7.5 channels overexpressed in oocytes, suggesting that it can activate Kv7.4 and Kv7.5 channels directly, to elicit vasodilatation.ConclusionsDirect and indirect activation of Kv7 channels by the APAP metabolite N-acetyl-p-benzoquinone imine decreases arterial tone, which can lead to a drop in blood pressure. Our findings provide a molecular mechanism and potential preventive intervention for the clinical phenomenon of intravenous APAP-dependent transient hypotension.

The cardiac conduction system in large carnivores, such as the African lion (Panthera leo), represents a significant knowledge gap in both veterinary science and in cardiac electrophysiology. Short QT intervals have been reported from zoo‐kept, anaesthetized lions, and our goal was to record the first ECGs from wild, conscious lions roaming freely, and compare them to zoo‐kept lions under the hypothesis that short QT is unique to zoo‐kept lions. Macroscopic and histological examinations were performed on heart tissue removed from nine healthy zoo lions. ECGs were recorded from the nine anaesthetized zoo‐kept lions, and from 15 anaesthetized and conscious wild lions in Africa. Our histological and topographical description of the lion's heart matched what has previously been published. In conscious lions, the ECG recordings revealed a mean heart rate of 70 ± 4 beats/min, with faster heart rates during the night. PQ and QT intervals were heart rate dependent in the conscious lions. Interestingly, QT intervals recorded in wild lions were markedly longer than QT intervals from zoo lions (398 ± 40 vs. 297 ± 9 ms, respectively; P < 0.0001). Anaesthesia or heart rate did not account for this difference. We provide a comprehensive description of the cardiac anatomy and electrophysiology of wild and zoo‐kept lions. QT intervals were significantly shorter in zoo lions, suggesting functional disparities in cardiac electrophysiology between wild and zoo‐kept lions, potentially related to physical fitness. These findings underscore the plasticity of cardiac electrophysiology and may be of value when reintroducing endangered species into the wild and when managing lions in human care. What is the central question of this study?How do electrocardiograms from zoo lions and free‐roaming wild lions compare?What is the main finding and its importance?QT intervals in zoo lions are shorter compared to wild lions, which may be relevant for our understanding of animals in human care and may influence conservation strategies. [ABSTRACT FROM AUTHOR]

: Amplification of the EGFR gene and its truncation mutant EGFRvIII are hallmarks of glioblastoma. Although coexpression of EGFR and EGFRvIII confers a growth advantage, how EGFR and EGFRvIII influence the tumor microenvironment remains incompletely understood. Here, we show that EGFR and EGFRvIII cooperate to induce macrophage infiltration via upregulation of the chemokine CCL2. EGFRvIII was significantly enriched in glioblastoma patient samples with high CCL2, and knockout of CCL2 in tumors coexpressing EGFR and EGFRvIII led to decreased infiltration of macrophages. KRAS was a critical signaling intermediate for EGFR- and EGFRvIII-induced expression of CCL2. Our results illustrate how EGFR and EGFRvIII direct the microenvironment in glioblastoma. SIGNIFICANCE: Full-length EGFR and truncated EGFRvIII work through KRAS to upregulate the chemokine CCL2 and drive macrophage infiltration in glioblastoma.

BackgroundThe rarity of renal trauma limits its study and the strength of evidence-based guidelines. Although management of renal injuries has shifted toward a nonoperative approach, nephrectomy remains the most common intervention for high-grade renal trauma (HGRT). We aimed to describe the contemporary management of HGRT in the United States and also evaluate clinical factors associated with nephrectomy after HGRT.MethodsFrom 2014 to 2017, data on HGRT (American Association for the Surgery of Trauma grades III-V) were collected from 14 participating Level-1 trauma centers. Data were gathered on demographics, injury characteristics, management, and short-term outcomes. Management was classified into three groups-expectant, conservative/minimally invasive, and open operative. Descriptive statistics were used to report management of renal trauma. Univariate and multivariate logistic mixed effect models with clustering by facility were used to look at associations between proposed risk factors and nephrectomy.ResultsA total of 431 adult HGRT were recorded; 79% were male, and mechanism of injury was blunt in 71%. Injuries were graded as III, IV, and V in 236 (55%), 142 (33%), and 53 (12%), respectively. Laparotomy was performed in 169 (39%) patients. Overall, 300 (70%) patients were managed expectantly and 47 (11%) underwent conservative/minimally invasive management. Eighty-four (19%) underwent renal-related open operative management with 55 (67%) of them undergoing nephrectomy. Nephrectomy rates were 15% and 62% for grades IV and V, respectively. Penetrating injuries had significantly higher American Association for the Surgery of Trauma grades and higher rates of nephrectomy. In multivariable analysis, only renal injury grade and penetrating mechanism of injury were significantly associated with undergoing nephrectomy.ConclusionExpectant and conservative management is currently utilized in 80% of HGRT; however, the rate of nephrectomy remains high. Clinical factors, such as surrogates of hemodynamic instability and metabolic acidosis, are associated with nephrectomy for HGRT; however, higher renal injury grade and penetrating trauma remain the strongest associations.Level of evidencePrognostic/epidemiologic study, level III; Therapeutic study, level IV.

The geotectonic setting for plumasite-type corundum occurrences is understudied, even though it is of importance for the understanding of trace-element patterns used for fingerprinting of ruby and sapphire. Mineral reactions related to metasomatism caused by pegmatite intrusion into ultramafic rock result in a characteristic trace element signature in corundum and thereby control its colour. The Nattivit area, Isertoq Terrane, South-East Greenland, provides a natural laboratory to investigate these mineral reactions and corundum trace element patterns given the excellent exposure of a typical plumasite-type occurrence where pegmatites intruded ultramafic rocks of different composition, namely lherzolite and dunite. The pegmatite dykes are 10 to 50 cm wide in the ultramafic rocks, whereas the adjacent alteration zone in the ultramafic rock reaches widths between 10 and 30 cm. Metasomatism resulted in desilication of the pegmatites and a decrease in Ca, Mg, K, Mn, Al and Fe away from the centre of the pegmatite dyke. Chromium, Ni, Mg, Fe, Sc, Co, V, Zn, Ti and Mn in the metasomatic reaction zones are predominantly derived from the ultramafic rock. We identify three zones with different mineral assemblages. In the lherzolite, tschermakite and biotite are formed in the centre of the reaction zone, which is followed by anorthite-rich plagioclase, hercynite, dolomite and ultimately pink corundum that occurs in the most heavily reacted part of the metasomatic reaction zone. The metasomatic reaction zones in the ultramafic rock include an intense reaction zone at direct contact to the pegmatite dyke with biotite and actinolite, and two alteration zones further away from the pegmatite dyke with enstatite, actinolite, anthophyllite, phlogopite, dolomite, sulphide, apatite and chrome-spinel. In the dunite, no biotite formed and hence, corundum contains more Fe, Mg and Ti. The plumasite-type corundum from Nattivit contains more Fe than Cr, which is typical of pink corundum hosted in mafic-ultramafic rocks. The corundum-forming reaction is dated from the pegmatite vein to 1843 ± 4 Ma (U–Pb zircon age), which is coinciding with convergence of the Rae and North Atlantic cratons resulting in the Nagssugtoqidian Orogen. Only syn-tectonic, corundum-normative, peraluminous, calc-alkaline pegmatites of granitic to granodioritic composition that intrude into ultramafic rocks in the upper plate formed corundum in this area. The pegmatites are classified as muscovite class granitic pegmatites and intruded at upper amphibolite facies conditions. These pegmatites possible originated from partial melting of mafic granulite or a subducted oceanic plate. The formation of granitic pegmatites and related corundum mineralization in the upper plate of a collisional orogen described here is comparable to other corundum occurrences, e.g. Polar Urals, and thus is regarded as a typical geotectonic setting for plumasite-type corundum. [ABSTRACT FROM AUTHOR]

Background Direct-to-implant breast reconstruction (DIR) is becoming more and more accepted. There is a lack of high-quality studies assessing differences in patient-reported quality of life (QoL) between different implant placement methods. The aim of this randomized controlled (clinical) trial was to compare QoL between women reconstructed by sub- or prepectoral implant placement. Methods We included women over 18 years eligible for DIR. Patients were randomly assigned to reconstruction by subpectoral or prepectoral implant placement. Assessment of QoL and patient satisfaction was made using the BREAST-Q questionnaire for postmastectomy breast reconstruction and compared between the sub- and prepectoral reconstructed groups preoperatively and after 3 and 12 months of follow-up. Results A total of 42 women were allocated to sub- or prepectoral reconstruction with 21 patients in each group. There were no differences in patient characteristics between groups. Regarding all the selected BREAST-Q scales: (1) satisfaction with the reconstructed breast, (2) satisfaction with the breast implant, (3) satisfaction with the overall outcome, (4) psychosocial well-being, (5) sexual well-being, and (6) physical well-being—we found no significant differences between the two groups. Assessing each group independently we found, that in both groups sexual well-being improved after surgery postoperatively compared to the preoperative scores. Conclusion We found high satisfaction and QoL following both sub- and prepectoral breast reconstruction. We found no significant differences between groups suggesting both methods for DIR can be used. Despite our high-quality data, a larger sample size and longer postoperative follow-up are needed to further investigate the differences in QoL between sub- and prepectoral breast reconstruction. [ABSTRACT FROM AUTHOR]

The article discusses the debate among cardiologists and veterinarians regarding the susceptibility of kangaroos to fatal ventricular arrhythmias. While previous studies suggested kangaroos were prone to such arrhythmias, new research conducted on Eastern grey kangaroos found that despite their short QT intervals, they were resistant to pacing-induced ventricular fibrillation. The study concluded that the kangaroo heart does not possess a vulnerable substrate for ventricular arrhythmias, contrary to previous beliefs. [Extracted from the article]

The ability to mount a strong immune response against pathogens is crucial for mammalian survival. However, excessive and uncontrolled immune reactions can lead to autoimmunity. Unraveling how the reactive versus tolerogenic state is controlled might point toward novel therapeutic strategies to treat autoimmune diseases. The surface receptor Toso/Faim3 has been linked to apoptosis, IgM binding, and innate immune responses. In this study, we used Toso-deficient mice to investigate the importance of Toso in tolerance and autoimmunity. We found that Toso(-/-) mice do not develop severe experimental autoimmune encephalomyelitis (EAE), a mouse model for the human disease multiple sclerosis. Toso(-/-) dendritic cells were less sensitive to Toll-like receptor stimulation and induced significantly lower levels of disease-associated inflammatory T-cell responses. Consistent with this observation, the transfer of Toso(-/-) dendritic cells did not induce autoimmune diabetes, indicating their tolerogenic potential. In Toso(-/-) mice subjected to EAE induction, we found increased numbers of regulatory T cells and decreased encephalitogenic cellular infiltrates in the brain. Finally, inhibition of Toso activity in vivo at either an early or late stage of EAE induction prevented further disease progression. Taken together, our data identify Toso as a unique regulator of inflammatory autoimmune responses and an attractive target for therapeutic intervention.