Evaluation of severe traumatic brain injury referrals to the National Tertiary Neurosurgical Centre in the Republic of Ireland.

BACKGROUND: Transfer of all severe TBI patients to a neurosurgical unit (NSU) has been advocated irrespective of levels of complexity and prognostic factors. Previous publications have suggested that only 50% of severe TBI patients in Ireland were managed in NSUs. AIMS: This study aims to audit severe TBI referrals to the National Neurosurgical Centre, to evaluate reasons for nonacceptance, assess for differences in the transferred and not transferred cohorts and to analyse observed and expected mortality rates. METHODS: Data on all patients with TBI referred in 2021 were prospectively collected using an electronic referral system. Patients with severe TBI (GCS ≤ 8 and AIS ≥ 3) were included and dichotomised into transferred and not transferred cohorts. RESULTS: Of 118 patients referred with severe TBI, 45 patients (38.1%) were transferred to the neurosurgical centre. Patients in the transferred cohort were significantly younger (p < 0.001), had a higher GCS score (p < 0.001) and a lower proportion of bilaterally unreactive pupils (p < 0.001) compared to the not transferred cohort. 93% (68/73) of those not transferred were either >65 years old, or had bilaterally unreactive pupils, or both. Based on the IMPACT model, the observed to expected mortality ratios in the transferred and not transferred cohorts were 0.65 (95% CI 0.25-1.05) and 0.88 (95% CI 0.65-1.11) respectively. CONCLUSION: The observed mortality rate for severe TBI in Ireland was similar to or better than expected mortality rates when adjusted for important prognostic factors. 93% of severe TBI patients not transferred to a neurosurgical centre were either elderly or had bilaterally unreactive pupils or both. These patients have an extremely poor prognosis and recommendation for transfer cannot be made based on current available evidence.

Complications of cranioplasty following decompressive craniectomy for traumatic brain injury: systematic review and meta-analysis.

BACKGROUND: Decompressive craniectomy (DC) is a common neurosurgical intervention for severe traumatic brain injury (TBI), as well as malignant stroke, malignancy and infection. DC necessitates subsequent cranioplasty. There are significant demographic differences between TBI and non-TBI patients undergoing cranioplasty, which may influence their relative risk profiles for infection, aseptic bone flap resorption (aBFR) and re-operation. OBJECTIVE: Perform a meta-analysis to determine the relative infection, aBFR and re-operation risk profiles of TBI patients as compared to other indications for DC. METHODS: A systematic review and meta-analysis was performed in accordance with the PRISMA guidelines. PubMed, MEDLINE, EMBASE and Google Scholar were searched until 26/11/2020. Studies detailing rates of infection, re-operation and/or aBFR in specific materials and the post-TBI population were included, while studies in paediatrics or craniosynostosis repair were excluded. RESULTS: Twenty-six studies were included. There was no difference in relative risk of infection between TBI and non-TBI cohorts (RR 0.81, 95% CI 0.57-1.17), with insignificant heterogeneity (I2 = 33%). TBI was a risk factor for aBFR (RR 1.54, 95% CI 1.25-1.89), with no significant heterogeneity (I2 = 13%). TBI was a risk factor for re-operation in the autologous sub-group (RR 1.49, 95% CI 1.05-2.11) but not in the alloplastic sub-group (RR = 0.86, 95% CI 0.34-2.18). Heterogeneity was insignificant (I2 = 11%). CONCLUSION: TBI is a risk factor for aBFR and re-operation following cranioplasty. Use of an alloplastic graft for primary cranioplasty in these patients may partially mitigate this increased risk.

Highly siderophile elements in Earth's mantle as a clock for the Moon-forming impact.

According to the generally accepted scenario, the last giant impact on Earth formed the Moon and initiated the final phase of core formation by melting Earth's mantle. A key goal of geochemistry is to date this event, but different ages have been proposed. Some argue for an early Moon-forming event, approximately 30 million years (Myr) after the condensation of the first solids in the Solar System, whereas others claim a date later than 50 Myr (and possibly as late as around 100 Myr) after condensation. Here we show that a Moon-forming event at 40 Myr after condensation, or earlier, is ruled out at a 99.9 per cent confidence level. We use a large number of N-body simulations to demonstrate a relationship between the time of the last giant impact on an Earth-like planet and the amount of mass subsequently added during the era known as Late Accretion. As the last giant impact is delayed, the late-accreted mass decreases in a predictable fashion. This relationship exists within both the classical scenario and the Grand Tack scenario of terrestrial planet formation, and holds across a wide range of disk conditions. The concentration of highly siderophile elements (HSEs) in Earth's mantle constrains the mass of chondritic material added to Earth during Late Accretion. Using HSE abundance measurements, we determine a Moon-formation age of 95 ± 32 Myr after condensation. The possibility exists that some late projectiles were differentiated and left an incomplete HSE record in Earth's mantle. Even in this case, various isotopic constraints strongly suggest that the late-accreted mass did not exceed 1 per cent of Earth's mass, and so the HSE clock still robustly limits the timing of the Moon-forming event to significantly later than 40 Myr after condensation.

Traumatic brain injury in the Republic of Ireland twenty-five years on: a comparison of two cohorts from a neurosurgical unit.

OBJECTIVE: We assessed for change in the number of admissions, demographics, mechanism, severity, operative management, length of stay, and in-hospital mortality of Traumatic Brain Injury (TBI) in patients admitted to a Neurosurgical Unit (NSU) in the Republic of Ireland in 2017 compared to 25 years previously. METHOD: We performed a retrospective cohort study of TBI admissions during 2017 and compared the results with a prospective cohort study covering a one-year period across 1992 and 1993. RESULTS: In 2017, 184 patients (5.78 per 100,000) were admitted, compared to 225 in 1992/1993 (7.31 per 100,000). Mean age increased by 8.5 years. The contribution of road traffic collisions (RTCs) decreased by 62% while sports injuries increased by 300%, led by soccer. Falls replaced RTCs as the leading mechanism of injury. We report a decrease in severe injuries (GCS≤8) of 52% while mild injuries (GCS≥13) increased by 58%. The number undergoing neurosurgery remained comparable (2017: 55%, 1992/1993: 48%), as did in-hospital mortality (13%, 16%). Mean length of stay decreased by four days. CONCLUSION: There has been a sizable change in the landscape of TBI as seen in the Republic of Ireland's national NSU including in demographics, mechanism of injury, and injury severity.

A low mass for Mars from Jupiter's early gas-driven migration.

Jupiter and Saturn formed in a few million years (ref. 1) from a gas-dominated protoplanetary disk, and were susceptible to gas-driven migration of their orbits on timescales of only ∼100,000 years (ref. 2). Hydrodynamic simulations show that these giant planets can undergo a two-stage, inward-then-outward, migration. The terrestrial planets finished accreting much later, and their characteristics, including Mars' small mass, are best reproduced by starting from a planetesimal disk with an outer edge at about one astronomical unit from the Sun (1 au is the Earth-Sun distance). Here we report simulations of the early Solar System that show how the inward migration of Jupiter to 1.5 au, and its subsequent outward migration, lead to a planetesimal disk truncated at 1 au; the terrestrial planets then form from this disk over the next 30-50 million years, with an Earth/Mars mass ratio consistent with observations. Scattering by Jupiter initially empties but then repopulates the asteroid belt, with inner-belt bodies originating between 1 and 3 au and outer-belt bodies originating between and beyond the giant planets. This explains the significant compositional differences across the asteroid belt. The key aspect missing from previous models of terrestrial planet formation is the substantial radial migration of the giant planets, which suggests that their behaviour is more similar to that inferred for extrasolar planets than previously thought.

Iron meteorites as remnants of planetesimals formed in the terrestrial planet region.

Iron meteorites are core fragments from differentiated and subsequently disrupted planetesimals. The parent bodies are usually assumed to have formed in the main asteroid belt, which is the source of most meteorites. Observational evidence, however, does not indicate that differentiated bodies or their fragments were ever common there. This view is also difficult to reconcile with the fact that the parent bodies of iron meteorites were as small as 20 km in diameter and that they formed 1-2 Myr earlier than the parent bodies of the ordinary chondrites. Here we show that the iron-meteorite parent bodies most probably formed in the terrestrial planet region. Fast accretion times there allowed small planetesimals to melt early in Solar System history by the decay of short-lived radionuclides (such as 26Al, 60Fe). The protoplanets emerging from this population not only induced collisional evolution among the remaining planetesimals but also scattered some of the survivors into the main belt, where they stayed for billions of years before escaping via a combination of collisions, Yarkovsky thermal forces, and resonances. We predict that some asteroids are main-belt interlopers (such as (4) Vesta). A select few may even be remnants of the long-lost precursor material that formed the Earth.

Timing of Martian Core Formation from Models of Hf-W Evolution Coupled with N-body Simulations.

Determining how and when Mars formed has been a long-standing challenge for planetary scientists. The size and orbit of Mars are difficult to reproduce in classical simulations of planetary accretion, and this has inspired models of inner solar system evolution that are tuned to produce Mars-like planets. However, such models are not always coupled to geochemical constraints. Analyses of Martian meteorites using the extinct hafnium-tungsten (Hf-W) radioisotopic system, which is sensitive to the timing of core formation, have indicated that the Martian core formed within a few million years of the start of the solar system itself. This has been interpreted to suggest that, unlike Earth's protracted accretion, Mars grew to its modern size very rapidly. These arguments, however, generally rely on simplified growth histories for Mars. Here, we combine likely accretionary histories from a large number of N-body simulations with calculations of metal-silicate partitioning and Hf-W isotopic evolution during core formation to constrain the range of conditions that could have produced Mars. We find that there is no strong correlation between the final masses or orbits of simulated Martian analogs and their 182W anomalies, and that it is readily possible to produce Mars-like Hf-W isotopic compositions for a variety of accretionary conditions. The Hf-W signature of Mars is very sensitive to the oxygen fugacity (fO2) of accreted material because the metal-silicate partitioning behavior of W is strongly dependent on redox conditions. The average fO2 of Martian building blocks must fall in the range of 1.3-1.6 log units below the iron-wüstite buffer to produce a Martian mantle with the observed Hf/W ratio. Other geochemical properties (such as sulfur content) also influence Martian 182W signatures, but the timing of accretion is a more important control. We find that while Mars must have accreted most of its mass within ~5 million years of solar system formation to reproduce the Hf-W isotopic constraints, it may have continued growing afterwards for over 50 million years. There is a high probability of simultaneously matching the orbit, mass, and Hf-W signature of Mars even in cases of prolonged accretion if giant impactor cores were poorly equilibrated and merged directly with the proto-Martian core.

Complications of Cranioplasty in Relation to Material: Systematic Review, Network Meta-Analysis and Meta-Regression.

BACKGROUND: Cranioplasty is a ubiquitous neurosurgical procedure consisting of reconstruction of a pre-existing calvarial defect. Many materials are available, including polymethylmethacrylate in hand-moulded (hPMMA) and prefabricated (pPMMA) form, hydroxyapatite (HA), polyetheretherketone (PEEK) and titanium (Ti). OBJECTIVE: To perform a network meta-analysis (NMA) to assess the relationship between materials and complications of cranioplasty. METHODS: PubMed/MEDLINE, Google Scholar, EMBASE, Scopus, and The Cochrane Library were searched from January 1, 1990 to February 14, 2021. Studies detailing rates of any of infections, implant exposure, or revision surgery were included. A frequentist NMA was performed for each complication. Risk ratios (RRs) with 95% CIs were calculated for each material pair. RESULTS: A total of 3620 abstracts were screened and 31 full papers were included. Surgical revision was reported in 18 studies and occurred in 316/2032 cases (14%; 95% CI 11-17). PEEK had the lowest risk of re-operation with a rate of 8/157 (5%; 95% CI 0-11) in 5 studies, superior to autografts (RR 0.20; 95% CI 0.07-0.57), hPMMA (RR 0.20; 95% CI 0.07-0.60), Ti (RR 0.39; 95% CI 0.17-0.92), and pPMMA (RR 0.14; 95% CI 0.04-0.51). Revision rate was 131/684 (19%; 95% CI 13-25; 10 studies) in autografts, 61/317 (18%; 95%CI 9-28; 7 studies) in hPMMA, 84/599 (13%; 95% CI 7-19; 11 studies) in Ti, 7/59 (9%; 95% CI 1-23; 3 studies) in pPMMA, and 25/216 (12%; 95% CI 4-24; 4 studies) in HA. Infection occurred in 463/4667 (8%; 95% CI 6-11) and implant exposure in 120/1651 (6%; 95% CI 4-9). CONCLUSION: PEEK appears to have the lowest risk of cranioplasty revision, but further research is required to determine the optimal material.

Radial mixing and Ru-Mo isotope systematics under different accretion scenarios.

The Ru-Mo isotopic compositions of inner Solar System bodies may reflect the provenance of accreted material and how it evolved with time, both of which are controlled by the accretion scenario these bodies experienced. Here we use a total of 116 N-body simulations of terrestrial planet accretion, run in the Eccentric Jupiter and Saturn (EJS), Circular Jupiter and Saturn (CJS), and Grand Tack scenarios, to model the Ru-Mo anomalies of Earth, Mars, and Theia analogues. This model starts by applying an initial step function in Ru-Mo isotopic composition, with compositions reflecting those in meteorites, and traces compositional evolution as planets accrete. The mass-weighted provenance of the resulting planets reveals more radial mixing in Grand Tack simulations than in EJS/CJS simulations, and more efficient mixing among late-accreted material than during the main phase of accretion in EJS/CJS simulations. We find that an extensive homogenous inner disk region is required to reproduce Earth's observed Ru-Mo composition. EJS/CJS simulations require a homogeneous reservoir in the inner disk extending to ≥3-4 AU (≥74-98% of initial mass) to reproduce Earth's composition, while Grand Tack simulations require a homogeneous reservoir extending to ≥3-10 AU (≥97-99% of initial mass), and likely to ≥6-10 AU. In the Grand Tack model, Jupiter's initial location (the most likely location for a discontinuity in isotopic composition) is ~3.5 AU; however, this step location has only a 33% likelihood of producing an Earth with the correct Ru-Mo isotopic signature for the most plausible model conditions. Our results give the testable predictions that Mars has zero Ru anomaly and small or zero Mo anomaly, and the Moon has zero Mo anomaly. These predictions are insensitive to wide variations in parameter choices.

A serum factor after intestinal resection stimulates epidermal growth factor receptor signaling and proliferation in intestinal epithelial cells.

BACKGROUND: In vivo, intestinal adaptation after massive small bowel resection (SBR) requires a functional epidermal growth factor (EGF) receptor (EGFR). In vitro studies have shown that serum from mice after SBR induces rat intestinal epithelial cells to proliferate. This study tested the hypothesis that the proliferative response to SBR serum is mediated by EGFR signaling. METHODS: Serum was collected from male Sprague-Dawley rats 7 days after 75% SBR or sham operation. Rat intestinal epithelial cells were incubated in the presence of sham or SBR serum. Total EGFR expression and phosphorylation of several EGFR downstream pathways were determined by Western blotting. In other experiments, a specific EGFR inhibitor (ZD1839) was added and cell growth determined over 5 days. RESULTS: SBR serum significantly increased total EGFR expression (3-fold) over sham operation and consistently activated the phosphatidylinositol 3-kinase pathway. Furthermore, SBR serum markedly augmented rat intestinal epithelial cell growth, an effect that was abolished by EGFR inhibition. CONCLUSIONS: SBR serum contains a factor or factors that stimulates proliferation of intestinal epithelial cells by an EGFR and phosphatidylinositol 3-kinase signaling mechanism. These data recapitulate in vivo studies supporting the hypothesis that EGFR is a central mediator of postresection intestinal adaptation. This in vitro model may provide a novel means to gain insight into the pathophysiology of intestinal adaptation.

Pelvic fracture in the elderly is associated with increased mortality.

OBJECTIVE: The elderly population is currently the fastest growing sector in America. The purpose of this study was to examine the age-related outcome in patients after blunt pelvic injury. METHODS: All patients admitted with a pelvic fracture during a 5-year period were identified from the trauma registry. Data retrieval included: demographics, shock (BP < 90 mm Hg) on admission, injury severity score (ISS), abbreviated injury score (AIS) for head, chest, and abdomen, intensive care unit (ICU) length of stay (LOS), hospital LOS, and mortality. All pelvic fracture patterns were classified. Patient data were then stratified by age for comparison: young (< 55 years) and elderly (> or = 55 years). Statistical analysis was performed using the Student t test, Wilcoxon rank-sum test, multiple logistic regression analysis, and chi-square test with significance set at P <.05. RESULTS: Three hundred five patients sustained a pelvic fracture (young [n = 248, 81.3%]; elderly [n = 57, 18.7%]). The only predictor of mortality was age. The 2 groups differed by gender (elderly = 54.4% females; young = 62.5% males) but not frequency of shock, ISS, or AIS for head, chest, and abdomen. Motor vehicle collision was the most common mechanism of injury (elderly = 68.4%; young = 73.8%). Lateral compression was the most common fracture pattern in both groups (elderly = 54.4%; young = 45.6%). There was no difference in transfusion (elderly = 2.5 +/- 0.7 vs young = 2.0 +/- 0.3; ns) but the elderly group was more frequently admitted to the ICU (elderly = 61.4% vs young = 46.8%; P =.065). Significantly more of the elderly group had a diagnosis of cardiovascular disease (43.9% vs 10.1%, P <.001) and diabetes mellitus (10.5% vs 2.4%, P <.014). Mortality was significantly greater in the elderly group (12.3% vs 2.3%). CONCLUSION: Elderly patients sustaining a pelvic fracture were more likely to have a lateral compression fracture pattern, longer hospital LOS, and die despite aggressive resuscitation. This difference in outcome should help trauma surgeons recognize that the elderly patient sustaining a pelvic fracture is at increased risk of death.

Intestinal and hepatic response to combined partial hepatectomy and small bowel resection in mice.

BACKGROUND: Both partial-hepatectomy (PHx) and massive small bowel resection (SBR) are strong mitogenic signals to the remnant liver and intestine, respectively. This study tested the hypothesis that PHx was an additive signal for intestinal adaptation after massive SBR. METHODS: Male mice underwent either sham SBR or 50% proximal SBR. Mice from these two groups were then subjected to a 70% PHx or sham PHx. After 3 days, parameters of intestinal adaptation and liver regeneration were recorded in the remnant intestine and liver, respectively. RESULTS: Intestinal adaptation following SBR occurred normally, but was not enhanced after concomitant PHx. On the other hand, SBR impaired the regenerative ability of the liver following PHx. CONCLUSIONS: Intestinal adaptation after SBR takes priority over liver regeneration after PHx. These data implicate a hierarchy with regard to adaptive alterations to organ loss and endorse an important role for the intestinal mucosa in the regulation of hepatic regeneration.

The geologically recent giant impact basins at Vesta's south pole.

Dawn's global mapping of Vesta reveals that its observed south polar depression is composed of two overlapping giant impact features. These large basins provide exceptional windows into impact processes at planetary scales. The youngest, Rheasilvia, is 500 kilometers wide and 19 kilometers deep and finds its nearest morphologic analog among large basins on low-gravity icy satellites. Extensive ejecta deposits occur, but impact melt volume is low, exposing an unusual spiral fracture pattern that is likely related to faulting during uplift and convergence of the basin floor. Rheasilvia obliterated half of another 400-kilometer-wide impact basin, Veneneia. Both basins are unexpectedly young, roughly 1 to 2 billion years, and their formation substantially reset Vestan geology and excavated sufficient volumes of older compositionally heterogeneous crustal material to have created the Vestoids and howardite-eucrite-diogenite meteorites.

Color and albedo heterogeneity of Vesta from Dawn.

Multispectral images (0.44 to 0.98 µm) of asteroid (4) Vesta obtained by the Dawn Framing Cameras reveal global color variations that uncover and help understand the north-south hemispherical dichotomy. The signature of deep lithologies excavated during the formation of the Rheasilvia basin on the south pole has been preserved on the surface. Color variations (band depth, spectral slope, and eucrite-diogenite abundance) clearly correlate with distinct compositional units. Vesta displays the greatest variation of geometric albedo (0.10 to 0.67) of any asteroid yet observed. Four distinct color units are recognized that chronicle processes--including impact excavation, mass wasting, and space weathering--that shaped the asteroid's surface. Vesta's color and photometric diversity are indicative of its status as a preserved, differentiated protoplanet.

Polyps in the ileal pouch.

Total proctocolectomy and ileal pouch-anal anastomosis is the operation of choice for patients with familial adenomatous polyposis. With this operation comes the risk of developing ileal pouch polyps. Although rare, ileal pouch carcinomas may also occur within the pouch. Periodic endoscopic surveillance of the retained rectum and ileal pouch is recommended. Endoscopic polypectomy of medium and large polyps should be performed. Sulindac is effective in the reduction and often in the elimination of numerous smaller pouch polyps. Future studies are necessary to determine the role of sulindac and other chemotherapeutic agents in preventing the development of these polyps.

Rectal prolapse.

Despite the innovation of more than 100 surgical procedures for the treatment of complete rectal prolapse, no one procedure is best and applicable to all patients. Traditionally, procedures have been divided into abdominal and perineal approaches. The application of the laparoscopic approach to colon and rectal disease has allowed an additional less invasive method of therapy to treat rectal prolapse successfully. In comparison with conventional approaches, laparoscopy has achieved similar functional results and recurrence rates while reducing postoperative pain and hospital length of stay.

Intestinal permeability and bacterial translocation are uncoupled after small bowel resection.

BACKGROUND/PURPOSE: Gut barrier failure and bacterial translocation have been proposed to cause infection and sepsis in patients with the short bowel syndrome. This study tested the hypothesis that permeability is increased in the adapting remnant ileum after massive small bowel resection (SBR). METHODS: Male ICR mice underwent a 50% proximal SBR or sham operation. At 3, 7, and 14 days, the ileum was mounted in an Ussing chamber. Mucosal-to-serosal flux of low (dextran) and high (horseradish peroxidase; HRP) molecular weight markers was determined. Additionally, bacterial translocation was measured by culturing blood, mesenteric lymph nodes, liver, and spleen at 3 and 14 days after SBR or sham operation. RESULTS: Permeability to dextran was reduced immediately after SBR but was no different at later time-points. HRP permeability was no different at any time-point. Translocation of Gram-negative bacteria to the mesenteric lymph nodes and liver was more frequent in the SBR animals 3 and 14 days postoperatively. CONCLUSIONS: Intestinal permeability to macromolecules is not increased after massive SBR, but the rate of translocation to the mesenteric lymph nodes and liver is elevated. This suggests that the mechanism for bacterial translocation after SBR does not involve alterations in gut permeability.

Enterocyte apoptosis after enterectomy in mice is activated independent of the extrinsic death receptor pathway.

Intestinal adaptation following small bowel resection (SBR) is associated with greater rates of enterocyte apoptosis by unknown mechanism(s). Because postresection adaptation is associated with increased translocation of luminal bacteria, we sought to characterize the role for the extrinsic, death receptor pathway for the activation of enterocyte apoptosis after massive SBR. We first performed SBR or sham operations in mice, and the temporal expression of caspases 8, 9, and 3, death receptors tumor necrosis factor receptor-1 (TNFR1) and Fas and corresponding ligands (TNF and Fas ligand) was determined in the remnant intestine at various postoperative time points. Ileal TNFR1 and Fas expression were then measured after SBR in the setting of increased (waved-2 mice) or decreased (exogenous EGF administration) apoptosis. Finally, intestinal adaptation and apoptosis were recorded in the remnant ileum after SBR in TNFR1-null and Fas-null mice. The expression of death receptor family proteins and caspases demonstrated only modest changes after SBR and did not correlate with the histological appearance of apoptosis. In the setting of accelerated apoptosis, TNFR1 and Fas expression were paradoxically decreased. Apoptotic and adaptive responses were preserved in both TNFR1-null and Fas-null mice. These results suggest that the mechanism for increased enterocyte apoptosis following massive SBR does not appear to involve the extrinsic, death receptor-mediated pathway.