Effects of brain tissue oxygen (PbtO2) guided management on patient outcomes following severe traumatic brain injury: A systematic review and meta-analysis.

Monitoring and optimisation of brain tissue oxygen tension (PbtO2) has been associated with improved neurological outcome and survival in observational studies of severe traumatic brain injury (TBI). We carried out a systematic review of randomized controlled trials to determine if PbtO2-guided management is associated with differential neurological outcomes, survival, and adverse events. Searches were carried out to 10 February 2022 in Medline (OvidSP), 11 February in EMBASE (OvidSP) and 8 February in Cochrane library. Randomized controlled trials comparing PbtO2 and ICP-guided management to ICP-guided management alone were included. The primary outcome was survival with favourable neurological outcome at 6-months post injury. Data were extracted by two independent authors and GRADE certainty of evidence assessed. There was no difference in the proportion of patients with favourable neurological outcomes with PbtO2-guided management (relative risk [RR] 1.42, 95% CI 0.97 to 2.08; p = 0.07; I2 = 0%, very low certainty evidence) but PbtO2-guided management was associated with reduced mortality (RR 0.54, 95% CI 0.31 to 0.93; p = 0.03; I2 = 42%; very low certainty evidence) and ICP (mean difference (MD) - 4.62, 95% CI - 8.27 to - 0.98; p = 0.01; I2 = 63%; very low certainty evidence). There was no significant difference in the risk of adverse respiratory or cardiovascular events. PbtO2-guided management in addition to ICP-based care was not significantly associated with increased favourable neurological outcomes, but was associated with increased survival and reduced ICP, with no difference in respiratory or cardiovascular adverse events. However, based on GRADE criteria, the certainty of evidence provided by this meta-analysis was consistently very low. MESH: Brain Ischemia; Intensive Care; Glasgow Outcome Scale; Randomized Controlled Trial; Craniocerebral Trauma

Recombinant human bone morphogenetic protein 2B stimulates PC12 cell differentiation: potentiation and binding to type IV collagen

Abstract. Bone morphogenetic protein 2B (BMP 2B, also known as BMP 4) induces cartilage and bone morphogenesis in ectopic extraskeletal sites. BMP 2B is one of several bone morphogenetic proteins which along with activins and inhibins are members of the transforming growth factor-/3 (TGF-B) family. Both BMP 2B and activin A, but not TGF-B~, induce rat pheochromocytoma PC12 neuronal cell differentiation and expression of VGF, a nervous system-specific mRNA. PC12 cells exhibited •2,500 receptors per cell for BMP 2B with an apparent dissociation constant of 19 pM. Extracellular matrix components, in-ROWTH and differentiation factors in bone enable demineralized bone matrix to induce endochondral bone formation at ectopic sites in rat (Reddi an

Long-term perturbation of the peripheral immune system months after SARS-CoV-2 infection

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly infectious respiratory virus which is responsible for the coronavirus disease 2019 (COVID-19) pandemic. It is increasingly clear that recovered individuals, even those who had mild COVID-19, can suffer from persistent symptoms for many months after infection, a condition referred to as "long COVID", post-acute sequelae of COVID-19 (PASC), post-acute COVID-19 syndrome, or post COVID-19 condition. However, despite the plethora of research on COVID-19, relatively little is known about the molecular underpinnings of these long-term effects.MethodsWe have undertaken an integrated analysis of immune responses in blood at a transcriptional, cellular, and serological level at 12, 16, and 24 weeks post-infection (wpi) in 69 patients recovering from mild, moderate, severe, or critical COVID-19 in comparison to healthy uninfected controls. Twenty-one of these patients were referred to a long COVID clinic and > 50% reported ongoing symptoms more than 6 months post-infection.ResultsAnti-Spike and anti-RBD IgG responses were largely stable up to 24 wpi and correlated with disease severity. Deep immunophenotyping revealed significant differences in multiple innate (NK cells, LD neutrophils, CXCR3+ monocytes) and adaptive immune populations (T helper, T follicular helper, and regulatory T cells) in convalescent individuals compared to healthy controls, which were most strongly evident at 12 and 16 wpi. RNA sequencing revealed significant perturbations to gene expression in COVID-19 convalescents until at least 6 months post-infection. We also uncovered significant differences in the transcriptome at 24 wpi of convalescents who were referred to a long COVID clinic compared to those who were not.ConclusionsVariation in the rate of recovery from infection at a cellular and transcriptional level may explain the persistence of symptoms associated with long COVID in some individuals

Delayed return of bowel function after general surgery in South Australia

Introduction: Reference ranges for determining pathological versus normal postoperative return of bowel function are not well characterised for general surgery patients. This study aimed to characterise time to first postoperative passage of stool after general surgery; determine associations between clinical factors and delayed time to first postoperative stool; and evaluate the association between delay to first postoperative stool and prolonged length of hospital stay. Methods: This study included consecutive admissions at two tertiary hospitals across a two-year period whom underwent a range of general surgery operations. Multivariable logistic regression analyses were conducted to determine associations between the explanatory variables and delayed first postoperative stool, and between delayed first postoperative stool and length of hospital stay. The previously specified explanatory variables were used, with the addition of the dichotomised ≥4-day delay to first postoperative stool. Prolonged length of hospital stay was considered ≥7 days. Results: 2,212 general surgery patients were included. Median time to first postoperative stool was 2.28 (IQR 1.06–3.96). Median length of stay was 7.19 (IQR 4.50–12.01). Several operative characteristics and medication exposures were associated with delayed first postoperative stool. There was a statistically significant association between delayed first postoperative stool (≥4 days) and prolonged length of stay (≥7 days) (OR 4.34, 95 %CI 3.27 to 5.77, p < 0.001). Conclusions: This study characterised expected reference ranges for time to return of bowel function across various general surgery operations and determined associations with clinical factors that may improve efficiency and identification of pathology within the postoperative course