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

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

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 &gt; 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

BMP treatment for improving tendon repair. Studies on rat and rabbit Achilles tendons

We wanted to improve tendon healing by adding a growth factor. Bone Morphogenetic Proteins (BMPs) are well known to stimulate bone healing and bone formation. The local environment is of major importance for cell differentiation after a BMP has been added. Cartilage Derived Morphogenetic Proteins (CDMPs) -1, -2 and -3 (BMP 14, 13 and 12 or GDF 5, 6 and 7) form a subgroup in the BMP-family and are closely related to OP-1 (BMP 7). CDMP implants have been shown to induce bone and cartilage as well as tendon and ligament-like tissue. Our hypothesis has therefore been that if a BMP were added in a tendon environment, a tendon-like tissue would be induced. We have developed models in rats and rabbits where the Achilles tendon is transsected. To influence tendon healing, different BMPs (OP-1, CDMP-1. -2 and -3) were added, either on a collagen carrier, or as a local injection into the tendon defect. The tendons were evaluated by histology and mechanical testing at different time-points after transection. The results show that also when the mechanical environment would favour the formation of a tendon-like tissue, OP-1 reduced tendon strength in aid of bone formation. In contrast, CDMP-1, -2 and -3 had a beneficial effect upon tendon healing in rats. More callus tissue was produced than in controls, and strength and stiffness were improved, although minor amounts of bone and cartilage were detected in the tendon callus. Cartilage and bone formation sometimes occur normally during Achilles tendon healing in rats. In the rabbit model, where the healing situation is more similar to the clinical situation, the positive result with CDMP-2 was repeated. Moreover, in rabbits no bone or cartilage was found. The results suggest that conservative treatment of Achilles tendon ruptures with injection of a CDMP in combination with early rehabilitation might afford a good alternative to surgical treatment

SARS-CoV-2 Omicron variant escapes neutralizing antibodies and T&nbsp;cell responses more efficiently than other variants in mild COVID-19 convalescents.

Coronavirus disease 2019 (COVID-19) convalescents living in regions with low vaccination rates rely on post-infection immunity for protection against re-infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluate humoral and T&nbsp;cell immunity against five variants of concern (VOCs) in mild-COVID-19 convalescents at 12&nbsp;months after infection with ancestral virus. In this cohort, ancestral, receptor-binding domain (RBD)-specific antibody and circulating memory B cell levels are conserved in most individuals, and yet serum neutralization against live B.1.1.529 (Omicron) is completely abrogated and significantly reduced for other VOCs. Likewise, ancestral SARS-CoV-2-specific memory T&nbsp;cell frequencies are maintained in &gt;50% of convalescents, but the cytokine response in these cells to mutated spike epitopes corresponding to B.1.1.529 and B.1.351 (Beta) VOCs were impaired. These results indicate that increased antigen variability in VOCs impairs humoral and spike-specific T&nbsp;cell immunity post-infection, strongly suggesting that COVID-19 convalescents are vulnerable and at risk of re-infection with VOCs, thus stressing the importance of vaccination programs

The interaction of thrombocytopenia, hemorrhage, and platelet transfusion in venoarterial extracorporeal membrane oxygenation: a multicenter observational study

Abstract Background Thrombocytopenia, hemorrhage and platelet transfusion are common in patients supported with venoarterial extracorporeal membrane oxygenation (VA ECMO). However, current literature is limited to small single-center experiences with high degrees of heterogeneity. Therefore, we aimed to ascertain in a multicenter study the course and occurrence rate of thrombocytopenia, and to assess the association between thrombocytopenia, hemorrhage and platelet transfusion during VA ECMO. Methods This was a sub-study of a multicenter (N = 16) study on transfusion practices in patients on VA ECMO, in which a retrospective cohort (Jan-2018–Jul-2019) focusing on platelets was selected. The primary outcome was thrombocytopenia during VA ECMO, defined as mild (100–150·109/L), moderate (50–100·109/L) and severe (< 50·109/L). Secondary outcomes included the occurrence rate of platelet transfusion, and the association between thrombocytopenia, hemorrhage and platelet transfusion, assessed through mixed-effect models. Results Of the 419 patients included, median platelet count at admission was 179·109/L. During VA ECMO, almost all (N = 398, 95%) patients developed a thrombocytopenia, of which a significant part severe (N = 179, 45%). One or more platelet transfusions were administered in 226 patients (54%), whereas 207 patients (49%) suffered a hemorrhagic event during VA ECMO. In non-bleeding patients, still one in three patients received a platelet transfusion. The strongest association to receive a platelet transfusion was found in the presence of severe thrombocytopenia (adjusted OR 31.8, 95% CI 17.9–56.5). After including an interaction term of hemorrhage and thrombocytopenia, this even increased up to an OR of 110 (95% CI 34–360). Conclusions Thrombocytopenia has a higher occurrence than is currently recognized. Severe thrombocytopenia is strongly associated with platelet transfusion. Future studies should focus on the etiology of severe thrombocytopenia during ECMO, as well as identifying indications and platelet thresholds for transfusion in the absence of bleeding. Trial registration: This study was registered at the Netherlands Trial Registry at February 26th, 2020 with number NL8413 and can currently be found at https://trialsearch.who.int/Trial2.aspx?TrialID=NL8413