Severe Morbidity Research Articles

Assessing Diagnostic Performance of Molecular Culture for Neonatal Sepsis: Protocol of the CHAMPIONS Study.

Managing neonatal sepsis is challenging due to nonspecific clinical signs, hematological markers with poor accuracy, and a lengthy turnaround time for the identification of microorganisms. Delaying the initiation of antibiotics in truly infected infants can lead to severe morbidity and mortality. Therefore, decisions regarding empiric antibiotic treatment are risk stratified, which exposes many uninfected infants to antibiotics. This causes gut microbiota perturbation, unnecessary hospital admissions, and the generation of multi-resistant organisms. High-speed diagnostic assays could expedite discontinuation or avert the initiation of antibiotics in uninfected infants. This study will evaluate the diagnostic performance of molecular culture (MC), a rapid broad-range PCR-based bacterial profiling technique, for diagnosing neonatal sepsis in infants below 90 days old. A multi-center prospective observational cohort study will include infants evaluated for early and late-onset sepsis. Routine evaluation for suspected sepsis includes microbiological cultures of blood. Additionally, blood for MC will be collected. For early-onset sepsis, umbilical cord blood may be used alternatively. Primary outcome is the agreement between MC and conventional blood culture results. Secondary outcome is the agreement of both assays with clinical sepsis using four different, commonly used definitions. Faster diagnostic pathways for sepsis may reduce antibiotic exposure time. Broad-range molecular assays may identify pathogens undetectable by conventional methods. Employment of umbilical cord blood samples for early-onset sepsis diagnosis can resolve challenges in collecting adequate blood volume and could further expedite treatment decisions.

Utility of placental biomarkers and fetoplacental Dopplers in predicting likely placental pathology in early and late fetal growth restriction – A prospective study

IntroductionThe aim of this study was to evaluate the association between placental abnormalities, placental biomarkers, and fetoplacental Dopplers in a cohort of pregnancies complicated by fetal growth restriction (FGR). We also ascertained the risk of perinatal mortality, severe neurological morbidity, and severe non-neurological morbidity by type of placental abnormality. MethodsThis was a prospective cohort study. Multivariable logistic regression was used to evaluate the effect of early vs. late FGR, placental biomarkers and fetoplacental Dopplers on Maternal Vascular Malperfusion (MVM) which was the commonest placental abnormality identified. ResultsThere were 161 (53.5 %) early FGR and 140 (46.5 %) late FGR cases. MVM abnormalities were present in 154 (51.2 %), VUE in 45 (14.6 %), FVM in 16 (5.3 %), DVM in 14 (4.7 %) and CHI in 4 (1.3 %) cases. The odds of MVM were higher in early compared to late FGR cohort (OR 1.89, 95%CI 1.14, 3.14, p = 0.01). Low maternal PlGF levels <100 ng/L (OR 2.34, 95%CI 1.27,4.31, p = 0.01), high sFlt-1 level (OR 2.13, 95%CI 1.35, 3.36, p = 0.001) or elevated sFlt-1/PlGF ratio (OR 3.48, 95%CI 1.36, 8.91, p = 0.01) were all associated with MVM. Increased UA PI > 95th centile (OR 2.91, 95%CI 1.71, 4.95, p=<0.001) and mean UtA PI z-score (OR 1.74, 95%CI 1.15, 2.64, p = 0.01) were associated with higher odds of MVM. Rates of severe non-neurological morbidity were highest in the MVM, FVM, and CHI cohorts (44.8 %, 50 %, and 50 % respectively). ConclusionMVM was the commonest placental abnormality in FGR, particularly in early-onset disease. Low maternal PlGF levels, high sFlt-1 levels, elevated sFlt-1/PlGF ratio, and abnormal fetoplacental Dopplers were also significantly associated with MVM. MVM, FVM, and CHI abnormalities were associated with lower median birthweight, higher rates of preterm birth, operative birth for non-reassuring fetal status, and severe neonatal non-neurological morbidity.

Obstetric and neonatal outcomes in pregnancies complicated by placental abruption with vs. without supporting sonographic findings- A retrospective cohort study

Placental abruption (PA) is a major obstetric complication associated with worse maternal and neonatal outcomes. Though ultrasound findings may support the diagnosis of PA, the association of such findings to the severity of PA and maternal and neonatal outcomes is not yet clear. We aimed to assess the maternal and neonatal outcomes of PA cases with vs. without related sonographic findings. In this retrospective cohort study, all deliveries complicated by PA between 2009 and 2022 were included. Placental histopathology, obstetric, and neonatal outcomes were compared between cases of PA with vs. without supporting sonographic findings. A composite of severe neonatal morbidity was compared between the groups, including ≥1 of the following: seizures, intraventricular hemorrhage, hypoxic-ischemic encephalopathy, periventricular leukomalacia, respiratory-distress syndrome, sepsis, anemia, blood transfusion or death. Of the 420 cases with PA eligible for the study, 50 patients (12%) were in the PA with sonographic features group and 370 (88%) were in the PA without sonographic features group. The PA with sonographic features group was characterized by significantly higher rates of prematurity (p<0.001), severe composite adverse neonatal outcome (p<0.01), and a composite maternal vascular malperfusion lesions in placental histopathology (p=0.001) In multivariable regression analyses, preterm birth was independently associated with the presence of sonographic features (aOR=8.79, 95% CI 2.41-31.93, p<0.001). PA with supporting sonographic features is associated with higher rates of adverse obstetric and neonatal outcomes and placental lesions. These findings emphasize the importance of sonographic evaluation for every case of PA before deciding upon management.

Fetoscopic laser photocoagulation: a medically reasonable treatment option in the management of types II and III vasa previa.

Vasa previa is a condition where unprotected fetal vessels cross the cervix within the membranes, posing a considerable risk of fetal death or severe morbidity if the membranes rupture before or during delivery. There has not been a definitive in utero treatment for this condition. Patients are typically closely monitored and hospitalized in the early third trimester and scheduled for cesarean delivery before term. This approach poses considerable physical, social, psychological, and financial challenges for pregnant patients and their families. Furthermore, fetal vessel rupture may lead to severe hypoxic-ischemic injury and consequent neurodevelopmental impairment. Finally, babies delivered early due to vasa previa may face both the short- and long-term consequences of prematurity. Recently, fetoscopic laser photocoagulation using a single-port fetoscope has emerged as a potential therapeutic option for patients with types II and III vasa previa. This innovative approach aims to reduce hospital stays, increases the chance of successful vaginal delivery, and potentially allows pregnancies to reach full term, providing lifelong benefits for the infant. Preliminary clinical studies on human subjects have demonstrated promising results concerning the feasibility, safety, and efficacy of this intervention for a subset of patients with types II and III vasa previa. After reviewing the current state of the art, we argued that offering fetoscopic laser photocoagulation in specialized centers under IRB supervision meets the ethical obligations of beneficence and non-maleficence for both pregnant and fetal patients, as well as the autonomy-based obligations for pregnant patients.

Improving lupus care index documentation in patients with childhood-onset systemic lupus erythematosus.

Childhood-onset systemic lupus erythematosus (c-SLE) presents unique challenges due to increased risk for severe morbidity and mortality compared to adult-onset SLE. Effective disease management relies on accurate disease assessment and documentation. Our project aimed to improve the documentation of the Lupus Care Index (LCI), a disease assessment bundle, by implementing a quality improvement (QI) initiative. A QI project was conducted at Nationwide Children's Hospital (NCH), targeting patients with c-SLE. The LCI, comprising the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2k) Physician Global Assessment (PGA) and patient-reported pain score, was introduced to capture comprehensive disease assessment. Interventions included provider education, standardization of documentation procedures, and electronic health record (EHR) modifications. Automated reports tracked documentation rates, and Pareto charts identified areas for targeted interventions. Baseline analysis revealed incomplete documentation of LCI components in only one-third of c-SLE patients. Following interventions, documentation rates improved from 38% to 90%, with sustained improvement over at least a year. Enhancing documentation of LCI in patients with c-SLE is crucial for optimizing disease management. Our quality improvement initiative demonstrated the feasibility of improving documentation practices through targeted interventions and system modifications. Future research should explore the impact of comprehensive documentation on clinical outcomes in pediatric lupus patients. Improving documentation of LCI in patients with c-SLE is essential for optimizing care delivery and clinical outcomes; our QI initiative highlights the effectiveness of systemic interventions in enhancing documentation practices and underscores the importance of continued efforts to improve pediatric lupus care.

Risk of Recurrent Severe Maternal Morbidity: A Population-Based Study

Risk of Recurrent Severe Maternal Morbidity: A Population-Based Study

Pathogenicity of duck circovirus and novel goose parvovirus co-infection in SPF ducks

ABSTRACT Duck circovirus (DuCV) is one of the most prevalent infectious viruses in the duck industry in China. Although the clinical signs vary, it often causes immunosuppression in the host and leads to secondary infection with other pathogens. Novel goose parvovirus (NGPV) mainly infects ducks and causes short beak and dwarfism syndrome in ducks. However, the incidence of infection in ducks has increased in recent years, and the phenomenon of mixed infection with DuCV is common, resulting in more severe clinical morbidity. However, there are no systematic studies evaluating the presence of mixed infections. In order to investigate the synergistic pathogenicity of DuCV and NGPV co-infection in SPF ducks, a comparative experiment using DuCV and NGPV co-infection and mono-infection bird models was established. The results showed that the clinical signs of short beak, dwarfism and immunosuppression were more obvious in DuCV and NGPV co-infected ducks; the tissue damage of target organs was more serious, and the viral titre in organs and cloacal swabs were more significant compared with those of SPF ducks infected with only one virus. The results indicated that co-infection with DuCV and NGPV could promote viral replication and cause more severe tissue damage and immunosuppression than single virus infection. The present study reveals that the co-infection of NGPV and DuCV has a synergistic pathogenic effect from the aspect of pathogenicity, and the conclusions drawn not only clarify the direction of the subsequent research on the mechanism of co-infection of NGPV and DuCV, but also provide a scientific basis for the research on the co-infection of immunosuppressive pathogens and other pathogens.

Decoding Pulmonary Embolism: Pathophysiology, Diagnosis, and Treatment.

Pulmonary Embolism (PE) is a life-threatening condition initiated by the presence of blood clots in the pulmonary arteries, leading to severe morbidity and mortality. Underlying mechanisms involve endothelial dysfunction, including impaired blood flow regulation, a pro-thrombotic state, inflammation, heightened oxidative stress, and altered vascular remodeling. These mechanisms contribute to vascular diseases stemming from PE, such as recurrent thromboembolism, chronic thromboembolic pulmonary hypertension, post-thrombotic syndrome, right heart failure, and cardiogenic shock. Detailing key risk factors and utilizing hemodynamic stability-based categorization, the review aims for precise risk stratification by applying established diagnostic tools and scoring systems. This article explores both conventional and emerging biomarkers as potential diagnostic tools. Additionally, by synthesizing existing knowledge, it provides a comprehensive outlook of the current enhanced PE management and preventive strategies. The conclusion underscores the need for future research to improve diagnostic accuracy and therapeutic effectiveness in PE.

External validation and comparison of four prediction scores for severe maternal morbidity

BackgroundSevere maternal morbidity (SMM) is increasing in the United States. Several tools and scores exist to stratify an individual's risk of SMM. ObjectiveWe sought to examine and compare the validity of four scoring systems for predicting SMM. Study DesignThis was a retrospective cohort study of all individuals in the Consortium on Safe Labor dataset, which was conducted from 2002 to 2008. Individuals were excluded if they had missing information on risk factors. SMM was defined based on the Centers for Disease Control and Prevention excluding blood transfusion. Blood transfusion was excluded due to concerns regarding the specificity of International Classification of Diseases codes for this indicator and its variable clinical significance. Risk scores were calculated for each participant using the Assessment of Perinatal Excellence (APEX), California Maternal Quality Care Collaborative (CMQCC), Obstetric Comorbidity Index (OB-CMI), and modified OB-CMI. We calculated the probability of SMM according to the risk scores. The discriminative performance of the prediction score was examined by the areas under receiver operating characteristic curves and their 95% confidence intervals (95% CI). The area under the curve for each score was compared using the bootstrap resampling. Calibration plots were developed for each score to examine the goodness-of-fit. The concordance probability method was used to define an optimal cutoff point for the best-performing score. ResultsOf 153, 463 individuals, 1115 (0.7%) had SMM. The CMQCC scoring system had a significantly higher area under the curve (95% CI) (0.78 [0.77–0.80]) compared to the APEX scoring system, OB-CMI, and modified OB-CMI scoring systems (0.75 [0.73–0.76], 0.67 [0.65–0.68], 0.66 [0.70–0.73]; P<.001). Calibration plots showed excellent concordance between the predicted and actual SMM for the APEX scoring system and OB-CMI (both Hosmer–Lemeshow test P values=1.00, suggesting goodness-of-fit). ConclusionThis study validated four risk-scoring systems to predict SMM. Both CMQCC and APEX scoring systems had good discrimination to predict SMM. The APEX score and the OB-CMI had goodness-of-fit. At ideal calculated cut-off points, the APEX score had the highest sensitivity of the four scores at 71%, indicating that better scoring systems are still needed for predicting SMM.

Combined pancreaticoduodenectomy for advanced gallbladder cancer: Indications, surgical outcomes, and limitations

BackgroundThis study aimed to elucidate the clinical value of combined pancreaticoduodenectomy (PD) for advanced gallbladder cancer according to the mode of cancer spread in the pancreaticoduodenal region. MethodsPatients who underwent combined PD for advanced gallbladder cancer were retrospectively reviewed. The mode of cancer spread in the pancreaticoduodenal region was defined as involvement of peripancreatic organs/structures alone, peripancreatic nodal metastasis alone, or both. Surgical outcomes were compared among these modes of spread. ResultsFifty-seven patients were included. Rates of severe morbidity and mortality were 52.6% and 3.5%, respectively. The mode of cancer spread was involvement of peripancreatic organs/structures alone in 16 patients, peripancreatic nodal metastasis alone in 17, and both in 24; R0 resection rates differed significantly among the groups (87.5% vs. 94.1% vs. 37.5%; p < 0.001). Overall survival (OS) was significantly worse in patients with both modes of spread (5-year OS, 8.3%) than in those with involvement of peripancreatic organs/structures alone (5-year OS, 37.9%; p < 0.001) and those with peripancreatic nodal metastasis alone (5-year OS, 29.4%; p = 0.011). OS was similar between pM0 patients with both modes of spread and pM1 patients (5-year OS, 16.7% vs. 8.7%; p = 0.605). Multivariate analysis identified mode of cancer spread as an independent prognostic factor (p = 0.006). ConclusionsCombined PD could be oncologically justified for advanced gallbladder cancer with involvement of peripancreatic organs/structures alone or peripancreatic nodal metastasis alone in the pancreaticoduodenal region. This procedure would not be indicated in patients with both modes of spread.

Community level factors and racial inequities in delivery hospitalizations involving severe maternal morbidity in the United States, 2016–2019

The objective of this study was to evaluate the racial and ethnic disparities in delivery hospitalizations involving severe maternal morbidity (SMM) by location of residence and community income. We used the 2016 to 2019 Healthcare Cost and Utilization Project National Inpatient Sample. International Classification of Diseases, Tenth Revision, Clinical Modification codes were used to identify delivery hospitalizations with SMM. Using logistic regression models, we examined the association between race and ethnicity and delivery hospitalizations involving SMM. In adjusted analyses, the models were stratified by location of residence and community income and adjusted for patient and hospital characteristics. In rural areas, non-Hispanic Black women (AOR 1.50; 95% CI 1.25–1.79) and women of other races (AOR 1.32; 95% CI 1.03–1.69) had an increased odds of experiencing a delivery hospitalization involving SMM when compared to non-Hispanic White women. In micropolitan areas, non-Hispanic Black women (AOR 1.88; 95% CI 1.79–1.97), non-Hispanic Asian/Pacific Islander women (AOR 1.54; 95% CI 1.16–2.05), and women of other races (AOR 1.31; 95% CI 1.03–1.67) had an increased odds of experiencing a delivery hospitalization involving SMM when compared to non-Hispanic White women. Non-Hispanic Black women also had increased odds of experiencing a delivery hospitalization involving SMM in communities with the lowest income (quartile 1) (AOR 1.59; 95% CI 1.49–1.66), middle income (quartiles 2 and 3) (AOR 1.81; 95% CI 1.72–1.91), and highest income (AOR 2.09; 95% CI 1.90–2.29) when compared to non-Hispanic White women. We found that location of residence and community income are associated with racial and ethnic differences in SMM in the United States. These factors, outside of individual factors assessed in previous studies, provide a better understanding of some of the structural and systemic factors that may contribute to SMM.

Pexidartinib Upfront in a Case of Tenosynovial Giant Cell Tumor: Proof of Concept for a Treatment Paradigm Shift.

Tenosynovial giant cell tumor (TGCT) is a rare, locally aggressive tumor of the joints, bursa, and tendon sheath that can cause considerable pain and substantial morbidity. Although surgery is the primary treatment for patients with TGCT, surgical resection is associated with high rates of recurrence, particularly for patients with diffuse TGCT. Pexidartinib, a colony-stimulating factor1 receptor inhibitor, is approved by the US Food and Drug Administration for the treatment of adult patients with symptomatic TGCT associated with severe morbidity or functional limitations and not amenable to improvement with surgery. A 32-year-old man presented with intra-articular diffuse TGCT with pain and received noncurative treatment for 5years (2014-2019). In 2019, the patient was found to have extensive disease accompanied by pain and limited range of motion. The patient's case was presented to a sarcoma multidisciplinary tumor board, who determined that surgery would cause significant morbidity and macroscopic residual tumor. As a result of the extent of disease, young age, and otherwise good health, treatment with pexidartinib was started through a compassionate use program at 800mg/day. After dose reductions to pexidartinib at 400mg/day and then 200mg/day as a result of creatine phosphokinase elevations, the patient achieved a complete response after 2years of treatment; pain was reduced and mobility was restored. The patient reported no side effects related to pexidartinib treatment. Treatment was stopped in 2022 for future family planning. After pexidartinib therapy was interrupted, the patient's wife had a successful pregnancy and delivery; however, the disease showed a slow but constant clinical deterioration, with a reduction in the range of movement of the affected knee and an apparent increase in widespread TGCT nodules. Our case is unique because it provides support for pexidartinib use as upfront therapy for TGCT, instead of surgery, in selected cases.

Neurodevelopment at age 5.5 years according to Ages & Stages Questionnaire at 2 years’ corrected age in children born preterm: the EPIPAGE-2 cohort study

ObjectiveTo report neurodevelopment at age 5.5 years according to developmental delay screening with the Ages & Stages Questionnaire (ASQ) in late infancy in preterm-born children.DesignPopulation-based cohort study, EPIPAGE-2.SettingFrance, 2011–2017.Participants2504 children...

Review of Advancements in Managing Cardiogenic Shock: From Emergency Care Protocols to Long-Term Therapeutic Strategies.

Cardiogenic shock (CS) is a complex multifactorial clinical syndrome of end-organ hypoperfusion that could be associated with multisystem organ failure, presenting a diverse range of causes and symptoms. Despite improving survival in recent years due to new advancements, CS still carries a high risk of severe morbidity and mortality. Recent research has focused on improving early detection and understanding of CS through standardized team approaches, detailed hemodynamic assessment, and selective use of temporary mechanical circulatory support devices, leading to better patient outcomes. This review examines CS pathophysiology, emerging classifications, current drug and device therapies, standardized team management strategies, and regionalized care systems aimed at optimizing shock outcomes. Furthermore, we identify gaps in knowledge and outline future research needs.

The Impact of Non-Dysentery Shigella Infection on the Growth and Health of Children over Time (INSIGHT)-A Prospective Case-Control Study Protocol.

(1) Shigella spp. (Shigella) is known for causing dysentery with blood in stool, but most children infected with Shigella have non-dysentery Shigella-associated diarrhea (NDSD). The World Health Organization recommends the use of antibiotics when diarrhea is bloody, leaving most NDSD cases untreated. The absence of dysentery may not indicate a low risk of death and severe morbidity. Rapid diagnosis and treatment of shigellosis in vulnerable, young children may be lifesaving. INSIGHT aims to determine the potential benefit of identifying NDSD cases (n = 296) and their outcomes compared to cases of Shigella dysentery [DS (n = 148)] and non-Shigella watery diarrhea [WD (n = 148)]. (2) Children seeking care at hospitals in Bangladesh will be enrolled and followed for 1 year (NDSD and DS) or 90 days (WD). We will determine the impact of NDSD on morbidity, mortality, gut health, nutritional status, and cognitive development compared to DS and WD in children and whether the simple "Rapid LAMP-based Diagnostic Test (RLDT)" can accelerate the detection and treatment of shigellosis in the clinical settings of rural Bangladesh. (3) INSIGHT will determine the impact of NDSD in children and determine if the treatment guidelines of shigellosis need to be revisited to improve clinical outcomes and the development of these children.

Brief Report: Low-Dose Methotrexate Does Not Affect Measures of HIV-1 Persistence in Individuals With Chronically Treated HIV-1 Infection.

People with HIV-1 often have chronic inflammation leading to severe non-AIDS morbidity and mortality. The AIDS Clinical Trials Group Study A5314 sought to lower inflammation with low-dose methotrexate (LDMTX). The primary study outcomes were reported previously but here we present the impact of LDMTX on multiple measures of HIV-1 persistence. A5314 was a phase 2 randomized, double-blind, multicenter trial in 176 adult people with HIV-1 on virally suppressive antiretroviral therapy. LDMTX (5-15 mg/wk) was administered for 24 weeks with an additional 12 weeks of participant follow-up. The current analyses of HIV-1 persistence were restricted to 60 participants (30 LDMTX and 30 placebo) randomly selected from the total population. Plasma HIV-1 RNA, total HIV-1 DNA, and cell-associated HIV-1 RNA (CA HIV-1 RNA) were measured by sensitive quantitative PCR assays. LDMTX treatment had no significant effect on sensitive measures of plasma HIV-1 RNA, HIV-1 DNA, CA HIV-1 RNA, or CA HIV-1 RNA/DNA ratio at any time point or from baseline to week 24. As observed in the main study, absolute peripheral CD4+ and CD8+ T-cell numbers decreased from baseline to week 24 among the 30 participants receiving LDMTX compared with placebo (median decrease of -31.5 CD4+ T cells/µL, -83.5 CD8+ T cells/µL). LDMTX had no significant effect on any measure of HIV-1 persistence in plasma or peripheral blood mononuclear cells. Further studies are needed to determine whether other immunosuppressive and/or immunoreductive interventions are safe and capable of affecting HIV-1 persistence.

Endocrine Disorders in Nephrotic Syndrome-A Comprehensive Review.

Nephrotic syndrome is a clinical syndrome characterized by massive proteinuria, called nephrotic range proteinuria (over 3.5 g per day in adults or 40 mg/m2 per hour in children), hypoalbuminemia, oncotic edema, and hyperlipidemia, with an increasing incidence over several years. Nephrotic syndrome carries severe morbidity and mortality risk. The main pathophysiological event in nephrotic syndrome is increased glomerular permeability due to immunological, paraneoplastic, genetic, or infective triggers. Because of the marked increase in the glomerular permeability to macromolecules and the associated urinary loss of albumins and hormone-binding proteins, many metabolic and endocrine abnormalities are present. Some of them are well known, such as overt or subclinical hypothyroidism, growth hormone depletion, lack of testosterone, vitamin D, and calcium deficiency. The exact prevalence of these disorders is unknown because of the complexity of the human endocrine system and the differences in their prevalence. This review aims to comprehensively analyze all potential endocrine and hormonal complications of nephrotic syndrome and, vice versa, possible kidney complications of endocrine diseases that might remain unrecognized in everyday clinical practice.

Obstetric anesthesia management of dilated cardiomyopathies and heart failure: a narrative review

Pregnancy in patients with dilated cardiomyopathy carries a significantly increased risk of maternal mortality or severe morbidity, and pregnancy is typically considered contraindicated for patients with severely reduced ventricular function. Nonetheless, anesthesiologists will still encounter patients with cardiomyopathy requiring delivery or termination care. This review describes how NT-ProBNP testing and echocardiography can help with early recognition of heart failure in pregnancy, and describes a suggested approach to anesthetic management of patients with cardiomyopathies or acute heart failure, including hemodynamic goals, use of vasoactive medications and mechanical support. Vaginal delivery, with effective neuraxial anesthesia is the preferred mode of delivery in most patients with cardiomyopathy, with cesarean delivery reserved for maternal or fetal indications. The Pregnancy Heart Team is vital in coordinating the multidisciplinary care necessary to safely support these patients through pregnancy.

ASO Visual Abstract: Surgical Outcome in Retroperitoneal Sarcoma Surgery: Accuracy of P-POSSUM, ACS-NSQIP, and Inflammatory Biomarkers Prognostic Index (IBPI) Risk-Calculators for Prediction of Severe and Overall Morbidity.

ASO Visual Abstract: Surgical Outcome in Retroperitoneal Sarcoma Surgery: Accuracy of P-POSSUM, ACS-NSQIP, and Inflammatory Biomarkers Prognostic Index (IBPI) Risk-Calculators for Prediction of Severe and Overall Morbidity.

Combining three-dimensionality and CaP glass-PLA composites: Towards an efficient vascularization in bone tissue healing

Bone regeneration often fails due to implants/grafts lacking vascular supply, causing necrotic tissue and poor integration. Microsurgical techniques are used to overcome this issue, allowing the graft to anastomose. These techniques have limitations, including severe patient morbidity and current research focuses on stimulating angiogenesis in situ using growth factors, presenting limitations, such as a lack of control and increased costs. Non-biological stimuli are necessary to promote angiogenesis for successful bone constructs. Recent studies have reported that bioactive glass dissolution products, such as calcium-releasing nanoparticles, stimulate hMSCs to promote angiogenesis and new vasculature. Moreover, the effect of 3D microporosity has also been reported to be important for vascularisation in vivo. Therefore, we used room-temperature extrusion 3D printing with polylactic acid (PLA) and calcium phosphate (CaP) based glass scaffolds, focusing on geometry and solvent displacement for scaffold recovery. Combining both methods enabled reproducible control of 3D structure, porosity, and surface topography. Scaffolds maintained calcium ion release at physiological levels and supported human mesenchymal stem cell proliferation. Scaffolds stimulated the secretion of vascular endothelial growth factor (VEGF) after 3 days of culture. Subcutaneous implantation in vivo indicated good scaffold integration and blood vessel infiltration as early as one week after. PLA-CaP scaffolds showed increased vessel maturation 4 weeks after implantation without vascular regression. Results show PLA/CaP-based glass scaffolds, made via controlled 3D printing, support angiogenesis and vessel maturation, promising improved vascularization for bone regeneration.