Morbidity In Survivors Research Articles

Predictors of acute ischemic strokes and subsequent mortality in patients hospitalized for percutaneous coronary interventions

Abstract Background Acute ischemic strokes (AIS) occurring post percutaneous coronary intervention (PCI) are an infrequent but severe complication, resulting in increased mortality rates and morbidity in survivors. Purpose We aimed to investigate independent predictors of AIS and subsequent mortality in patients hospitalized for PCI in a nationwide cohort. Methods A retrospective analysis using on ICD-10-GM and OPS-codes obtained from 2006-2021 from the German Federal Statistical Office was performed. Patients with a peri-interventional AIS aged ≥18 years which were admitted for PCI were included in this analysis. A stepwise regression analysis was employed to identify factors independently associated with AIS and to determine variables linked to in-hospital mortality. Results From 4,910,430 PCI cases registered from 2006-2021, AIS occurred in 4,098 (0.08%) patients. Patients with an AIS were 70.9±11.3 years of age, predominantly male (65.3%) and displayed a high burden of comorbidities such as diabetes (36.1%), a prior medical history of atrial fibrillation (34.6%) and chronic kidney disease (19.4%). In patients with AIS, 27.4% presented with a ST-elevation myocardial infarction (STEMI), whilst 38.9% were admitted with a Non-STEMI. Concerning procedural characteristics, 84.2% underwent a coronary stent implantation, and in 5.5% cases a coronary thrombectomy was carried out. Important predictors of peri-interventional AIS after a PCI were: carotid artery disease, history of stroke, presentation with myocardial infraction, atrial fibrillation, and coronary thrombectomy. For variables like hyperlipoproteinemia, obesity and stent implantation an inverse association was noted (also see Figure 1A). With regard to mortality, during a mean in-hospital stay of 18 ± 15.1 days, a total of 18.1% (n=742) patients died. We identified several independent predictors of mortality including clinical presentation with cardiogenic shock, dialysis and STEMI as indication for PCI. A negative correlation with in-hospital mortality was seen for variables such as arterial hypertension and coronary stent implantation (see Figure 1B for full set of independently associated variables). Conclusion In a nationwide cohort of patients hospitalized for PCI over 16 years, we identified important predictors of AIS including carotid artery disease and coronary thrombectomy. Moreover, a substantial rate of in-hospital mortality as well as several predictors of death were recognized. Our findings might help clinicians identify patients undergoing PCI who are at highest risk for ischemic cerebral complications and subsequent mortality.

Long-term morbidity and mortality of patients who survived past 30 days from bloodstream infection: A population-based retrospective cohort study

For bloodstream infections (BSI), treatment and research have focused on short term mortality. The objective of this study was to describe the 1-year mortality and morbidity in survivors of bloodstream infection when compared to patients with negative blood cultures. We conducted a population-based retrospective cohort study using Ontario administrative databases. Patients were included if they had a blood culture taken from January 1, 2014, to December 31, 2021, and survived past 30 days from blood culture collection. They were followed for the subsequent year. Outcomes were compared among patients with BSI and those without BSI, including all-cause mortality, stroke, myocardial infarction (MI), congestive heart failure (CHF) exacerbation, new start dialysis and admission to a long-term care (LTC) facility. Prognostic factors were balanced using overlap weighting of propensity scores, and a survival or competing risk model was used to describe time-to-event. Of 981,341 patients undergoing blood culture testing, 99,080 (10.1%) patients had a BSI and 882,261 (89.9%) patients did not. Outcomes were all more common among those with BSI as compared to those without BSI, including all-cause mortality (16,764 [16.9%] vs. 84,480 [9.6%]), stroke (1016 [1.0%] vs. 4680 [0.5%]), MI (1043 [1.1%] vs. 4547 [0.5%]), CHF exacerbation (2643 [2.7%] vs. 13,200 [1.5%]), new start dialysis (1703 [1.7%] vs. 2749 [0.3%]), and LTC admission (4231 [4.3%] vs. 13,016 [1.5%]). BSI had an adjusted hazard ratio of 1.10 (95% CI 1.08-1.12, P<0.0001) for mortality, subdistribution hazard ratio (sHR) of 1.27 (95% CI 1.19-1.37, P<0.0001) for stroke, sHR of 1.18 (95% CI 1.10-1.26, P<0.0001) for MI, sHR of 1.05 (95% CI 1.01-1.10, P=0.0176) for CHF exacerbation, sHR of 3.42 (95% CI 3.21-3.64, P<0.0001) for new start dialysis and sHR of 1.87 (95% CI 1.80-1.94, P<0.0001) for LTC admission. BSI survivors have substantial long-term mortality and morbidity including stroke, MI, new start dialysis and functional decline leading to LTC admission.

Postinfectious Pulmonary Complications: Establishing Research Priorities to Advance the Field: An Official American Thoracic Society Workshop Report.

Continued improvements in the treatment of pulmonary infections have paradoxically resulted in a growing challenge of individuals with postinfectious pulmonary complications (PIPCs). PIPCs have been long recognized after tuberculosis, but recent experiences such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic have underscored the importance of PIPCs following other lower respiratory tract infections. Independent of the causative pathogen, most available studies of pulmonary infections focus on short-term outcomes rather than long-term morbidity among survivors. In this document, we establish a conceptual scope for PIPCs with discussion of globally significant pulmonary pathogens and an examination of how these pathogens can damage different components of the lung, resulting in a spectrum of PIPCs. We also review potential mechanisms for the transition from acute infection to PIPC, including the interplay between pathogen-mediated injury and aberrant host responses, which together result in PIPCs. Finally, we identify cross-cutting research priorities for the field to facilitate future studies to establish the incidence of PIPCs, define common mechanisms, identify therapeutic strategies, and ultimately reduce the burden of morbidity in survivors of pulmonary infections.

Improving the future of clinical trials and translation of mesenchymal stromal cell therapies for neonatal disorders.

Despite recent advances in neonatal intensive care medicine, neonatal disorders such as (bronchopulmonary dysplasia [BPD], intraventricular hemorrhage [IVH], and hypoxic ischemic encephalopathy [HIE]) remain major causes of death and morbidity in survivors, with few effective treatments being available. Recent preclinical studies have demonstrated the pleiotropic host injury-responsive paracrine protective effects of cell therapy especially with mesenchymal stromal cells (MSCs) against BPD, IVH, and HIE. These findings suggest that MSCs therapy might emerge as a novel therapeutic modality for these currently devastating neonatal disorders with complex multifactorial etiologies. Although early-phase clinical trials suggest their safety and feasibility, their clinical therapeutic benefits have not yet been proven. Therefore, based on currently available preclinical research and clinical trial data, we focus on critical issues that need to be addressed for future successful clinical trials and eventual clinical translation such as selecting the right patient and optimal cell type, route, dose, and timing of MSCs therapy for neonatal disorders such as BPD, HIE, and IVH.

Physiological and radiological parameters predicting outcome from penetrating traumatic brain injury treated in the deployed military setting

IntroductionPenetrating traumatic brain injury (TBI) is the most common cause of death in current military conflicts, and results in significant morbidity in survivors. Identifying those physiological and radiological parameters associated...

FDA-approved disulfiram as a novel treatment for aggressive leukemia

Acute leukemia continues to be a major cause of death from disease worldwide and current chemotherapeutic agents are associated with significant morbidity in survivors. While better and safer treatments for acute leukemia are urgently needed, standard drug development pipelines are lengthy and drug repurposing therefore provides a promising approach. Our previous evaluation of FDA-approved drugs for their antileukemic activity identified disulfiram, used for the treatment of alcoholism, as a candidate hit compound. This study assessed the biological effects of disulfiram on leukemia cells and evaluated its potential as a treatment strategy. We found that disulfiram inhibits the viability of a diverse panel of acute lymphoblastic and myeloid leukemia cell lines (n = 16) and patient-derived xenograft cells from patients with poor outcome and treatment-resistant disease (n = 15). The drug induced oxidative stress and apoptosis in leukemia cells within hours of treatment and was able to potentiate the effects of daunorubicin, etoposide, topotecan, cytarabine, and mitoxantrone chemotherapy. Upon combining disulfiram with auranofin, a drug approved for the treatment of rheumatoid arthritis that was previously shown to exert antileukemic effects, strong and consistent synergy was observed across a diverse panel of acute leukemia cell lines, the mechanism of which was based on enhanced ROS induction. Acute leukemia cells were more sensitive to the cytotoxic activity of disulfiram than solid cancer cell lines and non-malignant cells. While disulfiram is currently under investigation in clinical trials for solid cancers, this study provides evidence for the potential of disulfiram for acute leukemia treatment.Key messagesDisulfiram induces rapid apoptosis in leukemia cells by boosting oxidative stress.Disulfiram inhibits leukemia cell growth more potently than solid cancer cell growth.Disulfiram can enhance the antileukemic efficacy of chemotherapies.Disulfiram strongly synergises with auranofin in killing acute leukemia cells by ROS induction.We propose testing of disulfiram in clinical trial for patients with acute leukemia.

Post hospital admission blood lactate measurements are associated with mortality but not neurologic morbidity in children with cerebral malaria.

In children with cerebral malaria (CM) admission blood lactate has previously guided intravenous fluid therapy and been validated as a prognostic biomarker associated with death. The usefulness of post-admission measurements of blood lactate in children with CM is less clear. The strength of association between blood lactate and neurological sequelae in CM survivors, as well as the optimal duration of post-admission measurements of blood lactate to identify children at higher risk of adverse outcomes is unknown. A retrospective cohort study of 1674 Malawian children with CM hospitalized from 2000 to 2018 who had blood lactate measurements every 6h for the first 24h after admission was performed. The strength of association between admission lactate or values measured at any time point in the first 24h post-admission and outcomes (mortality and neurological morbidity in survivors) was estimated. The duration of time after admission that lactate remained a valid prognostic biomarker was assessed. When lactate is analysed as a continuous variable, children with CM who have higher values at admission have a 1.05-fold higher odds (95% CI 0.99-1.11) of death compared to those with lower lactate values. Children with higher blood lactate at 6h have 1.16-fold higher odds (95% CI 1.09-1.23) of death, compared to those with lower values. If lactate levels are dichotomized into hyperlactataemic (lactate > 5.0 mmol/L) or not, the strength of association between admission lactate and mortality increases (OR = 2.49, 95% CI 1.47-4.22). Blood lactate levels obtained after 18h post-admission are not associated with outcomes. Similarly, the change in lactate concentrations through time during the first 24h of hospital admission is not associated with outcomes. Blood lactate during hospitalization is not associated with adverse neurologic outcomes in CM survivors. In children with CM, blood lactate is associated with death but not neurologic morbidity in survivors. To comprehensively estimate prognosis, blood lactate in children with CM should be assessed at admission and for 18h afterwards.

Neonatos con diagnóstico prenatal de hidrops fetal: experiencia durante 10 años en un centro de tercer nivel

IntroductionHydrops fetalis (HF) is a rare condition with a high mortality. This study analysed the obstetric and perinatal outcomes of antenatally diagnosed HF according to its aetiology and the possibility of intrauterine treatment (IUT). Patients and methodsWe carried out a retrospective review of the health records of 164 pregnant women with a prenatal diagnosis of HF in a tertiary care centre between 2011 and 2021. We analysed prenatal interventions, clinical findings, aetiologies and obstetric and live-born infant outcomes. ResultsAn invasive prenatal study had been performed in 79.3% cases. The most common aetiologies were genetic disorders (31%), TORCH and parvovirus B19 infections (9.7%) and structural heart diseases (9.1%). Intrauterine treatment was performed in 25.6%, and 74.4% of pregnancies were terminated. Pregnancies with a prenatal diagnosis of genetic or chromosomal disorders had higher rates of elective termination compared to other aetiologies (P<.01). Among all pregnancies, only 25.6% resulted in live births (LBs), most of them preterm. Perinatal and 1-year survival rates were higher in the group that received IUT (P<.001). Among the LBs, structural heart diseases had the worst survival rates, while the aetiology with the best outcomes was tachyarrhythmia. Survival at 1year of life among those born alive was 70%, but 58.6% of these infants had significant morbidity at discharge. ConclusionsDespite advances in the management of FH, the poor obstetric prognosis, perinatal mortality and morbidity of survivors is still significant. These data are important for the purpose of counselling families when HF is diagnosed antenatally.

Insight into COVID-19 associated liver injury: Mechanisms, evaluation, and clinical implications.

COVID-19 has affected millions worldwide, causing significant morbidity and mortality. While predominantly involving the respiratory tract, SARS-CoV-2 has also caused systemic illnesses involving other sites. Liver injury due to COVID-19 has been variably reported in observational studies. It has been postulated that liver damage may be due to direct damage by the SARS-CoV-2 virus or multifactorial secondary to hepatotoxic therapeutic options, as well as cytokine release syndrome and sepsis-induced multiorgan dysfunction. The approach to a COVID-19 patient with liver injury requires a thorough evaluation of the pattern of hepatocellular injury, along with the presence of underlying chronic liver disease and concurrent medications which may cause drug-induced liver injury. While studies have shown uneventful recovery in the majority of mildly affected patients, severe COVID-19 associated liver injury has been associated with higher mortality, prolonged hospitalization, and greater morbidity in survivors. Furthermore, its impact on long-term outcomes remains to be ascertained as recent studies report an association with metabolic-fatty liver disease. This present review provides insight into the subject by describing the postulated mechanism of liver injury, its impact in the presence of pre-existing liver disease, and its short- and long-term clinical implications.

Development and validation of a novel fetal vesico-amniotic shunt, the vortex shunt.

Fetal lower urinary tract obstruction (LUTO) is a severe malformation associated with an up to 80% mortality risk as well as significant renal and pulmonary morbidity in survivors. Fetal vesico-amniotic shunts (VAS) bypass the bladder obstruction, improve amniotic fluid volume and enhance in-utero pulmonary development. VAS has been shown to reduce respiratory morbidity and mortality in the neonatal period without proven benefit on long-term renal and bladder function. Clinically available shunts are associated with an up to 80% dislodgement rate, leading to repeat invasive procedures which increase fetal and maternal risks. We developed a novel "Vortex" shunt, which incorporates enhanced fixation to reduce dislodgement, a one-way valve to optimize in-utero bladder function, and enhanced sonographic echogenicity that optimizes the accurate deployment. Following the validation of these characteristics in initial benchtop experiments we have moved to feasibility studies in the fetal lamb model. We hope that the Vortex shunt may ultimately facilitate shunt deployment, reduce dislodgement risk, improve neonatal morbidity and mortality, and decrease the significant healthcare expenditures associated with long-term morbidity in LUTO survivors. In this manuscript, we review the natural history of LUTO, the risks and benefits of clinically available fetal shunts, and our development and early validation experiments.

Neurosteroids as Novel Anticonvulsants for Refractory Status Epilepticus and Medical Countermeasures for Nerve Agents: A 15-Year Journey to Bring Ganaxolone from Bench to Clinic.

This article describes recent advances in the use of neurosteroids as novel anticonvulsants for refractory status epilepticus (RSE) and as medical countermeasures (MCs) for organophosphates and chemical nerve agents (OPNAs). We highlight a comprehensive 15-year journey to bring the synthetic neurosteroid ganaxolone (GX) from bench to clinic. RSE, including when caused by nerve agents, is associated with devastating morbidity and permanent long-term neurologic dysfunction. Although recent approval of benzodiazepines such as intranasal midazolam and intranasal midazolam offers improved control of acute seizures, novel anticonvulsants are needed to suppress RSE and improve neurologic function outcomes. Currently, few anticonvulsant MCs exist for victims of OPNA exposure and RSE. Standard-of-care MCs for postexposure treatment include benzodiazepines, which do not effectively prevent or mitigate seizures resulting from nerve agent intoxication, leaving an urgent unmet medical need for new anticonvulsants for RSE. Recently, we pioneered neurosteroids as next-generation anticonvulsants that are superior to benzodiazepines for treatment of OPNA intoxication and RSE. Because GX and related neurosteroids that activate extrasynaptic GABA-A receptors rapidly control seizures and offer robust neuroprotection by reducing neuronal damage and neuroinflammation, they effectively improve neurologic outcomes after acute OPNA exposure and RSE. GX has been selected for advanced, Biomedical Advanced Research and Development Authority-supported phase 3 trials of RSE and nerve agent seizures. In addition, in mechanistic studies of neurosteroids at extrasynaptic receptors, we identified novel synthetic analogs with features that are superior to GX for current medical needs. Development of new MCs for RSE is complex, tedious, and uncertain due to scientific and regulatory challenges. Thus, further research will be critical to fill key gaps in evaluating RSE and anticonvulsants in vulnerable (pediatric and geriatric) populations and military persons. SIGNIFICANCE STATEMENT: Following organophosphate and nerve agent intoxication, refractory status epilepticus (RSE) occurs despite benzodiazepine treatment. RSE occurs in 40% of status epilepticus patients, with a 35% mortality rate and significant neurological morbidity in survivors. To treat RSE, neurosteroids are better anticonvulsants than benzodiazepines. Our pioneering use of neurosteroids for RSE and nerve agents led us to develop ganaxolone as a novel anticonvulsant and neuroprotectant with significantly improved neurological outcomes. This article describes the bench-to-bedside journey of bringing neurosteroid therapy to patients, with ganaxolone leading the way.

The Impact of Spontaneous versus Indicated Preterm Birth on Neonatal Outcomes among Extremely Premature Neonates.

This study aimed to investigate whether neonatal morbidity differs in spontaneous compared with indicated preterm births in extremely premature neonates. This is a retrospective cohort study including births ≤28 weeks at a single institution from 2011 to 2020. Births were categorized as either medically indicated or spontaneous preterm deliveries. The primary outcome was inhospital mortality and serious morbidity in survivors. t-tests, Fisher's exact tests, chi-square tests, and logistic regression models were utilized as appropriate. p < 0.05 was significant. Two hundred and twenty-seven births were included, with two-thirds representing spontaneous births (65.6%, 149/227) and one-third categorized as medically indicated births (34.4%, 78/227). Inhospital mortality was more common in the spontaneous preterm birth group (p = 0.04), while inhospital morbidity did not significantly vary between the medically indicated and spontaneous birth groups (p = 0.32). There was no difference in inhospital morbidity or mortality by maternal race. In multivariate models of inhospital morbidity and mortality, gestational age was the only significant predictor of adverse outcomes. Despite inhospital mortality being more common in spontaneous preterm births, inhospital mortality and significant morbidity are best accounted for by gestational age alone. · Inhospital death is more common in spontaneous preterm births.. · Perinatal outcomes do not differ on the basis of racial/ethnic group.. · Gestational age is the best predictor of inhospital morbidity and mortality..

Neurocognitive impairment associated with chronic morbidity in long-term survivors of Hodgkin Lymphoma

AbstractThoracic radiation is associated with significant cardiopulmonary morbidities in survivors of long-term Hodgkin lymphoma and may affect neurocognitive outcomes. Survivors (N = 204; 52.5% female; mean [standard deviation] age, 36.6 [8.01] years) treated with thoracic radiation and age-, sex-, and race/ethnicity-matched community controls (N = 205; 51.7% female; age, 36.7 [9.17] years) completed standardized neurocognitive testing, echocardiography, pulmonary function tests, and vascular studies during the same visit. Treatments were abstracted from medical records. Cardiac (ie, left ventricular ejection fraction [LVEF], global longitudinal strain [GLS]), vascular (ie, large and small artery elasticity [SAE]), pulmonary (ie, diffusing capacity of the lungs for carbon monoxide [DLCO] and forced expiratory volume [FEV1]), and chronic health conditions were evaluated for associations with age-adjusted neurocognitive performance using multivariable linear regression. Compared with controls, survivors had lower performance (P < 0.05) in visuomotor (0.11 vs 0.41), visual processing speed (0.25 vs 0.64), short-term recall (−0.24 vs 0.12), and flexibility (−0.04 vs 0.28). Survivors had lower pulmonary (FEV1, DLCOcorr), cardiac (LVEF, GLS), and vascular function (SAE) than controls (all P < 0.001). FEV1 was associated with visuomotor (P = .008) and visual processing speed (P = .05), and flexibility (P = .05). GLS was associated with short-term recall (P = .03). SAE was associated with flexibility (P = .007). Neurocognitive outcomes were also associated with moderate-to-severe neurologic chronic conditions (P < .05). Findings suggest a link between subclinical cardiopulmonary and vascular findings, neurologic morbidity, and neurocognitive impairments. Prevention of health morbidity may benefit neurocognitive outcomes.

A qualitative exploration of parental caregivers' experience caring for children who have survived medulloblastoma.

Approximately 70% of children diagnosed with a medulloblastoma will become long-term survivors. Medulloblastoma therapy frequently causes long-term morbidities in survivors, which places a considerable burden on parental caregivers. We aimed to explore the experience of parental caregivers caring for medulloblastoma survivors. We conducted a qualitative study using grounded theory thematic analysis. We used semi-structured parental caregiver interviews to explore family experiences, social circumstances, and family-reported impact within families of children who had survived medulloblastoma. Parental caregivers were recruited from specialized survivor clinics at two large quaternary centers in Toronto, Canada. Sixteen of 22 eligible families participated, and 20 parental caregiver interviews were completed. Survivors were a median age of 6years (range: 1-9years) at diagnosis, and were 9.5years (range: 5-12years) from treatment at the time of the interview. Three major themes and associated subthemes emerged: (i) parental caregivers described significant long-term challenges associated with their child's survivorship. Subthemes included medical treatment sequelae, school issues and behavioral concerns, and surveillance and access to care. (ii) Parental caregivers recognized the impact that their child's quality of life (QOL) had on both their personal and family QOL. Subthemes included parental QOL, parental mental health and coping, spousal relationships, and effects on the family unit as a whole. (iii) Parental caregivers reported experiencing conflicting emotions related to their child's survivorship status and long-term effects. Subthemes included feeling happiness with concurrent worry, fear, and stress, as well as concerns about the future. Parental caregivers of medulloblastoma survivors experience long-term challenges, with personal and family impacts. Further work is needed to improve care models and support systems for families with a child who has survived medulloblastoma.

Cardiovascular events among recipients of hematopoietic stem cell transplantation-A systematic review and meta-analysis.

Cardiovascular diseases are an emerging cause of mortality and morbidity in survivors of hematopoietic stem cell transplantation (HSCT); however, the incidence of cardiovascular events (CVEs) in this population is not well described. This systematic review summarizes the evidence on the incidence of CVEs in HSCT recipients. Medline and Embase were searched from inception to December 2020. Inclusion criteria were cohort studies and phase 3 randomized controlled trials that reported CVEs among adults who underwent HSCT for hematological malignancies. After reviewing 8386 citations, 57 studies were included. The incidence of CVEs at 100 days was 0.19 (95% CI: 0.17-0.21) per 100 person-days after autologous HSCT and 0.06 (95% CI: 0.05-0.07) per 100 person-days after allogeneic HSCT. This higher incidence after autologous HSCT was driven by reports of arrhythmia from one population-based study in patients with multiple myeloma. The incidence of long-term CVEs was 3.98 (95% CI; 3.44-4.63) per 1000 person-years in survivors of autologous HSCT and 3.06 (95% CI; 2.69-3.48) per 1000 person-years in survivors of allogeneic HSCT. CVEs remain an important but under-reported cause of morbidity and mortality in recipients of HSCT. Future studies are required to better understand the incidence and risk factors for CVEs in HSCT recipients.

Oropharyngeal tumor cells induce COX-2 expression in peripheral blood monocytes by secretion of IL-1α.

Oropharyngeal squamous cell cancer (OPC) accounts for 3% of all cancers and greater than 1.5% of all cancer deaths in the United States, with marked treatment-associated morbidity in survivors. More than 80% of OPC is caused by HPV16. Tumors induced by HPV have been linked to impaired immune functions, with most studies focused on the local tumor microenvironment. Fewer studies have characterized the effects of these tumors on systemic responses in OPC, especially innate responses that drive subsequent adaptive responses, potentially creating feed-back loops favorable to the tumor. Here we report that elevated plasma levels of PGE2 are expressed in half of patients with OPC secondary to overexpression of COX-2 by peripheral blood monocytes, and this expression is driven by IL-1α secreted by the tumors. Monocytes from patients are much more sensitive to the stimulation than monocytes from controls, suggesting the possibility of enhanced immune-modulating feed-back loops. Furthermore, control monocytes pre-exposed to PGE2 overexpress COX-2 in response to IL-1α, simulating responses made by monocytes from some OPC patients. Disrupting the PGE2/IL-1α feed-back loop can have potential impact on targeted medical therapies.

Respiratory diseases in survivors of adult cancer compared with the general population: a systematic review protocol

IntroductionThere is concern that survivors of adult cancers may be at increased risk of respiratory infections and of exacerbations of pre-existing respiratory conditions. Considering the high prevalence of respiratory disease...

Late effects and treatment related morbidity associated with treatment of neuroblastoma patients in a tertiary paediatric centre.

Survival of neuroblastoma patients has improved over recent decades, but chronic health issues and treatment related late effects cause significant morbidity in survivors. We aimed to describe late effects and long-term toxicity in neuroblastoma patients treated at a tertiary, paediatric institution in Australia. Patients with neuroblastoma treated primarily at The Children's hospital at Westmead were eligible for inclusion. Retrospective analysis of 65 (45 with high-risk and 20 with non-high-risk disease) neuroblastoma patients were performed via medical record review. Approximately 60% of patients were >5 years from diagnosis and termed the "full effects cohort" who had a range of medical and psychosocial late effects analysed through descriptive means. The remaining 26 patients who had not yet reached 5 years post treatment had audiometry analysis only. Of the 65 patients, 72% were alive at last follow-up. The median length of follow-up was 7 years from diagnosis amongst survivors. Therapy was according to contemporary protocols for neuroblastoma and ranged from standard cytotoxic therapies to intensive multimodal regimens and/or experimental therapy depending on risk group/relapse status. Of the 39 full effects cohort, 85% suffered from at least one late effect. Late effects were common in the endocrine, dental and audiometry domains with 38%, 49% and 72% of patients affected in these areas, respectively. Neuro-cognitive domains were also notably affected with 46% of patients suffering a deficit. Two thirds of survivors were disease free at last follow-up. Survivors of high-risk neuroblastoma suffer from a range of chronic illnesses, which lead to morbidity and affect quality of life of survivors.

Subaqueous Bioprinting: A Novel Strategy for Fetal Membrane Repair with 7‐Axis Robot‐Assisted Minimally Invasive Surgery

AbstractPremature rupture of membranes (PROM), defined as breakage of the amniotic sac prior to delivery, complicates 2–4% of pregnancies, leads to one‐third of preterm births, and increases the risk of perinatal mortality and morbidity in survivors. In situ bioprinting enables the fabrication of 3D structures directly for tissue repair or reconstruction in living animals, but is challenging to perform in the subaqueous narrow space where fetal membranes are located. This study reports a novel strategy consisting of an ultrafast photoresponsive hydrogel (1.5 s) and a 7‐axis bioprinting robot to perform subaqueous in situ bioprinting in a minimally invasive approach. Specially, a hydrogel patch with designed gel rivets is printed subaqueously for the therapeutic needs of PROM, and the patch displays robust tissue adhesion, favorable biocompatibility, mechanical properties resembling native tissues, and an appropriate sealing timescale to prolong pregnancy. Experiments performed in an in vitro uterus model and a mid‐gestational rabbit model show a favorable sealing effect for PROM, which validates the potential of this subaqueous bioprinting approach for application. This study not only expands upon in situ bioprinting techniques, but also provides valuable insights for the treatment of PROM and other diseases involving tissue injury in clinical settings.

Time-dependent prognostic value of bispectral index and suppression ratio during targeted temperature management: an early triage tool for treatment escalation plans

Abstract Funding Acknowledgements Type of funding sources: None. Background Post-cardiac arrest myocardial dysfunction contributes to morbidity in survivors of cardiac arrest (CA) and, in case of refractory shock, some patients will benefit from aggressive mechanical support. In this scenario, a non-invasive, reliable and real-time estimation of potential neurological recovery is required to establish personalized treatment escalation plans. Methods We prospectively collected data of bispectral index (BIS) and suppression ratio (SR) monitoring of adult comatose survivors of CA consecutively admitted to an acute cardiac care unit and managed with targeted temperature management (TTM). Neurological status was assessed according to the Cerebral Performance Category (CPC) scale. Results We included 340 patients, 72.1% had an initial shockable rhythm, 72 (21.2%) were females and their mean age was 61.7 ± 14.3 years. Throughout 3-month follow-up, 210 patients (61.8%) achieved a CPC of 1-2 and 130 (38.2%) a CPC of 3-5. Mean BIS values were significantly higher and median SR lower in patients with CPC 1-2 (Figure 1). An average BIS value &amp;gt;26 during first 12 hours of TTM predicted good outcome with 89.3% sensitivity and 75.2% specificity (AUC of 0.86), while average SR values &amp;gt;24 during first 12 hours of TTM predicted poor outcome (CPC 3-5) with 83.6% of sensitivity and 91.8% of specificity (AUC of 0.92). Hourly BIS and SR values exhibited a good predictive performance (AUC &amp;gt; 0.85), starting as soon as hour 2 for SR and 4 for BIS. Conclusions BIS and SR real-time monitoring correlates with patient´s potential of neurological recovery after CA. This finding could help establish personalized treatment escalation plans that reduce consequences of inappropriate interventions, economic costs and uncertainty burden of the patient´s family.