Reduction In Oxygen Requirements Research Articles

Respiratory physiological changes post initiation of neurally adjusted ventilatory assist in preterm infants with evolving or established bronchopulmonary dysplasia.

To assess respiratory changes after neurally adjusted ventilatory assist (NAVA) initiation in preterm infants with evolving or established bronchopulmonary dysplasia (BPD). Premature infants born less than 32weeks gestation with evolving or established BPD initiated on invasive or non-invasive (NIV) NAVA were included. Respiratory data: PCO₂ and SpO₂/FiO₂ (S/F) ratio before and at 4, 24, 48h post-NAVA initiation were collected. Eighty-eight infants, median GA 25.1 (range 22.7-30.3) weeks, with 191 NAVA episodes were included. Infants born < 32weeks with evolving and established BPD showed improvements in PCO₂ and S/F ratio 48h post-NAVA compared to prior: 7.6 (4.5-11.8) versus 8.1 (4.7-13.1) kPa; p < 0.001 and 285 (118-471) versus 276 (103-471); p = 0.013, respectively. Improvements were observed in invasive NAVA: 7.6 (4.5-11.8) versus 8.5 (4.7-12.4) kPa; p = 0.001, 290 (148-471) versus 271 (103-467); p = 0.002, and NIV-NAVA: 7.5 (4.6-11.7) versus 7.9 (5.2-13.1) kPa; p = 0.001, 283 (128-471) versus 294 (114-471); p = 0.002. Severe BPD infants had reductions in PCO₂ 48h post-initiation: 7.2 (5.6-9.7) versus 8.0 (5.4-11.7) kPa; p = 0.002, with lower FiO₂ requirements 0.37 (0.21-0.65) versus 0.43 (0.21-0.8); p = 0.011, and improved S/F ratios 263 (146-471) versus 219 (114-457); p = 0.006. On subgroup analysis, similar improvements were noted in; PCO2 levels in invasive NAVA (p = 0.011) and NIV-NAVA (p = 0.002), S/F ratios in invasive NAVA (p = 0.046) and NIV-NAVA (p = 0.002) and FiO₂ in invasive NAVA (p = 0.034) and NIV-NAVA (p = 0.053).Conclusion: NAVA improves CO₂ clearance and oxygenation in infants with evolving or established and severe BPD at 48h post-initiation. In severe BPD, NAVA also reduced oxygen requirements What is Known: • NAVA has the potential to improve CO2 clearance and oxygenation by optimising alveolar ventilation, adapting to the infant's breathing patterns, and enhancing gas exchange. What is New: • The beneficial effects of NAVA are sustained in infants with evolving or established bronchopulmonary dysplasia (BPD), improving carbon dioxide clearance and oxygenation at 48 hours after initiation.

Effectiveness of Paracetamol in Treating Hemodynamically Significant Patent Ductus Arteriosus in Preterm Newborns

Background: Patent ductus arteriosus (PDA) is a common condition in preterm infants, often requiring medical intervention for closure. Traditional treatments such as indomethacin and ibuprofen are associated with adverse effects, prompting the exploration of alternative therapies. Paracetamol (acetaminophen) has emerged as a potential alternative with a favorable safety profile, but its efficacy in preterm infants remains under investigation. Aim: The aim of this study is to evaluate the efficacy of paracetamol in the management of hemodynamically significant PDA in preterm newborns, focusing on ductal closure rates, respiratory improvement, and the need for further interventions. Methods: This prospective observational study was conducted at Jawaharlal Nehru Medical College &amp; Hospital, enrolling 50 preterm infants diagnosed with hemodynamically significant PDA. Paracetamol (15 mg/kg iv every 6 hours) was administered for 120 hours. Clinical outcomes, including PDA closure, respiratory status, and the need for additional treatments, were monitored. Data were analyzed using SPSS version 23.0. Results: Out of 50 infants, 35 (70%) achieved complete PDA closure after 120 hours of paracetamol therapy. Respiratory improvement was observed in 28 (56%) infants, with a reduction in oxygen requirements. The mean duration of paracetamol treatment was 4.8 ± 0.9 days, and the mean NICU stay was 14.3 ± 3.2 days. No severe adverse events were noted, though 3 (6%) infants experienced mild transient liver enzyme elevation. Conclusion: Paracetamol was found to be an effective treatment for PDA in preterm infants, with high closure rates and a favorable safety profile compared to traditional treatments. It may serve as a viable alternative to indomethacin or surgical ligation in managing PDA. Recommendations: Paracetamol should be considered as a first-line pharmacological treatment for PDA in preterm infants, particularly in cases where traditional treatments are contraindicated or carry a high risk of adverse effects. Further studies with larger cohorts are needed to confirm these findings and assess long-term outcomes. Keywords: Paracetamol, Patent Ductus Arteriosus, Preterm Infants, Pharmacological Treatment, Neonatal Care.

Routine use of ultrasound-assisted catheter-directed thrombolysis for the management of intermediate-high risk pulmonary embolism: a service evaluation project

Abstract Background Intermediate-high risk Pulmonary Embolism (PE) has considerable morbidity. Conservative management could be sub-optimal. Ultrasound-Assisted Catheter-Directed Thrombolysis (UACDT) is used in our centre for the routine management of this presentation. Purpose We assessed the procedure safety and short-term outcomes by reviewing locally performed procedures. Methods This is an observational retrospective cohort study, with a historic control group. Our centre is a District General Hospital (DGH) in the United Kingdom, and we receive referrals from local acute hospitals. Since the introduction of this service in June 2018 until November 2023, 129 patients (2 patients/month) received routine management with UACDT for intermediate-high risk PE. The controls are 75 acute PE patients of comparable risk classes, managed from January to December 2016. We assessed procedural and in-hospital outcomes including minor, major bleeding/complications and death. We also assessed Length of Stay (LoS) in hospital, recurrent Venous Thrombo-Embolism (VTE) and re-admission rates for recurrent PE at 30 days. Reduction of oxygen requirements and improved estimated systolic Pulmonary Artery Pressure (sPAP) post-procedure were assessed as surrogate measures. Continuous variables were analysed with a Mann-Whitney U test, and categorical variables with a Chi-square Test. Results Baseline demographics are listed in Table 1. Mean duration between CT Pulmonary Angiography (CTPA) and the UACDT procedure was 1.6 (±SD 1.4) days, including inter-hospital transfer. Only 6% (8/129) of UACDT cohort received ≤12 mg standard alteplase dose. In the control group, 4% (3/75) of patients received standard 100mg systemic thrombolysis. There was no significant difference in the rates of minor (p= 0.9), major bleeding/complications (p= 0.8), or death (p= 1.0) between both groups. There was also no significant difference in rates of recurrent VTE (p= 1.0) or re-admission within 30 days for PE (p=0.1) (Table 2). LoS in hospital data were ratified, to exclude inappropriate delays (e.g. physiotherapy requirements, etc). We used the date when the patient was declared medically fit for discharge, and no significant difference was noted (p= 0.2). This was confirmed with a regression analysis of UACDT treatment effect (p= 0.9, CI= -3.5 to 3.1). Nonetheless, there was a 25% reduction of median LoS in hospital from 8 days in the controls to 6 days with UACDT. The proportion of patients requiring O2 was also reduced from 69% (89/129) to 41% (54/129) on day 1 post-procedure. A significant reduction of the estimated sPAP by TTE post-procedure was detected by a mean of 10.4 (±SD 13.9) mmHg (p= &amp;lt;0.01). Conclusion UACDT is generally safe with low complications rate. Compared to the control group, there was a reduction in absolute deaths and median LoS in hospital. This can be secondary to the significant acute reduction of systolic pulmonary artery pressure identified.

Comparison of nasal masks or binasal prongs for delivering continuous positive airway pressure in preterm neonates of gestational age less than 32 weeks

Background: Aim was to compare the efficacy and safety of continuous positive airway pressure (CPAP) delivered by nasal masks vs binasal prongs. Methods: This was observational trial where preterm infants less than 32 weeks of gestation with respiratory distress were enrolled after parental consent. Participants: 145 neonates less than 32 weeks gestation requiring nasal CPAP (NCPAP) as a primary mode for respiratory distress, who were treated with either nasal mask (n=45) or nasal prongs (n=99) as interface. Primary outcome: Was the incidence of CPAP failure (need for mechanical ventilation at less than 72 hours). Results: Failure rate in nasal mask group was 13% vs nasal prongs group was 39.4% and the difference was statistically significant. Secondary outcomes were mean FiO2 requirement at 6 hours, duration of CPAP therapy, hospital stay and nasal trauma. There was 3.7±5.78% reduction in oxygen requirement at 6 hours of CPAP initiation with nasal mask as compared to nasal prongs and the difference was statistically significant (p&lt;0.05). the CPAP duration in nasal mask group was 3.4± 4.04 days vs nasal prongs group was 4.5±3.52 days and duration of hospital stay in nasal mask group was 15.4±14.19 vs in nasal prongs group was 20.2±13.86 and the both differences were also statistically significant(p&lt;0.05). Nasal mask had no nasal injury (0%) as compared to infants on nasal prongs (23.2%) and the difference was statistically significant (p&lt;0.05). Conclusions: NCPAP with mask as interface is as effective as prongs but causes less nasal trauma and less CPAP duration and hospital stay.

A straightforward strategy to modulate ROS generation of AIE photosensitizers for type-I PDT

Type-I photodynamic therapy (PDT), valued for its reduced oxygen requirement, generates highly cytotoxic •OH radicals. However, conventional strategies for developing type-I photosensitizers (PSs) are complex and involve intricate organic synthesis. Herein, we present a novel strategy to alter the generation of reactive oxygen species (ROS) by simply manipulating the twisting degree of donor–acceptor (D–A) type aggregation-induced emission (AIE) PSs. Specifically, natural saturated fatty acids are employed to modulate the twisting state of AIE PSs, with higher doping ratios yielding more twisted structures and increased type-I ROS generation. In contrast, fatty acids with higher crystallinity promote planar structures and type-II ROS generation. Theoretical calculations suggest that AIE PSs with highly twisted structures lead to a prominent reduction in ΔEST and effective separation of electron–hole pairs, thereby favoring efficient intersystem crossing and charge transfer. The PDT system primarily driven by type-I ROS exhibits efficient bactericidal activity against clinically drug-resistant bacteria, which remarkably accelerates the recovery of bacteria-infected wounds in mice. This study demonstrates the first example of modulating ROS generation type by manipulating the twisting degree of D–A type AIE PSs, eliminating the need for intricate molecular design and organic synthesis. The proposed strategy opens up new avenues for advancing PDT applications.

Functional outcome after interdisciplinary, acute rehabilitation in COVID-19 patients: a retrospective study

BackgroundSurvivors of severe COVID-19 often exhibit a variety of sequelae including loss of mobility and ADL (activities of daily living) capacity. Acute rehabilitation (AR) is an interdisciplinary rehabilitation intervention applied early while still in a hospital setting. The goal of AR is to improve functional limitations and to increase functional independence at discharge. It is established in the treatment of patients with other severe diseases such as sepsis, polytrauma, or stroke. Data concerning AR in COVID-19 are sparse.AimTo evaluate the changes in physical function during AR in patients after severe COVID-19.MethodsThis monocentric, retrospective observational study examined the functional outcomes of a sample of COVID-19-patients who received interdisciplinary AR at a university hospital. Inclusion criteria were a positive SARS-CoV-2 test in 05/2020–01/2022 and transfer to AR after intensive care treatment. 87 patients were elegible for evaluation, 3 of whom were excluded because of death during AR. Data were extracted from the hospital information system. In a pre-post analysis, mobility (Charité Mobility Index), ADL (Barthel Index), and oxygen demand were assessed. In addition, discharge location after AR, factors associated with AR unit length of stay, and functional improvements were analyzed.ResultsData of 84 patients were analyzed. Mobility increased significantly from a median of 4 [1.25-6] CHARMI points at admission to a median of 9 [8.25-9] at discharge (p < 0.001). ADL increased significantly from a median of 52.5 [35.0-68.75] Barthel Index points at admission to a median of 92.5 [85–95] at discharge (p < 0.001). Oxygen demand decreased from 80.7 to 30.5% of patients. The majority (55.9%) of patients were discharged home, while 36.9% received direct follow-up rehabilitation. Older age correlated significantly with lower scores on the discharge assessment for mobility (Spearman’s ϱ = -0.285, p = 0.009) and ADL (Spearman’s ϱ = -0.297, p = 0.006).ConclusionAcute rehabilitation is a viable option for COVID-19 patients with severe functional deficits after ICU treatment to achieve functional progress in mobility and ADL, reduce oxygen requirements and enable follow-up rehabilitation.Trial registration number and date of registration for prospectively registered trialsTrial registration number: DRKS00025239. Date of registration: 08 Sep 2021.

Ammonium oxidation from concentrated synthetic wastewater and landfill leachate using partial nitritation in sequencing batch reactor.

Partial nitritation (PN) is a novel treatment for nitrogen removal using aerobic ammonium oxidation with reduced oxygen requirements compared to conventional nitrification. This study evaluated the performance of the PN process and the factors influencing nitrogen removal from landfill leachate. During the reactivation of biomass, the results showed 70% ammonium removal, but only 20% total nitrogen removal. Further analysis showed that low nitrite accumulation and high nitrate production promoted the growth of nitrite-oxidizing bacteria (NOB). The ammonium removal activity after soaking the cultivated biomass in synthetic water and leachate was measured to be 0.57, 0.1, 0.17, and 0.25 g N•g VSS-1•d-1 for synthetic wastewater and leachate soaking for synthetic wastewater, 12 h, 3days, and 7days, respectively. The study found abundant ammonium-oxidizing bacteria (AOB) and NOBs in biomass soaked in synthetic wastewater. However, soaking in leachate promoted AOB growth and inhibited NOB growth making leachate suitable for PN. PRACTITIONER POINTS: The study found that with a longer leachate-soaking period for biomass, ammonium removal activity increases, which in turn increases ammonium conversions during the PN process. Ammonium-oxidizing bacteria (AOB) can acclimate to landfill leachate substrate and grow with a longer soaking period. Nitrite-oxidizing bacteria (NOB) were inhibited by landfill leachate substrate, which is beneficial for nitrite accumulation. Anabolized DO can convert nitrite to nitrate rapidly, which results in higher nitrate accumulation compared to nitrite accumulation. Hence, the DO level has to be sufficiently low to prevent nitrite oxidation and nitrate accumulation.

Normalization of eosinophil count is predictive of oxygen weaning over the course of COVID-19 infection among hospitalized adults during the first wave of 2020 pandemic

BackgroundUnderstanding COVID-19 outcomes remains a challenge. While numerous biomarkers have been proposed for severity at admission, limited exploration exists for markers during the infection course, especially for the requirement of oxygen therapy. This study investigates the potential of eosinophil count normalization as a predictor for oxygen weaning during the initial wave of the pandemic.MethodsA retrospective study was conducted between March and April 2020 (first wave) among adults admitted directly to a medicine ward. Biological abnormalities, including lymphocyte count, eosinophil count, and C-reactive protein (CRP), were gathered daily during the first week of admission according to oxygen level. In case of worsening, oxygen level was censored at 15 L/min. The primary aim was to assess whether eosinophil count normalization predicts a subsequent decrease in oxygen requirements.ResultsOverall, 132 patients were admitted, with a mean age of 59.0 ± 16.3 years. Of the patients, 72% required oxygen, and 20.5% were admitted to the intensive care unit after a median delay of 48 hours. The median CRP at admission was 79 (26–130) mg/L, whereas the eosinophil count was 10 (0–60)/mm3. Eosinophil count normalization (≥100/mm3) by day 2 correlated significantly with decreased oxygen needs (&amp;lt;2 L) with hazard ratio (HR) = 3.7 [1.1–12.9] (p = 0.04). Likewise, CRP &amp;lt; 80 mg/L was associated with reduced oxygen requirements (p &amp;lt; 0.001). Predictors, including underlying chronic respiratory disease, exhibited a trend toward a negative association (p = 0.06).ConclusionThe study highlights the relationship between eosinophil count and CRP, with implications for predicting oxygen weaning during COVID-19. Further research is warranted to explore the relevance of these biomarkers in other respiratory infections.

Optimizing Invasive Neonatal Respiratory Care: A Systematic Review of Invasive Neurally Adjusted Ventilatory Assist.

Mechanical ventilation in preterm neonates aims for synchrony, preventing complications such as lung injury. Neurally Adjusted Ventilatory Assist (NAVA) is a unique mode relying on diaphragmatic electrical signals for synchronization. We conducted a review focusing on the long-term consequences of using invasive NAVA in neonates with a focus on bronchopulmonary dysplasia (BPD). A systematic review following PRISMA explored invasive NAVA in preterm neonates. Primary objectives compared NAVA to conventional ventilation, assessing BPD incidence, ventilation duration, length of stay, and adverse events. Secondary objectives analyzed ventilator parameters. After screening 282 records, the review incorporated two randomized controlled trials for primary outcomes and seven trials for secondary outcomes, including two randomized crossovers, four prospective crossovers, and one retrospective study. NAVA showed reduced oxygen requirement at 28 days but no significant differences in oxygen need at 36 weeks postmenstrual age, total length of stay, or ventilator days. Substantial variations were not observed in adverse events. Ventilator variables favored NAVA, indicating decreased peak inspiratory pressure, tidal volume, work of breathing, and respiratory severity score. Our study found no significant reduction in BPD with NAVA despite short-term benefits. Future large-scale trials are essential to assess NAVA's impact on long-term outcomes comprehensively.

Safety and Efficacy of Anakinra in Haemophagocytic Lymphohistiocytosis Associated with Acute Leukaemia

Haemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition in which immune hyperactivation and dysregulation results in a cytokine storm. It may be primary or secondary to infection, autoimmune disorders or malignancies (HLH-M). Lymphoma is the most widely described association in HLH-M; there is very limited data linking acute leukaemia and HLH. Current recommended treatments for HLH-M include steroids, IVIG and etoposide-containing regimens. In contrast, the recommended treatment in HLH- Macrophage activation syndrome is anti-IL1 directed therapy such as anakinra. In 2021 NHS England approved the use of anakinra to treat HLH of any cause, but the safety and efficacy data of anakinra in HLH-M is limited. We report a retrospective review of all patients diagnosed with HLH and acute leukaemia (AML) or acute lymphoblastic leukaemia (ALL) in a single London tertiary referral centre (University College London Hospitals NHS Foundation Trust (UCLH)), between 1 January2019 and 31 December 2022. We analysed electronic health records (EHR) of all patients diagnosed with ALL or AML and cross-referenced this with records of all patients referred to the UCLH HLH MDT. This identified 468 patients with acute leukaemia, of whom 13 (2.8%) were diagnosed with HLH. For diagnostic purposes, we utilised H scores (comprising laboratory and clinical parameters providing an HLH probability for each patient) using clinical and laboratory data collected from the EHR. HLH was diagnosed in patients with a clinical suspicion of HLH and an H score of &amp;gt;169. Patients were treated with various types of immunosuppressive therapy (IST). Twelve (92%) received anakinra, three (17%) of whom had anakinra monotherapy whilst the remainder had anakinra with steroids (38%), steroids and IVIG (15%), or steroids, IVIG and etoposide (8%). Anakinra was given intravenously in eleven patients and subcutaneously in one, with a mean daily dose of 4.6mg/kg. All patients required critical care input during their HLH treatment. Eight (62%) were admitted to intensive care unit (ICU) on diagnosis with HLH and required ventilatory and vasopressor support; the remainder were reviewed by critical care outreach. 92% patients had an initial rapid clinicopathological response following IST, becoming afebrile, reduction in oxygen requirement and haemodynamic stability seen within 24-72 hours. One patient (8%) had an initial clinical response to anakinra, methylprednisolone and IVIG triple therapy, but displayed subsequent rapid deterioration in the context of pseudomonal infection and died of multiorgan failure. Nine patients (69%) had no clinicopathological recurrence of HLH following initial treatment. Three (23%) had an initial clinical response to IST but had subsequent biochemical and clinical relapse of HLH. These patients all had relapsed/refractory disease on HLH recurrence. Only one (8%) patient died from HLH. Eight (62%) remain in remission from leukaemia at the end of the study period. Three patients (23%) died of refractory leukaemia, whilst a fourth patient is receiving palliative care for refractory disease. Although the link between HLH and lymphoma is well characterised, there is limited data on HLH in the context of acute leukaemia. In this case series, 2.8% of the patients treated with acute leukaemia developed HLH, which is comparable to the 3% for lymphoma quoted elsewhere. Although 92% of patients had microbiological or radiological evidence of infection on HLH diagnosis, many infections involved organisms not classically associated with HLH e.g. rhinovirus, indicating that the underlying leukaemia may play a central role in HLH-M pathogenesis. This is highlighted by the relapse of HLH which occurred alongside leukaemia relapse in three patients. Treatment responses and outcomes were favourable compared to the existing literature. Tamamyan et al reported an overall survival rate of 15% in 13 patients with HLH-M. Delavigne et al reported a three-month mortality rate of 36% in AML patients presenting with HLH during induction, compared to our figure of 23% for this time period and our overall survival rate of 62%. We believe this is the first case series demonstrating the effectiveness and high overall survival of HLH-M patients with concurrent leukaemia diagnosis using anakinra. Early treatment with anakinra alongside other immunosuppression may explain the trend towards improved outcomes in our cohort.

2620. Normalization of eosinophil count is predictive of reduced oxygen requirement during Covid-19 infection

Abstract Background The initial need for oxygen during Covid-19 has been correlated with the severity of lung involvement observed on CT-scan caused by the cytokine storm. A recent study showed that the normalization of eosinophil count (≥100/mm3) after 48 hours of appropriate regimen was related to a favorable outcome in sepsis. Our work intends to assess the kinetics of eosinophil count over time based on oxygen levels during the acute phase of this viral infection. Methods Retrospective study, conducted between March-April 2020 (first wave), among adults admitted directly to a medicine ward. Biological abnormalities, including lymphocyte count, eosinophil count, and CRP were gathered daily during the first week of admission (day 0) according to oxygen level. In case of worsening requiring ICU, oxygen level was censored at 15 L/min. Aim of the study was to investigate whether normalization of eosinophil count could predict a decrease in oxygen requirements, and potentially patient’s outcome. Values were presented as median with 95% CI and statistical analysis utilized the Chi-2 square test. Results 132 patients were admitted, mean age 59.0±16.3 years. Mean onset of symptoms was 7±4 days. Majority of patients had cardiovascular disease (43.1%), underlying respiratory disease (16.7%), diabetes (18.9%), immunosuppression (8.3%) and obesity (10.6%). At admission, median (IQR) CRP=79(26-130) mg/L, lymphocyte count=1005(730-1380)/mm3 and eosinophil count=10(0-60)/mm3. 72% of patients required oxygen supply. Lung CT-scan (n=103) revealed: 53.5% had moderate (25-50%) to severe ( &amp;gt;50%) involvement. Twenty-seven patients (20.5%) required ICU due to condition worsening. Eosinophil count increased continuously until normalization from day0 to day3, while the oxygen level started to decrease on day 3 without any rebound observed thereafter (Figure 1). Similarly, CRP decreased to 43 mg/L on day2, but ultimately increased again. Patients requiring &amp;lt; 2L/min of oxygen were significantly associated with an eosinophil count≥100/mm3 on day 2 OR=0.2 [0.07-0.56] (p=0.002). Conclusion Normalization of eosinophil count over time seems predictive of a decrease of oxygen requirement during Covid-19. Those data should be confirmed on other type of respiratory tract infections. Disclosures All Authors: No reported disclosures

The clinical course of COVID-19 in pregnant and non-pregnant women

Aims: Pregnancy is a physiological condition that predisposes women to respiratory complications of viral infections thus, bringing the risk of developing more severe disease. The aim of this research was to elucidate the clinical course of COVID-19 in pregnant and non-pregnant women of childbearing age. Mortality rate, laboratory parameters, the occurence of cytokine storm in both groups and the response to treatment have been investigated.&#x0D; Methods: A total of 88 women of childbearing age with a diagnosis of COVID-19 disease has been retrospectively analyzed. Age, comorbidity, length of stay in the intensive care unit and treatment regimen of patients have been obtained from hospital database. Ferritin, IL-6, CRP, procalcitonin, D-dimer, urea, creatinine, GFR, ALT, AST, LDH, lymphocyte count, neutrophil count, white blood cell count were evaluated. Clinical response such as reduction in oxygen requirement and vasopressor utilization before and after treatment were examined&#x0D; Results: The rate of RT - PCR positive results were statistical significantly higher in pregnant women (p=0.003). The median WBC, lymphocyte and leukocyte values of the pregnant patients were higher (p=0.038, p=0.006 and p=0.035, respectively). The median hemoglobin, LDH and ferritin values of pregnant women were lower than those of non-pregnant individuals (p=0.032, p

Normoxia exposure reduces hemoglobin concentration and gill size in a hypoxia-tolerant tropical freshwater fish

Hypoxia is a widespread environmental stressor that shapes fish physiology and morphology. Plasticity in traits that improve oxygen uptake and delivery or reduce oxygen requirements may be critical for fish to cope with fluctuating dissolved oxygen (DO) conditions in their natural habitat or adapt to new environments. In this study, we characterized a suite of morpho-physiological respiratory traits of a naturally hypoxia-acclimated weakly electric mormyrid fish, Petrocephalus degeni, and quantified their plasticity in response to long-term normoxia exposure. We captured P. degeni from a hypoxic swamp habitat (PO2 = 2.43 ± 1.85 kPa) surrounding Lake Nabugabo, Uganda, and acclimated them to normoxia (PO2 > 16 kPa) for up to 75 days. At various time points throughout normoxia exposure, we measured blood hemoglobin and lactate concentration, gill size, routine metabolic rate (RMR), regulation index (RI), and critical oxygen tension (Pcrit). We found that 62–75 days of normoxia exposure significantly reduced blood hemoglobin concentration (− 17%), gill filament length (− 14%), and hemibranch area (− 18%), whereas RMR, RI, Pcrit, and blood lactate showed no significant change. Our results support earlier findings that swamp-dwelling P. degeni are well adapted to life in chronic and severe hypoxia and indicate that they possess a limited capacity for phenotypic plasticity in response to a change in their DO environment.

Megakaryoblasts in pleural fluid in neonate with transient leukaemia of Down's syndrome.

Twin baby boy born at 35+2 weeks gestation with a birth weight of 2070 grams via emergency cesarean section secondary to abnormal CTG and foetal distress. Full blood count obtained at birth showed haemoglobin 159 g/L, total white cell count 99.54 × 109/L platelet count 779 × 109/L. Manual differential showed an absolute neutrophil count of 2.01 × 109/L absolute lymphocyte count of 45.27 × 109/L and blast count of 50.3 × 109/L (50%). Initial peripheral blood smear morphology review revealed a thrombocytosis, platelet anisocytosis and micromegakaryocytes. It also demonstrated neutropenia, myeloid left shift, large blasts with a high N/C ratio and nucleoli. Additionally, numerous nucleated red blood cells were seen with marked red cell dysplasia including binucleate forms and abnormal haemoglobinisation. There was no prenatal diagnosis of Down's syndrome (DS). The above blood results along with the baby's clinical signs raised suspicion of DS and subsequently transient leukaemia of DS. This baby was then transferred to the regional neonatal intensive care unit on day 2 of life. On admission, he was noted to have bilateral pleural effusion, synthetic liver dysfunction with elevated creatinine and ammonia levels as well as ascites. He was intubated, and ventilated and required inotropic support. Due to adverse features of elevated white cell count, hepatosplenomegaly, pleural effusion as well as ascites [1] and following the multidisciplinary team (MDT) discussion and parental consent, the patient was commenced on low dose cytarabine for 7 days. He tolerated that well, however, did experience mild cytopenias and pyrexic episodes, followed by recovery during the following two weeks with a reduction in pleural effusions, hepatosplenomegaly and reduction in oxygen requirement which enabled successful extubation and commencement of continuous positive airway pressure. Unfortunately, on day 19 of life he was noted to have slowly increasing oxygen requirements with re-accumulation of pleural effusions and increasing hepatosplenomegaly as well as increasing blast count in peripheral blood. He proceeded to require intubation and ventilation again as well as placement of a chest drain to remove pleural fluid to improve respiratory compliance. A review of pleural fluid morphology had shown frequent ‘blast-like’ cells; these were medium-sized with a high N/C ratio with finely condensed chromatin nucleoli and budded basophilic cytoplasm thought to most likely represent megakaryoblasts [2]. As a result of the deterioration, a decision by MDT was made to give another cycle of low-dose cytarabine on days 1 through 5. Following the second cycle of cytarabine, the patient again experienced mild cytopenias and pyrexic episodes, was treated with antibiotics and supportive management and transfusions of packed red cells. He had complete count recovery and no blast population identified morphologically on peripheral blood film on day 26 of the second cycle of cytarabine. His GATA1 mutation was subsequently found to be positive. He continued to improve and was discharged home on day 67 of life Figures 1-3. Karolina Chmielowiec—wrote the manuscript, Gary Beattie—manuscript review, obtained image, obtained and analysed flow cytometry data, Kathryn Clarke—manuscript review, obtained and analysed flow cytometry, Ellen McCloy—manuscript review, morphology review, Bethany Mitchell—manuscript review, morphology review, Christine Macartney—manuscript review, supervising consultant. All authors discussed the results and commented on the manuscript. None. The authors declare no conflict of interest. No funding was required for this submission. Not applicable. Not Applicable. Not Applicable All authors have contributed to the acquisition, analysis and interpretation of data as well as either drafting the paper or revising it critically. All authors approved the submitted and final versions. For original data, please contact [email protected]

Follow-up of Interleukin 6 and Other Blood Markers during the Hospitalization of COVID-19 Patients: A Single-Center Study

COVID-19 is a recent respiratory illness with high morbidity and mortality; therefore, the study and characterization of blood markers associated with the improvement or deterioration of COVID-19 patients are crucial. This study compared levels of interleukin 6 (IL-6), procalcitonin (PCT), D-dimer, cortisol, dehydroepiandrosterone sulfate (DHEA-S), c-reactive protein (CRP), 25-OH vitamin D, anti-SARS-CoV-2 IgG antibodies, and viremia in mild–moderate and severe–critical COVID-19 patients. In addition, the time course of blood markers was studied in severe–critical cases. The results show that levels of IL-6, PCT, D-dimer, and CRP, the cortisol/DHEA-S ratio, as well as positive viremia and anti-Spike IgGs were higher in severe–critical patients requiring hospitalization. During follow-up, most severe–critical cases displayed similar time patterns of IL-6 and viral load, whereas anti-SARS-CoV-2 antibody curves showed an inverse pattern. A decrease in IL-6 levels was associated with the improvement of COVID-19 patients, mostly through a reduced oxygen requirement. This preliminary study suggests that an increase in serum IL-6, PCT, D-dimer and CRP levels and the cortisol/DHEA-S ratio could support the selection of patients with poorer prognosis and the need for an intensive or alternative treatment. Additionally, changes in IL-6 during hospitalization were associated with changes in patient’s status mainly with a decrease in oxygen requirements, which indicates that serial measurements of IL-6 could predict the outcome of severe–critical patients with COVID-19 pneumonia.

TRAFFIC JAM IN THE VASCULATURE: A CASE OF PULMONARY LEUKOSTASIS

TRAFFIC JAM IN THE VASCULATURE: A CASE OF PULMONARY LEUKOSTASIS

Nonthyroidal Illness Syndrome: To Treat or Not to Treat? Have We Answered the Question? A Review of Metanalyses.

Background and ObjectiveNonthyroidal Illness Syndrome (NTIS) occurs in approximately 70% of patients admitted to Intensive Care Units (ICU)s and has been associated with increased risk of death. Whether patients with NTIS should receive treatment with thyroid hormones (TH)s is still debated. Since many interventional randomized clinical trials (IRCT)s were not conclusive, current guidelines do not recommend treatment for these patients. In this review, we analyze the reasons why TH treatment did not furnish convincing results regarding possible beneficial effects in reported IRCTs.MethodsWe performed a review of the metanalyses focused on NTIS in critically ill patients. After a careful selection, we extracted data from four metanalyses, performed in different clinical conditions and diseases. In particular, we analyzed the type of TH supplementation, the route of administration, the dosages and duration of treatment and the outcomes chosen to evaluate the results.ResultsWe observed a marked heterogeneity among the IRCTs, in terms of type of TH supplementation, route of administration, dosages and duration of treatment. We also found great variability in the primary outcomes, such as prevention of neurological alterations, reduction of oxygen requirements, restoration of endocrinological and clinical parameters and reduction of mortality.ConclusionsNTIS is a frequent finding in critical ill patients. Despite several available IRCTs, it is still unclear whether NTIS should be treated or not. New primary endpoints should be identified to adequately validate the efficacy of TH treatment and to obtain a clear answer to the question raised some years ago.

Peripartum Severe COVID-19 Pneumonia: Fetal and Neonatal Implications.

Peripartum Severe COVID-19 Pneumonia: Fetal and Neonatal Implications.

Nitazoxanide in Patients Hospitalized With COVID-19 Pneumonia: A Multicentre, Randomized, Double-Blind, Placebo-Controlled Trial

BackgroundNitazoxanide exerts antiviral activity in vitro and in vivo and anti-inflammatory effects, but its impact on patients hospitalized with COVID-19 pneumonia is uncertain.MethodsA multicentre, randomized, double-blind, placebo-controlled trial was conducted in 19 hospitals in Brazil. Hospitalized adult patients requiring supplemental oxygen, with COVID-19 symptoms and a chest computed tomography scan suggestive of viral pneumonia or positive RT-PCR test for COVID-19 were enrolled. Patients were randomized 1:1 to receive nitazoxanide (500 mg) or placebo, 3 times daily, for 5 days, and were followed for 14 days. The primary outcome was intensive care unit admission due to the need for invasive mechanical ventilation. Secondary outcomes included clinical improvement, hospital discharge, oxygen requirements, death, and adverse events within 14 days.ResultsOf the 498 patients, 405 (202 in the nitazoxanide group and 203 in the placebo group) were included in the analyses. Admission to the intensive care unit did not differ between the groups (hazard ratio [95% confidence interval], 0.68 [0.38–1.20], p = 0.179); death rates also did not differ. Nitazoxanide improved the clinical outcome (2.75 [2.21–3.43], p < 0.0001), time to hospital discharge (1.37 [1.11–1.71], p = 0.005), and reduced oxygen requirements (0.77 [0.64–0.94], p = 0.011). C-reactive protein, D-dimer, and ferritin levels were lower in the nitazoxanide group than the placebo group on day 7. No serious adverse events were observed.ConclusionsNitazoxanide, compared with placebo, did not prevent admission to the intensive care unit for patients hospitalized with COVID-19 pneumonia.Clinical Trial RegistrationBrazilian Registry of Clinical Trials (REBEC) RBR88bs9x; ClinicalTrials.gov, NCT04561219.

SAVING AND EARLY DICHARGE OF A NEONATE WITH SEVERE MECONIUM ASPIRATION SYNDROME

Animal experiments have shown the resolution of radiological infiltrates of meconium aspiration syndrome (MAS) after using surfactant lavage. Intra-tracheal instillation of surfactant, as well as surfactant lavage, is studied in MAS. However, INSURE (INtubation, administration of SURfactant, Extubation) is never reported to have been used for meconium aspiration syndrome although it is used as the standard method of delivery of surfactant for respiratory distress syndrome. This is a case report of the use of INSURE technique for severe Meconium Aspiration syndrome. The baby was born at term gestational age to a primigravida mother by C-section for fetal distress. The baby was vigorous with chest retractions. Hence baby was supported with delivery room Continuous positive airway pressure (CPAP) and shifted to Neonatal Intensive Care Unit (NICU). In NICU, the baby was stabilized and given surfactant using the INSURE technique. Subsequently, a Chest X-ray showed clearing of lung infiltrates and drastically reduced oxygen requirement of the baby and the baby was discharged early to home.