Search Results (45)

The development of severe SARS-CoV-2 pneumonia is characterized by extensive lung inflammation, which, in turn, leads to respiratory distress and a decline in blood oxygen levels. Hospital admission, along with intensive care or ventilator usage, becomes necessary because this condition leads to serious respiratory problems. This review aims to provide a comprehensive overview of the pathophysiological mechanisms, diagnostic methods, and current therapeutic options for pneumonia caused by the SARS-CoV-2 virus. The pathophysiological process of severe pneumonia due to SARS-CoV-2 infection is characterized by direct lung damage from viral replication, an excessive immune system response, inflammation, impaired gas exchange, and multi-organ failure. The coexistence of various medical conditions leads to substantial lung impairment, resulting in hypoxia and respiratory failure, which can ultimately lead to fatal outcomes. The diagnosis of severe SARS-CoV-2 pneumonia is made through a combination of clinical, radiologic, and laboratory findings. A multifaceted approach integrating antiviral therapy, corticosteroids, oxygen supplementation, ventilatory management, and immunomodulation is imperative to control inflammation and enhance clinical outcomes. Early intervention, meticulous monitoring, and personalized care are paramount for enhancing survival and mitigating complications in critically ill patients with COVID-19 pneumonia. Full article

Acute lung injury (ALI), a life-threatening clinical syndrome with multifactorial origins, is characterized by uncontrolled pulmonary inflammation and disrupted alveolar–capillary barrier integrity, leading to progressive hypoxemia and respiratory failure. In this hypoxic setting, hypoxia-inducible factor (HIF)-1 is activated, acting as a central regulator of the inflammatory response and reparative processes in injured lung tissue during ALI. The role of HIF-1 is distinctly dualistic; it promotes both anti-inflammatory and reparative mechanisms to a certain extent, while potentially exacerbating inflammation, thus having a complex impact on disease progression. We explore the latest understanding of the role of hypoxia/HIF-mediated inflammatory and reparative pathways in ALI and consider the potential therapeutic applications of drugs targeting these pathways for the development of innovative treatment strategies. Therefore, this review aims to guide future research and clinical applications by emphasizing HIF-1 as a key therapeutic target for ALI. Full article

Background: Among patients with congenital heart disease, particularly those with a history of undergoing the Fontan operation, pregnancy presents a significant maternal–fetal risk, especially when complicated by severe valvular dysfunction. Lung reperfusion syndrome (LRS) is a rare but life-threatening complication occurring following valve intervention. Multidisciplinary management, including by Cardio-Obstetrics teams, is essential for optimizing outcomes in such high-risk cases. Methods: We present the case of a 37-year-old pregnant patient with previously repaired tetralogy of Fallot (via the Fontan procedure) who presented at 24 weeks gestation with worsening severe pulmonary stenosis and right-ventricular dysfunction. The patient had been lost to cardiac follow-up for over a decade. She experienced recurrent arrhythmias, including supraventricular and non-sustained ventricular tachycardia, prompting hospital admission. A multidisciplinary team recommended transcatheter pulmonic valve replacement (TPVR), performed at 28 weeks’ gestation. Results: Post-TPVR, the patient developed acute hypoxia and hypotension, consistent with Lung Reperfusion Syndrome, necessitating intensive cardiopulmonary support. Despite initial stabilization, progressive maternal respiratory failure and fetal compromise led to an emergent cesarean delivery. The neonate’s neonatal intensive care unit (NICU) course was complicated by spontaneous intestinal perforation, while the mother required intensive care unit (ICU)-level care and a bronchoscopy due to new pulmonary findings. She was extubated and discharged in stable condition on postoperative day five. Conclusions: This case underscores the complexity of managing severe congenital heart disease and valve pathology during pregnancy. Lung reperfusion syndrome should be recognized as a potential complication following TPVR, particularly in pregnant patients with Fontan physiology. Early involvement of a multidisciplinary Cardio-Obstetrics team and structured peripartum planning are critical to improving both maternal and neonatal outcomes. Full article

The rapid worldwide transmission of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to severe cases of hypoxia, acute respiratory distress syndrome, multi-organ failure, and ultimately death. Small-scale molecular interactions have been analyzed by focusing on several genes/single genes, providing important insights; however, genome-wide multi-omics comprehensive molecular interactions have not yet been well investigated with the exception of GWAS and eQTLm, both of which show genetic risks. From April of 2020 until now, we have created a Japan-wide system, initially named the Japan COVID-19 Task Force. This system has collected more than 6500 COVID-19 patients’ peripheral blood and as much associated clinical information as possible from a network of more than 120 hospitals. DNA, RNA, serum, and plasma were extracted and stored in this bank. This study unravels the interplay of inflammatory gene networks that induce different COVID-19 severity levels (mild, moderate, severe, and critical) by using multi-omics data from the Japan COVID-19 Task Force. We analyze RNA and protein expressions to estimate severity-specific inflammation networks that uncover the interplay between RNA and protein networks via ligand–receptor pairs. Our large-scale RNA/protein expression data analysis reveals that the atypical chemokine receptor 2 (ACKR2) acts as a key broker linking RNA and protein inflammation networks to induce COVID-19 critical severity. ACKR2 emerges in RNA and protein inflammation networks, showing active interplay in high-severity cases and weak interactions in mild cases. The results also show severity-specific molecular interactions between interleukin (IL), cytokine receptor activity, cell adhesion, and interactions involving the CC chemokine ligand (CCL) gene family and ACKR2. Full article

Background/Objectives: Management of complex congenital heart defects with functionally single ventricle remains one of the greatest challenges of pediatric cardiology. The multistage surgical treatment completed with Fontan procedure is related to multiple complications. Due to non-pulsatile continuous pulmonary flow and chronic hypoxia, Fontan circulation may induce pulmonary endothelial dysfunction. However, the impact of Fontan physiology on respiratory system function is not well studied. The aim of the research was to assess respiratory function in Fontan pediatric patients with hypoplastic left heart syndrome (HLHS) and other morphologies of functionally single ventricle. The article presents the preliminary results drawn from the pilot study, focusing on Fontan patients, without a healthy children control group. Methods: A cross-sectional study involved Fontan patients hospitalized in the Pediatric Cardiology Clinic of the Medical University of Silesia in Katowice between August 2023 and November 2024. The exclusion criteria were lack of parental and/or patient’s consent, age < 6 years old, decompensated heart failure, asthma, atopy, respiratory infection within two weeks before the hospitalization, or significant psychomotor disability. Respiratory function assessment involved spirometry and fractional exhaled nitric oxide (FeNO) measurement. Results: A total of 32 patients who met inclusion criteria performed respiratory measurements. The mean age was 12.9 years old; there were 12 females. A total of 12 patients had HLHS and 20 patients had other morphologies of univentricular heart. FeNO values were relatively high with a mean of 30 ppb. Spirometry showed restrictive or mixed restrictive and obstructive ventilatory pattern. The mean forced vital capacity (FVC) levels were 79.2 ± 12.3% of predicted value (%pv) and forced expiratory volume in the first second (FEV1) 77.3 ± 13.8%pv. Children with HLHS presented statistically significantly lower percentages of predicted value of FEV1. There were statistically significant negative correlations between NT-proBNP concentrations and FEV1, FEV1%pv, MEF25-75 and MEF25-75%pv. Conclusions: Fontan pediatric patients present a restrictive or mixed restrictive and obstructive ventilatory pattern and relatively high FeNO levels. Patients with HLHS have worse pulmonary function than patients with other univentricular heart morphologies. This may be related to worse ventricular function in patients with HLHS. Full article

Recovery from traumatic spinal cord injury (tSCI) is challenging due to the limited regenerative capacity of the central nervous system to restore cells, myelin, and neural connections. At the clinical level, the fundamental pillars of treatment are the reduction in secondary damage (neuroprotection) and rehabilitation; these are the tools we have to mitigate the disability caused by spinal cord injury (SCI). To date, the treatments on which neuroprotection has been based are the prevention of acute respiratory failure to avoid hypoxia, early hemodynamic control, neuroprotective drugs and surgical management. Optimizing early hemodynamic control to ensure adequate spinal cord perfusion may be key to the management of SCI. While neuroprotective agents like methylprednisolone have fallen into disuse, several promising therapies are currently being tested in clinical trials. In terms of surgical treatment, although their impact on neurological recovery remains debated, appropriate early bone decompression followed by duroplasty in selected cases is increasingly recommended. Advances in cell therapies hold significant potential for enhancing both clinical and functional outcomes in SCI patients. Moreover, emerging neuromodulation techniques, such as transcutaneous and epidural stimulation, along with innovations in rehabilitation technologies—such as robotic systems and exoskeletons—are becoming indispensable tools for improving locomotion and overall mobility in individuals with SCI. This article provides an update on the advances in neuroprotection against secondary damage caused by tSCI, in cellular therapies, and in new rehabilitation therapies. Full article

Background: A reduction in carotid artery blood flow (CABF) and ultimately in wall shear stress (WSS) is a major driver of heightened peripheral chemoreceptor (PCh) activity in animal models of heart failure. However, it is yet to be translated to humans. To provide more insight into this matter, we considered severe aortic stenosis (AS) before and after transcatheter aortic valve implantation (TAVI) as a human model of carotid and aortic body function under dramatically different hemodynamic conditions. Materials and Methods: A total of 26 severe AS patients (aged 77 ± 6 y, body mass index: 29.1 ± 5.1 kg/m², left ventricular ejection fraction (LVEF): 50 ± 15%) were subjected to a transient hypoxia test twice: immediately before vs. 1–4 months after TAVI (median follow-up: 95 days). PCh function was analyzed in terms of ventilatory (HVR, L/min/SpO₂%) and heart rate responses to hypoxia (HR slope, bpm/SpO₂%). Standard ultrasound (inc. aortic valve area [AVA], mean aortic valve gradient, peak aortic jet velocity, LVEF, and CABF), respiratory, hemodynamic, and blood parameters were collected at both visits. Pre- vs. post-TAVI data regarding HVR and HR slopes were available for N = 26 and N = 10 patients, respectively. Results: HVR did not change following TAVI (pre- vs. post-TAVI: 0.42 ± 0.29 vs. 0.39 ± 0.33 L/min/SpO₂%, p = 0.523). The HR slope increased after TAVI (pre- vs. post-TAVI: 0.26 ± 0.23 vs. 0.37 ± 0.30 bpm/SpO₂%, p = 0.019), and the magnitude of the increase was strongly associated with an increase in AVA (Spearman’s R = 0.80, p = 0.006). No other significant relations between pre- vs. post-TAVI changes in PCh activity measures vs. hemodynamic parameters were found (all p > 0.12). Conclusions: The ventilatory component of the PCh reflex (defined as HVR) in severe AS patients is not affected by TAVI, and pre-TAVI values in this group are fairly comparable to those reported previously for healthy subjects. On the contrary, HR responses to hypoxia are increased after TAVI, and pre-TAVI values appear to be lower compared to the healthy population. An extraordinarily strong correlation between post-TAVI increases in HR slope and AVA may suggest that hemodynamic repercussions of the surgery in the aortic body area (most likely reduced WSS) play a critical role in determining aortic body function with a negligible effect on the carotid bodies. However, caution is needed when interpreting the results of the HR response to hypoxia in our study due to the small sample size (N = 10). Full article

Background: There is a growing concern that opioids and benzodiazepines can depress the respiratory drive and could contribute to worsening respiratory failure and higher exacerbation frequency in COPD. However, the relationship between the exacerbation rate and medication taken is poorly understood in patients with chronic respiratory failure due to COPD. Methods: As part of a service evaluation project, we analysed 339 patients with COPD who were established on long-term non-invasive ventilation (LT-NIV) at our tertiary centre. We investigated the relationship between benzodiazepine and opioid prescription and clinical outcomes as well as their impact on the exacerbation rate and overall survival following setup. Results: Before LT-NIV setup, 40 patients took benzodiazepines and 99 patients took opioids. Neither benzodiazepine nor opioid use was associated with changes in daytime blood gases, overnight hypoxia or annual exacerbations before NIV setup, but patients taking opioids were more breathless as assessed by modified Medical Research Council scores (3.91 ± 0.38 vs. 3.65 ± 0.73, p < 0.01). Long-term NIV significantly reduced the number of yearly exacerbations (from 3.0/2.0–5.0/ to 2.8/0.71–4.57/, p < 0.01) in the whole cohort, but the effect was limited in those who took benzodiazepines (from 3.0/2.0–7.0/ to 3.5/1.2–5.5/) or opioids (3.0/2.0–6.0/ to 3.0/0.8–5.5/). Benzodiazepine use was associated with reduced exacerbation-free survival and overall survival (both p < 0.05). However, after adjustment with relevant covariates, the relationship with exacerbation-free survival became insignificant (p = 0.12). Opioids were not associated with adverse outcomes. Conclusions: Benzodiazepines and opiates are commonly taken in this cohort. Whilst they do not seem to contribute to impaired gas exchange pre-setup, they, especially benzodiazepines, may limit the benefits of LT-NIV. Full article

Background: Neonatal hypoxic respiratory failure (HRF) secondary to PPHN (persistent pulmonary hypertension of the newborn) is an uncommon but life-threatening complication. Despite advances in therapeutic interventions, there are neonates who may require ECMO (extracorporeal membrane oxygenation), which improves survival. In establishing the capability of ECMO in transport in New South Wales, significant variation in referral thresholds and management of PPHN in referring hospitals has been noted. Aim: To review cases referred to the Newborn and paediatric Emergency Transport Service (NETS) for consideration of ECMO due to HRF in neonates. The aetiology of HRF, the number of retrievals and their short-term outcomes were reported. Methods: A retrospective audit of referrals to NETS (January 2019 to December 2022) of infants aged <28 days with HRF for ECMO. Patient demographics, management, advice at the time of call and the outcome are described. Results: The mean weight was 3511 g, mean gestation was 37.1 weeks and 69% of the patients were male. The main diagnoses were MAS/PPHN (50%), and there was variation in inotropes and ventilation strategies at the time of the referral. Six (25%) of the fifteen babies who were transported by NETS to paediatric intensive care were placed on ECMO at the referring hospital. A further six babies were stabilised at the referral centre following NETS co-ordinated specialist advice and did not require retrieval or ECMO. All the babies who received ECMO and survived had normal early development (<6 months) with normal head US or MRI imaging. Conclusions: Optimising ventilation and inotrope management can eliminate the need for ECMO prior to or following retrieval. Early referral for the consideration of ECMO and a collaborative discussion can assist in optimising conventional therapy, thus eliminating the need for ECMO. Neonates requiring ECMO for HRF have good survival rates with good short-term neurological outcomes. Full article

Both obstructive sleep apnea (OSA) and acute lower respiratory tract infections (LRTIs) are important global health issues. The pathophysiological links between OSA and LRTIs include altered immune responses due to chronic intermittent hypoxia and sleep fragmentation, increased aspiration risk, and a high burden of comorbidities. In this narrative review, we evaluated the current evidence on the association between OSA and the incidence and outcomes of acute LRTIs in adults, specifically community-acquired pneumonia and viral pneumonia caused by influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Studies have demonstrated that OSA patients are more likely to develop bacterial pneumonia and exhibit a higher risk of invasive pneumococcal disease. The risk intensifies with the severity of OSA, influencing hospitalization rates and the need for intensive care. OSA is also associated with an increased risk of contracting influenza and suffering more severe disease, potentially necessitating hospitalization. Similarly, OSA contributes to increased COVID-19 disease severity, reflected by higher rates of hospitalization, longer hospital stays, and a higher incidence of acute respiratory failure. The effect of OSA on mortality rates from these infections is, however, somewhat ambiguous. Finally, we explored antibiotic therapy for OSA patients with LRTIs, addressing care settings, empirical regimens, risks, and pharmacokinetic considerations. Given the substantial burden of OSA and its significant interplay with acute LRTIs, enhanced screening, targeted vaccinations, and optimized management strategies for OSA patients should be prioritized. Full article

Extracorporeal membrane oxygenation (ECMO) is a cardiac or pulmonary function support system that is used in cases of refractory organ failure in addition to conventional treatment. Currently, Level I evidence is not yet available, which reflects improved outcomes with ECMO in pregnant women, the use in pregnancy should be indicated in selected cases and only in specialized centers. We searched articles in the most important scientific databases from 2009 until 31 December 2023 consulting also the site ClinicalTrials.com to find out about studies that have been recently conducted or are currently ongoing. We matched the combination of the following keywords: “ECMO and pregnancy”, “H1N1 and pregnancy”, “COVID-19 and pregnancy”, “ARDS and pregnancy”, “ECMO and pregnancy AND (cardiac arrest)”. We selected the following number of articles for each keyword combination: “ECMO and pregnancy” (665 articles); “ECMO and influenza H1N1” (384 articles); “pregnancy and influenza H1N1” (1006 articles); “pregnancy and ARDS” (2930 articles); “ECMO and pregnancy and ARDS and influenza H1N1” (24 articles); and “[ECMO and pregnancy AND (cardiac arrest)]” (74 articles). After careful inspection, only 43 papers fitted our scope. There are two types of ECMO: venous-venous (VV-ECMO) and venous-arterial (VA-ECMO). The first-one is necessary to cope with severe hypoxia: oxygen-depleted blood is taken from the venous circulation, oxygenated, and carbon dioxide removed from the extracorporeal circuit and returned to the same venous system. The VA-ECMO is a type of mechanical assistance to the circulatory system that allows to put the failing organ at rest by ensuring adequate oxygenation and systemic de-oxygenation, avoiding multi-organ failure. The main indications for ECMO support in pregnant women are cardiogenic shock, acute respiratory distress syndrome (ARDS), pulmonary embolism, and eclampsia. There are also fetal indications for ECMO, and they are fetal distress, hypoxic-ischemic encephalopathy (HIE), and twin-to-twin transfusion syndrome (TTTS). Until now, based on the outcomes of the numerous clinical studies conducted, ECMO has been shown to be a successful therapeutic strategy in cases where medical treatment has been unsuccessful. In well-selected pregnant patients, it appears to be safe and associated with a low risk of maternal and fetal complications. The aim of this review is to report the main properties of ECMO (VV and VA) and the indications for its use in pregnant women. Full article

Chest trauma is one of the most serious and difficult injuries, with various complications that can lead to ventilation–perfusion (V/Q) mismatch and systemic hypoxia. We are presenting a case of a 53-year-old male with no chronic therapy who was admitted to the Intensive Care Unit due to severe respiratory failure after chest trauma. He developed a right-sided pneumothorax, and then a thoracic drain was placed. On admission, the patient was hemodynamically unstable and tachypneic. He was intubated and mechanically ventilated, febrile (38.9 °C) and unconscious. A lung CT showed massive non-ventilated areas, predominantly in the right lung, guiding repeated therapeutic and diagnostic bronchoalveolar lavages. He was ventilated with PEEP of 10 cmH₂O with a FiO₂ of 0.6–0.8. Empirical broad-spectrum antimicrobial therapy was immediately initiated. Both high FiO₂ and moderate PEEP were maintained and adjusted according to the current blood gas values and oxygen saturation. He was weaned from mechanical ventilation, and non-invasive oxygenation was continued. After Stenotrophomonas maltophilia was identified and treated with sulfamethoxazole/trimethoprim, a regression of lung infiltrates was observed. In conclusion, both ventilatory and antibiotic therapy were needed to improve the oxygenation and outcome of the patient with S. maltophilia pneumonia and V/Q mismatch. Full article

COVID-19 is primarily a respiratory disease, but numerous studies have indicated the involvement of various organ systems during the course of illness. We conducted a comprehensive review of atypical complications of COVID-19 with their incidence range (IR) and their impact on hospitalization and mortality rates. We identified 97 studies, including 55 research articles and 42 case studies. We reviewed four major body organ systems for various types of atypical complications: (i) Gastro-intestinal (GI) and hepatobiliary system, e.g., bowel ischemia/infarction (IR: 1.49–83.87%), GI bleeding/hemorrhage (IR: 0.47–10.6%), hepatic ischemia (IR: 1.0–7.4%); (ii) Neurological system, e.g., acute ischemic stroke/cerebral venous sinus thrombosis/cerebral hemorrhage (IR: 0.5–90.9%), anosmia (IR: 4.9–79.6%), dysgeusia (IR: 2.8–83.38%), encephalopathy/encephalitis with or without fever and hypoxia (IR: 0.19–35.2%); (iii) Renal system, e.g., acute kidney injury (AKI)/acute renal failure (IR: 0.5–68.8%); (iv) Cardiovascular system, e.g., acute cardiac injury/non-coronary myocardial injury (IR: 7.2–55.56%), arrhythmia/ventricular tachycardia/ventricular fibrillation (IR: 5.9–16.7%), and coagulopathy/venous thromboembolism (IR: 19–34.4%). This review encourages and informs healthcare practitioners to keenly monitor COVID-19 survivors for these atypical complications in all major organ systems and not only treat the respiratory symptoms of patients. Post-COVID effects should be monitored, and follow-up of patients should be performed on a regular basis to check for long-term complications. Full article

Acute hypoxic respiratory failure (AHRF) is a prominent feature of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) critical illness. The severity of gas exchange impairment correlates with worse prognosis, and AHRF requiring mechanical ventilation is associated with substantial mortality. Persistent impaired gas exchange leading to hypoxemia often warrants the prolonged administration of a high fraction of inspired oxygen (FiO₂). In SARS-CoV-2 AHRF, systemic vasculopathy with lung microthrombosis and microangiopathy further exacerbates poor gas exchange due to alveolar inflammation and oedema. Capillary congestion with microthrombosis is a common autopsy finding in the lungs of patients who die with coronavirus disease 2019 (COVID-19)-associated acute respiratory distress syndrome. The need for a high FiO₂ to normalise arterial hypoxemia and tissue hypoxia can result in alveolar hyperoxia. This in turn can lead to local alveolar oxidative stress with associated inflammation, alveolar epithelial cell apoptosis, surfactant dysfunction, pulmonary vascular abnormalities, resorption atelectasis, and impairment of innate immunity predisposing to secondary bacterial infections. While oxygen is a life-saving treatment, alveolar hyperoxia may exacerbate pre-existing lung injury. In this review, we provide a summary of oxygen toxicity mechanisms, evaluating the consequences of alveolar hyperoxia in COVID-19 and propose established and potential exploratory treatment pathways to minimise alveolar hyperoxia. Full article

Remdesivir is one of the most attractive options for patients with hypoxemic respiratory failure due to coronavirus disease 2019 (COVID-19). The aim of our study was to evaluate the effect of remdesivir on the hypoxic and inflammatory state in patients with moderate to severe COVID-19. We retrospectively enrolled 112 patients admitted for COVID-19 pneumonia, requiring low-flow oxygen, 57 treated with remdesivir plus standard of care (SoC) and 55 treated only with SoC that were similar for demographic and clinical data. We evaluated changes in hypoxemia and inflammatory markers at admission (Day 0) and after 5 days of treatment (Day 5) and the clinical course of the disease. From Day 0 to Day 5, the ratio of arterial oxygen partial pressure to fractional inspired oxygen (P/F) increased from 222 ± 62 to 274 ± 97 (p < 0.0001) in the remdesivir group and decreased from 223 ± 62 to 183 ± 76 (p < 0.05) in the SoC group. Interleukine-6 levels decreased in the remdesivir (45.9 to 17.5 pg/mL, p < 0.05) but not in the SoC group. Remdesivir reduced the need for ventilatory support and the length of hospitalization. In conclusion, compared to standard care, remdesivir rapidly improves hypoxia and inflammation, causing a better course of the disease in moderate to severe COVID-19. Full article