Category Archives: issue

Insights into sepsis-induced apoptosis: Interplay between programmed cell death and interleukin-7

Anca Meda Văsiesiu, Oana Coman, Raluca Stefania Fodor, Anca Bacârea, Bianca‐Liana Grigorescu

George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania

DOI: 10.2478/jccm-2025-0003

The pathophysiology of sepsis is orchestrated by a delicate and dynamic interaction between pro-inflammatory and anti-inflammatory responses. Essential factors influencing this process include interleukin-7 (IL-7), the programmed cell death protein 1/programmed death ligand 1 (PD-1/PD-L1) axis, and cellular apoptosis. These elements shape the immune response in sepsis, influencing its progression and outcomes. IL-7 is an important cytokine maintaining lymphocyte function and survival. At the same time, the PD-1/PD-L1 axis acts as a modulatory checkpoint suppressing immune activation to prevent overreaction but can exacerbate immunosuppression during sepsis. Cellular apoptosis impairs the host’s ability to mount an effective defence, especially against secondary infections.
Despite extensive research, the precise mechanisms through which sepsis results in organ dysfunction and immune dysregulation remain incompletely understood. The global burden of sepsis emphasizes the urgent need for innovative approaches, paving the way for personalized, immune-based therapies.
This review aims to delve into and synthesize the current knowledge regarding cellular apoptosis, the regulatory role of the PD-1/PD-L1 axis, and the critical functions of IL-7 in sepsis, with a focus on their underlying mechanisms, clinical relevance, and potential as targets for future immunomodulatory treatments.

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Intraabdominal hypertension is less common than it used to be: A pilot step wedge trial

Shane Smith¹,²,³, Fran Priestap³, Neil Parry¹,²,³, Robert Arntfield⁴, Patrick Murphy⁵, Kelly Vogt²,³, Ian Ball¹,³,⁴

1 Office of Academic Military Medicine, Western University, London, Ontario, Canada
2 Department of Surgery, Western University, London, Ontario, Canada
3 London Health Sciences Centre Trauma Program, London, Ontario, Canada
4 Department of Medicine, Western University, London, Ontario, Canada
5 Department of Surgery, Division of Trauma and Acute Care Surgery, Medical College of Wisconsin, Milwaukee, WI, USA

DOI: 10.2478/jccm-2025-0002

Objective: This is a pilot study to determine the feasibility of a multicentre stepped wedge cluster randomized trial of implementing the 2013 World Society of the Intraabdominal Compartment Syndrome (WSACS) guidelines as an intervention to treat intraabdominal hypertension (IAH) and abdominal compartment syndrome (ACS) in critically ill patients.
Design: Single-centre before-and-after trial, with an observation / baseline period of 3 months followed by a 9-month intervention period.
Setting: A 35 bed medical-surgical-trauma intensive care unit in a tertiary level, Canadian hospital.
Patients: Recruitment from consecutively admitted adult intensive care unit patients.
Intervention: In the intervention period, treatment teams were prompted to implement WSACS interventions in all patients diagnosed with IAH.
Measurements and Main Results: 129 patients were recruited, 59 during the observation period and 70 during the intervention period. Only 17.0% and 12.9%, respectively, met diagnostic criteria for IAH. Many recruited patients did not have intraabdominal pressures measured regularly per study protocol. There was no difference in ICU mortality for patients in either cohort or between those with and without IAH.
Conclusions: The incidence of IAH in our patient population has decreased significantly since 2015. This is likely due to a significant change in routine care of critically ill patients, especially with respect to judicious goal-directed fluid resuscitation. Patient recruitment and protocol adherence in this study were low, exacerbated by other staffing and logistical pressures during the study period. We conclude that a larger multicentre trial is unlikely to yield evidence of a detectable treatment effect.

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Evaluation of monitoring critical ill children with traumatic brain injury

Merve Misirlioglu1, Dincer Yildizdas2, Faruk Ekinci2, Ozden Ozgur Horoz2, Gulen Gul Mert3

1 Department of Pediatric Intensive Care, Mersin University Faculty of Medicine, Mersin, Türkiye
2 Department of Pediatric Intensive Care, Cukurova University Faculty of Medicine, Adana, Türkiye
3 Department of Pediatric Neurology, Cukurova University Faculty of Medicine, Adana, Türkiye

DOI: 10.2478/jccm-2025-0001

Introduction: In traumatic brain injury (TBI), direct information can be obtained about cerebral blood flow, brain tissue oxygenation and cerebral perfusion pressure values. More importantly, an idea about the changes in these measurements can be obtained with multidimensional monitoring and widely used monitoring methods.
Aim of the study: We aimed to evaluate the monitoring of critically ill children who were followed up in our pediatric intensive care unit (PICU) due to TBI.
Material and Method: Twenty-eight patients with head trauma who were followed up in our tertiary PICU between 2018 and 2020 were included in the study. Cerebral tissue oxygenation, optic nerve sheath diameter (ONSD), Glasgow coma score (GCS) and Glasgow Outcome Score (GOSE) values were obtained from retrospective file records and examined.
Results: Male gender was 71.4% (n=20). When we classified TBI according to GCS, 50% (n=14) had moderate TBI and 50% had severe TBI. On the first day in the poor prognosis group, ONSD and nICP were found to be higher than in the good prognosis group (for ONSD, p=0.01; and for nICP, p=0.004). On the second day of hospitalization, the ONSD and nICP were significantly higher in the poor prognosis group than in the good prognosis group (for ONSD p=0.002; and for nICP p= 0.001). Cerebral tissue oxygenation values measured on the first and second days decreased significantly on the second day in both the good and poor prognosis groups (p=0.03, 0.006). In the good prognosis group, a statistically significant decrease was found in ONSD and nICP measurements taken on the 2nd day compared to the measurements taken at the time of hospitalization (for ONSD p=0.004; for nICP p<0.001).
Conclusion: The aim of multidimensional follow-up in traumatic brain injury is to protect the brain from both primary and secondary damage; for this reason, it should be followed closely with multimonitoring methods that are possibly multidisciplinary.

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The use of intraventricular vancomycin in subacute brain abscess in an adolescent male: A case report

Tomas Leng1, Ibrahim Serhat Karakus2

1 Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA
2 Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN, USA

DOI: 10.2478/jccm-2024-0046

Introduction: Brain abscess is a serious condition in children, leading to rapid deterioration, and permanent neurological damage associated with significant morbidity and mortality. Current management protocols for brain abscesses focus on intravenous antibiotics and surgical excision and drainage.
Case Presentation: A 12-year-old adolescent male who had headache and photophobia and was diagnosed with multiple brain abscesses and was refractory to conventional medical and neurosurgical intervention. A single dose of 10 mg vancomycin was administered through endo-ventricular drain , resulting in resolution of abscesses and alleviation of symptoms.
Conclusion: We describe the first instance of intraventricular vancomycin use in the pediatric age group for the treatment of multiple brain abscesses. Given the variability in dosing reported in the literature, our case report warrants further studies to standardize dosage for this rare intervention.

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The effect of pre-existing sarcopenia on outcomes of critically ill patients treated for COVID-19

Thomas Bradier1, Sébastien Grigioni2, Céline Savoye-Collet3, Gaétan Béduneau1,4, Dorothée Carpentier1, Christophe Girault1,4, Maximillien Grall1, Grégoire Jolly1, Najate Achamrah2, Fabienne Tamion1,5, Zoé Demailly1,5

1 Intensive Care Unit, Charles Nicolle University Hospital, Rouen, France
2 Department of Nutrition, Charles Nicolle University Hospital, Rouen, France
3 Radiology Department, QUANTIF-LITIS EA 4108, Charles Nicolle University Hospital, Rouen, France
4 Normandie Univ, UNIROUEN, UR 3830-GRHVN, CHU Rouen, F-76000 Rouen, France
5 Normandie Univ, UNIROUEN, INSERM U1096, CHU Rouen, France

DOI: 10.2478/jccm-2024-0045

Background: Sarcopenia, defined by a loss of skeletal muscle mass and function, has been identified as a prevalent condition associated with poor clinical outcome among critically ill patients. This study aims to evaluate the impact of pre-existing sarcopenia on outcomes in critically ill patients with acute respiratory failure (ARF) due to COVID-19.
Material and Methods: A retrospective study was carried out on COVID-19 patients admitted to intensive care. Pre-existing sarcopenia was assessed using early CT scans. Clinical outcomes, including duration of high-flow oxygenation (HFO), mechanical ventilation (MV), length of hospital stay (LOS) and ICU mortality, were evaluated according to sarcopenia status.
Results: Among the studied population, we found a high prevalence (75 patients, 50%) of pre-existing sarcopenia, predominantly in older male patients. Pre-existing sarcopenia significantly impacted HFO duration (6.8 (+/-4.4) vs. 5 (+/-2.9) days; p=0.005) but did not significantly affect MV requirement (21 (28%) vs. 23 (37.3%); p=185), MV duration (7 vs. 10 days; p=0.233), ICU mortality (12 (16%) vs. 10 (13.3 %); p=0.644) or hospital LOS (27 vs. 25 days; p=0.509). No differences in outcomes were observed between sarcopenic and non-sarcopenic obese patients.
Conclusions: Pre-existing sarcopenia in critically ill COVID-19 patients is associated with longer HFO duration but not with other adverse outcomes. Further research is needed to elucidate the mechanisms and broader impact of sarcopenia on septic critically ill patient outcomes.

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The Use of Biomarkers Testing in Emergency Department

Sonia Luka1,2, Adela Golea2,3, Raluca Mihaela Tat1, Eugenia Maria Lupan Mureșan2,3, George Teo Voicescu2,3,4, Ștefan Cristian Vesa5, Maria Adriana Albu6, Daniela Ionescu7

1 Faculty of Medicine, Iuliu Hagieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
2 Clinical Emergency County Hospital, Cluj-Napoca, Romania
3 Discipline of Emergency Medicine, Faculty of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
4 CRIMEDIM Center for Research and Training in Disaster Medicine, Humanitarian Aid and Global Health, Università del Piemonte Orientale, Novara, Italy
5 Discipline of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
6 Department of Emergency Medicine and First Aid, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
7 Discipline of Anaesthesia and Intensive Care I, Faculty of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania

DOI: 10.2478/jccm-2024-0041

Introduction: In the fast-paced environment of Emergency Departments (EDs), biomarkers are essential for the rapid diagnosis and management of critical conditions.
Aim of the study: This study evaluates the current clinical practice on key biomarkers in Romanian EDs, addressing the needs of emergency medicine physicians, and the challenges associated with biomarker testing.
Material and Methods: An online survey was sent to physicians working in ED to explore their perceptions, needs, and barriers regarding biomarkers, including Point-of-care (POC). Data was collected anonymously through an online platform and subsequently analyzed.
Results: This survey analyzed data from 168 completed responses, with 95.2% of respondents being specialists in emergency medicine. Procalcitonin and presepsin were most preferred for PoCT, while troponin and D-dimer were highly rated regardless of the testing method, reflecting their utility in sepsis and cardiovascular emergencies. Neuron-specific enolase, interleukin-6, and procalcitonin were the biomarkers considered needed.
Conclusions: The most frequently used biomarkers in ED were troponin, D-dimer, BNP/NT-proBNP, and procalcitonin. NSE, IL-6, and procalcitonin were the most recommended for future integration. High costs, limited availability, and false-positive concerns remain significant challenges in biomarker use.

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Effect of sleep quality on weaning from mechanical ventilation: A scoping review

Hana Locihová1, Darja Jarošová2, Karolína Šrámková3, Jana Slonková4, Renáta Zoubková5, Klára Maternová6, Karel Šonka7

1 Department of Anesthesiology, Resuscitation and Intensive Care Medicine, Faculty of Medicine, University of Ostrava, Ostrava -Vítkovice, Czech Republic; Department of Nursing and Midwifery, Faculty of Medicine, University of Ostrava, Ostrava – Vítkovice, Czech Republic
2 Department of Nursing and Midwifery, Faculty of Medicine, University of Ostrava, Ostrava – Vítkovice, Czech Republic
3 Department of Neurology, University Hospital Ostrava, Ostrava -Vítkovice, Czech Republic
4 Department of Neurology, University Hospital Ostrava; Department of Clinical Neurosciences, Faculty of Medicine, University of Ostrava, Ostrava -Vítkovice, Czech Republic
5 Department of Anesthesiology, Resuscitation and Intensive Care Medicine, Faculty of Medicine, University of Ostrava; Department of Anesthesiology, Resuscitation and Intensive Care Medicine, University Hospital Ostrava, Ostrava -Vítkovice, Czech Republic
6 2nd Department of Surgery – Department of Cardiovascular Surgery, First Faculty of Medicine, Charles University, General University Hospital in Prague, Prague, Czech Republic
7 Department of Neurology and Center of Clinical Neurosciences, First Faculty of Medicine, Charles University, General University Hospital in Prague, Prague, Czech Republic

DOI: 10.2478/jccm-2024-0043

Introduction: Mechanically ventilated patients have disturbed sleep.
Aim of the study: To explore whether there is a relationship between successful or unsuccessful weaning of patients and their sleep quality and circadian rhythm.
Materials and Methods: A scoping review. The search process involved four online databases: CINAHL, MEDLINE, ProQuest, and ScienceDirect. Original studies published between January 2020 and October 2022 were included in the review.
Results: Six studies met the inclusion criteria. These studies showed that patients with difficult weaning were more likely to have atypical sleep, shorter REM sleep, and reduced melatonin metabolite excretion. Muscle weakness was an independent factor associated with prolonged weaning from mechanical ventilation and was significantly more frequent in patients with atypical sleep. Heterogeneous patient samples and the methodology of the studies hamper a clear interpretation of the results.
Conclusions: A relationship was found between abnormal sleep patterns, reduced melatonin metabolite (6-sulfatoxymelatonin) excretion, and unsuccessful weaning. However, the causality is not clear from the existing research.

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Tracheoesophageal Iatrogenic Fistulas in ICU: Still a Pandora’s Box?

Radu Stoica

Clinical Hospital Sanador Bucharest, Romania

DOI: 10.2478/jccm-2024-0044

Tracheoesophageal fistulas (TEF) in the ICU are still considered a relatively rare, but life-threatening complication of prolonged intubation, with an incidence of approximately 0.5% of cases [1]. Classically, their occurrence was considered the result of the direct interaction between two mechanical factors: the endotracheal tube (ETT) or the tracheostomy tube placement on the membranous wall of the trachea, and the esophageal feeding tube that affects esophageal mucosa, leading to ischemic lesions and decubitus injury. The question that arises is why, despite this simple explanation, the incidence of TEF remains low? In reality, the occurrence of TEF in ICU is related to the complex interactions between patients’ comorbidities and the particularities of pathophysiology and management in critically ill patients, leading to local tissue metabolic disorders and favoring fistulas’ occurrence. Malnutrition, diabetes, chronic anemia, reflux esophagitis, prolonged inflammation, sepsis, hemodynamic instability, prolonged hypoxemia, vasoactive drugs or corticosteroids are the mainly factors favoring fistulas’ development. [More]

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The Analgesic Effect of Morphine on Peripheral Opioid Receptors: An Experimental Research

Nader-Mugurel Jafal, Smaranda Stoleru, Aurelian Zugravu, Carmen Orban, Mihai Popescu, Ruxandra Cristina Marin, Ion-Gigel Fulga

“Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania

DOI: 10.2478/jccm-2024-0042

Opioids represent one of the key pillars in postoperative pain management, but their use has been associated with a variety of serious side effects. Thus, it is crucial to investigate the timing and course of opioid administration in order to ensure a best efficacy to side-effect profile. The aim of our article was to investigate the analgesic effects of locally administered morphine sulfate (intraplantar) in a carrageenan-induced inflammation model in rats. After carrageenan administration, the rats were divided into 10 equal groups and were injected with either morphine 5 mg/kg or 0.9% saline solution at different time intervals, depending on the assigned group. The analgesic effect was assessed through thermal stimulation. Our results showed that paw withdrawal time was significantly higher in rats treated with morphine compared to those in the control group 9.18 ± 3.38 compared to 5.14 ± 2.21 seconds, p=0.012). However, differences were more pronounced at certain time intervals post-carrageenan administration (at 180 minutes compared to 360 minutes, p=0.003 and at 180 minutes compare to 1440 minutes p<0.001), indicating that efficacy varies depending on the timing of treatment. In conclusion, our findings support the hypothesis that locally administered morphine may alleviate pain under inflammatory conditions and underscores the importance of considering treatment timing when evaluating the analgesic effect.

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