A Study to Compare Ultrasound-guided and Clinically Guided Fluid Management in Children with Septic Shock.

Background: To evaluate the role of ultrasound during initial fluid resuscitation along with clinical guidance in reducing the incidence of fluid overload on day 3 in children with septic shock. Materials and methods: It was a prospective, parallel limb open-labeled randomized controlled superiority trial done in the PICU of a government-aided tertiary care hospital in Eastern India. Patient enrolment took place between June 2021 and March 2022. Fifty-six children aged between 1 month and 12 years, with proven or suspected septic shock, were randomized to receive either ultrasound-guided or clinically guided fluid boluses (1:1 ratio) and subsequently followed up for various outcomes. The primary outcome was frequency of fluid overload on day 3 of admission. The treatment group received ultrasound-guided fluid boluses along with the clinical guidance and the control group received the same but without ultrasound guidance upto 60 mL/kg of fluid boluses. Results: The frequency of fluid overload on day 3 of admission was significantly lower in the ultrasound group (25% vs 62%, p = 0.012) as was the median (IQR) cumulative fluid balance percentage on day 3 [6.5 (3.3-10.3) vs 11.3 (5.4-17.5), p = 0.02]. The amount of fluid bolus administered was also significantly lower by ultrasound [median 40 (30-50) vs 50 (40-80) mL/kg, p = 0.003]. Resuscitation time was shorter in the ultrasound group (13.4 ± 5.6 vs 20.5 ± 8 h, p = 0.002). Conclusion: Ultrasound-guided fluid boluses were found to be significantly better than clinically guided therapy, in preventing fluid overload and its associated complications in children with septic shock. These factors make ultrasound a potentially useful tool for resuscitation of children with septic shock in the PICU. How to cite this article: Kaiser RS, Sarkar M, Raut SK, Mahapatra MK, Uz Zaman MA, Roy O, et al. A Study to Compare Ultrasound-guided and Clinically Guided Fluid Management in Children with Septic Shock. Indian J Crit Care Med 2023;27(2):139-146.

Systemic inflammation and protease profile of Afro-Caribbean patients with sepsis.

OBJECTIVES: Sepsis is one of the leading causes of morbidity and mortality within the healthcare system and remains a diagnostic and therapeutic challenge. A major issue in the diagnosis of sepsis is understanding the pathophysiologic mechanism, which revolves around host immune system activation and dysregulated responses. African Americans are more likely to experience severe sepsis with higher mortality rates compared to the general population. This pilot study characterized multiple inflammatory markers and proteases in plasma of primarily African American and Afro-Caribbean patients with mild sepsis. METHODS: Plasma was collected from 16 healthy controls and 15 subjects presenting with sepsis, on admission, and again upon resolution of the signs of sepsis, defined as a resolution of sepsis criteria. Plasma samples were analyzed for cytokines, chemokines, and proteases using multiplex bead assays. RESULTS: Elevated levels of granulocyte colony-stimulating factor, interleukin-10, interleukin-15, interleukin-1 receptor antagonist, interleukin-8, interferon gamma-induced protein 10, monocyte chemoattractant protein-1, matrix metallopeptidase 12, and cathepsin S were identified in plasma from sepsis patients on admission compared to control subjects. Interleukin-6, interleukin-8, granulocyte colony-stimulating factor, and cathepsin S were reduced in sepsis patients upon clinical resolution of sepsis. CONCLUSION: These findings profile the circulating inflammatory cytokines, chemokines, and proteases in African Americans and Afro-Caribbean patients during sepsis. The role of these targets in sepsis needs addressing in this patient population.

Elevated S100A9 expression in chronic rhinosinusitis coincides with elevated MMP production and proliferation in vitro.

Chronic rhinosinusitis (CRS) is a common condition associated with inflammation and tissue remodeling of the nose and paranasal sinuses, frequently occurring with nasal polyps and allergies. Here we investigate inflammation and the protease profile in nasal tissues and plasma from control non-CRS patients and CRS patients. Gene expression for several cytokines, proteases, and antiproteases was quantified in nasal tissue from non-CRS and CRS subjects with nasal polyps. Elevated expression of S100A9, IL1A, MMP3, MMP7, MMP11, MMP25, MMP28, and CTSK was observed in tissue from CRS subjects with nasal polyps compared to control tissue. Tissue protein analysis confirmed elevated levels of these targets compared to controls, and increased MMP3 and MMP7 observed in CRS subjects with nasal polyps compared to CRS subjects without polyps. Plasma concentrations of MMP3 and MMP7 were elevated in the CRS groups compared to controls. The nasal cell line, CCL-30, was exposed to S100A9 protein, resulting in increased MMP3, MMP7, and CTSK gene expression and elevated proliferation. Silencing MMP3 significantly reduced S100A9-mediated cell proliferation. Therefore, the elevated expression of S100A9 and MMPs are observed in CRS nasal tissue and S100A9 stimulated MMP3 responses to contribute to elevated nasal cell proliferation.

Cathepsin S: investigating an old player in lung disease pathogenesis, comorbidities, and potential therapeutics.

Dysregulated expression and activity of cathepsin S (CTSS), a lysosomal protease and a member of the cysteine cathepsin protease family, is linked to the pathogenesis of multiple diseases, including a number of conditions affecting the lungs. Extracellular CTSS has potent elastase activity and by processing cytokines and host defense proteins, it also plays a role in the regulation of inflammation. CTSS has also been linked to G-coupled protein receptor activation and possesses an important intracellular role in major histocompatibility complex class II antigen presentation. Modulated CTSS activity is also associated with pulmonary disease comorbidities, such as cancer, cardiovascular disease, and diabetes. CTSS is expressed in a wide variety of immune cells and is biologically active at neutral pH. Herein, we review the significance of CTSS signaling in pulmonary diseases and associated comorbidities. We also discuss CTSS as a plausible therapeutic target and describe recent and current clinical trials examining CTSS inhibition as a means for treatment.

An Unusual Etiology of Cerebellar Ataxia.

Cerebellar ataxia, which is the lack of coordination, has a number of causes none of which are as uncommon or unheard of as Scrub typhus. Scrub typhus very rarely presents itself with CNS manifestations. Here, we present the case of a 7-year-old girl from the Hooghly district in West Bengal, who presented to us with the history of fever, cerebellar signs, and sudden onset of visual loss. She was ultimately diagnosed with scrub typhus cerebellitis.