Multiple Organ Failure Research Articles

Low T3 vs low T3T4 euthyroid sick syndrome in septic shock patients: A prospective observational cohort study.

Both phases of euthyroid sick syndrome (ESS) are associated with worse prognosis in septic shock patients. Although there are still no indications for supplementation therapy, there is no evidence that both phases (initial and prolonged) are adaptive or that only prolonged is maladaptive and requires supplementation. To analyze clinical, hemodynamic and laboratory differences in two groups of septic shock patients with ESS. A total of 47 septic shock patients with ESS were divided according to values of their thyroid hormones into low T3 and low T3T4 groups. The analysis included demographic data, mortality scores, intensive care unit stay, mechanical ventilation length and 28-day survival and laboratory with hemodynamics. The Simplified Acute Physiology Score II score (P = 0.029), dobutamine (P = 0.003) and epinephrine requirement (P = 0.000) and the incidence of renal failure and multiple organ failure (MOF) (P = 0.000) were significantly higher for the low T3T4. Hypoalbuminemia (P = 0.047), neutrophilia (P = 0.038), lymphopenia (P = 0.013) and lactatemia (P = 0.013) were more pronounced on T2 for the low T3T4 group compared to the low T3 group. Diastolic blood pressure at T0 (P = 0.017) and T1 (P = 0.007), as well as mean arterial pressure at T0 (P = 0.037) and T2 (P = 0.033) was higher for the low T3 group. The low T3T4 population is associated with higher frequency of renal insufficiency and MOF, with worse laboratory and hemodynamic parameters. These findings suggest potentially maladaptive changes in the chronic phase of septic shock.

Cardiogenic shock in phaeochromocytoma multisystem crisis- a case report

Abstract Background Phaeochromocytoma multisystem crisis (PMC) is characterised by labile blood pressures (extremes of hypo- and/or hypertension) and multiorgan failure as a result of catecholamine excess. Initial stabilisation requires pharmacological and/or mechanical circulatory support, followed by institution of antihypertensives to correct the underlying pathophysiology. Case summary A previously well 40-year-old male developed sudden onset of breathlessness. On presentation, he was in shock with multiorgan failure. He required intubation, mechanical ventilation, dual inotropic support and renal replacement therapy. Bedside echocardiogram showed a severely impaired left ventricular ejection fraction (LVEF) of 25%. Coronary angiography revealed normal coronary arteries. In view of raised inflammatory markers and transaminitis, a CT abdomen/pelvis was performed. An incidental left adrenal mass was found. Further work-ups revealed raised plasma metanephrine and normetanephrine, 24-hour urine epinephrine and norepinephrine. A cardiac magnetic resonance (CMR) showed myocardial inflammation and reverse Takotsubo pattern of regional wall motion abnormality (RWMA). The diagnosis of cardiogenic shock and stress cardiomyopathy secondary to phaeochromocytoma multisystem crisis was made. He was subsequently initiated on α- and β-blockers and goal-directed medical therapy for heart failure. A 68Ga-DOTATATE scan showed avid tracer uptake of the left phaeochromocytoma. An interval CMR 3 weeks from presentation showed near normalisation of the LVEF and RWMA. He underwent a successful laparoscopic left adrenalectomy and was antihypertensive-free since. Conclusion The clinical suspicion for PMC as the cause of cardiogenic shock requires astute clinical judgement, while the management requires understanding of the underlying pathophysiology that call for multidisciplinary inputs.

The Cardiac Manifestations of Post-streptococcal Infection in Paediatrics: Case Series

Introduction: Group A streptococcus (GAS) remains a global burden, particularly in developing countries, with long-term morbidity and mortality complications. Different strains and immune responses to GAS can lead to various disease patterns, from predominantly throat and skin manifestations to renal and cardiac involvement. Myocarditis associated with glomerulonephritis can progress to carditis, which may present with signs and symptoms similar to rheumatic heart disease. Although uncommon, this condition can deteriorate into dilated cardiomyopathy, potentially leading to cardiogenic shock and death, necessitating early recognition, intervention, and preventive measures. Case Presentation: We report three pediatric cases of post-streptococcal infection with cardiac manifestations. The first case involves an 8-year-old female with palpitations and a recurring cough, diagnosed with acute rheumatic carditis. The second case is a 10-year-old female presenting with hemoptysis and edema in the lungs and extremities due to acute rheumatic carditis and prior suspected vegetation. The third case is a 9-year-old male initially diagnosed with post-streptococcal glomerulonephritis (PSGN), who deteriorated into dilated cardiomyopathy with an ejection fraction of 32% and multiple organ dysfunction syndrome. All three patients recovered well, received prophylactic management, and were referred for further investigation. Conclusions: Identifying specific features on echocardiography can help differentiate between rheumatic heart disease (RHD) and PSGN-associated cardiac involvement. Additionally, echocardiography is a more readily available and cost-effective screening method, especially in endemic populations. Early recognition and management of post-streptococcal cardiac complications may prevent long-term morbidity and mortality.

ThP5.3 - A Clinical Audit on Assessing Severe Acute Pancreatitis: Improving the use of the Glasgow-Imrie Criteria and outcomes

Abstract Introduction Severe acute pancreatitis (SAP) is defined by pancreatic and extra-pancreatic necrosis, ITU admission, multisystem organ failure and death. Severity should be predicted on admission using the Glasgow-Imrie Criteria (GIC) to stratify patients and scores ≥ 3 are indicative of SAP and requires review by a senior and/or HDU/ITU to determine possible transfer to HDU/ITU. Methods We performed a 2-cycle audit on the use of the GIC to score 140 patients with acute pancreatitis (AP) from November 2022 – October 2023. Initial interventions included a presentation, posters and an email. The second intervention was the insertion of a scoring tick box into the electronic clerking notes. Results At baseline 44% (22/50) of patients with AP were scored using the GIC. Post first intervention this was 66% (21/32), post second intervention it was 84% (49/58). Post interventions the proportion of patients scoring ≥3 escalated to a senior and/or HDU/ITU increased from 17% to 100% and mean length of stay reduced from 14.5 to 11 days, also the completeness of documentation rose from 78% to 96%. There were 18 Glasgow-Imrie scores ≥ 3 and 8 of these patients developed clinical SAP. Conclusion Our audit showed that simple interventions and incorporation of the scoring system into the electronic notes increased the percentage of patients being scored on admission and resulted in all patients with a score ≥ 3 being reviewed by a senior and/or HDU/ITU. Incorporating the scoring into the electronic clerking document was relatively straightforward and could be adopted by other Trusts.

Study of Correlation of Apgar Score and Thompson Score with Hepatic Function in Perinatal Asphyxia Affected Neonates—A Prospective Observational Study

Background: Perinatal asphyxia is one of the leading causes of neonatal morbidity and mortality in the country. It leads to multi-organ failure with brain involvement as the major organ of concern (hypoxic-ischemic encephalopathy). Hepatic dysfunction is also a feature of perinatal asphyxia. Objectives: To detect hepatic dysfunction in birth asphyxia. To correlate the liver damage with increasing severity of birth asphyxia and hypoxic-ischemic encephalopathy through Apgar score and Thompson score. Methods: In this prospective observational study, after ethical clearance and informed consent from the parents, babies of gestational age >35 weeks weighing >1.8 kg, Apgar score <7 at 1 minute received in the newborn unit of a tertiary care hospital in West Bengal, India were enrolled. Thompson’s score was assessed every day. The liver function test of these patients was assessed on days 1, 3, 10, and 15. Ultrasonography of the whole abdomen was performed on days 1 and 14 of life to rule out other probable causes of hepatic injury. Results: A total of 308 neonates were studied, of which Apgar score at 1 minute indicates that 99 (32.14%) of the newborns had severe birth asphyxia and the rest had moderate birth asphyxia. All the liver enzymes except total protein and albumin showed a significant rise on days 1 and 3 with increasing severity of asphyxia. This correlation was seen with Apgar score at 1 minute on day 1 with TSB (r = -0.256, P < .001), AST (r = -0.209, P < .01), ALT (r = -0.178, P < .002), ALP (r = -0.174, P < .002). As per Thompson score, total serum bilirubin, aspartate aminotransferase and alkaline phosphatase showed maximum correlation on days 1 (r = 0.253, P < .001, r = 0.187, P < .001 and r = 0.268, P < .001, respectively) and on day 3 (r = 0.159, P < .005, r = 0.231, P < .001, and r = 0.190, P < .002, respectively). Conclusion: Thompson score and Apgar score can be correlated to perinatal asphyxia-related hepatic injury.

DeBakey Type III Aortic Dissection Causing Bowel Necrosis: A Case Report

Rationale: Aortic dissection is a life-threatening medical emergency associated with high morbidity and mortality. Preoperative mesenteric malperfusion increases the surgical risk and mortality in patients with type B aortic dissection. For DeBakey type III B patients involving most of the thoracoabdominal aorta, endovascular treatment to improve true lumen perfusion may have limited benefits. Organ reperfusion on-time is crucial. Patient concerns: A 38-year-old man was admitted with sudden severe upper abdominal pain. Emergency CTA of the entire aorta revealed an aortic dissection with an entry tear in the descending aortic arch involving the celiac trunk, superior mesenteric artery, bilateral common iliac arteries and right external iliac artery, with thrombosis in the superior mesenteric artery. Diagnoses: The patient was diagnosed with DeBakey type III aortic dissection with mesenteric artery embolism. Enhanced chest CT showed the entry tear location and involvement of major arteries. Angiography confirmed partial blood flow in the superior mesenteric artery. Interventions: The patient underwent endovascular aortic stent-graft implantation through the left femoral artery, covering the descending aortic arch and sealing the entry tear. Postoperatively, the patient received intensive care, including ventilatory support, CRRT, anti-infection therapy, vasoactive drugs and lumbar cistern drainage. Outcomes: Two weeks postoperatively, the patient developed massive black stools, indicative of intestinal obstruction and necrosis. Exploratory laparotomy revealed ischemic necrosis and rupture of the stomach, small intestine, and colon. Despite surgical efforts, the patient’s condition deteriorated, leading to death from severe infection, acid-base imbalance and multiple organ failure.

Hypoglycemia and hyperglycemia in neonatal encephalopathy: A narrative review.

Neonatal encephalopathy (NE) is a serious condition with various neurological dysfunctions in newborns. Disruptions in glucose metabolism, including both hypoglycemia and hyperglycemia, are common in NE and can significantly impact outcomes. Hypoglycemia, defined as blood glucose below 45 mg/dL, is associated with increased mortality, neurodevelopmental disabilities, and brain lesions on MRI. Conversely, hyperglycemia, above 120 to 150 mg/dL, has also been linked to heightened mortality, hearing impairment, and multiorgan dysfunction. Both aberrant glucose states appear to worsen prognosis compared to normoglycemic infants. Therapeutic hypothermia is the standard of care for NE that provides neuroprotection by reducing metabolic demands and inflammation. Adjunct therapies like glucagon and continuous glucose monitoring show promise in managing dysglycemia and improving outcomes. Glucagon can enhance cerebral blood flow and glucose supply, while continuous glucose monitoring enables real-time monitoring and personalized interventions. Maintaining balanced blood sugar levels is critical in managing NE. Early detection and intervention of dysglycemia are crucial to improve outcomes in neonates with encephalopathy. Further research is needed to optimize glycemic management strategies and explore the potential benefits of interventions like glucagon therapy.

Effect of sodium-glucose co-transporter-2 inhibitors on survival free of organ support in patients hospitalised for COVID-19 (ACTIV-4a): a pragmatic, multicentre, open-label, randomised, controlled, platform trial.

Patients hospitalised for COVID-19 are at risk for multiorgan failure and death. Sodium-glucose co-transporter-2 (SGLT2) inhibitors provide cardiovascular and kidney protection in patients with cardiometabolic conditions and could provide organ protection during COVID-19. We aimed to investigate whether SGLT2 inhibitors can reduce the need for organ support in patients hospitalised for COVID-19. This pragmatic, multicentre, open-label, randomised, controlled, platform trial was conducted across 63 sites in the USA, Spain, Brazil, Italy, and Mexico. Patients aged at least 18 years hospitalised for COVID-19 (moderate or severe illness) were randomly assigned (1:1), via an interactive voice system or web-response system, to receive locally available SGLT2 inhibitor (administered orally, once daily) plus standard-of-care or standard-of-care for 30 days. The primary outcome was organ support-free days evaluated through 21 days, assessed using intention-to-treat approach. This trial is registered on ClinicalTrials.gov, NCT04505774. The first patient was randomly assigned to the SGLT2 inhibitor domain on Dec 3, 2021. On March 31, 2023, at the recommendation of the data and safety monitoring board, enrolment in the SGLT2 inhibitor domain for both moderately and severely ill hospitalised patients was stopped prematurely for futility due to a low likelihood of finding a treatment benefit. The final randomised population consisted of 575 patients (mean age 72 years [SD 13], 242 (42%) female and 154 (27%) Hispanic; 504 in the moderate illness group and 71 in the severe illness group). 573 patients had a known 21-day outcome; 215 (75%) of 285 patients in the SGLT2 inhibitor plus standard-of-care group did not require respiratory or cardiovascular organ support versus 231 (80%) of 288 patients in the standard-of-care group. The adjusted odds ratio (OR) for an SGLT2 inhibitor effect on organ support-free days was 0·74 (95% Credible Interval [CrI] 0·48-1·13; where OR higher than 1 indicated treatment benefit, yielding a posterior probability of futility P(OR <1·2) of 99% and a posterior probability of inferiority P(OR<1·0) of 91%). There were 37 deaths (13%) in the SGLT2 inhibitor plus standard-of-care group and 42 deaths (15%) in the standard-of-care group at 90 days (hazard ratio 0·91 [95% CrI 0·58-1·43], probability of hazard ratio <1 of 66%). No safety concerns were observed with SGLT2 inhibitors, including no cases of ketoacidosis. SGLT2 inhibitors did not significantly increase days free of organ support or reduce mortality in patients hospitalised with COVID-19. SGLT2 inhibitors were well tolerated with no observed safety concerns. Overall, these findings do not support the use of SGLT2 inhibitors as standard care in patients hospitalised with COVID-19. National Institutes of Health.

Multiple organ failure: What you need to know.

Multiple organ failure (MOF) remains a significant challenge for the acute care surgeon, often leading to poor patient outcomes. This comprehensive review explores the etiology, pathophysiology, clinical presentation, diagnosis, management strategies, prognosis, and prevention strategies associated with MOF and chronic critical illness. Understanding the intricate etiology and pathophysiology of MOF and chronic critical illness is essential for effectively managing these syndromes and developing targeted treatment strategies aimed at mitigating the underlying inflammatory, immune, and microvascular disturbances, in order to redirect patients onto a trajectory of recovery.

Эффективность препарата «Ипекон®» при инфекционном перитоните кошек, доказанная в официально зарегистрированных мультицентровых рандомизированных клинических и постклинических исследованиях

Feline infectious peritonitis is a difficult-to-treat disease caused by a highly virulent biotype of a widespread feline coronavirus. Vetstem LLC has developed a drug Ipecon® based on a low-molecular compound with a direct antiviral effect against RNA-containing viruses. Ipekon® has passed all preclinical studies. The purpose of the study: to evaluate the therapeutic efficacy of the veterinary drug Ipecon® in the treatment of feline infectious peritonitis. Materials and methods: the study included 28 cats, aged 6 months to 11 years: 18 animals with exudative and 8 with non-exudative («dry») form of IPK/FIP. The animals were divided into 3 groups, taking into account the starting single dose of the drug Ipecon®: 8 mg/kg, 10 mg/kg, 12 mg/kg. The finished solution was administered subcutaneously daily, once a day, with an interval between injections of 24 hours during the entire course of treatment. The assessment of the treatment effectiveness was comprehensive, taking into account the data of the clinical examination, the results of general clinical and biochemical blood tests, ultrasound of internal organs. Results: of the 28 animals with diagnosed IPC/FIP included in the study, 4 (14.3%) patients had a fatal outcome caused by multiple organ failure; 85.7 % of patients had the status of «clinical recovery» at the end of the course of treatment. Good tolerability of the drug Ipecon® has been established with repeated subcutaneous use. Despite the noted discomfort during administration, there were no signs of intoxication or clinically pronounced abnormalities, deterioration in the functions of organs and systems. During the use of the drug Ipecon®, only one case was noted.

Familial thrombotic microangiopathy in a child with coenzyme Q10 deficiency-associated glomerulopathy.

We report a child with biallelic COQ6 variants presenting with familial thrombotic microangiopathy (TMA). A Chinese boy presented with steroid-resistant nephrotic syndrome at 8months old and went into kidney failure requiring peritoneal dialysis at 15months old. He presented with hypertensive encephalopathy with the triad of microangiopathic haemolytic anaemia, thrombocytopenia, and acute on chronic kidney injury at 25months old following a viral illness. Kidney biopsy showed features of chronic TMA. He was managed with supportive therapy and plasma exchanges and maintained on eculizumab. However, he had another TMA relapse despite complement inhibition a year later. Eculizumab was withdrawn, and supportive therapies, including ubiquinol (50mg/kg/day) and vitamins, were optimized. He remained relapse-free since then for 4years. Of note, his elder sister succumbed to multiple organ failure with histological evidence of chronic TMA at the age of 4. Retrospective genetic analysis revealed the same compound heterozygous variants in the COQ6 gene.

Significance of detecting cardiac troponin I and creatine kinase MB in critically Ill children without primary cardiac illness.

To investigate the incidence of myocardial injury in children with critically ill children without primary cardiac disease and the association between elevated cardiac troponin I (cTnl) and creatine kinase MB (CK-MB) concentrations and disease progression and prognosis to guide early treatment. The serum cTnI and CK-MB concentrations of 292 children with critically ill children without primary cardiac disease in Yantai Yuhuangding Hospital between January 2021 and January 2024 were retrospectively analyzed within 24 h after entering the Pediatric Intensive Care Unit (PICU). The children were divided into normal and abnormal groups according to the myocardial marker results. The abnormal group was further divided into the cTnI-elevated, CK-MB-elevated, single-elevated (cTnI- or CK-MB-elevated) and double-elevated (cTnI- and CK-MB-elevated) groups. The differences in the clinical indicators and their relationships with prognosis for the groups were compared. The incidence of myocardial injury among the critically ill children without primary cardiac disease was 55.1%. The incidence of myocardial injury in children with infectious diarrhea combined with moderate and severe dehydration reached 85.19%. The pediatric critical illness score; frequency of use of vasoactive drugs; hypotension, shock, heart failure, respiratory failure, and multiple organ dysfunction syndrome; and mortality indexes differed significantly for the normal and abnormal myocardial marker groups (P < 0.05). The single-elevated and normal groups only showed a difference in mortality (P < 0.017). The cTnI and CK-MB concentrations were negatively correlated with prognosis (P < 0.01). Myocardial injury, as evidenced by elevated cardiac biomarkers, is common in critically ill children without primary cardiac illness. cTnI and CK-MB are associated with outcomes. Shock, heart failure, and multiple organ dysfunction syndromes are independently associated with simultaneous elevations of CK-MB and cTnI concentrations. Further prospective studies are needed to elucidate the clinical utility of these biomarkers.

Cytokine release syndrome following COVID-19 infection during treatment with nivolumab for cancer of esophagogastric junction carcinoma: a case report and review

BackgroundCytokine release syndrome (CRS) is an acute systemic inflammatory syndrome characterized by fever and multiple organ failure, which is triggered by immunotherapy or certain infections. Immune checkpoint inhibitors rarely cause immune-related adverse event- cytokine release syndrome (irAE-CRS). This article presents a case report of irAE-CRS triggered by coronavirus disease 2019 (COVID-19).Case presentationA 60-year-old man with type 2 diabetes received nivolumab treatment for esophagogastric junction carcinoma and experienced two immune-related adverse events: hypothyroidism and skin disorder. Eleven days before his visit to our hospital, he had a fever and was diagnosed with COVID-19. Five days before his visit, he developed a fever again, along with general malaise, water soluble diarrhea, and myalgia of the extremities. On admission, the patient was in a state of multiple organ failure, and although the source of infection was unknown, a tentative diagnosis of septic shock was made. The patient's condition was unstable despite systemic management with antimicrobial agents, high-dose vasopressors, and intravenous fluids. We suspected CRS due to irAE (irAE-CRS) based on his history of nivolumab use. Steroid pulse therapy (methylprednisolone 1 g/day) was started, and the patient temporarily recovered. However, his respiratory condition worsened; consequently, he was placed on a ventilator and tocilizumab was added to the treatment. His muscle strength recovered to the point where he could live at home, and was subsequently discharged.ConclusionIn patients previously treated with immune checkpoint inhibitors, irAE-CRS should be considered as a differential diagnosis when multiple organ damage is observed in addition to inflammatory findings. It is recommended to start treatment with steroids; if the disease is refractory, other immunosuppressive therapies such as tocilizumab should be introduced as early as possible.

MicroRNAs Regulate the Expression of Genes Related to the Innate Immune and Inflammatory Response in Rabbits Infected with Lagovirus europaeus GI.1 and GI.2 Genotypes.

MicroRNAs (miR) are a group of small, non-coding RNAs of 17-25 nucleotides that regulate gene expression at the post-transcriptional level. Dysregulation of miRNA expression or function may contribute to abnormal gene expression and signaling pathways, leading to disease pathology. Lagovirus europaeus (L. europaeus) causes severe disease in rabbits called rabbit hemorrhagic disease (RHD). The symptoms of liver, lung, kidney, and spleen degeneration observed during RHD are similar to those of acute liver failure (ALF) and multi-organ failure (MOF) in humans. In this study, we assessed the expression of miRs and their target genes involved in the innate immune and inflammatory response. Also, we assessed their potential impact on pathways in L. europaeus infection-two genotypes (GI.1 and GI.2)-in the liver, lungs, kidneys, and spleen. The expression of miRs and target genes was determined using quantitative real-time PCR (qPCR). We assessed the expression of miR-155 (MyD88, TAB2, p65, NLRP3), miR-146a (IRAK1, TRAF6), miR-223 (TLR4, IKKα, NLRP3), and miR-125b (MyD88). We also examined biomarkers of inflammation: IL-1β, IL-6, TNF-α, and IL-18 in four tissues at the mRNA level. Our study shows that the main regulators of the innate immune and inflammatory response in L. europaeus/GI.1 and GI.2 infection, as well as RHD, are miR-155, miR-223, and miR-146a. During infection with L. europaeus/RHD, miR-155 has both pro- and anti-inflammatory effects in the liver and anti-inflammatory effects in the kidneys and spleen; miR-146a has anti-inflammatory effects in the liver, lungs and kidneys; miR-223 has anti-inflammatory effects in all tissues; however, miR-125b has anti-inflammatory effects only in the liver. In each case, such an effect may be a determinant of the pathogenesis of RHD. Our research shows that miRs may regulate three innate immune and inflammatory response pathways in L. europaeus infection. However, the result of this regulation may be influenced by the tissue microenvironment. Our research shows that infection of rabbits with L. europaeus/GI.1 and GI.2 genotypes causes an overexpression of two critical acute phase cytokines: IL-6 in all examined tissues and TNF-α (in the liver, lungs, and spleen). IL-1β was highly expressed only in the lungs after L. europaeus infection. These facts indicate a strong and rapid involvement of the local innate immune and inflammatory response in L. europaeus infection-two genotypes (GI.1 and GI.2)-and in the pathogenesis of RHD. Profile of biomarkers of inflammation in rabbits infected with L. europaeus/GI.1 and GI.2 genotypes are similar regarding the nature of changes but are different for individual tissues. Therefore, we propose three inflammation profiles for L. europaeus infection for both GI.1 and GI.2 genotypes (pulmonary, renal, liver, and spleen).

Understanding, assessing and treating immune, endothelial and haemostasis dysfunctions in bacterial sepsis.

The interplay between the immune system, coagulation, and endothelium is critical in regulating the host response to infection. However, in sepsis and other critical illnesses, a dysregulated immune response can lead to excessive alterations in these mechanisms, resulting in coagulopathy, endothelial dysfunction, and multi-organ dysfunction. This review aims to provide a comprehensive analysis of the pathophysiological mechanisms that govern the complex interplay between immune dysfunction, endothelial dysfunction, and coagulation in sepsis. It emphasises clinical significance, evaluation methods, and potential therapeutic interventions. Understanding these mechanisms is essential for developing effective treatments that can modulate the immune response, mitigate thrombosis, restore endothelial function, and ultimately improve patient survival.

Nitroglycerin challenge identifies microcirculatory target for improved resuscitation in patients with circulatory shock

BackgroundCirculatory shock and multi-organ failure remain major contributors to morbidity and mortality in critically ill patients and are associated with insufficient oxygen availability in the tissue. Intrinsic mechanisms to improve tissue perfusion, such as up-regulation of functional capillary density (FCD) and red blood cell velocity (RBCv), have been identified as maneuvers to improve oxygen extraction by the tissues; however, their role in circulatory shock and potential use as resuscitation targets remains unknown. To fill this gap, we examined the baseline and maximum recruitable FCD and RBCv in response to a topical nitroglycerin stimulus (FCDNG, RBCvNG) in patients with and without circulatory shock to test whether this may be a method to identify the presence and magnitude of a microcirculatory reserve capacity important for identifying a resuscitation target.MethodsSublingual handheld vital microscopy was performed after initial resuscitation in mechanically ventilated patients consecutively admitted to a tertiary medical ICU. FCD and RBCv were quantified using an automated computer vision algorithm (MicroTools). Patients with circulatory shock were retrospectively identified via standardized hemodynamic and clinical criteria and compared to patients without circulatory shock.Results54 patients (57 ± 14y, BMI 26.3 ± 4.9 kg/m2, SAPS 56 ± 19, 65% male) were included, 13 of whom presented with circulatory shock. Both groups had similar cardiac index, mean arterial pressure, RBCv, and RBCvNG. Heart rate (p < 0.001), central venous pressure (p = 0.02), lactate (p < 0.001), capillary refill time (p < 0.01), and Mottling score (p < 0.001) were higher in circulatory shock after initial resuscitation, while FCD and FCDNG were 10% lower (16.9 ± 4.2 and 18.9 ± 3.2, p < 0.01; 19.3 ± 3.1 and 21.3 ± 2.9, p = 0.03). Nitroglycerin response was similar in both groups, and circulatory shock patients reached FCDNG similar to baseline FCD found in patients without shock.ConclusionCritically ill patients suffering from circulatory shock were found to present with a lower sublingual FCD. The preserved nitroglycerin response suggests a dysfunction of intrinsic regulation mechanisms to increase the microcirculatory oxygen extraction capacity associated with circulatory shock and identifies a potential resuscitation target. These differences in microcirculatory hemodynamic function between patients with and without circulatory shock were not reflected in blood pressure or cardiac index.

Early selective enteral feeding in combination with active decompression of duodenum in treatment of moderate and severe acute pancreatitis – a proof-of-concept clinical study.

BackgroundAcute pancreatitis (AP) is a significant clinical challenge with rising global incidence and substantial mortality rates, necessitating effective treatment strategies. Current guidelines recommend pain and fluid management and early enteral feeding to mitigate complications, yet optimal feeding route remains debated. MethodsWe conducted a prospective, randomized, controlled trial at nine centers from October 2020 to May 2023, enrolling 154 patients with moderate to severe AP. Patients were stratified into biliary and non-biliary categories and randomized 1:1 to receive either standard of care (SoC) or SoC plus PandiCath®, a novel catheter enabling selective enteral feeding and duodenal decompression. The primary clinical endpoint (PCE) was a composite of de novo multiple organ dysfunction syndrome (MODS), infectious complications, pancreatic and intestinal fistula formation, bleeding, abdominal compartment syndrome, obstructive jaundice, and AP-related mortality. ResultsIn the primary modified intention-to-treat analysis, PandiCath® significantly reduced the PCE compared to SoC alone (P = 0.032). The Relative Risk (RR = 0.469, 95% CI 0.228-0.964) and Number Needed to Treat (NNT = 6.384, 95% CI 3.349-68.167) indicated its substantial clinical benefit, primarily driven by reduced rates of de novo MODS and infectious complications. These findings were further supported by the evaluation of other populations, including the standard intention-to-treat analysis. ConclusionPandiCath®, facilitating targeted enteral feeding while isolating and decompressing the duodenum, demonstrates promise in improving outcomes for AP patients at risk of severe complications. Further studies are warranted to validate these findings and explore optimal timing and patient selection for this intervention.

The unavoidable pressure injury/ulcer: a review of skin failure in critically ill patients.

Due to an ageing population and prolonged lifespan, pressure injury (PI) incidence is increasing. Patients with a PI typically endure longer hospital stays, which create a significant burden on healthcare resources and costs. With appropriate preventive interventions, most PIs can be avoided; however, skin failure may become inevitable in particular instances. These are classified as unavoidable PIs. Patients in a critical condition are exposed to a unique set of therapies, medications and bodily states. Oftentimes, these instances decrease tissue tolerance, which may promote PI formation. Patients who are critically ill, especially those with extended stays in the intensive care unit, are susceptible to skin failure due to: prolonged immobility; mechanical ventilation; acute respiratory distress syndrome; COVID-19; sepsis; multiorgan system dysfunction; vasopressor use; and treatment with extracorporeal membrane oxygenation. Poor perfusion leading to skin breakdown results from the compounding factors of circulatory collapse, build-up of metabolites, compromised lymphatic drainage, patient comorbidities, and ischaemia via capillary blockage in patients who are critically ill. In addition, similar physiology is present during end-of-life multisystem organ failure, which creates unavoidable skin deterioration. The aim of this review is to provide an overview of circumstances which decrease tissue tolerance and ultimately lead to PI development, despite adequate preventive measures in patients who are critically ill.

Understanding Causes of Death in Patients With Acute Respiratory Distress Syndrome: A Narrative Review.

To provide a comprehensive summary of the published data on cause of death in patients with acute respiratory distress syndrome (ARDS). PubMed (January 2015 to April 2024), bibliographies of relevant articles, and ARDS Network and Prevention & Early Treatment of Acute Lung Injury (PETAL) network websites. Observational studies and clinical trials that reported on cause of death in greater than or equal to 30 patients with ARDS, not obtained from death certificates. Animal studies, case reports, review articles, study protocols, and studies in pediatrics were excluded. Causes of death among ARDS patients who died were extracted and tabulated along with other pertinent study characteristics. We identified 15 observational studies (nine non-COVID ARDS, five COVID-related ARDS; one both) and five clinical trials (all non-COVID ARDS). Mutually exclusive prespecified categories were used for recording the cause of death in only eight studies although studies differed in the categories included and their definitions. When multiple organ failure was a predetermined category, it was the most common cause of death recorded (~50% of deaths), followed by respiratory causes with proportions varying from 16% to 42% depending on nomenclature (e.g., refractory hypoxemia, pulmonary causes) and definitions. However, the largest observational study in non-COVID ARDS (964 deaths), did not include multiple organ failure as a predetermined category, and found that pulmonary failure (42%) and cardiac failure (37%) were the most common causes of death. In COVID-related ARDS observational studies, pulmonary reasons were the most reported cause of death (up to 88%). Few studies have reported cause of death in patients with ARDS. In those that do, cause of death categories and definitions used are heterogeneous. Further research is needed to see whether a more rigorous and unified approach to assigning and reporting cause of death in ARDS would help identify more relevant endpoints for the assessment of targeted treatments in clinical trials.

The effect of acellular scaffold loaded with Wharton's jelly-derived stem cells and mineral pitch on healing of burn model in rat.

Severe burns often result in an exacerbated inflammatory response, which can contribute to further injury. This inflammatory response may lead to an increased risk of infection, multiple organ failure, and death. This study aimed to investigate the potential of reducing inflammation to enhance burn wound healing in rats using ovine's small intestinal submucosa as a carrier for Wharton's jelly mesenchymal stem cells (WJ-MSCs) and Mineral Pitch (MP). A rat burn model was developed, and the animals were divided into four groups: control group: burn, placebo group: scaffold-treated burn, cell experimental group: WJ-MSCs seeded scaffold-treated burn, and cell and MP experimental group: scaffolds loaded with WJ-MSCs and MP-treated burn. After treating the wounds in the relevant groups and sampling them on days 5, 14 and 21, histological and pathological parameters, and the expression of genes involved in angiogenesis and epithelialization were evaluated. The study results revealed several findings in the burn wounds. These included changes in mast cell populations, a decrease in inflammatory neutrophils and lymphocytes, an increase in fibroblasts and blood vessels, and upregulation of angiogenesis and epithelialization genes. These changes collectively contributed to enhanced wound healing in cell and MP experimental group compared to the other groups. The findings suggest that scaffolds loaded with Wharton's jelly-derived stem cells and MP can serve as engineered tools to modulate inflammatory conditions during the burn wound healing process. These interventions can improve burn wound management and promote better outcomes.