Search Results (26)

Objective: This article evaluates the reconstructive potential and functional outcomes, as well as the risks and potential perioperative complications of using free flaps in patients with advanced-stage malignant laryngeal neoplasms who require salvage surgery and reconstruction. Additionally, it assesses the effectiveness of various flap harvesting and in-setting techniques, including the performance of microvascular anastomoses. Materials and Methods: This retrospective study included 13 male patients (age range 47–76 years) diagnosed with laryngeal neoplasms, who were referred to the Department of Otolaryngology at the University of Verona between 2017 and 2022. All patients underwent salvage total laryngectomy followed by concurrent reconstructive surgery utilizing microvascular flaps. Recovery of function (phonation) and incidence of complications were evaluated in a follow-up of at least three years. Results: Only one patient experienced necrotic failure of the microvascular free flap, probably due to post-op complications. The patient required revision on the 10th day after surgery and was reconstructed using a pedicled pectoralis major muscle flap. Two patients developed a pharyngocutaneous fistula. Other three patients had pharyngoesophageal stenosis, two experienced recurrence, and one patient passed away due to septic shock. All patients achieved satisfactory functional outcomes regarding vocalization, while complete oral intake was restored in eight patients. Conclusions: Considering the limited sample size, the findings suggest that microvascular flaps represent a feasible option for reconstructing advanced laryngeal tumors, though complication rate may still be considerable. Tailoring reconstructive approaches to individual patients may enhance surgical outcomes. Full article

Introduction: Sternoclavicular joint infections (SCJIs) are extremely rare, making up less than 1% of all septic arthritis cases. This retrospective study aims to evaluate the management and outcomes of SCJIs, including both surgical and non-surgical approaches. Methods: This retrospective study included 55 patients treated between January 2005 and December 2023 at the Division of Thoracic and Hyperbaric Surgery in Graz, Austria. Data on patient characteristics, treatment approach, and outcome were analyzed. Results: Out of the 55 patients, 50 (90.91%) underwent surgery. Among them, 21 (38.18%) had pleural involvement and 9 (16.36%) developed sepsis. Primary debridement and sternoclavicular joint resection with muscle flap closure were performed in 5 patients (9.3%), whilst debridement and negative pressure wound therapy (NPWT) followed by joint resection were applied in 32 patients (59.3%). In total, 15 (27.2%) of these cases required a secondary muscle flap. Positive cultures were found in 35 patients (63.64%), with Staphylococcus aureus being the most common pathogen. Multivariate analysis identified elevated CRP and leukocyte levels as significant predictors of sepsis. Defects requiring myoplastic procedures were associated with a higher risk of complications, sepsis, and prolonged hospital stays. Postoperative complications occurred in 20 patients (36.36%), but there was no 30-day mortality. Conclusions: SCJI is a rare but serious condition that requires prompt surgical intervention. Our findings suggest that combining surgical resection with NPWT and/or myocutaneous flap techniques is effective. Close monitoring of inflammatory markers is crucial for identifying sepsis risk and improving patient outcomes. Full article

Objective: A controversial aspect of pediatric septic shock management is corticosteroid therapy. Current guidelines do not recommend its use in forms responsive to fluids and inotropes but leave the decision to physicians in forms refractory to the first steps of therapy. Data Sources: Review of literature from January 2013 to December 2023 from online libraries Pubmed, Medline, Cochrane Library, and Scopus. Study Selection: The keywords “septic shock”, “steroids” and “children” were used. Data Extraction: Of 399 articles, 63 were selected. Data Synthesis: Regarding mortality, although the 2019 Cochrane review supports reduced mortality, benefits on long-term mortality and in patients with CIRCI (critical illness-related corticosteroid insufficiency) are not clear. Yang’s metanalysis and retrospective studies of Nichols and Atkinson show no difference or even an increase in mortality. Regarding severity, the Cochrane review claims that hydrocortisone seems to reduce the length of intensive care hospitalization but influences the duration of ventilatory and inotropic support, and the degree of multi-organ failure appears limited. Further controversies exist on adrenal function evaluation: according to literature, including the Surviving Sepsis Campaign guidelines, basal or stimulated hormonal dosages do not allow the identification of patients who could benefit from hydrocortisone therapy (poor reproducibility). Regarding side effects, muscle weakness, hypernatremia, and hyperglycemia are the most observed. Conclusions: The literature does not give certainties about the efficacy of corticosteroids in pediatric septic shock, as their influence on primary outcomes (mortality and severity) is controversial. A subgroup of patients suffering from secondary adrenal insufficiency could benefit from it, but it remains to be defined how to identify and what protocol to use to treat them. Full article

The biological activities of plant-derived soluble dietary fibres (SDFs) have been widely investigated. Pectin from yellow passion fruit (YPF-peSDF) peels was suggested as a protective macromolecule in ulcers and colitis due to its antioxidant and anti-inflammatory properties. Sepsis has high mortality and morbidity and is characterised by inflammatory and oxidative stress imbalances. Evidence suggests that pectins may aid sepsis treatment; however, the effects of YPF-peSDF on sepsis remain unclear. Herein, polymicrobial sepsis was induced by cecal-ligation and puncture in mice treated with YPF-peSDF (1 and 10 mg/kg; gavage). YPF-peSDF accelerated mortality, reaching 100% in 24 h. Inflammation was present in the colons and small intestines (SI) of both vehicle- and fibre-treated mice. Although crypt depth and width, and villus height were preserved in the SI of septic mice administered YPF-peSDF, they exhibited exacerbated muscle layer atrophy and mucosa and submucosa hypertrophy, along with shortened enterocytes. Larger crypts and shorter enterocytes were noted in their colons in comparison with vehicle-controls. YPF-peSDF also reduced inflammatory cell numbers and exacerbated IL-6 levels in peritoneal lavage fluid (PELF) samples. YPF-peSDF modulated SI but not colon cytokines. Lipoperoxidation and antioxidant capacity levels were attenuated in PELF samples. Overall, in contrast to previous evidence, YPF-peSDF worsened polymicrobial sepsis outcomes in mice. Full article

OBJECTIVE: Medical nutrition therapy provides the opportunity to compensate for muscle wasting and immune response activation during stress and trauma. The objective of this systematic review is to assess the safety and effectiveness of early enteral nutrition (EEN) in adults with sepsis or septic shock. METHODS: The MEDLINE, Embase, CENTRAL, CINAHL, ClinicalTrials.gov, and ICTRP tools were searched from inception until July 2023. Conference proceedings, the reference lists of included studies, and expert content were queried to identify additional publications. Two review authors completed the study selection, data extraction, and risk of bias assessment; disagreements were resolved through discussion. Inclusion criteria were randomized controlled trials (RCTs) and non-randomized studies (NRSs) comparing the administration of EEN with no or delayed enteral nutrition (DEE) in adult populations with sepsis or septic shock. RESULTS: Five RCTs (n = 442 participants) and ten NRSs (n = 3724 participants) were included. Low-certainty evidence from RCTs and NRSs suggests that patients receiving EEN could require fewer days of mechanical ventilation (MD −2.65; 95% CI, −4.44–0.86; and MD −2.94; 95% CI, −3.64–−2.23, respectively) and may show lower SOFA scores during follow-up (MD −1.64 points; 95% CI, −2.60–−0.68; and MD −1.08 points; 95% CI, −1.90–−0.26, respectively), albeit with an increased frequency of diarrhea episodes (OR 2.23, 95% CI 1.115–4.34). Even though the patients with EEN show a lower in-hospital mortality rate both in RCTs (OR 0.69; 95% CI, 0.39–1.23) and NRSs (OR 0.89; 95% CI, 0.69–1.13), this difference does not achieve statistical significance. There were no apparent differences for other outcomes. CONCLUSIONS: Low-quality evidence suggests that EEN may be a safe and effective intervention for the management of critically ill patients with sepsis or septic shock. Full article

(1) Background: Sepsis-induced muscle atrophy is characterized by a loss of muscle mass and function which leads to decreased quality of life and worsens the long-term prognosis of patients. N-acetylcysteine (NAC) has powerful antioxidant and anti-inflammatory properties, and it relieves muscle wasting caused by several diseases, whereas its effect on sepsis-induced muscle atrophy has not been reported. The present study investigated the effect of NAC on sepsis-induced muscle atrophy and its possible mechanisms. (2) Methods: The effect of NAC on sepsis-induced muscle atrophy was assessed in vivo and in vitro using cecal ligation and puncture-operated (CLP) C57BL/6 mice and LPS-treated C2C12 myotubes. We used immunofluorescence staining to analyze changes in the cross-sectional area (CSA) of myofibers in mice and the myotube diameter of C2C12. Protein expressions were analyzed by Western blotting. (3) Results: In the septic mice, the atrophic response manifested as a reduction in skeletal muscle weight and myofiber cross-sectional area, which is mediated by muscle-specific ubiquitin ligases—muscle atrophy F-box (MAFbx)/Atrogin-1 and muscle ring finger 1 (MuRF1). NAC alleviated sepsis-induced skeletal muscle wasting and LPS-induced C2C12 myotube atrophy. Meanwhile, NAC inhibited the sepsis-induced activation of the endoplasmic reticulum (ER) stress signaling pathway. Furthermore, using 4-Phenylbutyric acid (4-PBA) to inhibit ER stress in LPS-treated C2C12 myotubes could partly abrogate the anti-muscle-atrophy effect of NAC. Finally, NAC alleviated myotube atrophy induced by the ER stress agonist Thapsigargin (Thap). (4) Conclusions: NAC can attenuate sepsis-induced muscle atrophy, which may be related to downregulating ER stress. Full article

The main causes of mortality in horses are the gastrointestinal pathologies associated with septic shock. Stem cells have shown, through systemic injection, a capacity to decrease inflammation and to regenerate injured tissue faster. Nevertheless, to achieve this rapid and total regeneration, systemic injections of 1 to 2 million cells per kilogram of body weight must be considered. Here, we demonstrate for the first time the feasibility and expansion capacity of equine muscle-derived mesenchymal stromal cells (mdMSCs) in a functionally closed, automated, perfusion-based, hollow-fiber bioreactor (HFBR) called the Quantum™ Cell Expansion System (Terumo Blood and Cell Technologies). This feature greatly increases the number of generated cells with a surface area of 1.7 m². The expansion of mdMSCs is very efficient in this bioreactor. The maximum expansion generated twenty times more cells than the initial seeding in nine days. The best returns were observed with an optimal seeding between 10 and 25 million mdMSCs, using the Bull’s eye loading method and with a run duration between 7 and 10 days. Moreover, all the generated cells kept their stem properties: the ability to adhere to plastic and to differentiate into chondroblasts, osteoblasts and adipocytes. They also showed the expression of CD-44 and CD-90 markers, with a positive rate above 93%, while CD-45 and MHCII were non-expressed, with a positive rate below 0.5%. By capitalizing on the scalability, automation and 3D culture capabilities of the Quantum™, it is possible to generate large quantities of high-quality equine mdMSCs for gastrointestinal disorders and other clinical applications. Full article

We describe the case of a 43-year-old female with hereditary hemochromatosis, previously without cardiac issues, who presented with a severe fever (>40 to 41 °C) to our hospital. Initial assessments, including transthoracic echocardiography, showed no typical signs of infective endocarditis. A contrast-enhanced CT scan revealed a hypodense area in the right subscapular muscle, alongside pleural thicknesses. Due to the critical condition, a central venous catheter (CVC) was implanted for immediate intravenous treatment. Subsequent blood cultures, positive for Staphylococcus aureus, and transesophageal echocardiography led to a diagnosis of multivalvular infective endocarditis (MIE). Subsequently, the patient underwent positron emission tomography/computed tomography (PET/CT) with [¹⁸F]Fluorodeoxyglucose ([¹⁸F]FDG), which detected increased tracer incorporation in the muscle lesion, CVC, and pleural thicknesses. The final diagnosis was CVC infection and septic embolism to the subscapular muscle in a patient with pleuritis. This case showcases the critical role of [¹⁸F]FDG PET/CT as whole-body imaging modality in diagnosing and managing complex infective cases. Full article

Sepsis is a risk factor for diaphragm dysfunction and ICU-acquired weakness (ICU-AW); however, the impact of mechanical ventilation (MV) on these relationships has not been thoroughly investigated. This study aimed to compare the incidence of diaphragm dysfunction and ICU-AW in patients with septic shock, with and without MV. We conducted a single-center prospective observational study that included consecutive patients diagnosed with septic shock admitted to the ICU between March 2021 and February 2022. Ultrasound measurements of diaphragm thickness and manual measurements of limb muscle strength were repeated after ICU admission. The incidences of diaphragm dysfunction and ICU-AW, as well as their associations with clinical outcomes, were compared between patients with MV and without MV (non-MV). Twenty-four patients (11 in the MV group and 13 in the non-MV group) were analyzed. At the final measurements in the MV group, eight patients (72.7%) had diaphragm dysfunction, and six patients (54.5%) had ICU-AW. In the non-MV group, 10 patients (76.9%) had diaphragm dysfunction, and three (23.1%) had ICU-AW. No association was found between diaphragm dysfunction and clinical outcomes. Patients with ICU-AW in the MV group had longer ICU and hospital stays. Among patients with septic shock, the incidence of diaphragm dysfunction was higher than that of ICU-AW, irrespective of the use of MV. Further studies are warranted to examine the association between diaphragm dysfunction and clinical outcomes. Full article

Colistin is often used as a last resort for treating multidrug-resistant infections, particularly in critically ill patients in intensive care units. Nonetheless, its side effects, including myopathy, require careful monitoring. Vasoconstrictive drugs are also used in intensive care to increase blood pressure and improve blood flow to vital organs, which can be compromised in critically ill patients. The exact mechanism of colistin-induced muscle toxicity is of significant interest due to its potential intensive-care clinical implications. Colistin alone or in combination with vasoconstrictive agents was administrated in non-septic and LPS-induced septic animals for 10 days. Histopathological evaluation of the gastrocnemius muscle and dot-blot protein tissue analysis were performed. Increased intramuscular area, de-organization of the muscle fibers and signs of myopathy were observed in colistin-treated animals. This effect was ameliorated in the presence of vasoconstrictive drugs. Administration of colistin to septic animals resulted in a decrease of AMPK and cyclin-D1 levels, while it had no effect on caspase 3 levels. Vasoconstrictive drugs’ administration reversed the effects of colistin on AMPK and cyclin D1 levels. Colistin’s effects on muscle depend on septic state and vasoconstriction presence, highlighting the need to consider these factors when administering it in critically ill patients. Full article

Sodium-glucose cotransporter-2 (SGLT2) inhibitors have been suggested to have anti-inflammatory properties in diabetes. The goal of this study was to evaluate the role of the SGLT2 inhibitor dapagliflozin (DAPA) in the attenuation of lipopolysaccharide (LPS)-induced hypotension. Male Wistar albino rats were divided into normal and diabetic groups and received DAPA (1 mg/kg/day) for two weeks followed by a single dose of 10 mg/kg LPS. Blood pressure was recorded throughout the study and the circulatory levels of cytokines were assessed using a multiplex array, while the aortas were harvested for analysis. DAPA attenuated the vasodilation and hypotension caused by LPS. Mean arterial pressure (MAP) was preserved in the normal and diabetic DAPA-treated septic groups (MAP = 83.17 ± 5.27, 98.43 ± 5.57 mmHg) compared to the vehicle-treated septic groups (MAP = 65.60 ± 3.31, 68.21 ± 5.88 mmHg). Most of the cytokines induced by LPS were decreased in the DAPA-treated septic groups. In the aorta, the inducible nitric oxide synthase-derived nitric oxide had lower expression in the DAPA-treated rats. In contrast, the expression of α-smooth muscle actin, a marker of the vessel’s contractile state, was higher in the DAPA-treated rats in comparison with non-treated septic rats. These findings revealed that the protective role of DAPA against LPS-induced hypotension is likely to be glucose-lowering independent, as was observed in the non-diabetic septic group. Taken together, the results show that DAPA has a potential effect in the prevention of the hemodynamic disturbances of sepsis regardless of glycemia levels. Full article

Optimizing the entire therapeutic regimen in septic critically ill patients should be based not only on improving antibiotic use but also on optimizing the entire therapeutic regimen by considering possible drug–drug or drug–nutrient interactions. The aim of this narrative review is to provide a comprehensive overview on recent advances to optimize the therapeutic regimen in septic critically ill patients based on a pharmacokinetics and pharmacodynamic approach. Studies on recent advances on TDM-guided drug therapy optimization based on PK and/or PD results were included. Studies on patients <18 years old or with classical TDM-guided therapy were excluded. New approaches in TDM-guided therapy in septic critically ill patients based on PK and/or PD parameters are presented for cefiderocol, carbapenems, combinations beta-lactams/beta-lactamase inhibitors (piperacillin/tazobactam, ceftolozane/tazobactam, ceftazidime/avibactam), plazomicin, oxazolidinones and polymyxins. Increased midazolam toxicity in combination with fluconazole, nephrotoxic synergism between furosemide and aminoglycosides, life-threatening hypoglycemia after fluoroquinolone and insulin, prolonged muscle weakness and/or paralysis after neuromuscular blocking agents and high-dose corticosteroids combinations are of interest in critically ill patients. In the real-world practice, the use of probiotics with antibiotics is common; even data about the risk and benefits of probiotics are currently spares and inconclusive. According to current legislation, probiotic use does not require safety monitoring, but there are reports of endocarditis, meningitis, peritonitis, or pneumonia associated with probiotics in critically ill patients. In addition, probiotics are associated with risk of the spread of antimicrobial resistance. The TDM-guided method ensures a true optimization of antibiotic therapy, and particular efforts should be applied globally. In addition, multidrug and drug–nutrient interactions in critically ill patients may increase the likelihood of adverse events and risk of death; therefore, the PK and PD particularities of the critically ill patient require a multidisciplinary approach in which knowledge of clinical pharmacology is essential. Full article

The goal of the study was to compare laparoscopic and open radical cystectomy in treatment of muscle-invasive bladder cancer in the Department of Urology and Oncological Urology PUM in Szczecin. A total of 78 patients in the study group underwent laparoscopic cystectomy between 2016–2018, and 81 patients from the control group had open cystectomy between 2014–2016. Both groups were comparable in terms of age, stage, and concomitant diseases. The 3 year overall survival was comparable in both groups (37.7% for laparoscopy and 44.4% for open, p = 0.64). There was no difference in positive surgical margin rate. Lymph node yield during cystectomy was higher in open cystectomy (14 vs. 11.5, p = 0.001). Post-operative blood loss and transfusion rates were lower in laparoscopic cystectomy. Decrease in hemoglobin level was lower in laparoscopy (0.9 mmol/L, p < 0.001). Intraoperative transfusion rate was 11.8% in laparoscopy vs. 34.8% in open cystectomy (p = 0.002). Operation time, duration of hospitalisation, and time to full oral alimentation were comparable in both groups. Patients with BMI > 30 kg/m² and those with pT3-T4 cancer in the laparoscopy group had less septic complications post-operatively. Patients with ASA score ≥ 3 from the laparoscopy group had fewer reoperations due to ileus. Laparoscopic cystectomy is less invasive and offers similar oncological outcomes to the open method. Patients benefit from less tissue trauma, less blood loss, and faster recovery. The presented results, as well as other publications, should encourage a wider use of this procedure in everyday urological practice. Full article

Thrombosis, the common and deadliest disorder among human diseases, develops as a result of the intravascular hemostasis following an intravascular injury, which can be caused by a variety of trauma, non-traumatic insults or clinical illnesses. Thrombosis can occur at any location of the vascular system supplied by blood from the heart to large and smallest arterial and venous systems and may affect the function and anatomy of the organ and tissue. It more commonly occurs in the smaller circulatory system of the vascular tree such as arterioles and capillaries, and venules of the organs, especially in the brain, lungs, heart, pancreas, muscle and kidneys, and sinusoids of the liver. Thrombosis has been referred as the disease of “blood clots”, which concept is incompletely defined, but represents many different hemostatic diseases from microthrombosis to fibrin clot disease, macrothrombosis, and combined micro-macrothrombosis. Thrombosis is produced following an intravascular injury via one or more combination of four different mechanisms of thrombogenesis: microthrombogenesis, fibrinogenesis, macrothrombogenesis and micro-macrothrombogenesis initiated by normal physiological hemostasis in vivo. The clinical phenotype expression of thrombosis is determined by: (1) depth of the intravascular wall injury, (2) extent of the injury affecting the vascular tree system, (3) physiological character of the involved vascular system, (4) locality of the vascular injury, and (5) underlying non-hemostatic conditions interacting with hemostasis. Recent acquisition of “two-path unifying theory” of hemostasis and “two-activation theory of the endothelium” has opened a new frontier in science of medicine by identifying the pathophysiological mechanism of different thrombotic disorders and also contributing to the better understanding of many poorly defined human diseases, including different phenotypes of stroke and cardiovascular disease, trauma, sepsis and septic shock, multiorgan dysfunction syndrome, and autoimmune disease, and others. Reviewed are the fundamentals in hemostasis, thrombogenesis and thrombosis based on hemostatic theories, and proposed is a novel classification of thrombotic disorders. Full article

The impact of myosteatosis on septic patients has not been fully revealed. The aim of the study was to evaluate the impact of the myosteatosis area and percentage on the 28-day mortality in patients with septic shock. We conducted a single center, retrospective study from a prospectively collected registry of adult patients with septic shock who presented to the emergency department and performed abdominal computed tomography (CT) from May 2016 to May 2020. The myosteatosis area defined as the sum of low attenuation muscle area and intramuscular adipose tissue at the level of the third lumbar vertebra was measured by CT. Myosteatosis percentages were calculated by dividing the myosteatosis area by the total abdominal muscle area. Of the 896 patients, 28-day mortality was 16.3%, and the abnormal myosteatosis area was commonly detected (81.7%). Among variables of body compositions, non-survivors had relatively lower normal attenuation muscle area, higher low attenuation muscle area, and higher myosteatosis area and percentage than that of survivors. Trends of myosteatosis according to age group were different between the male and female groups. In subgroup analysis with male patients, the multivariate model showed that the myosteatosis percentage (adjusted OR 1.02 [95% CI 1.01–1.03]) was an independent risk factor for 28-day mortality. However, this association was not evident in the female group. Myosteatosis was common and high myosteatosis percentage was associated with short-term mortality in patients with septic shock. Our results implied that abnormal fatty disposition in muscle could impact on increased mortality, and this effect was more prominent in male patients. Full article