Hemoperfusion with CytoSorb to Manage Multiorgan Dysfunction in the Spectrum of Hemophagocytic Lymphohistiocytosis Syndrome in Critically Ill Children.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition characterized by a state of hyperinflammation. Blood purification techniques can blunt the inflammatory process with a rapidly relevant nonselective effect on the cytokine storm, thus potentially translating into survival benefit for these patients. In this cohort, we evaluated the impact of hemoadsorption with CytoSorb combined with continuous kidney replacement therapy used as adjunctive therapy in 6 critically ill children with multiple organ dysfunction due to HLH. In our series, we found a reduction in inflammatory biomarkers in patients with HLH secondary to infection. Ferritin, one of the most important bedside biomarkers of HLH, showed a reduction in most of the treated patients. The same results were found measuring interleukin-6 and interleukin-10. The same patients showed hemodynamic stabilization measured by the Vasopressor-Inotropic-Score, and reduction in the organ disease score measured with the Pediatric Logistic Organ Dysfunction score. In our cohort, mortality was less than expected based on the Pediatric Index of Mortality 3 score at pediatric intensive care unit admission. Our study shows that hemoperfusion could be a valuable therapeutic option in HLH: stronger scientific evidence is needed to confirm our preliminary experience.

Pediatric extracorporeal cardiopulmonary resuscitation settled in an emergency department for a propafenone intentional intoxication.

The use of drugs in suicide attempts is becoming more and more frequent among adolescents. Intentional intoxication with propafenone is very rare and mainly reported in adults associated with other drugs. The therapeutic approach is symptomatic, since there is no specific antidote for propafenone. We present a pediatric case of intentional ingestion of 1.8 g of propafenone that caused refractory cardiogenic shock. The patient was successfully rescued with extracorporeal cardiopulmonary resuscitation in the emergency department of a secondary level peripheral hospital.

Severe viral respiratory infections in the pre-COVID era: A 5-year experience in two pediatric intensive care units in Italy.

BACKGROUND: Viral respiratory infections are one of the main causes of hospitalization in children. Even if mortality rate is low, 2% to 3% of the hospitalized children need mechanical ventilation. Risk factors for admission to the pediatric intensive care unit (PICU) are well known, while few studies have described risk factors for invasive ventilator support and prolonged hospitalization. METHODS: A retrospective study including all patients aged between 2 and 18 months with a confirmed viral respiratory infection, requiring admission to PICU from September to March between 2015 and 2019, was conducted at Bambino Gesù Children's Hospital in Rome, Italy. RESULTS: One hundred ninety patients were enrolled, with a median age of 2.7 months; 32.1% had at least one comorbidity, mainly prematurity. The most frequent isolated viruses were RSV-B, rhinovirus, and RSV-A; 38.4% needed mechanical ventilation. This subgroup of patients had lower median birth weight compared with patients not requiring mechanical ventilation (2800 g vs. 3180 g, p = 0.02); moreover, comorbidities were present in 43.8% of intubated patients and in 24.8% of patients treated with non-invasive ventilation (p = 0.006). Viral coinfection did not result to be a risk factor for mechanical support, while virus-bacteria coinfection was significantly associated with mechanical ventilation (p < 0.001). Similar risk factors were identified for prolonged hospitalization. CONCLUSIONS: Early identification of patients who could have a sudden respiratory deterioration and need of mechanical ventilation is crucial to reduce complications due to orotracheal intubation and prolonged hospitalization in PICU. Further studies are needed to define high-risk group of patients and to design targeted interventions.

Case report: Microcirculatory leukocytes in a pediatric patient with severe SARS-CoV-2 pneumonia. Findings of leukocytes trafficking beyond the lungs.

Background: SARS-CoV-2 can lead to excessive coagulation and thrombo-inflammation with deposition of microthrombi and microvascular dysfunction. Several studies in human and animal models have already evidenced biomarkers of endothelial injury during SARS-CoV-2 infection. Real-time observation of sublingual microcirculation using an handheld vital microscopy with an Incident Dark Field (IDF) technique could represent a non-invasive way to assess early signs of microvascular dysfunction and endothelial inflammation in patients with severe COVID-19 infection. Clinical case: We report for the first time in a pediatric patient with severe SARS-CoV-2 pneumonia findings about microcirculatory leukocytes in the sublingual microcirculation of a 7 month-old patient admitted to our PICU using handheld vital microscopy with IDF technique. Results: Sublingual microcirculation analysis revealed the presence of microcirculatory alterations and an extensive presence of leukocytes in the patient's sublingual microcirculation. It's significant to underline how the patient didn't show a contextual significant increase in inflammatory biomarkers or other clinical signs related to an inflammatory response, beyond the presence of severe hypoxic respiratory failure. Conclusion: Leukocyte activation in multiple organs can occur at the endothelial lining of the microvasculature where a surge of pro-inflammatory mediators can result in accumulation of activated leukocytes and degradation of the endothelium. The introduction of a method to assess in a non-invasive, real-time manner the extent of inflammation in a patient with COVID19 could lead to potential clinical and therapeutic implications. However, more studies are required to prove that studying leukocytes microcirculation using sublingual microcirculation analysis could be useful as a bedside point of care monitor to predict the presence of systemic inflammation associated with the impact of COVID-19, leading in a late phase of severe SARS-CoV-2 infection to a microvascular dysfunction and micro-thrombosis.

Mindful organizing as a healthcare strategy to decrease catheter-associated infections in neonatal and pediatric intensive care units. A systematic review and grading recommendations (GRADE) system.

PURPOSE: To explore the clinical evidence available on mindful organizing (MO) that will improve teamwork for positioning and managing central venous catheters in patients admitted to neonatal intensive care and other pediatric intensive care units to decrease central-line-associated and catheter-related bloodstream infections (CLABSI and CRBSI). METHODS: We searched several databases (PubMed, Embase, CINAHL, CENTRAL, SCOPUS, and Web of Science) up to June 2018. We included studies investigating the effectiveness of MO teamwork in reducing CLABSI and CRBSI. The systematic review followed the PRISMA guidelines. We used validated appraisal checklists to assess quality. RESULTS: Seven studies were included: only one was a non-randomized case-controlled trial (CCT). All the others had a pre-post intervention design, one a time-series design and one an interrupted time-series design. The methodological heterogeneity precluded a meta-analysis. Despite the low certainty of evidence with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system, three studies including thousands of participants provided numerical data for calculating risk ratios (RR) and 95% confidence intervals (CI) comparing MO with no intervention for decreasing the CLABSI rate in neonatal and pediatric ICUs. The one CCT disclosed no significant difference in the CLABSI rate decrease between groups (RR = 0.96; 95%CI 0.47-1.97). Nor did the pre- and post-intervention interrupted time-series design disclose a significant decrease (RR = 0.80; 95%CI 0.36 1.77). In the study using a before-after study design, the GRADE system found that the CLABSI rate decrease differed significantly in favor of post-intervention (RR = 0.13; 95%CI 0.03 0.57; p = 0.007). CONCLUSIONS: Despite the decreased CLABSI rate, the available evidence is low in quality. To reduce the unduly high CLABSI rates in neonatal and pediatric intensive care settings, custom-designed clinical trials should further define the clinical efficacy of MO to include it in care bundles as a new international standard.

[Immediate and long-term results after laparoscopic primary ventral hernia repair]. / La chirurgia laparoscopica nelle ernie ventrali primitive della parete addominale: risultati immediati ed a distanza.

OBJECTIVE: Umbilical and epigastric hernias are relatively frequent amounting to about 10% of all primary hernias. The aim of this study was to evaluate the efficacy and safety of laparoscopic primary ventral hernia repair. MATERIAL AND METHODS: From January 2002 through July 2007 a total of 23 consecutive patients were treated by laparoscopy for primary ventral hernia. Main demographics, intraoperative and postoperative data were collected. RESULTS: There were 14 males and 9 females with a mean age of 53.1 yrs (range 28-70 yrs). Mean body mass index was 25.2 kg/m2 (range 19.4 - 35.2). Fifteen patients had an umbilical hernia, 6 patients had an epigastric hernia and 2 a Spigelian hernia. Mean defect size was 8,4 cm2 (range 1.7 - 81.6). Mean mesh size was 115.9 cm2 (range 62.8-310.8). Mean operating time was 76.1 min (range 50-130). Mean hospital stay was 3,4 days (range 2-8). The median postoperative pain score (evaluated by a visual analog scale - VAS) was 2 at day 1, 4 at day 3 and 1 at day 7. Morbidity rate was 4.3%. After a mean follow-up of 28.5 months none recurrences were observed. CONCLUSIONS: Our study confirmed the feasibility of laparoscopic repair in terms of postoperative morbidity and recurrence rate. Thus laparoscopic primary ventral hernia repair should be considered an effective alternative to open techniques.

Laparoscopic approach to recurrent incisional hernia repair: a 3-year experience.

BACKGROUND: Incisional hernias are one of the most frequent complications of open abdominal surgery. The incidence of relapses after a conventional repair procedure is higher in recurrent than in primary cases (30%-50% vs. 11%-20%). The laparoscopic approach can prevent the complications associated with the conventional approach when dealing with recurrent incisional hernias. The aim of this study was to evaluate the efficacy of laparoscopic treatment in such cases. MATERIALS AND METHODS: We prospectively analyzed data from 41 consecutive patients with recurrent incisional hernias, who submitted to a laparoscopic repair procedure with an expanded polytetrafluoroethylene Dual Mesh (Gore-Tex Dual Mesh Plus Biomaterial; W.L. Gore 8 Associates) from December 2001 to December 2004. All of the patients underwent clinical follow-up at 1, 6, and 12 months and then yearly. An ultrasound scan of the abdominal wall was performed at 6 and 12 months after the procedure. The parameters considered for the analysis were: mesh size, operating time, hospital stay, postoperative complications, and recurrences. RESULTS: The defects were usually localized along midline laparotomies. The mean mesh size was 400 cm2, the mean operating time was 68 minutes, and the mean length of hospital stay was 2.7 days. Complications were encountered in 17% of patients. The mean follow-up was 38 months (range, 18-54). Recurrence was reported in 1 case only (2.4%), which occurred within the first 6 months after the operation. CONCLUSIONS: The laparoscopic repair of recurrent incisional hernia seems to be an effective alternative to the conventional approach, as it can give lower recurrence and complication rates.

WNT-pathway components as predictive markers useful for diagnosis, prevention and therapy in inflammatory bowel disease and sporadic colorectal cancer.

The key role of the Wnt/ß-catenin signaling in colorectal cancer (CRC) insurgence and progression is now recognized and several therapeutic strategies targeting this pathway are currently in developing. Wnt/ß-catenin signaling not only dominates the early stages of sporadic colorectal cancer (SCC), but could also represent the connection between inflammatory bowel diseases (IBD) and increased risk of developing SCC. The knowledge on the sequential molecular events of Wnt-signaling cascade in IBD and during colorectal carcinogenesis, might provide new diagnostic/prognostic markers and could be helpful for optimizing the treatment protocols, thus improving the efficacy of Wnt-targeting therapies. We performed a comparative evaluation of the expression of some crucial molecules participating to Wnt signaling in an animal model of chemically-induced CRC and in human tissues obtained from patients suffering from IBD or at sequential stages of SCC. Specifically, we analyzed upstream events of Wnt signaling including ß-catenin nuclear translocation and loss of E-cadherin and APC functions, and downstream events including c-Myc and Cyclin-D1 expression. We demonstrated that these crucial components of the Wnt/ß-catenin pathway, when evaluated by immunohistochemistry using a multiparametric approach that includes the analyses of both expression and localization, could be potent markers for diagnosis, prevention and therapy in IBD and SCC, also possessing a predictive value for responsiveness to Wnt-targeting therapies. Furthermore, we showed that the animal model of chemically-induced CRC mimics the molecular events of Wnt signaling during IBD and SCC development in humans and may therefore be suitable for testing chemopreventive or therapeutic drugs targeting this pathway.