Background Tocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients. Methods A multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival. Results In the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6–24.0, P = 0.52) and 22.4% (97.5% CI: 17.2–28.3, P < 0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline. Conclusions Tocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline. Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092).

This contribution draws from the experience of intensive care unit psychologists at 2 frontline hospitals in Milan, Italy, during the acute phase of the COVID-19 pandemic. In this contribution, we describe the main psychological needs observed in clinicians and in the families of COVID-19 patients and illustrate some psychological interventions implemented to respond to these needs. Containing emotions and promoting resilience were the aims of our interventions. In the future, psychological interventions should focus on the elaboration of traumatic experiences and losses.

BackgroundCurrently, both the step-up approach, combining percutaneous drainage (PD) and video-assisted retroperitoneal debridement (VARD), and endoscopic transgastric necrosectomy (ETN) are mini-invasive techniques for infected necrosis in severe acute pancreatitis. A combination of these approaches could maximize the management of necrotizing pancreatitis, conjugating the benefits from both the experiences. However, reporting of this combined strategy is anecdotal. This is the first reported case of severe necrotizing pancreatitis complicated by biliary fistula treated by a combination of ETN, PD, VARD, and endoscopic biliary stenting. Moreover, a systematic literature review of comparative studies on minimally invasive techniques in necrotizing pancreatitis has been provided.Case presentationA 59-year-old patient was referred to our center for acute necrotizing pancreatitis associated with multi-organ failure. No invasive procedures were attempted in the first month from the onset: enteral feeding by a naso-duodenal tube was started, and antibiotics were administered to control sepsis. After 4 weeks, CT scans showed a central walled-off pancreatic necrosis (WOPN) of pancreatic head communicating bilateral retroperitoneal collections. ETN was performed, and bile leakage was found at the right margin of the WOPN. Endoscopic retrograde cholangiopancreatography confirmed the presence of a choledocal fistula within the WOPN, and a biliary stent was placed. An ultrasound-guided PD was performed on the left retroperitoneal collection. Due to the subsequent repeated onset of septic shocks and the evidence of size increase of the right retroperitoneal collection, a VARD was decided. The CT scans documented the resolution of all the collections, and the patient promptly recovered from sepsis. After 6 months, the patient is in good clinical condition.ConclusionsNo mini-invasive technique has demonstrated significantly better outcomes over the others, and each technique has specific indications, advantages, and pitfalls. Indeed, ETN could be suitable for central WOPNs, while VARD or PD could be suggested for lateral collections. A combination of different approaches is feasible and could significantly optimize the clinical management in critically ill patients affected by complicated necrotizing pancreatitis.

Rationale:We present a case of hemophagocytic lymphohistiocytosis (HLH) with severe pulmonary complication and acute respiratory distress syndrome (ARDS) hospitalized in our intensive care unit (ICU) in 2014; distinctive trait of this case has been the challenging diagnosis, with a bone marrow biopsy always negative, the severe pulmonary complication with ARDS and severe pulmonary hypertension, and the ferritin temporal kinetics that precisely followed the clinical course of disease.Patient concerns:A 32-year-old woman from the Philippines first diagnosed with upper airway infection, was subsequently hospitalized in infectious disease department and treated for community acquired pneumonia.Diagnoses:After clinical picture worsened with a profound respiratory insufficiency, the patient was intubated and transferred to our ICU. During this hospitalization, the clinical picture of fever, cutaneous rashes, lymphadenitis, hepatitis, leukopenia, anemia, hyperferritinemia, hypertriglyceridemia, high level of auto-antibodies, and low NK activity suggested an hemophagocytic lymphohistiocytosis syndrome, even if bone marrow biopsy was negative for hemophagocytosis.Interventions:Immunosuppressive therapy with dexamethasone and etoposide was started, and the patient was discharged from ICU 4 months after admission.Lessons:HLH is a rare disorder of the mononuclear phagocytic system, characterized by systemic proliferation of non- neoplastic histiocytes. The diagnosis is often challenging and not all of the diagnostic criteria may be present at the same time; this case shows how complex the diagnosis could be, how hematic ferritin levels could help in following the course of the disease, and the possibility of severe pulmonary complication either due to the disease itself and to possible sovra infections.

Endotoxin activity (EA) plays an essential role in sepsis syndrome pathogenesis. There has been considerable interest in measuring and removing EA to predict and improve the morbidity and mortality of patients with sepsis. We performed a prospective study to assess the prevalence of EA in critically ill patients and its association with organ dysfunction and outcome, as well as in septic shock. EA (EAA(TM)) was measured within 24 h from onset of refractory septic shock in an intensive care unit. Our study demonstrated that EA level is independent from the type or the source of infection, but reflects the severity of illness in critically ill septic shock patients. Extracorporeal EA removal (PMX-HP) was assessed following our ICU clinical practice. PMX-HP seems to have better outcome, but further studies are required to verify this hypothesis.