Rapid and Impressive Response to a Combined Treatment with Single-Dose Tocilizumab and NIV in a Patient with COVID-19 Pneumonia/ARDS.

Treatment of acute respiratory distress syndrome (ARDS) due to COVID-19 pneumonia (CARDS) represents a clinical challenge, requiring often invasive mechanical ventilation (IMV). Since the pathogenesis of CARDS it probably involves a direct viral attack to pulmonary and endothelium cells, and immune-mediated inflammation with dysfunctional coagulation, it was suggested to interfere with interleukin-6 (IL-6) activity by using the IL-6 receptor monoclonal antibody tocilizumab (TCZ). We reported the case of a 54-year-old 100 kg male COVID-19 patient (BMI 29) with severe respiratory insufficiency featuring dyspnea and hypoxia (SpO2 89% on room; PaO2 53 mmHg). Despite treatment with antiviral and non-invasive ventilation (NIV), after 24 h there was a progressive worsening of clinical conditions with higher fever (40 °C), increased dyspnea, and hypoxia (PaO2/FiO2 or P/F ratio of 150). The patient was at the limit to be sedated and intubated for IMV. He was treated with tocilizumab (8 mg/Kg i.v., single shot 800 mg) and NIV in the prone positioning. After only 96 h, the clinical, laboratory, and imaging findings showed incredible improvement. There was an important gain in oxygenation (P/F 300), a decrease of C-reactive protein values, and a decrease of the fever. Both the neutrophil-to-lymphocyte ratio (NLR) and the derived NLR ratio dropped down to 44%. Chest imaging confirmed the favorable response. This case suggested that for CARDS management efforts are needed for reducing its underlying inflammatory processes. Through a multiprofessional approach, the combination of IL-6-targeting therapies with calibrated ventilatory strategies may represent a winning strategy for improving outcomes.

COVID-Pain: Acute and Late-Onset Painful Clinical Manifestations in COVID-19 - Molecular Mechanisms and Research Perspectives.

Although the respiratory manifestations of COVID-19 are predominant, signs and symptoms of an extra-pulmonary involvement are usually encompassed among the clinical picture of the disease. Several painful manifestations can occur during the acute phase but also as short- or long-term complications. Myalgia, joint pain, sore throat, abdominal pain, chest pain, and headache usually accompany respiratory symptoms, but they can also occur as isolated clinical findings or can be expressed regardless of the severity of COVID-19. On these premises, given the vast spectrum of clinical manifestations and the complexity of their pathogenesis, it would be more appropriate to refer to "COVID-pain", an umbrella term useful for encompassing all these clinical manifestations in a separate chapter of the disease. In this scenario, we addressed the topic from a molecular perspective, trying to provide explanations for the underlying pathophysiological processes. Consequently, this narrative review is aimed at dissecting the mechanisms of acute and chronic painful manifestations, summarizing fundamental concepts on the matter, controversies, current research gaps, and potential developments in this field.

[Perioperative strategies: taking care of the elderly patient with severe advanced comorbidities needing acute surgery.] / Strategie perioperatorie: presa in carico dell'anziano con gravi comorbilità e fase avanzata di malattia con patologia chirurgica acuta.

In the common clinical practice the perioperative risk assessment of an acute surgical patient with advanced chronic comorbidities is carried out independently by surgeon and anesthesiologist, usually in two different steps. While the surgeon evaluates the risk mainly in relation to the surgical outcome, the perioperative risk assessment regarding the weight of the coexisting medical condition on the quality of recovery in the short- mid- and long-term is all about the anesthesiologist evaluation. When frailty and/or comorbidities are so serious that will make surgery seem futile, the patient's assessment on one hand, and the decisions regarding the further clinical waypoint on the other, have to be discussed firstly between surgeons and anesthesiologists before being shared with the patients and their relatives. This is mostly true in the event of an emergency surgical procedure. In regard, a consensus conference attended by a panel of experts respectively from the Italian Society of Anesthesia Analgesia Resuscitation and Intensive Care (SIAARTI) and the Italian Society of Surgery (SIC) was called for developing a shared clinical pathway aimed to select the best care option - operative vs palliative - in the best interest of the surgical patient with advanced chronic comorbidities, in emergency or elective condition. After two years, the panel of experts developed a position paper recommending, in case of potentially futile surgery, to assess the patient verifying two coexisting conditions ("Two Steps method"): Palliative Performance Scale <50%, and at least one of the following general clinical criteria: 1) more than one hospital admission within the last 12 months; 2) hospital admission from or awaiting admission to long-term care facilities, home care service, hospice; 3) chronic renal failure requiring weekly dialysis sessions; 4) home oxygen use and/or non-invasive ventilation. Under these conditions, the surgeon together with the anesthesiologist can share with the patient and/or his relatives the decision between palliative surgery or palliative care taking into account his wishes and preferences.

Good clinical practice for the use of vasopressor and inotropic drugs in critically ill patients: state-of-the-art and expert consensus.

Vasopressors and inotropic agents are widely used in critical care. However, strong evidence supporting their use in critically ill patients is lacking in many clinical scenarios. Thus, the Italian Society of Anesthesia and Intensive Care (SIAARTI) promoted a project aimed to provide indications for good clinical practice on the use of vasopressors and inotropes, and on the management of critically ill patients with shock. A panel of 16 experts in the field of intensive care medicine and hemodynamics has been established. Systematic review of the available literature was performed based on PICO questions. Basing on available evidence, the panel prepared a summary of evidence and then wrote the clinical questions. A modified semi-quantitative RAND/UCLA appropriateness method has been used to determine the appropriateness of specific clinical scenarios. The panel identified 29 clinical questions for the use of vasopressors and inotropes in patients with septic shock and cardiogenic shock. High level of agreement exists among the panel members about appropriateness of inotropes/vasopressors' use in patients with septic shock and cardiogenic shock.

Strategies to evaluate outcomes in long-COVID-19 and post-COVID survivors.

SARS-CoV-2 infection can impact the physical, cognitive, mental health of patients, especially in those recovered in intensive care units. Moreover, it was proved that the effects of the virus may persist for weeks or months. The term long-COVID or post-COVID syndrome is commonly used for indicating a variety of physical and psychological symptoms that continue after the resolution of the acute phase. This narrative review is aimed at providing an updated overview of the impact of physical, cognitive, and psychological health disorders in COVID-19 survivors, by summarizing the data already published in literature in the last year. Studies cited were found through PubMed searches. We also presented an overview of the post-COVID-19 health consequences on three important aspects: nutritional status, neurological disorders, and physical health. Moreover, to activate a correct health planning policy, a multidisciplinary approach for addressing the post- COVID-19 issue, has been proposed. Finally, the involvement of health professionals is necessary even after the pandemic, to reduce expected post-pandemic psychosocial responses and mental health disorders.

Orthopedic injuries in patients with multiple injuries: Results of the 11th trauma update international consensus conference Milan, December 11, 2017.

BACKGROUND: In blunt trauma, orthopedic injuries are often associated with cerebral and torso injuries. The optimal timing for definitive care is a concern. The aim of the study was to develop evidence-based guidelines for damage-control orthopedic (DCO) and early total care (ETC) of pelvic and long-bone fractures, closed or open, and mangled extremities in adult trauma patients with and without associated injuries. METHODS: The literature since 2000 to 2016 was systematically screened according to Preferred Reporting Items for Systematic Reviews and meta-analyses protocol. One hundred twenty-four articles were reviewed by a panel of experts to assign grade of recommendation and level of evidence using the Grading of recommendations Assessment, Development, and Evaluation system, and an International Consensus Conference, endorsed by several scientific societies was held. RESULTS: The choice between DCO and ETC depends on the patient's physiology, as well as associated injuries. In hemodynamically unstable pelvic fracture patient, extraperitoneal pelvic packing, angioembolization, external fixation, C-clamp, and resuscitative endovascular balloon occlusion of the aorta are not mutually exclusive. Definitive reconstruction should be deferred until recovery of physiological stability. In long bone fractures, DCO is performed by external fixation, while ETC should be preferred in fully resuscitated patients because of better outcomes. In open fractures early debridement within 24 hours should be recommended and early closure of most grade I, II, IIIa performed. In mangled extremities, limb salvage should be considered for non-life-threatening injuries, mostly of upper limb. CONCLUSION: Orthopedic priorities may be: to save a life: control hemorrhage by stabilizing the pelvis and femur fractures; to save a limb: treat soft tissue and vascular injuries associated with fractures, stabilize fractures, recognize, and prevent compartmental syndrome; to save functionality: treat dislocations, articular fractures, distal fractures. While DCO is the best initial treatment to reduce surgical load, ETC should be applied in stable or stabilized patients to accelerate the recovery of normal functions. LEVEL OF EVIDENCE: Systematic review of predominantly level II studies, level II.

Reversible post-traumatic bilateral extensive restricted diffusion of the brain. A case study and review of the literature.

PRIMARY OBJECTIVE: To increase the knowledge about diffuse traumatic brain injury (TBI) by reporting the magnetic resonance imaging (MRI) findings observed in a patient with reversible extensive restricted diffusion of the brain at diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) maps. CASE STUDY: An 18-year-old patient was admitted after high-energy closed TBI. Glasgow Coma Scale score was 4. Head computed tomography showed small left frontal and temporal haemorrhagic contusions and a small haemorrhage in the left thalamus. Ten days later, brain MRI showed diffuse high-signal intensity on T2-weighted images and DWI and restricted diffusion in the subcortical white matter of both centri semiovali, genu and splenium of corpus callosum and parietal cortex bilaterally (mean ADC value = 0.434-0.811 x 10(-3) mm(2) s(-1)). Eleven days later, follow-up brain MRI showed gliotic changes in the left splenium of corpus callosum, a clearcut decrease of T2-weighted high-signal intensity and resolution of abnormalities at DWI and ADC maps in all other involved sites. This was confirmed 36 days later. Three months later, the patient did not show neurological, cognitive or neuropsychiatric deficits. CONCLUSIONS: In the patient reported herein, closed TBI most likely induced diffuse excitotoxic injury of the brain which resulted in mainly reversible cytotoxic or intramyelinic oedema.

Blood Component Therapy and Coagulopathy in Trauma: A Systematic Review of the Literature from the Trauma Update Group.

BACKGROUND: Traumatic coagulopathy is thought to increase mortality and its treatment to reduce preventable deaths. However, there is still uncertainty in this field, and available literature results may have been overestimated. METHODS: We searched the MEDLINE database using the PubMed platform. We formulated four queries investigating the prognostic weight of traumatic coagulopathy defined according to conventional laboratory testing, and the effectiveness in reducing mortality of three different treatments aimed at contrasting coagulopathy (high fresh frozen plasma/packed red blood cells ratios, fibrinogen, and tranexamic acid administration). Randomized controlled trials were selected along with observational studies that used a multivariable approach to adjust for confounding. Strict criteria were adopted for quality assessment based on a two-step approach. First, we rated quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. Then, this rating was downgraded if other three criteria were not met: high reporting quality according to shared standards, absence of internal methodological and statistical issues not detailed by the GRADE system, and absence of external validity issues. RESULTS: With few exceptions, the GRADE rating, reporting and methodological quality of observational studies was "very low", with frequent external validity issues. The only two randomized trials retrieved were, instead, of high quality. Only weak evidence was found for a relation between coagulopathy and mortality. Very weak evidence was found supporting the use of fibrinogen administration to reduce mortality in trauma. On the other hand, we found high evidence that the use of 1:1 vs. 1:2 high fresh frozen plasma/packed red blood cells ratios failed to obtain a 12% mortality reduction. This does not exclude lower mortality rates, which have not been investigated. The use of tranexamic acid in trauma was supported by "high" quality evidence according to the GRADE classification but was downgraded to "moderate" for external validity issues. CONCLUSIONS: Tranexamic acid is effective in reducing mortality in trauma. The other transfusion practices we investigated have been inadequately studied in the literature, as well as the independent association between mortality and coagulopathy measured with traditional laboratory testing. Overall, in this field of research literature quality is poor.

International consensus conference on open abdomen in trauma.

BACKGROUND: A part of damage-control laparotomy is to leave the fascial edges and the skin open to avoid abdominal compartment syndrome and allow further explorations. This condition, known as open abdomen (OA), although effective, is associated with severe complications. Our aim was to develop evidence-based recommendations to define indications for OA, techniques for temporary abdominal closure, management of enteric fistulas, and methods of definitive wall closure. METHODS: The literature from 1990 to 2014 was systematically screened according to PRISMA [Preferred Reporting Items for Systematic Reviews and Meta-analyses] protocol. Seventy-six articles were reviewed by a panel of experts to assign grade of recommendations (GoR) and level of evidence (LoE) using the GRADE [Grading of Recommendations Assessment, Development, and Evaluation] system, and an international consensus conference was held. RESULTS: OA in trauma is indicated at the end of damage-control laparotomy, in the presence of visceral swelling, for a second look in vascular injuries or gross contamination, in the case of abdominal wall loss, and if medical treatment of abdominal compartment syndrome has failed (GoR B, LoE II). Negative-pressure wound therapy is the recommended temporary abdominal closure technique to drain peritoneal fluid, improve nursing, and prevent fascial retraction (GoR B, LoE I). Lack of OA closure within 8 days (GoR C, LoE II), bowel injuries, high-volume replacement, and use of polypropylene mesh over the bowel (GoR C, LoE I) are risk factors for frozen abdomen and fistula formation. Negative-pressure wound therapy allows to isolate the fistula and protect the surrounding tissues from spillage until granulation (GoR C, LoE II). Correction of fistula is performed after 6 months to 12 months. Definitive closure of OA has to be obtained early (GoR C, LoE I) with direct suture, traction devices, component separation with or without mesh. Biologic meshes are an option for wall reinforcement if bacterial contamination is present (GoR C, LoE II). CONCLUSION: OA and negative-pressure techniques improve the care of trauma patients, but closure must be achieved early to avoid complications.