Prognostic value of immune cell infiltration, tertiary lymphoid structures and PD-L1 expression in Merkel cell carcinomas

Merkel cell carcinoma (MCC) is an aggressive, virus-associated, neuroendocrine tumor of the skin mainly affecting immunocompromised patients. Higher intratumoral infiltration with CD3 and CD8 positive T-cells is associated with a better prognosis, highlighting the relevance of the immune system for MCC development and progression. In this study 21 primary MCCs were stained with immune cell markers including CD3, CD4, CD8, CD68, CD20, and S100. Furthermore, tumor-infiltrating neutrophils, tertiary lymphoid structures and PD-L1 expression were analyzed and correlated with overall and recurrence free survival. All MCCs were Merkel Cell Polyomavirus positive. Overall and recurrence-free survival did not correlate with intra-and peritumoral CD3 and CD8 T-cell infiltration. In addition, no significant association regarding prognosis was found for tumor-associated neutrophils, tumor-associated macrophages or PD-L1 positivity in MCCs. Interestingly, the presence of tertiary lymphoid structures (TLS) in the tumor microenvironment significantly correlated with recurrence-free survival (P=0.025). In addition, TLS were significantly associated with a higher CD8/CD4 ratio in the tumor periphery (P=0.032), but not in the center of the tumor (P > 0.999). These results demonstrate for the first time that TLS, easily assessed in paraffin-embedded tissue in the tumor periphery of MCCs, may be a valuable prognostic factor indicating prolonged recurrence free survival

Murine iNKT cells are depleted by liver damage via activation of P2RX7

Invariant natural killer T cells (iNKT) constitute up to 50% of liver lymphocytes and contribute to immunosurveillance as well as pathogenesis of the liver. Systemic activation of iNKT cells induces acute immune-mediated liver injury. However, how tissue damage events regulate iNKT cell function and homeostasis remains unclear. We found that specifically tissue-resident iNKT cells in liver and spleen express the tissue-damage receptor P2RX7 and the P2RX7-activating ectoenzyme ARTC2. P2RX7 expression restricted formation of iNKT cells in the liver suggesting that liver iNKT cells are actively restrained under homeostatic conditions. Deliberate activation of P2RX7 in vivo by exogenous NAD resulted in a nearly complete iNKT cell ablation in liver and spleen in a P2RX7-dependent manner. Tissue damage generated by acetaminophen-induced liver injury reduced the number of iNKT cells in the liver. The tissue-damage-induced iNKT cell depletion was driven by P2RX7 and localized to the site of injury, as iNKT cells in the spleen remained intact. The depleted liver iNKT cells reconstituted only slowly compared to other lymphocytes such as regulatory T cells. These findings suggest that tissue-damage-mediated depletion of iNKT cells acts as a feedback mechanism to limit iNKT cell-induced pathology resulting in the establishment of a tolerogenic environment

The role of beta-blocker drugs in critically ill patients: a SIAARTI expert consensus statement

Background: The role of β-blockers in the critically ill has been studied, and data on the protective effects of these drugs on critically ill patients have been repeatedly reported in the literature over the last two decades. However, consensus and guidelines by scientific societies on the use of β-blockers in critically ill patients are still lacking. The purpose of this document is to support the clinical decision-making process regarding the use of β-blockers in critically ill patients. The recipients of this document are physicians, nurses, healthcare personnel, and other professionals involved in the patient's care process. Methods: The Italian Society of Anesthesia, Analgesia, Resuscitation and Intensive Care (SIAARTI) selected a panel of experts and asked them to define key aspects underlying the use of β-blockers in critically ill adult patients. The methodology followed by the experts during this process was in line with principles of modified Delphi and RAND-UCLA methods. The experts developed statements and supportive rationales in the form of informative text. The overall list of statements was subjected to blind votes for consensus. Results: The literature search suggests that adrenergic stress and increased heart rate in critically ill patients are associated with organ dysfunction and increased mortality. Heart rate control thus seems to be critical in the management of the critically ill patient, requiring careful clinical evaluation aimed at both the differential diagnosis to treat secondary tachycardia and the treatment of rhythm disturbance. In addition, the use of β-blockers for the treatment of persistent tachycardia may be considered in patients with septic shock once hypovolemia has been ruled out. Intravenous application should be the preferred route of administration. Conclusion: β-blockers protective effects in critically ill patients have been repeatedly reported in the literature. Their use in the acute treatment of increased heart rate requires understanding of the pathophysiology and careful differential diagnosis, as all causes of tachycardia should be ruled out and addressed first

Ultrasound-Guided PECS II + Serratus Plane Fascial Blocks Are Associated with Reduced Opioid Consumption and Lengths of Stay for Minimally Invasive Cardiac Surgery: An Observational Retrospective Study

This study tested the hypothesis that pectoralis II (PECS II) + serratus plane blocks would reduce opioid consumption and improve outcomes compared with standard practice in minimally invasive cardiac surgery. A retrospective and observational study was realized in the intensive care unit (ICU) setting of “ICLAS GVM, Istitituto Clinico Ligure Alta Specialità, (Rapallo, Italy)”, including adult patients who underwent right minithoracotomy for replacement/plastic aortic, mitral and tricuspid valve or atrial myxoma resection in cardiac surgery. Seventy-eight patients were extracted by the database and divided into two groups. Group 1 (41 patients) received ultrasound-guided PECS II + serratus plane blocks with Ropivacaine 0.25% 10 mL + 20 mL + 30 mL. Group 2 (37 patients) received intravenous opioids analgesia with morphine 20–25 mg/day or tramadol 200–300 mg/day. The primary outcomes were: the pain perceived: Critical-Care Pain Observation Tool (CPOT) score; the opioids consumption: mg morphine or tramadol, or μg sufentanyl administered; and mg paracetamol, toradol, tramadol or morphine administered as a rescue. The secondary outcomes were the hours of orotracheal intubation and of stay in ICU, and the number of episodes of nausea, vomiting, delayed awakening and respiratory depression. Group 1 vs. Group 2 consumed less opioids (Sufentanyl p < 0.0001; Morphine p < 0.0001), had a lower pain perceived (p = 0.002 at 6 h, p = 0.0088 at 12 h, p < 0.0001 at 24 h), need for rescue analgesia (p = 0.0005), episodes of nausea and vomiting (p = 0.0237) and intubation time and ICU stay (p = 0.0147 time of IOT, p < 0.0001 stay in ICU). Ultrasound-guided PECS II + serratus plane blocks demonstrated better than intravenous opioids analgesia in patients undergoing minimally invasive cardiac surgery

Ultrasound-Guided Interpectoral and Pectoserratus Plane Blocks in Breast Surgery: An Alternative Option to General Anaesthesia in an Elderly Woman with a Complex Medical History

With an incidence of over 1.5 million worldwide per annum, breast cancer continues to be the most common cancer affecting the female population. The main and most effective treatment in over 40% of these patients is a primary neoplasm resection. General anaesthesia, at times in association with loco-regional anaesthetics, is the most commonly used anaesthesia technique for radical mastectomies. Nausea, vomiting, and considerable postoperative pain, which are commonly experienced side effects and complications of general anaesthesia, tend, however, to augment most patients&rsquo; post-surgical morbidity. A growing body of research has shown that loco-regional anaesthesia often used together with and, in some cases, in the substitution of general anaesthesia can be a safe, effective alternative. This work is a case report regarding a 94-year-old elderly patient who was anaesthetised during a left radical mastectomy using exclusively combined interpectoral and pectoserratus plane blocks

Blocking around the transversalis fascia: behind the scene

The transversalis fascia plane and the quadratus lomborum blocks target the branches of T12-L1 nerves and provide analgesia in patients undergoing surgery involving the corresponding dermatomes. The transversalis fascia is believed to contribute to determine the spread of local anesthetic in such blocks. Nonetheless, the anatomy of this fascia and its possible role in these blocks still have to be precisely defined