Past, Present, and Future of Informed Consent in Pain and Genomics Research: Challenges Facing Global Medical Community.

In recent decades, there has been a revision of the role of institutional review boards with the intention of protecting human subjects from harm and exploitation in research. Informed consent aims to protect the subject by explaining all of the benefits and risks associated with a specific research project. To date, there has not been a review published analyzing issues of informed consent in research in the field of genetic/Omics in subjects with chronic pain, and the current review aims to fill that gap in the ethical aspects of such investigation. Despite the extensive discussion on ethical challenges unique to the field of genetic/Omics, this is the first attempt at addressing ethical challenges regarding Informed Consent Forms for pain research as the primary focus. We see this contribution as an important one, for while ethical issues are too often ignored in pain research in general, the numerous arising ethical issues that are unique to pain genetic/Omics suggest that researchers in the field need to pay even greater attention to the rights of subjects/patients. This article presents the work of the Ethic Committee of the Pain-Omics Group (www.painomics.eu), a consortium of 11 centers that is running the Pain-Omics project funded by the European Community in the 7th Framework Program theme (HEALTH.2013.2.2.1-5-Understanding and controlling pain). The Ethic Committee is composed of 1 member of each group of the consortium as well as key opinion leaders in the field of ethics and pain more generally.

A case of pneumococcal pneumonia and pelvic-peritonitis in a menstrual endovaginal cup user, which came first?

INTRODUCTION: Streptococcus pneumoniae infrequently causes genital tract infections but - in particular predisposing circumstances - it can be a transient part of vaginal flora and thus pelvic infections can occur. Possible conditions associated with pneumococcal pelvic-peritonitis include the use of intrauterine contraceptive devices, recent birth and gynecologic surgery. The underlying mechanism of these occurrences is likely to be the ascending infection from the genital tract via the fallopian tubes. CASE PRESENTATION: We present a case of pelvic-peritonitis and pneumonia due to Streptococcus pneumoniae in a healthy young woman wearing a menstrual endovaginal cup. Following the radiological findings of a cystic formation in the right ovary and ascites effusions in all peritoneal recesses an emergency exploratory laparoscopy with right ovariectomy was performed. After resolution of abdominal sepsis, parenchymal consolidation complicated into necrotizing pneumonia, hence the patient underwent a right lower lobectomy. DISCUSSION: The menstrual cup is a self-retaining intravaginal menstrual fluid collection device, considered as a safe alternative to tampons and pads, which use is associated with rare adverse effects. Few cases of infectious disease have been described, where the underlying mechanism may consist of bacterial replication within the blood accumulated in the uterine environment, with subsequent ascension into the genital tract. CONCLUSION: In the rare occurrence of pneumococcal pelvic-peritonitis considering all possible infectious sources is paramount, as is assessing the possible involvement of intravaginal devices, increasingly used nowadays but of which potential complications are still poorly described.

The Clinical Researcher Journey in the Artificial Intelligence Era: The PAC-MAN's Challenge.

Artificial intelligence (AI) is a powerful tool that can assist researchers and clinicians in various settings. However, like any technology, it must be used with caution and awareness as there are numerous potential pitfalls. To provide a creative analogy, we have likened research to the PAC-MAN classic arcade video game. Just as the protagonist of the game is constantly seeking data, researchers are constantly seeking information that must be acquired and managed within the constraints of the research rules. In our analogy, the obstacles that researchers face are represented by "ghosts", which symbolize major ethical concerns, low-quality data, legal issues, and educational challenges. In short, clinical researchers need to meticulously collect and analyze data from various sources, often navigating through intricate and nuanced challenges to ensure that the data they obtain are both precise and pertinent to their research inquiry. Reflecting on this analogy can foster a deeper comprehension of the significance of employing AI and other powerful technologies with heightened awareness and attentiveness.

Wireless Peripheral Nerve Stimulation for The Upper Limb: A Case Report.

Peripheral neuro-stimulation (PNS) has been proved to be effective for the treatment of neuropathic pain as well as other painful conditions. We discuss two approaches to PNS placement in the upper extremity. The first case describes a neuropathic syndrome after the traumatic amputation of the distal phalanx of the fifth digit secondary to a work accident with lack of responsiveness to a triple conservative therapy. An upper arm region approach for the PNS was chosen. The procedure had a favorable outcome; in fact, after one month the pain symptoms were absent (VAS 0) and the pharmacological therapy was suspended. The second case presented a patient affected by progressive CRPS type II in the sensory regions of the ulnar and median nerve in the hand, unresponsive to drug therapy. For this procedure, the PNS device was implanted in the forearm. Unfortunately, in this second case the migration of the catheter affected the effectiveness of the treatment. After examining the two cases in this paper, we changed our practice and suggest the implantation of PNS for radial, median and/or ulnar nerve stimulation in the upper arm region, which has significant advantages over the forearm region.

Artificial intelligence and "the Art of Kintsugi" in Anesthesiology: ten influential papers for clinical users.

Artificial intelligence refers to the simulation of human intelligence in machines that are programmed to think like humans and mimic their actions. In the present review we chose ten influential papers from the last five years and through Kintsugi, shed the light on recent evolution of artificial intelligence in anesthesiology. A comprehensive search in in Medline, Embase, Web of Science and Scopus databases was conducted. Each author searched the databases independently and created a list of six articles that influenced their clinical practice during this period, with a focus on their area of competence. During a subsequent step, each researcher presented his own list and most cited papers were selected to create the final collection of ten articles. In recent years purely methodological works with a cryptic technology (black-box) represented by the intact and static vessel, translated to a "modern artificial intelligence" in clinical practice and comprehensibility (glass-box). The purposes of this review are to explore the ten most cited papers about artificial intelligence in anesthesiology and to understand how and when it should be integrated in clinical practice.

Prolonged continuous wound infusion of local anesthetic and steroid after major abdominal surgery to reduce opioid consumption: a randomized, double-blind trial.

BACKGROUND: Continuous wound infusion (CWI) is effective for post-operative pain management, but the effect of prolonged infusions and the use of steroids in the infused mixture have never been addressed. We investigate the effect of prolonged CWI with ropivacaine 0.2% (R) over seven days and methylprednisolone (Mp) 1 mg/kg infused in the wound in the first 24 hours. METHODS: This is a randomized, double blind, phase III trial (RCT) in major abdominal surgery with laparotomy. After a 24-hours pre-peritoneal CWI of R-Mp, patients were randomized to receive either R-Mp or placebo for the next 24 hours. Then, patient-controlled CWI with only ropivacaine 0.2% or placebo (according to the randomization group) was planned between 48 hours and seven days after surgery. Morphine equivalents at seven days were analyzed, together with any catheter- or drug-related side effect and PPSP at 3 months. RESULTS: We enrolled 120 patients (63 in the CWI group, 57 in the placebo group). Prolonged CWI did not reduce opioid consumption in the first seven postoperative days (P=0.08). CWI was associated with reduced consumption of non-opioid analgesics (P=0.03). Most of the patients continued to require bolus in the surgical wound beyond 48 hours. PPSP prevalence was not different between groups. CONCLUSIONS: Prolonged infusion with R-Mp is safe and effective but did not reduce opioid consumption in the seven days after surgery or PPSP prevalence.

Double epidural catheter technique in a patient with severe COPD undergoing major abdominal surgery: A case report.

INTRODUCTION AND IMPORTANCE: Chronic Obstructive Pulmonary Disease (COPD) leads to the development of postoperative pulmonary complications (PPC), such as atelectasis, pneumonia and respiratory failure. The use of epidural anesthesia, alone or combined with general anesthesia, is known to reduce the incidence of PPC and shorten tracheal intubation time. In major procedures involving both the lower and upper abdomen, central neuraxial block at a single level may be inadequate to provide sufficient metameric extension of anesthesia. This limitation could be overcome with the use of double epidural catheter (DEC), has proved effective in diverse surgical scenarios. CASE PRESENTATION AND CLINICAL DISCUSSION: We present the case of a woman affected by moderate-severe COPD scheduled for major abdominal cytoreductive surgery due to ovarian malignancy with planned xypho-pubic laparotomy. We developed and implemented a DEC-based strategy for perioperative pain management based on the extent of surgical incision and the high risk of difficult weaning from ventilation and PPC. We used intraoperative monitoring to guarantee adequate antinociception throughout the entire 350 min long demolitive surgical procedure. No additional top-ups of intravenous analgesia or neuromuscular blocking agent (NMBA) was needed during surgery; at the end of the procedure, the patient was extubated in the operating theatre, maintaining adequate respiratory function during the whole postoperative period. CONCLUSIONS: The DEC technique could be beneficial for patients undergoing cytoreductive surgery. In our case, this technique granted optimal analgesic coverage and was instrumental in achieving fast weaning from mechanical ventilation and early tracheal extubation. Systematic studies on this subject are warranted.

Artificial intelligence enhanced ultrasound (AI-US) in a severe obese parturient: a case report.

BACKGROUND: Neuraxial anesthesia in obese parturients can be challenging due to anatomical and physiological modifications secondary to pregnancy; this led to growing popularity of spine ultrasound in this population for easing landmark identification and procedure execution. Integration of Artificial Intelligence with ultrasound (AI-US) for image enhancement and analysis has increased clinicians' ability to localize vertebral structures in patients with challenging anatomical conformation. CASE PRESENTATION: We present the case of a parturient with extremely severe obesity, with a Body Mass Index (BMI) = 64.5 kg/m2, in which the AI-Enabled Image Recognition allowed a successful placing of an epidural catheter. CONCLUSIONS: Benefits gained from AI-US implementation are multiple: immediate recognition of anatomical structures leads to increased first-attempt success rate, making easier the process of spinal anesthesia execution compared to traditional palpation methods, reducing needle placement time for spinal anesthesia and predicting best needle direction and target structure depth in peridural anesthesia.

Understanding basic principles of Artificial Intelligence: a practical guide for intensivists.

BACKGROUND AND AIM: Artificial intelligence was born to allow computers to learn and control their environment, trying to imitate the human brain structure by simulating its biological evolution. Artificial intelligence makes it possible to analyze large amounts of data (big data) in real-time, providing forecasts that can support the clinician's decisions. This scenario can include diagnosis, prognosis, and treatment in anesthesiology, intensive care medicine, and pain medicine. Machine Learning is a subcategory of AI. It is based on algorithms trained for decisions making that automatically learn and recognize patterns from data. This article aims to offer an overview of the potential application of AI in anesthesiology and analyzes the operating principles of machine learning Every Machine Learning pathway starts from task definition and ends in model application. CONCLUSIONS: High-performance characteristics and strict quality controls are needed during its progress. During this process, different measures can be identified (pre-processing, exploratory data analysis, model selection, model processing and evaluation). For inexperienced operators, the process can be facilitated by ad hoc tools for data engineering, machine learning, and analytics.

Emergently planned exclusive hub-and-spoke system in the epicenter of the first wave of COVID-19 pandemic in Italy: the experience of the largest COVID-19-free ICU hub for time-dependent diseases.

BACKGROUND: Lombardy was the epicenter in Italy of the first wave of COVID-19 pandemic. To face the contagion growth, from March 8 to May 8, 2020, a regional law redesigned the hub-and-spoke system for time-dependent diseases to better allocate resources for COVID-19 patients. METHODS: We report the reorganization of the major hospital in Lombardy during COVID-19 pandemic, including the rearrangement of its ICU beds to face COVID-19 pandemic and fulfill its role as extended hub for time-dependent diseases while preserving transplant activity. To highlight the impact of the emergently planned hub-and-spoke system, all patients admitted to a COVID-19-free ICU hub for trauma, neurosurgical emergencies and stroke during the two-month period were retrospectively collected and compared to 2019 cohort. Regional data on organ procurement was retrieved. Observed-to-expected (OE) in-ICU mortality ratios were computed to test the impact of the pandemic on patients affected by time-dependent diseases. RESULTS: Dynamic changes in ICU resource allocation occurred according to local COVID-19 epidemiology/trends of patients referred for time-dependent diseases. The absolute increase of admissions for trauma, neurosurgical emergencies and stroke was roughly two-fold. Patients referred to the hub were older and characterized by more severe conditions. An increase in crude mortality was observed, though OE ratios for in-ICU mortality were not statistically different when comparing 2020 vs. 2019. An increase in local organ procurement was observed, limiting the debacle of regional transplant activity. CONCLUSIONS: We described the effects of a regional emergently planned hub-and-spoke system for time-dependent diseases settled in the epicenter of COVID-19 pandemic in Italy.

Traumatic brain injury after frontal crashes: relationship with body mass index.

BACKGROUND: Previous studies had demonstrated that injury severity and risk of death after motor-vehicle crashes are related to human body characteristics. The purpose of this study was to clarify the relationship between body mass index (BMI) and head injury severity in front seat passengers after a frontal collision. METHODS: Data from all front seat occupants with at least one injury, older than 16 years old involved in a frontal collision from 1993 to 2005 were retrieved from the National Automotive Sampling System (NASS) database. Patient and collision characteristics were analyzed. Two cohorts were defined according to BMI < or > or =30 kg/m2. RESULTS: A total of 6,977 patients were included in this study, 5,918 (85%) had complete data on weight and height. Patient's mean age was 37 +/- 18 years old, the median ISS was 6, interquartile range (IQR) 15, and 61% were men. The mortality rate was positively associated to the crash delta velocity (DV) (p < 0.0001). The use of restraint system reduced the risk of death (p = 0.01). There was a significant increase in fatal outcome (p < 0.0001; RR 1.84 95% CI 1.61-2.1) and injury severity (ISS >25 p < 0.0001; RR 1.36 95% CI 1.19-1.54) in the obese cohort. Obese patients had higher chances of having a maximum head injury (Abbreviated Injury Score head = 6) than those not obese (p = 0.003; RR 1.97 95% CI 1.52-2.55). CONCLUSION: Obese passengers are more likely to suffer a more severe head trauma after a frontal collision. Further studies with computational models are needed to determine the precise role of BMI on brain injury-related biomechanical metrics.

Global cerebral blood flow and CPP after severe head injury: a xenon-CT study.

OBJECTIVE: To evaluate the association between global cerebral blood flow and different cerebral perfusion pressure ranges in severe head injury. DESIGN: A retrospective study SETTING: Neurosurgical and trauma patients in an intensive care unit in a regional hospital. PATIENTS AND PARTICIPANTS: Out of a series of 237 consecutive patients with severe head injuries (GCS

Xenon-CT and transcranial Doppler in poor-grade or complicated aneurysmatic subarachnoid hemorrhage patients undergoing aggressive management of intracranial hypertension.

OBJECTIVE: To evaluate whether elevated flow velocimetry values are associated with critically reduced cerebral blood flow values in deeply sedated patients with acute aneurysmatic subarachnoid hemorrhage and in whom the detection of clinical vasospasm is not feasible. DESIGN: Retrospective analysis of prospectively collected data. SETTING: Neurosurgical and trauma patients in an intensive care unit in a regional hospital. PATIENTS AND PARTICIPANTS: Twenty-nine patients in the acute phase following subarachnoid hemorrhage who were sedated and ventilated for elevated intracranial pressure, transcranial Doppler vasospasm, or respiratory failure and were studied with at least a coupled xenon-CT/transcranial Doppler study. MEASUREMENTS AND RESULTS: Combined measurement and comparison of cerebral blood flow by means of xenon-CT and of mean velocity by means of transcranial Doppler in middle cerebral artery territories. The case mix studied was consistent with patients' predominantly poor grade and with a complicated course. The results suggest that in sedated patients flow velocity and measured cortical mixed cerebral blood flow are not correlated, and, more specifically, that flow velocities values above 120 or 160 cm/s and Lindegaard index above 3 are not associated with an ischemic regional cerebral blood flow. Conversely, as many as 55% of the xenon-CT studies were associated with hyperemia. CONCLUSIONS: In patients with elevated intracranial pressure, mean middle cerebral artery flow velocity or Lindegaard Index does not help to detect critical cerebral blood flow nor elevated cerebral blood flow.

Perineural catheter infection: a systematic review of the literature.

Perineural catheter infection is a rare but potentially dramatic complication of continuous peripheral nerve block. Different risk factors have been identified and the incidence of infection is increased in trauma victims, intensive care unit patients, immunodeficient individuals, and diabetic patients. Also, postoperative hyperglycemia, the absence of antibiotic prophylaxis, and catheter lasting more than 48 hours seem to be associated with a greater risk of infection. Skin disinfection and a strict aseptic technique during catheter placement are fundamental. The use of micropore filters, antiseptic dressings, catheter tunneling, and aseptic preparation of the infused drug has all been hypothesized to reduce infection rate, but the existing evidence is conflicting. Infection is a rare complication of continuous peripheral nerve blocks. Severe and even fatal cases have been reported, even if morbidity is generally very low. The identification of high risk patients and adoption of preventive measures might reduce the incidence of this complication.