Supraspinal neuroinflammation and anxio-depressive-like behaviors in young- and older- adult mice with osteoarthritis pain: the effect of morphine.

RATIONALE: Asteoarthritis (OA) is a leading cause of chronic pain in the elderly population and is often associated with emotional comorbidities such as anxiety and depression. Despite age is a risk factor for both OA and mood disorders, preclinical studies are mainly conducted in young adult animals. OBJECTIVES: Here, using young adult (11-week-old) and older adult (20-month-old) mice, we evaluate in a monosodium-iodoacetate-(MIA)-induced OA model the development of anxio-depressive-like behaviors and whether brain neuroinflammation may underlie the observed changes. We also test whether an effective pain treatment may prevent behavioral and biochemical alterations. METHODS: Mechanical allodynia was monitored throughout the experimental protocol, while at the end of protocol (14 days), anxio-depressive-like behaviors and cognitive dysfunction were assessed. Neuroinflammatory condition was evaluated in prefrontal cortex, hippocampus and hypothalamus. Serum IFNγ levels were also measured. Moreover, we test the efficacy of a 1-week treatment with morphine (2.5 mg/kg) on pain, mood alterations and neuroinflammation. RESULTS: We observed that young adult and older adult controls (CTRs) mice had comparable allodynic thresholds and developed similar allodynia after MIA injection. Older adult CTRs were characterized by altered behavior in the tests used to assess the presence of depression and cognitive impairment and by elevated neuroinflammatory markers in brain areas compared to younger ones. The presence of pain induced depressive-like behavior and neuroinflammation in adult young mice, anxiety-like behavior in both age groups and worsened neuroinflammation in older adult mice. Morphine treatment counteracted pain, anxio-depressive behaviors and neuroinflammatory activation in both young adult and older adult mice. CONCLUSIONS: Here, we demonstrated that the presence of chronic pain in young adult mice induces mood alterations and supraspinal biochemical changes and aggravates the alterations already evident in older adult animals. A treatment with morphine, counteracting the pain, prevents the development of anxio-depressive disorders and reduces neuroinflammation.

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.

Osteoarthritis Pain in Old Mice Aggravates Neuroinflammation and Frailty: The Positive Effect of Morphine Treatment.

Knee osteoarthritis is a common cause of pain and disability in old subjects. Pain may predispose to the development of frailty. Studies on mechanisms underlying pain in osteoarthritis models during aging are lacking. In this work, we used the monosodium iodoacetate model of osteoarthritis in adult (11-week-old) and old (20-month-old) C57BL/6J mice to compare hypersensitivity, locomotion, neuroinflammation, and the effects of morphine treatment. After osteoarthritis induction in adult and old mice, weight-bearing asymmetry, mechanical allodynia, and thermal hyperalgesia similarly developed, while locomotion and frailty were more affected in old than in adult animals. When behavioral deficits were present, the animals were treated for 7 days with morphine. This opioid counteracts the behavioral alterations and the frailty index worsening both in adult and old mice. To address the mechanisms that underlie pain, we evaluated neuroinflammatory markers and proinflammatory cytokine expression in the sciatic nerve, DRGs, and spinal cord. Overexpression of cytokines and glia markers were present in osteoarthritis adult and old mice, but the activation was qualitatively and quantitatively more evident in aged mice. Morphine was able to counteract neuroinflammation in both age groups. We demonstrate that old mice are more vulnerable to pain's detrimental effects, but prompt treatment is successful at mitigating these effects.

Artificial intelligence and anesthesia: a narrative review.

Background and Objective: The aim of this narrative review is to analyze whether or not artificial intelligence (AI) and its subsets are implemented in current clinical anesthetic practice, and to describe the current state of the research in the field. AI is a general term which refers to all the techniques that enable computers to mimic human intelligence. AI is based on algorithms that gives machines the ability to reason and perform functions such as problem-solving, object and word recognition, inference of world states, and decision-making. It includes machine learning (ML) and deep learning (DL). Methods: We performed a narrative review of the literature on Scopus, PubMed and Cochrane databases. The research string comprised various combinations of "artificial intelligence", "machine learning", "anesthesia", "anesthesiology". The databases were searched independently by two authors. A third reviewer would mediate any disagreement the results of the two screeners. Key Content and Findings: The application of AI has shown excellent results in both anesthesia and in operating room (OR) management. In each phase of the perioperative process, pre-, intra- and postoperative ones, it is able to perform different and specific tasks, using various techniques. Conclusions: Thanks to the use of these new technologies, even anesthesia, as it is happening for other disciplines, is going through a real revolution, called Anesthesia 4.0. However, AI is not free from limitations and open issues. Unfortunately, the models created, provided they have excellent performance, have not yet entered daily practice. Clinical impact analyzes and external validations are needed before this happens. Therefore, qualitative research will be needed to better understand the ethical, cultural, and societal implications of integrating AI into clinical workflows.

Is lung ultrasound score a useful tool to monitoring and handling moderate and severe COVID-19 patients in the general ward? An observational pilot study.

Lung ultrasound is a well-established diagnostic tool in acute respiratory failure, and it has been shown to be particularly suited for the management of COVID-19-associated respiratory failure. We present exploratory analyses on the diagnostic and prognostic performance of lung ultrasound score (LUS) in general ward patients with moderate-to-severe COVID-19 pneumonia receiving O2 supplementation and/or noninvasive ventilation. From March 10 through May 1, 2020, 103 lung ultrasound exams were performed by our Forward Intensive Care Team (FICT) on 26 patients (18 males and 8 females), aged 62 (54 - 76) and with a Body Mass Index (BMI) of 30.9 (28.7 - 31.5), a median 6 (5 - 9) days after admission to the COVID-19 medical unit of the University Hospital of Parma, Italy. All patients underwent chest computed tomography (CT) the day of admission. The initial LUS was 16 (11 - 21), which did not significantly correlate with initial CT scans, probably due to rapid progression of the disease and time between CT scan on admission and first FICT evaluation; conversely, LUS was significantly correlated with PaO2/FiO2 ratio throughout patient follow-up [R = - 4.82 (- 6.84 to - 2.80; p < 0.001)]. The area under the receiving operating characteristics curve of LUS for the diagnosis of moderate-severe disease (PaO2/FiO2 ratio ≤ 200 mmHg) was 0.73, with an optimal cutoff value of 11 (positive predictive value: 0.98; negative predictive value: 0.29). Patients who eventually needed invasive ventilation and/or died during admission had significantly higher LUS throughout their stay.

Frailty and pain, human studies and animal models.

The hypothesis that pain can predispose to frailty development has been recently investigated in several clinical studies suggesting that frailty and pain may share some mechanisms. Both pain and frailty represent important clinical and social problems and both lack a successful treatment. This circumstance is mainly due to the absence of in-depth knowledge of their pathological mechanisms. Evidence of shared pathways between frailty and pain are preliminary. Indeed, many clinical studies are observational and the impact of pain treatment, and relative pain-relief, on frailty onset and progression has never been investigated. Furthermore, preclinical research on this topic has yet to be performed. Specific researches on the pain-frailty relation are needed. In this narrative review, we will attempt to point out the most relevant findings present in both clinical and preclinical literature on the topic, with particular attention to genetics, epigenetics and inflammation, in order to underline the existing gaps and the potential future interventional strategies. The use of pain and frailty animal models discussed in this review might contribute to research in this area.

COVID-19 respiratory support outside the ICU's doors. An observational study for a new operative strategy.

BACKGROUND AND AIM: During the first wave of the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) pandemic, we faced a massive clinical and organizational challenge having to manage critically ill patients outside the Intensive Care Unit (ICU). This was due to the significant imbalance between ICU bed availability and the number of patients presenting Acute Hypoxemic Respiratory Failure caused by SARS-CoV-2-related interstitial pneumonia. We therefore needed to perform Non-Invasive Ventilation (NIV) in non-intensive wards to assist these patients and relieve pressure on the ICUs and subsequently implemented a new organizational and clinical model. This study was aimed at evaluating its effectiveness and feasibility. METHODS: We recorded the anamnestic, clinical and biochemical data of patients undergoing non-invasive mechanical ventilation while hospitalized in non-intensive CoronaVirus Disease 19 (COVID-19) wards. Data were registered on admission, during anesthesiologist counseling, and when NIV was started and suspended. We retrospectively registered the available results from routine arterial blood gas and laboratory analyses for each time point. RESULTS: We retrospectively enrolled 231 patients. Based on our criteria, we identified 46 patients as NIV responders, representing 19.9% ​​of the general study population and 29.3% of the patients that spent their entire hospital stay in non-ICU wards. Overall mortality was 56.2%, with no significant differences between patients in non-intensive wards (57.3%) and those later admitted to the ICU (54%) Conclusions: NIV is safe and manageable in an emergency situation and could become part of an integrated clinical and organizational model.

24-Month Effectiveness of Periduoscopic Adhesiolysis in Reducing the Use of Spinal Cord Stimulation in Patient With Chronic Lumbar Pain: A Possible Therapeutic Regimen?

Objectives Epiduroscopy is a minimally invasive procedure that is used in pain therapy to treat lumbar and root pain that is resistant to medical and infiltrative therapies. The indications for periduroscopy are partly shared with those of spinal cord stimulation (SCS): failed back surgery syndrome (FBSS) and stenosis of the vertebral canal in particular. The costs and risks of periduroscopy are considerably lower than those of SCS. The purpose of this study is to evaluate the clinical and economic advantages of integrating periduroscopy as a step prior to SCS for patients with severe lumbar or radicular pain that is unresponsive to pharmacological and infiltrative treatments. Materials and Methods Patients were enrolled if they had FBSS and spinal stenosis with indications for SCS and accepted periduroscopy treatment before the possible SCS trial. Patients were followed up for 24 months with evaluations of clinical data on the day after the procedure and at one and 24 months. The pain trend, satisfaction with the periduroscopy procedure, and the incidence of SCS implants in the study period were analyzed. Results A total of 106 patients were enrolled. Immediately after the procedure and in the first month, the reduction of pain and the level of patient satisfaction were high, but they were drastically reduced at 24 months with a progressive reappearance of symptoms that substantially overlapped with the pre-surgery levels. At 24 months, 48% of the patients underwent a neurostimulation trial, and a significant percentage of them were able to avoid the implantation of an SCS. Conclusions Periduroscopy appears to be rational as a step prior to SCS in terms of the improvement of pain symptoms in the short term, the definitive results in a significant percentage of patients, and the significant economic savings for the health system.

Pain management during labor: use of intermittent drug delivery devices for improvement of obstetric and neonatal outcome and reduction of healthcare burden: A large non-inferiority randomized clinical trial.

BACKGROUND: Automated continuous epidural administration of local anesthetics provides a more stable analgesic block with decreasing of healthcare staff compared to manual boluses administration (TOP-UP) but is associated to high rate of operative vaginal delivery. We hypothesized that the use of programmed intermittent automated boluses (PIEB) is able to provide a good quality of analgesia and decreasing of anesthesiologic workload without increasing the rate of instrumental vaginal birth in comparison with TOP-UP technique. Laboring nulliparous woman aged between 18 and 46 years were randomized to epidural analgesia with 0.0625% levobupivacaine and sufentanil administered by PIEB or by TOP-UP techniques. Primary outcome was instrumental vaginal delivery rate and secondary outcomes were quality of analgesia, total and time-related drugs doses used, motor block, newborn outcome, and anesthesiologic workload. RESULTS: Six hundred twenty-nine were randomized, and 628 were included in the intention-to-treat analysis. The rate of instrumental vaginal delivery was similar in the PIEB and TOP-UP groups (13.2% vs 9.7%, OR 1.4 95% CI 0.8 to 2.5; p 0.21). There was no difference between groups regarding mode of delivery (cesarean section vs vaginal birth), newborn outcome, and motor block. Patients in the PIEB group received more total and time-related drugs doses and a better quality of analgesia. Anesthesiological workload was significantly reduced in the PIEB group. CONCLUSIONS: Our study demonstrated that epidural anesthesia with programmed intermittent epidural boluses by an automated device provides an effective and safe management of labor analgesia with improvement of pain control and sparing of man workload compared to manual top-up protocols.

X(-rays) sometimes mark the spot: A case of occult central venous catheter embolization.

INTRODUCTION: Breakage and fragment embolization is a rare but feared complication of peripherally inserted central catheter use. While chest radiographs are no longer the gold standard for determining peripherally inserted central catheter tip position, their use in diagnosing complications is still warranted. We report a case of occult catheter embolization discovered by routine chest X-ray. CASE DESCRIPTION: A patient with a right brachial vein peripherally inserted central catheter was admitted to our Emergency Department for palpitations and dyspnea. The peripherally inserted central catheter was not visible at presentation, and she was unclear as to what had happened; she left the Emergency Department before workup was performed. Catheter embolization was discovered upon implantation of a new peripherally inserted central catheter. CONCLUSION: Although routine chest radiographs are no longer necessary after peripherally inserted central catheter implantation, they are in diagnosing peripherally inserted central catheter-related complications even in asymptomatic patients. We discuss their use and the possible role of securement devices in preventing some instances of catheter embolization.

The "pandemic" increase in lung ultrasound use in response to Covid-19: can we complement computed tomography findings? A narrative review.

Coronavirus disease of 2019 (COVID-19) is a highly infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has rapidly spread to a global pandemic in March 2020. This emergency condition has been putting a severe strain on healthcare systems worldwide, and a prompt, dynamic response is instrumental in its management. While a definite diagnosis is based on microbiological evidence, the relationship between lung ultrasound (LU) and high-resolution computed tomography (HRCT) in the diagnosis and management of COVID-19 is less clear. Lung ultrasound is a point-of-care imaging tool that proved to be useful in the identification and severity assessment of different pulmonary conditions, particularly in the setting of emergency and critical care patients in intensive care units; HRCT of the thorax is regarded as the mainstay of imaging evaluation of lung disorders, enabling characterization and quantification of pulmonary involvement. Aims of this review are to describe LU and chest HRCT main imaging features of COVID-19 pneumonia, and to provide state-of-the-art insights regarding the integrated role of these techniques in the clinical decision-making process of patients affected by this infectious disease.

Oncologic outcome, side effects and comorbidity of high-intensity focused ultrasound (HIFU) for localized prostate cancer. A review.

INTRODUCTION: Prostate cancer is considered one of the most important health problems. Due to the increased number of diagnosed patients and the inability to distinguish aggressive tumors, minimally-invasive procedures have become increasingly interesting. High-intensity focused ultrasound (HIFU) is an alternative option to radical surgery to treat prostate cancer. To date, however, data on side effects and comorbidities of this technique are still not conclusive. METHODS AND RESULTS: We reviewed the literature to concentrate on side effects and comorbidities of HIFU treatment of prostate cancer with the following key words: hifu, high intensity focused ultrasound, ultrasonic therapy, transrectal hifu, prostate ablation, side effects, comorbidities. MedLine and Embase via Ovid database were searched. Selection criteria were: English language, articles published between 2001 and 2015, case series including at least 100 participants and reported data on side effects and comorbidities. Sixteen uncontrolled studies were identified. No randomized controlled trials (RCT) were found in the literature comparing side effects and comorbidities of HIFU to other routine approaches to prostate cancer treatment. CONCLUSION: HIFU seems to be a promising minimally-invasive treatment for low- and intermediate-risk prostate cancer, especially for patients who are unfit for radical surgery. Prospective studies with longer follow-up periods and RCT are required to properly assess the impact of side effects and comobidities related to the HIFU technique in comparison with other therapies to treat prostate cancer.

Lung Ultrasound in COVID-19 Pneumonia: Correlations with Chest CT on Hospital admission.

BACKGROUND: Lung ultrasound (LUS) is an accurate, safe, and cheap tool assisting in the diagnosis of several acute respiratory diseases. The diagnostic value of LUS in the workup of coronavirus disease-19 (COVID-19) in the hospital setting is still uncertain. OBJECTIVES: The aim of this observational study was to explore correlations of the LUS appearance of COVID-19-related pneumonia with CT findings. METHODS: Twenty-six patients (14 males, age 64 ± 16 years) urgently hospitalized for COVID-19 pneumonia, who underwent chest CT and bedside LUS on the day of admission, were enrolled in this observational study. CT images were reviewed by expert chest radiologists, who calculated a visual CT score based on extension and distribution of ground-glass opacities and consolidations. LUS was performed by clinicians with certified competency in thoracic ultrasonography, blind to CT findings, following a systematic approach recommended by ultrasound guidelines. LUS score was calculated according to presence, distribution, and severity of abnormalities. RESULTS: All participants had CT findings suggestive of bilateral COVID-19 pneumonia, with an average visual scoring of 43 ± 24%. LUS identified 4 different possible -abnormalities, with bilateral distribution (average LUS score 15 ± 5): focal areas of nonconfluent B lines, diffuse confluent B lines, small subpleural microconsolidations with pleural line irregularities, and large parenchymal consolidations with air bronchograms. LUS score was significantly correlated with CT visual scoring (r = 0.65, p < 0.001) and oxygen saturation in room air (r = -0.66, p < 0.001). CONCLUSION: When integrated with clinical data, LUS could represent a valid diagnostic aid in patients with suspect COVID-19 pneumonia, which reflects CT findings.

Point-of-Care Chest Ultrasonography as a Diagnostic Resource for COVID-19 Outbreak in Nursing Homes.

OBJECTIVE: Bedside chest ultrasonography, when integrated with clinical data, is an accurate tool for improving the diagnostic process of many respiratory diseases. This study aims to evaluate the feasibility of a chest ultrasonographic screening program in nursing homes for detecting coronavirus disease-19 (COVID-19)-related pneumonia and improving the appropriateness of hospital referral of residents. DESIGN: Pragmatic, descriptive, feasibility study from April 2 to April 9, 2020. SETTING AND PARTICIPANTS: A total of 83 older residents (age 85 ± 8) presenting mild to moderate respiratory symptoms and not previously tested for COVID-19, residing in 5 nursing homes in Northern Italy. METHODS: Chest ultrasonography was performed at the bedside by a team of hospital specialists with certified expertise in thoracic ultrasonography, following a systematic approach exploring 4 different areas for each hemithorax, from the anterior and posterior side. Presence of ultrasonographic signs of interstitial pneumonia, including comet-tail artifacts (B-lines) with focal or diffuse distribution, subpleural consolidations, and pleural line indentation, was detected. The specialist team integrated ultrasonography data with clinical and anamnestic information, and gave personalized therapeutic advice for each patient, including hospital referral when needed. RESULTS: The most frequent reasons for ultrasonographic evaluation were fever (63% of participants) and mild dyspnea (40%). Fifty-six patients (67%) had abnormal ultrasonographic findings. The most common patterns were presence of multiple subpleural consolidations (32 patients) and diffuse B-lines (24 patients), with bilateral involvement. A diagnosis of suspect COVID-19 pneumonia was made in 44 patients, and 6 of them required hospitalization. Twelve patients had ultrasonographic patterns suggesting other respiratory diseases, and 2 patients with normal ultrasonographic findings were diagnosed with COPD exacerbation. CONCLUSIONS AND IMPLICATIONS: In nursing home residents, screening of COVID-19 pneumonia with bedside chest ultrasonography is feasible and may represent a valid diagnostic aid for an early detection of COVID-19 outbreaks and adequate patient management.

If it looks like a catheter and winds like a catheter . . . fibroblastic sheath mimicking a central venous catheter fragment: A case report.

INTRODUCTION: Fibroblastic sheath formation is a well-known complication of long-term central venous catheters. When calcified, fibroblastic (formerly known as "fibrin") sheaths may be easily mistaken for retained catheter fragments. We describe one such case and how imaging was used to recognize the sheath and avoid unnecessary interventions. CASE DESCRIPTION: A patient with systemic sclerosis was referred for port removal because of suspected infection. A later computed tomography scan showed a persistent tubular structure coursing behind the right clavicle, which was also seen in an anteroposterior chest radiograph. Three-dimensional reconstruction and analysis of the structure's lumen in comparison to previous imaging studies allowed us to confirm that it was, in fact, a calcified fibroblastic sheath. The patient's course was uneventful thereafter. CONCLUSION: Three-dimensional computed tomography reconstruction, as well as the hollow appearance of a tubular structure after removal of a central catheter may help differentiate a fibroblastic sheath from a retained catheter fragment. Accurate surgical notes mentioning the length of the catheter at implant and explant are also of paramount importance.

Multidisciplinary management of a large pheochromocytoma presenting with cardiogenic shock: a case report.

BACKGROUND: Pheochromocytoma is well-known for sudden initial presentations, particularly in younger patients. Hemodynamic instability may cause serious complications and delay a patient's ability to undergo surgical resection. Larger tumors present a further challenge because of the risk of catecholamine release during manipulations. In the case we present, increases in systemic vascular resistance caused cardiogenic shock, and the size of the lesion prompted surgeons to veer off from their usual approach. CASE PRESENTATION: A 38-year-old female patient was admitted to our intensive care unit with hypertension and later cardiogenic shock. Profound systolic dysfunction (left ventricular ejection fraction of 0.12) was noted together with severely increased systemic vascular resistance, and gradually responded to vasodilator infusion. A left-sided 11-cm adrenal mass was found with computed tomography and confirmed a pheochromocytoma with a meta-iodo-benzyl-guanidine scintigraphy. Surgical treatment was carefully planned by the endocrinologist, anesthesiologist and surgeon, and was ultimately successful. After prolonged hemodynamic stabilization, open adrenalectomy and nephrectomy were deemed safer because of lesion size and the apparent invasion of the kidney. Surgery was successful and the patient was discharged home 5 days after surgery. She is free from disease at almost 2 years from the initial event. CONCLUSIONS: Large, invasive pheochromocytoma can be safely and effectively managed with open resection in experienced hands, provided all efforts are made to achieve hemodynamic stabilization and to minimize. Catecholamine release before and during surgery.