HOPS/TMUB1 Enhances Apoptosis in TP53 Mutation-Independent Setting in Human Cancers.

TP53 mutations are prevalent in various cancers, yet the complexity of apoptotic pathway deregulation suggests the involvement of additional factors. HOPS/TMUB1 is known to extend the half-life of p53 under normal and stress conditions, implying a regulatory function. This study investigates, for the first time, the potential modulatory role of the ubiquitin-like-protein HOPS/TMUB1 in p53-mutants. A comprehensive analysis of apoptosis in the most frequent p53-mutants, R175, R248, and R273, in SKBR3, MIA PaCa2, and H1975 cells indicates that the overexpression of HOPS induces apoptosis at least equivalent to that caused by DNA damage. Immunoprecipitation assays confirm HOPS binding to p53-mutant forms. The interaction of HOPS/TMUB1 with p53-mutants strengthens its effect on the apoptotic cascade, showing a context-dependent gain or loss of function. Gene expression analysis of the MYC and TP63 genes shows that H1975 exhibit a gain-of-function profile, while SKBR3 promote apoptosis in a TP63-dependent manner. The TCGA data further corroborate HOPS/TMUB1's positive correlation with apoptotic genes BAX, BBC3, and NOXA1, underscoring its relevance in patient samples. Notably, singular TP53 mutations inadequately explain pathway dysregulation, emphasizing the need to explore additional contributing factors. These findings illuminate the intricate interplay among TP53 mutations, HOPS/TMUB1, and apoptotic pathways, providing valuable insights for targeted cancer interventions.

10 kHz stimulation as rescue therapy for spinal cord stimulation trial failure or loss of efficacy: A retrospective study.

INTRODUCTION: Spinal cord stimulation (SCS) is currently used for the management of pain of different origin, and since its inception, many waveforms have been developed. Some patients experience no pain relief already during SCS trial, while other patients go through a loss of efficacy due to habituation after a variable period of satisfying pain control. Our retrospective study represents the first report exploring the potential role of 10 kHz stimulation as rescue therapy for patients who did not benefit not only from conventional stimulation but even from other waveforms during SCS trial or follow-up. METHODS: This study was conducted in Germany; we retrospectively enrolled patients with no pain relief during SCS trial or with loss of efficacy of other waveforms over time; and we recorded visual analogic scale (VAS), Oswestry Disability Index (ODI), and daily opioid consumption expressed as morphine milligram equivalents (MME), right before and 12 months after the switching to 10 kHz simulation. RESULTS: The rate of successful switching to 10 kHz stimulation was comparable in patients enrolled during the SCS trial and during the follow-up (43% vs. 40%, respectively); notably, the highest rate of failed rescue was recorded in case of persistent spinal pain syndrome (PSPS) II. Patients who responded to the switching showed a significant improvement in VAS and ODI after 12 months of treatment compared to baseline (3.6 ± 1.0 vs. 8.2 ± 0.9, p < 0.00001 and 34.0 ± 7.8 vs. 64.3 ± 8.7, p < 0.0001, respectively), whereas there was no reduction in the consumption of opioids in terms of MME (3 (0-16) vs. 5 (0-8.75), p = 0.1003). CONCLUSIONS: Rescue therapy with 10 kHz stimulation could be an important strategy to avoid SCS explant in both patients non-responsive during trial or experiencing a loss of efficacy during the years with other waveforms.

Dexamethasone versus Dexmedetomidine as Adjuvants in Ultrasound Popliteal Sciatic Nerve Block for Hallux Valgus Surgery: A Mono-Centric Retrospective Comparative Study.

Background and Aim: Ultrasound popliteal sciatic nerve block (UPSNB) is commonly performed in foot and ankle surgery. This study aims to assess the use of dexmedetomidine and dexamethasone as adjuvants in UPSNB for hallux valgus (HV) surgery, comparing their efficacy in producing motor and sensory block and controlling postoperative pain. The adverse event rate was also evaluated. Methods: This mono-centric retrospective study included 62 adult patients undergoing HV surgery: 30 patients received lidocaine 2% 200 mg, ropivacaine 0.5% 50 mg and dexamethasone 4 mg (Group 1), whereas 32 patients received lidocaine 2% 200 mg, ropivacaine 0.5% 50 mg, and dexmedetomidine 1 mcg/Kg (Group 2). At first, the visual analogue scale (VAS) was evaluated after 48 hours. The other outcomes were time to motor block regression, evaluation of the first analgesic drug intake, analgesic effect, adverse effects (hemodynamic disorders, postoperative nausea and vomiting (PONV)) and patient satisfaction. The continuous data were analyzed with student's t-test and the continuous one with χ2. Statistical significance was set at a p-value lower than 0.05. Results: No significant difference was found in VAS after 48 hours (4.5 ± 1.6 vs 4.7 ± 1.7, p = 0.621) to motor block regression (18.9 ± 6.0 vs 18.7 ± 6, p = 0.922). The number of patients that took their first analgesic drug in the first 48 h (p = 0.947 at 6 hours; p = 0.421 at 12 hours; p = 0.122 at 24 hours and p = 0.333 at 48 hours) were not significant. A low and similar incidence of intraoperative hemodynamic disorders was recorded in both groups (hypotension p = 0.593; bradycardia p = 0.881). Neither PONV nor other complication was found. Patients in Group 1 reported a lower degree of interference with sleep (p = 0.001), less interference with daily activities (P = 0.002) and with the affective sphere (P = 0.015) along with a more satisfactory postoperative pain management (p < 0.001) as compared to Group 2. Conclusion: No significant differences were observed in the duration of motor and sensory blockade between patients in both groups. Additionally, both groups showed good pain control with a low rate of adverse effects, even if there was no clinical difference between the groups. However, patients who received dexamethasone reported experiencing less interference with their sleep, daily activities and overall emotional well-being, and overall pain control.

Follow-up short and long-term mortalities of tracheostomized critically ill patients in an Italian multi-center observational study.

The effects of tracheostomy on outcome as well as on intra or post-operative complications is yet to be defined. Admission of patients with tracheostomy to rehabilitation facility is at higher risk of suboptimal care and increased mortality. The aim of the study was to investigate ICU mortality, clinical outcome and quality of life up to 12 months after ICU discharge in tracheostomized critically ill patients. This is a prospective, multi-center, cohort study endorsed by Italian Society of Anesthesia, Analgesia, Reanimation, and Intensive Care (SIAARTI Prot. n° 643/13) registered in Clinicaltrial.gov (NCT01899352). Patients admitted to intensive care unit (ICU) and requiring elective tracheostomy according to physician in charge decision were included in the study. The primary outcome was ICU mortality. Secondary outcomes included risk factors for ICU mortality, prevalence of mortality at follow-up, rate of discharge from the hospital and rehabilitation, quality of life, performance status, and management of tracheostomy cannula at 3-, 6, 12-months from the day of tracheostomy. 694 critically ill patients who were tracheostomized in the ICU were included. ICU mortality was 15.8%. Age, SOFA score at the day of the tracheostomy, and days of endotracheal intubation before tracheostomy were risk factors for ICU mortality. The regression tree analysis showed that SOFA score at the day of tracheostomy and age had a preeminent role for the choice to perform the tracheostomy. Of the 694 ICU patients with tracheostomy, 469 completed the 12-months follow-up. Mortality was 33.51% at 3-months, 45.30% at 6-months, and 55.86% at 12-months. Patients with tracheostomy were less likely discharged at home but at hospital facilities or rehabilitative structures; and quality of life of patients with tracheostomy was severely compromised at 3-6 and 12 months when compared with patients without tracheostomy. In patients admitted to ICU, tracheostomy is associated with high mortality, difficult rehabilitation, and decreased quality of life. The choice to perform a tracheostomy should be carefully weighed on family burden and health-related quality of life.Clinical trial registration: Clinicaltrial.gov (NCT01899352).

Potential Role of Focal Microvibration (Equistasi®) in the Management of Chronic Pain: A Pilot Study.

INTRODUCTION: Chronic pain is one of the leading causes of medical consultation with a dramatic psychophysical and socioeconomic impact. Focal microvibration (Equistasi®) is a revolutionary technology that converts the thermal energy of the skin into vibration. Equistasi® was shown to be effective in the treatment of gait and balance dysfunction in many pathological conditions such as Parkinson's disease and multiple sclerosis. Our aim was to explore the efficacy of focal microvibration in the management of chronic pain. METHODS: We randomized 60 patients with pain of different origin into two groups: an experimental group (group E) treated with Equistasi, and a control group (group C) treated with standard pharmacological therapy. Pain, disability, and working capacity were evaluated by Brief Pain Inventory (BPI), Oswestry Disability Index (ODI), and Work Ability Index (WAI) at the baseline and after 7 (T7), 15 (T15), 30 (T30), 60 (T60), and 90 (T90) days. RESULTS: According to BPI, average and worst pain in the last 24 h significantly decreased in group E at T15 and this result persisted up to T90; pain interference on general activity, mood, waling ability, normal work, relations with other people, sleep, and enjoyment of life decreased in group E with a significant improvement from T15. Lifting activity and work ability in relation to demands also significantly improved in group E. No significant changes in BPI, ODI, and WAI scores were recorded in group C during the follow-up. CONCLUSIONS: Focal microvibration can be an effective tool for managing chronic pain in combination with other therapies.

The PATIENT Approach: A New Bundle for the Management of Chronic Pain.

BACKGROUND: Chronic pain is one of the most challenging diseases for physicians as its etiology and manifestations can be extremely varied. Many guidelines have been published and many therapeutic options are nowadays available for the different types of pain. Given the enormous amount of information that healthcare providers must handle, it is not always simple to keep in mind all the phases and strategies to manage pain. We here present the acronym PATIENT (P: patient's perception; A: assessment; T: tailored approach; I: iterative evaluation; E: education; N: non-pharmacological approach; T: team), a bundle which can help to summarize all the steps to follow in the management of chronic pain. METHODS: We performed a PubMed search with a list of terms specific for every issue of the bundle; only English articles were considered. RESULTS: We analyzed the literature investigating these topics to provide an overview of the available data on each bundle's issue; their synthesis lead to an algorithm which may allow healthcare providers to undertake every step of a patient's evaluation and management. DISCUSSION: Pain management is very complex; our PATIENT bundle could be a guide to clinicians to optimize a patient's evaluation and treatment.

Impact of ventilation strategies on pulmonary and cardiovascular complications in patients undergoing general anaesthesia for elective surgery: a systematic review and meta-analysis.

BACKGROUND: Many RCTs have evaluated the influence of intraoperative tidal volume (tV), PEEP, and driving pressure on the occurrence of postoperative pulmonary complications, cardiovascular complications, and mortality in adult patients. Our meta-analysis aimed to investigate the association between tV, PEEP, and driving pressure and the above-mentioned outcomes. METHODS: We conducted a systematic review and meta-analysis of RCTs from inception to May 19, 2022. The primary outcome was the incidence of postoperative pulmonary complications; the secondary outcomes were intraoperative cardiovascular complications and 30-day mortality. Primary and secondary outcomes were evaluated stratifying patients in the following groups: (1) low tV (LV, tV 6-8 ml kg-1 and PEEP ≥5 cm H2O) vs high tV (HV, tV >8 ml kg-1 and PEEP=0 cm H2O); (2) higher PEEP (HP, ≥6 cm H2O) vs lower PEEP (LP, <6 cm H2O); and (3) driving pressure-guided PEEP (DP) vs fixed PEEP (FP). RESULTS: We included 16 RCTs with a total sample size of 4993. The incidence of postoperative pulmonary complications was lower in patients treated with LV than with HV (OR=0.402, CI 0.280-0.577, P<0.001) and lower in DP than in FP group (OR=0.358, CI 0.187-0.684, P=0.002). Postoperative pulmonary complications did not differ between HP and LP groups; the incidence of intraoperative cardiovascular complications was higher in HP group (OR=1.385, CI 1.027-1.867, P=0.002). The 30-day mortality was not influenced by the ventilation strategy. CONCLUSIONS: Optimal intraoperative mechanical ventilation is unclear; however, our meta-analysis showed that low tidal volume and driving pressure-guided PEEP strategies were associated with a reduction in postoperative pulmonary complications.

Low serum 25­hydroxy-vitamin D levels are associated with cognitive impairment in multiple sclerosis.

BACKGROUND: Cognitive impairment frequently affects people with multiple sclerosis (MS). Low vitamin D has been associated with cognitive dysfunction in different neurodegenerative diseases, and, in MS, with motor disability and disease activity. We aim to investigate associations between vitamin D and cognitive status in MS. METHODS: In this cross-sectional study, we included 181 MS patients, recruited consecutively at the MS Unit of the Policlinico Federico II University Hospital of Naples, Italy, between January and April 2022, with serum 25­hydroxy (25-OH) vitamin D measurements using Chemiluminescence-ImmunoAssay, and cognitive assessment using the Brief International Cognitive Assessment for MS (BICAMS), which includes Symbol Digit Modalities Test (SDMT), California Verbal Learning Test-II (CVLT-II) and Brief Visuospatial Memory Test-Revised (BVMT-R). We collected demographics (age, sex, education), and clinical variables (disease duration, disease subtype, expanded disability status scale (EDSS), disease modifying treatment, relapses in previous 12 months, vitamin D supplementation, comorbidities). For a subset of patients (n = 41, 23.2% of the total sample), we collected Beck Depression Inventory-II, Beck Anxiety Inventory, and Modified Fatigue Impact Scale. RESULTS: At univariable linear regression models, serum 25-OH-vitamin D levels were 0.9 ng/mL higher for each unit increase of SDMT adjusted scores (Coeff=0.93; 95%CI=0.81, 1.04; p<0.01), 0.7 ng/mL higher for each unit increase of CVLT-II adjusted scores (Coeff=0.68; 95%CI=0.53, 0.83; p<0. 01), 0.6 ng/mL higher for each unit increase of BVMT-R adjusted scores (Coeff=0.58; 95%CI=0.43, 0.73; p<0.01), -9.63 ng/mL lower for each impaired BICAMS test (Coeff=-9.63; 95%CI=-11.48, -7.79; p<0.01), and -2.2 ng/mL lower for each unit increase of EDSS (Coeff=-2.16; 95%CI=-3.57, -0.75; p<0.01). At multivariable linear regression models, we confirmed associations between 25-OH-vitamin D and EDSS (Coeff=-2.09; 95%CI=-4.45, -0.43; p<0.01), SDMT (Coeff=0.75; 95%CI=0.60, 0.90; p<0.01), and CVLT-II (Coeff=0.14; 95%CI=0.01, 0.28; p = 0. 04). Results remained unchanged when including depression, anxiety and fatigue scores. CONCLUSIONS: Lower serum 25-OH-vitamin D was associated with worse cognitive function in MS. Future studies should consider longitudinal variations in cognitive function in relation to vitamin D supplementation.

The Twenty-Five Most Cited Articles About Adductor Canal Block: A Bibliometric Analysis from 1980 to 2022.

Introduction: Loco-regional anesthesia role is increasingly important in surgery, especially in postoperative pain control. Using ultrasound-guided techniques has made the loco-regional approach increasingly safe and manageable, guaranteeing excellent analgesic results and patient compliance. This bibliometric research aimed to identify the most influential papers on the adductor canal blocks and outline their characteristics. Methods: All articles published from 1980 to 2022 were included in the Web of Science, PubMed, and Scopus databases and found using the keywords "Adductor canal block" or "Saphenous nerve block" or "Peripheral nerve block" or "Hunter canal block" or "Subsartorial canal block" or "ACB" or "Knee" or "TKR" or "TKA" or "Analgesia" or "Arthroplasty" or "Replacement" in the title section had bibliometric analysis performed. The first 25 papers were selected and analyzed by the number of citations. The correlation between numerical variables was evaluated using the Pearson Correlation coefficient. Results: Literature screening found 252 publications. One hundred ten were only about the adductor canal block. Of these, 25 articles were selected for our bibliometric study, published in 8 different journals and with a total number of citations equal to 1.457. "Regional Anesthesia and pain medicine" journal - with 9 articles - was the one that produced the most. There was a significant strong correlation between the n. of citations and the citation rate (R = 0.84, p < 0.001). Conclusion: The purpose of this study is to be a guide on regional anesthesia and, particularly, on adductor canal block, making the most effective as well as the most cited articles available to anesthesiologists or other researchers interested in this topic.

Postoperative pulmonary complications and mortality after major abdominal surgery. An observational multicenter prospective study.

BACKGROUND: Postoperative pulmonary complications (PPCs) significantly contribute to postoperative morbidity and mortality. We conducted a study to determine the incidence of PPCs after major elective abdominal surgery and their association with early and 1-year mortality in patient without pre-existing respiratory disease. METHODS: We conducted a multicenter observational prospective clinical study in 40 Italian centers. 1542 patients undergoing elective major abdominal surgery were recruited in a time period of 14 days and clinically managed according to local protocol. The primary outcome was to determine the incidence of PPCs. Further, we aimed to identify independent predictors for PPCs and examine the association between PPCs and mortality. RESULTS: PPCs occurred in 12.6% (95% CI 11.1-14.4%) of patients with significant differences among general (18.3%, 95% CI 15.7-21.0%), gynecological (3.7%, 95% CI 2.1-6.0%) and urological surgery (9.0%, 95% CI 6.0-12.8%). PPCs development was associated with known pre- and intraoperative risk factors. Patients who developed PPCs had longer length of hospital stay, higher risk of 30-days hospital readmission, and increased in-hospital and one-year mortality (OR 3.078, 95% CI 1.825-5.191; P<0.001). CONCLUSIONS: The incidence of PPCs in patients without pre-existing respiratory disease undergoing elective abdominal surgery is high and associated with worse clinical outcome at one year after surgery. General surgery is associated with higher incidence of PPCs and mortality compared to gynecological and urological surgery.

Trends for Percutaneous Tracheostomy in Italian Acute Care Setting over a 5-Year Period.

Background: Tracheostomy is a widespread procedure usually performed with a percutaneous approach for prolonged mechanical ventilation. Little is known about the population-based trends for percutaneous tracheostomies (PT). The aim of this study was to evaluate the order to analyze the characteristics, rates, and costs of PTs performed in Italy from 2009 to 2014. Methods: We analyzed 102,646 PTs performed in Italy between 2009 and 2014. We obtained the data of patients from the section of the discharge report of the Italian Ministry of Health (National Archive for Hospital Discharge Form, Ministry of Health) about age, gender, length of stay (LOS), hospital types, and hospital region for code 541 and 542 for the years 2009, 2010, 2011, 2012, 2013 and 2014. Our additional source of data was the Annual Discharge Reports of the Italian Ministry of Health. Results: In this study, including 102,646 PTs performed from 2009 to 2014, we found that (1) the rates of PTs significantly decreased over time; (2) PTs were mostly performed in patients aged less than 65 years and hospitalized in ICUs for less than 40 days; and (3) the costs of PTs severely decreased over time, with a breakpoint between 2011 and 2012. Conclusions: Percutaneous tracheostomy is still a procedure frequently performed in the setting of acute care. Although percutaneous tracheostomy still results in high medical care reimbursement, it is a safe and cost-saving procedure.

Venous thromboembolism and major bleeding in severe and critical COVID-19 hospitalized patients.

Venous thromboembolism (VTE) and major bleeding (MB) are life-threatening complications described in COVID-19 hospitalized patients and they can be considered as two sides of the same coin. This retrospective study aims to evaluate the risk factors for VTE and MB in COVID-19 patients admitted to two Italian hospitals. The medical records of all COVID-19 patients (males 139; 62.3%, mean age 67.2±13.6 years, body weight 88.2±20.6 kg) hospitalized from March 11th to July 31st, 2020 to the Federico II University Hospital and to Sea Hospital, Naples, Italy, were analyzed. The COVID-19 patients were classified into four groups: COVID-19 patients developing VTE and/or MB, COVID-19 patients developing only VTE, COVID-19 patients developing only MB, and COVID-19 patients not developing neither VTE nor MB. During the hospitalization, 53 COVID-19 patients (24.7%; males 40; 75.5%, mean age 67.2±13.6 years, weight 88.2±20.6 kg) developed VTE, 33 COVID-19 patients (15.3 %; males 17; 51.5, mean age 67.3±14.9 years, weight 74.1±14.3 kg) developed MB, and 129 COVID-19 patients not developed neither TVP nor MB. No parameters to identify severe COVID-19 complicated by VTE and/or MB were found. However, some clinical and biochemical parameters can be evaluated to predict the risk of MB in order to modify the treatment and take prompt action to reduce mortality.

Role of spinal anesthesia in robot-assisted radical prostatectomy: Gamble or opportunity?

To the Editor, Although postoperative pain associated with robot-assisted radical prostatectomy (RARP) is less than pain following the open technique, it remains a fundamental issue as it can be a significant source of discomfort for the patient and lengthen recovery times after surgery. The optimal management of pain after RARP is far from being fully elucidated and many factors have to be evaluated to choose the best analgesic approach. [...].

Tetra-block: ultrasound femoral, lateral femoral-cutaneous, obturator, and sciatic nerve blocks in lower limb anesthesia: a case series.

BACKGROUND: The gold standard anesthesiologic procedure for urgent femur fracture surgery is Spinal Anesthesia. It is not always feasible because of patients' severe comorbidities and difficulties in optimizing drug therapy in the appropriate time frame such as discontinuation of anticoagulant drugs. The use of four peripheral nerve blocks (tetra-block) can be a winning weapon when all seems lost. CASE PRESENTATION: We present, in this case series, three Caucasian adult femur fractures (an 83-year-old woman, a 73-year-old man, and a 68-year-old woman) with different and major comorbidities (cardiac or circulatory disorders on anticoagulants therapy that were not discontinued on time; breast cancer and others) underwent the same anesthesiologic approach in the urgent setting. Ultrasound peripheral nerve blocks, that is femoral, lateral femoral cutaneous, obturator, and sciatic with parasacral approach were successfully performed in all patients who underwent intramedullary nailing for intertrochanteric fracture. We evaluated the adequacy of the anesthesia plane, postoperative pain control with the VAS scale, and the incidence of postoperative side effects. CONCLUSIONS: Four peripheral nerve blocks (Tetra-block) can be alternative anesthesiologic management in urgent settings, in patients where drug therapy cannot be optimized, as in antiplatelet and anticoagulant therapy.

Effects of depth of neuromuscular block on surgical operating conditions in women undergoing gynecologic laparoscopic surgery: a randomized clinical trial.

BACKGROUND: In recent years, the relationship between the advantages and disadvantages of a deep neuromuscular block (DNMB), compared to a moderate block (MNMB) in laparoscopic surgery, has been increasingly studied. OBJECTIVE: Evaluate the effect of D-NMB compared to M-NMB in gynecological laparoscopic surgery. METHODS: This was a parallel-group, double-blind, randomized clinical trial, conducted at a single center in Italy between February 2020 and July 2020. American Society of Anesthesiologist (ASA) I-II risk class patients scheduled for elective gynecological laparoscopic surgery were randomized into a 1:1 ratio to either experimental or control group. The first one included DNMB with a rocuronium bolus at the starting dose of 1.2 mg/kg and a maintenance dose (0.3-0.6 mg/kg/h). The second one included MNMB with a rocuronium bolus at the starting dose of 0.6 mg/kg, and a maintenance dose in boluses (0.15-0.25 mg/kg). The primary outcome was the intraoperative surgical condition assessed every 15 min by the surgeon as a 5-point scale. The secondary outcome was the time needed to discharge patients from post-anesthesia care unit (PACU). The tertiary outcome was the assessment of the intra-operative hemodynamic instability. A sample size of 50 patients was planned. RESULTS: One hundred five patients were assessed for eligibility, 55 were excluded. Fifty patients met the inclusion criteria and were enrolled. The average score for the operative field was 4 for the D-NMB group and 3 for the M-NMB group (p value < 0.01). The length of stay in PACU was 13 min for the DNMB group and 22 min for the MNMB group (p value = 0.02). CONCLUSIONS: Deep neuromuscular block improves intraoperative surgical condition during gynecological laparoscopic surgery. TRIAL REGISTRATION: clinicalTrials.gov NCT03441828.

Robot-assisted radical prostatectomy: comparison of subarachnoid analgesia, erector spine plane block, and intravenous analgesia for postoperative pain management.

Background: Laparoscopic and robotic prostatectomy allows a higher precision and a magnified view of the surgical field but it did not show to be characterized by a lower pain compared to open surgery so the management of postoperative pain still remains an important issue. Methods: We enrolled 60 patients randomized in 1:1:1 ratio into three groups: group SUB: treated with a lumbar subarachnoid injection of 10.5 mg ropivacaine, 30 µg clonidine, 2 µg/kg morphine, and 0.03 µg/kg sufentanil; groups ESP: treated with a bilateral erector spinae plane (ESP) block with 30 µg clonidine, 4 mg dexamethasone, 100 mg ropivacaine; group IV: treated with 10 mg morphine intramuscular 30 minutes before the end of the surgery and a postoperative iv continuous infusion of 0.625 mg/hr morphine in the first 48 hours after the intervention. Results: Numeric rating scale score in the first 12 hours after intervention was significantly lower in SUB group compared to both IV group and ESP group with a maximum difference at 3 hours after intervention (0.14±0.35 vs 2.05±1.10, P <0.001 and 0.14±0.35 vs 1.15±0.93, P <0.001, respectively). Intraoperative supplemental doses of sufentanil were not required by SUB group, whereas IV and ESP groups required an additional dose of 24±10.7 µg and 7.5±5.5 µg, respectively (P <0.001). Conclusions: Subarachnoid analgesia is an effective strategy to manage postoperative pain in robot-assisted radical prostatectomy; it allows to reduce both intraoperative and postoperative opioid consumption and the amount of inhalation anesthetics compared to intravenous analgesia. ESP block might be an effective alternative in patients with contraindications to subarachnoid analgesia.

Concomitant diagnosis of multiple sclerosis and human immunodeficiency virus (HIV) infection: case report and the review of literature.

BACKGROUND: To date, few cases of multiple sclerosis (MS) patients with concomitant Human Immunodeficiency Virus (HIV) infection have been described. However, none of the previously described cases has been treated with Natalizumab, probably due to the increasing risk of progressive multifocal leukoencephalopathy (PML). CASE: We report the case of a patient concomitantly diagnosed for HIV infection and MS treated with combined antiretroviral therapy (cART) and Natalizumab for 19 months, without clinical or radiological MS activity. CONCLUSIONS: Our case might suggest considering Natalizumab in patients with concomitant HIV infection, especially for those with significant disease activity requiring a high efficacy disease modifying treatment.

Electric impedance tomography and protective mechanical ventilation in elective robotic-assisted laparoscopy surgery with steep Trendelenburg position: a randomized controlled study.

Electrical impedance tomography (EIT) reconstructs functional lung images and evaluates the variations of impedance during the breathing cycle. The aim of this study was to evaluate the effect of protective mechanical ventilation on ventilation distributions recorded by the EIT during elective robotic-assisted laparoscopy surgery with steep Trendelenburg position. This prospective, randomized single center study included patients with healthy lungs undergoing elective robot-assisted laparoscopic urological surgery in general anesthesia. Patients were randomly assigned to either protective lung ventilation or conventional ventilation. In the protective ventilation group, tidal volume (TV) was set at 6 ml/Kg predicted body weight (PBW), with PEEP 6 cmH2O, and recruitment maneuvers (RM) as needed. In the conventional ventilation group, TV was set at 9 ml/Kg PBW, with PEEP 2 cmH2O and RM only as needed. Ventilation distribution was assessed using an EIT device. This study included 40 patients in the functional image analysis. Significant differences were found in ventilation distribution in the region of interest (p < 0.05). Driving pressure was significantly lower in protective ventilation group (p < 0.05). Peak and plateau pressures were not different between the groups while statical significance was found in tidal volume and respiratory rate. EIT may be a valuable tool for monitoring lung function during general anesthesia. During elective robotic-assisted laparoscopy surgery with steep Trendelenburg position, protective mechanical ventilation may have a more homogenous distribution of intraoperative and postoperative ventilation. Larger sample size and long-term evaluation are needed in future studies to assess the benefit of EIT monitoring in operation room.Clinical trial registration ClinicalTrials.gov Identifier: NCT04194177 registered at 11th December 2019.

Liver Regeneration and Immunity: A Tale to Tell.

The physiological importance of the liver is demonstrated by its unique and essential ability to regenerate following extensive injuries affecting its function. By regenerating, the liver reacts to hepatic damage and thus enables homeostasis to be restored. The aim of this review is to add new findings that integrate the regenerative pathway to the current knowledge. An optimal regeneration is achieved through the integration of two main pathways: IL-6/JAK/STAT3, which promotes hepatocyte proliferation, and PI3K/PDK1/Akt, which in turn enhances cell growth. Proliferation and cell growth are events that must be balanced during the three phases of the regenerative process: initiation, proliferation and termination. Achieving the correct liver/body weight ratio is ensured by several pathways as extracellular matrix signalling, apoptosis through caspase-3 activation, and molecules including transforming growth factor-beta, and cyclic adenosine monophosphate. The actors involved in the regenerative process are numerous and many of them are also pivotal players in both the immune and non-immune inflammatory process, that is observed in the early stages of hepatic regeneration. Balance of Th17/Treg is important in liver inflammatory process outcomes. Knowledge of liver regeneration will allow a more detailed characterisation of the molecular mechanisms that are crucial in the interplay between proliferation and inflammation.