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Francesco Coppolino, Simona Brunetti, Leonardo Maria Bottazzo, Gianluigi Cosenza, Pasquale Sansone, Marco Fiore, Maria Beatrice Passavanti, Vincenzo Pota, Maria Caterina Pace Department of Women, Children and General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples, ItalyCorrespondence: Simona Brunetti, Department of Women, Children and General and Specialized Surgery, University of Campania Luigi Vanvitelli, Piazza Luigi Miraglia N.2, Naples, 80134, Italy, Tel +393492424108, Email simona.brunetti@studenti.unicampania.itPurpose: Thoracic surgery often results in severe chronic postoperative pain. Current evidence favors two locoregional techniques. Thoracic Epidural Anesthesia (TEA), the gold standard, and Thoracic Paravertebral Block (TPVB), which is associated with fewer side effects but is limited by short duration of action of local anesthetics (LA) and potential failure due to improper drug distribution. This study investigates the use of dexmedetomidine (DEX) as adjuvant to prolong the effects of LA in TPVB, with methylene blue used for visual confirmation of accurate injectate spread.Patients and Methods: We observed 6 patients undergoing Video-Assisted Thoracoscopy (VATS) lobectomy who received TPVB with ropivacaine, DEX and methylene blue. The primary endpoint was postoperative pain recorded at 1, 12, 24, 48 hours using Numeric Rating Scale (NRS); the secondary endpoints were cumulative opioid consumption in the first 24 hours in Milligram Morphine Equivalents (MME); adverse events: occurrence of bradycardia, hypotension, Postoperative Nausea and Vomiting (PONV); length of hospital stay. All patients completed the study.Results: Our results showed optimal pain scores, with NRS scores always below 4, decreased need for opioids, and prolonged analgesia. None of the patients had bradycardia nor PONV, but two patients experienced acute and self-limited hypotension following TPVB.Conclusion: Thoracic Paravertebral Block with Dexmedetomidine and methylene blue was effective and safe in controlling postoperative pain. Methylene blue could help improving knowledge on anesthetics distribution to reduce failure rates.Keywords: locoregional anesthesia, paravertebral block, post-operative pain, thoracic surgery

Salvatore Sardo,1 Giustino Varrassi,2 Mario Scartozzi,3 Maria Caterina Pace,4 Vittorio Schweiger,5 Stefano Tamburin,6 Mario Musu,1 Gabriele Finco1 1Department of Medical Sciences and Public Health, University of Cagliari, Monserrato, Italy; 2Paolo Procacci Foundation, Rome, Italy; 3Medical Oncology Unit, University Hospital and University of Cagliari, Monserrato, Italy; 4Department of Anesthesia and Pain Medicine, University of Napoli, Napoli, Italy; 5Department of Anesthesia and Pain Medicine, University of Verona, Verona, Italy; 6Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, ItalyCorrespondence: Salvatore Sardo, Department of Medical Sciences and Public Health, University of Cagliari, Monserrato, Italy, Email salvatore.sardo@unica.itIntroduction: Chemotherapy-induced peripheral neurotoxicity (CIPN) affects nearly 70% of cancer patients after chemotherapy, causing sensory, motor, autonomic dysfunction, and neuropathic pain. The Desirability of Outcome Ranking (DOOR) framework is proposed as a better way to assess preventive or therapeutic interventions for CIPN.Methods: A survey was conducted among Italian healthcare professionals and researchers affiliated to the Italian Chapter of the International Association for the Study of Pain (AISD) to identify the most important outcomes in clinical management and research.Results: Among the 73 respondents, 61 qualified for the survey, with an overall response rate of 1.2%. The vast majority were physicians (77%), most of whom were anesthesiologists (47.5%). The results showed that pain, survival, sensory impairment, motor impairment, and quality of life were consistently ranked as the most important outcomes, but there was significant disagreement in the outcomes relative ranking, making it difficult to develop a DOOR algorithm. The study also revealed that clinicians commonly use structured interviews to evaluate patients with CIPN, and the most prescribed drugs or supplements were palmitoylethanolamide, pregabalin, gabapentin and alpha lipoic acid as preventive agents and pregabalin, palmitoylethanolamide, duloxetine, gabapentin, and amitriptyline as therapeutic agents. However, many of these drugs have not been clinically proven to be effective for CIPN.Discussion: This study suggests that the implementation of a DOOR framework for CIPN using healthcare professionals is more difficult than expected, given the significant disagreement in our respondents’ ranking of outcomes. Our work provides interesting topics for future research in CIPN, but its limitations include a small sample size, a low response rate, and a possible selection bias.Keywords: neuropathic pain, peripheral neuropathy, cancer, taxane, Desirability of Outcome Ranking, survey, chemotherapy induced peripheral neuropathy

Marco Fiore,1,* Marco Cascella,2,* Sabrina Bimonte,2 Alberto Enrico Maraolo,3 Ivan Gentile,3 Vincenzo Schiavone,4 Maria Caterina Pace1 1Department of Anaesthesiological, Surgical and Emergency Sciences, University of Campania “Luigi Vanvitelli”, Naples, Italy; 2Department of Support for Clinical Activities and Critical Area, Division of Anesthesia and Pain Medicine, Istituto Nazionale Tumori – IRCCS “Fondazione G. Pascale”, Via Mariano Semmola, Naples, Italy; 3Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, Naples, Italy; 4Division of Anesthesia and Intensive Care, Hospital “Pineta Grande”, Castel Volturno, Italy *These authors contributed equally to this work Abstract: Fungal infections of the liver, most commonly caused by Candida spp., often occur in patients with hematologic malignancies treated with chemotherapy. Colonization of the gastrointestinal tract is thought to be the main origin of dissemination of Candida; mucositis and neutropenia facilitate the spread of Candida from the gastrointestinal tract to the liver. Hepatic involvement due to other fungi is a less common infectious complication in this setting. Fungal infections represent a less common cause of hepatic abscesses in non-oncohematologic population and the trend appears to be decreasing in recent years. Understanding of the etiology and epidemiology of fungal infections of the liver is indicated for an appropriate antimicrobial therapy and an overall optimal management of fungal liver infections. Keywords: fungal liver infections, antifungal agents, hepatosplenic candidiasis, acute disseminated candidiasis, life-threatening infections

Marco Fiore,1 Alberto Enrico Maraolo,2 Sebastiano Leone,3 Ivan Gentile,2 Arturo Cuomo,4 Vincenzo Schiavone,5 Sabrina Bimonte,4 Maria Caterina Pace,1 Marco Cascella4 1Department of Anaesthesiological, Surgical and Emergency Sciences, University of Campania “Luigi Vanvitelli”, Naples, Italy; 2Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, Naples, Italy; 3Division of Infectious Diseases, “San Giuseppe Moscati” Hospital, Avellino, Italy; 4Division of Anesthesia, Department of Anesthesia and Pain Medicine, Istituto Nazionale Tumori – IRCCS – Fondazione G. Pascale, Naples, Italy; 5Division of Anesthesia and Intensive Care, Hospital “Pineta Grande”, Castel Volturno, Italy Abstract: Spontaneous peritonitis (SP) is the most common infection among decompensated end-stage liver disease patients. SP is the infection of ascitic fluid (neutrophil ascitic count ≥250/mL) without an alternative focus of abdominal infection. According to the causative agent, clinicians can make the diagnosis of spontaneous bacterial peritonitis or spontaneous fungal peritonitis. The mortality rate is very high, ranging from one-fifth of the patients with spontaneous bacterial peritonitis to four-fifths of the patients with spontaneous fungal peritonitis. An immediate and accurate diagnosis can improve the outcome in end-stage liver disease patients. The aim of this work is to provide physicians with a practical diagnostic guidance for SP diagnosis according to current evidence, in order to improve the management of cirrhotic patients with infected ascitic fluid. Keywords: cirrhosis, spontaneous bacterial peritonitis, spontaneous fungal peritonitis, bacteriascites, fungal ascites

Abstract Background Due to tolerance development and adverse side effects, chronic pain patients frequently need to be switched to alternative opioid therapy Objective To assess the efficacy and tolerability of an alternative transdermally applied (TDS) opioid in patients with chronic cancer pain receiving insufficient analgesia using their present treatment. Methods A total of 32 patients received alternative opioid therapy, 16 were switched from buprenorphine to fentanyl and 16 were switched from fentanyl to buprenorphine. The dosage used was 50% of that indicated in equipotency conversion tables. Pain relief was assessed at weekly intervals for the next 3 weeks Results Pain relief as assessed by VAS, PPI, and PRI significantly improved (p < 0.0001) in all patients at all 3 follow up visits. After 3 weeks of treatment, the reduction in the mean VAS, PPI, and PRI scores in the fentanyl and buprenorphine groups was 68, 77, 74, and 69, 79, and 62%, respectively. Over the same time period the use of oral morphine as rescue medication was reduced from 27.5 ± 20.5 (mean ± SD) to 3.75 ± 8.06, and 33.8 ± 18.9 to 3.75 ± 10.9 mg/day in the fentanyl and buprenorphine groups, respectively. There was no significant difference in either pain relief or rescue medication use between the two patient groups The number of patient with adverse events fell during the study. After the third week of the treatment the number of patients with constipation was reduced from 11 to 5, and 10 to 4 patients in the fentanyl and buprenorphine groups, respectively. There was a similar reduction in the incidence of nausea and vomiting. No sedation was seen in any patient after one week of treatment. Conclusion Opioid switching at 50% of the calculated equianalgesic dose produced a significant reduction in pain levels and rescue medication. The incidence of side effects decreased and no new side effects were noted. Further studies are required to provide individualized treatment for patients according to their different types of cancer.

Background and Aims: Heterotrophic plants have long been a challenge for systematists, exemplified by the base of the orchid subfamily Epidendroideae, which contains numerous mycoheterotrophic species., Methods: Here we address the utility of organellar genomes in resolving relationships at the epidendroid base, specifically employing models of heterotachy, or lineage-specific rate variation over time. We further conduct comparative analyses of plastid genome evolution in heterotrophs and structural variation in matK., Key Results: We present the first complete plastid genomes (plastomes) of Wullschlaegelia, the sole genus of the tribe Wullschlaegelieae, revealing a highly reduced genome of 37 kb, which retains a fraction of the genes present in related autotrophs. Plastid phylogenomic analyses recovered a strongly supported clade composed exclusively of mycoheterotrophic species with long branches. We further analysed mitochondrial gene sets, which recovered similar relationships to those in other studies using nuclear data, but the placement of Wullschlaegelia remains uncertain. We conducted comparative plastome analyses among Wullschlaegelia and other heterotrophic orchids, revealing a suite of correlated substitutional and structural changes relative to autotrophic species. Lastly, we investigated evolutionary and structural variation in matK, which is retained in Wullschlaegelia and a few other 'late stage' heterotrophs and found evidence for structural conservation despite rapid substitution rates in both Wullschlaegelia and the leafless Gastrodia., Conclusions: Our analyses reveal the limits of what the plastid genome can tell us on orchid relationships in this part of the tree, even when applying parameter-rich heterotachy models. Our study underscores the need for increased taxon sampling across all three genomes at the epidendroid base, and illustrates the need for further research on addressing heterotachy in phylogenomic analyses., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Encephalitis affects 1.9 to 14.3 people per 100,000 each year, and the mortality rate varies but can be up to 40%. After the identification of a particular microorganism in a patient with encephalitis, appropriate antimicrobial therapy should be initiated. Corticosteroid therapy represents a therapeutic option in the treatment of primary central nervous system diseases due to its ability to reduce the inflammatory commitment of CNS and consequently reduce mortality rates regardless of the causative agent of injury. Corticosteroid therapy represents a therapeutic option in the treatment of primary central nervous system diseases. Their use is also recommended in meningitis with autoimmune etiology. While corticosteroids have repeatedly been used as adjunctive treatment in encephalitis of viral etiology, the scientific evidence supporting their effectiveness remains scarce. The use of standard doses recommended by the guidelines seems reasonable as an initial setting, especially when a definitive diagnosis of the causal agent is still awaited. The subsequent adjustment should be personalized based on the individual clinical response.

Opioid-induced constipation (OIC) is a very common and troublesome gastrointestinal side effect following the use of opioids. Despite existing international guidelines, OIC is largely underdiagnosed and undertreated. ECHO OIC is a European project designed to improve the diagnosis and management of OIC at the primary care level. The next phase of the ECHO OIC project is to review and adapt the proposed European pathway at national level, considering the local patient journey and clinical practice. A multidisciplinary group of 12 Italian experts reviewed and discussed the European path and formulated a seven-step guide for the practical management of OIC that is also easily applicable in primary care: 1. When prescribing long-term opioids, the physician should inform the patient of the possibility of the onset of OIC; 2. At opioid prescription, doctors should also prescribe a treatment for constipation, preferably macrogol or stimulant laxatives; 3. The patient should be evaluated for OIC within the second week of initiating opioid treatment, by clinical history and Rome IV criteria; 4. In the presence of constipation despite laxatives, prescription of a PAMORA (Peripherally Acting Mu Opioid Receptor Antagonist) should be considered; 5. When prescribing a PAMORA, prescribing information should be carefully reviewed, and patients should be accurately instructed for appropriate use; 6. Efficacy and tolerability of the PAMORA should be monitored regularly by Bowel Function Index, considering a cut-off of 30 for the possible step-up of OIC treatment; 7. After 4 weeks of treatment, if the efficacy of PAMORA is deemed inadequate, discontinuation of the PAMORA, addition of an anti-constipation drugs, change of opioid type, or referral to a specialist should be considered. Spreading knowledge about the OIC problem as much as possible to the health community is crucial to obtain not only an early treatment of the condition but also to promote its prevention.

Background: The use of opioids for pain is linked to an increased risk of developing opioid use disorder, and has resulted in the emergence of the opioid crisis over the last few years., Aim: The systematic review question is "How does the use of opioid medications in pain management, compared with non-opioid medications, affect pain intensity over the short, intermediate, and long-term in adults with acute traumatic pain?"., Methods: The protocol was prospectively registered on the International Prospective Register of Systematic Reviews: CRD42021279639. Medline and Google Scholar were electronically searched for controlled peer-reviewed studies published in full, with the PICO framework: P: Adult patients with traumatic injuries, I: Opioid medications, C: Non-opioid medications, O: A minimum clinically important difference (MCID) in pain., Results: After full-text screening, we included 14 studies in the qualitative synthesis. Of these 14 studies, 12 were randomized clinical trials (RCTs) and 2 were pseudo-RCTs with a total of 2347 patients enrolled. There was heterogeneity in both medication utilized and outcome in these studies; only two studies were homogeneous regarding the type of study conducted, the opioid used, its comparator, and the outcome explored. The MCID was evaluated in 8 studies, while in 6 studies, any measured pain reduction was considered as an outcome. In 11 cases, the setting of care was the Emergency Department; in 2 cases, care occurred out-of-hospital; and in one case, the setting was not well-specified. The included studies were found to have a low-moderate risk of bias., Conclusion: Non-opioids can be considered an alternative to opioids for short-term pain management of acute musculoskeletal injury. Intravenous ketamine may cause more adverse events than other routes of administration., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest. They did not receive any funding for the work undertaken., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Alcohol withdrawal syndrome (AWS) is defined as the cessation or reduction in heavy and prolonged alcohol use within several hours to a few days of cessation. The recommended first-line therapy for AWS ranging from mild to severe or complicated remains benzodiazepines; in cases where benzodiazepines are not adequate in controlling persistent autonomic hyperactivity or anxiety, dexmedetomidine could be utilized. The possible advantage of dexmedetomidine compared to benzodiazepines is that it does not cause respiratory depression, thus reducing the risk of intubation and hospitalization in the ICUs, with the potential reduction in healthcare costs. The purpose of this systematic review and meta-analysis (PROSPERO CRD42018084370) is to evaluate the effectiveness and safety of dexmedetomidine as adjunctive therapy to the standard of care for the treatment of AWS. We retrieved literature from PubMed, EMBASE, and CENTRAL until 10 January 2024. Eligible studies were both randomized trials and nonrandomised studies with a control group, published in the English language and peer-reviewed journals. The primary outcome was tracheal intubation; secondary outcomes were (i) bradycardia and (ii) hypotension. A total of 3585 papers were retrieved: 2635 from EMBASE, 930 from Medline, and 20 from CENTRAL. After eliminating duplicates, 2960 papers were screened by title and abstract; 75 out of the 2960 papers were read in full text. The qualitative synthesis included nine of all manuscripts read in full text. The quantitative synthesis included eight studies for the primary outcome (tracheal intubation), seven for the secondary outcome bradycardia, and six for the secondary outcome hypotension. The meta-analysis showed that Dexmedetomidine, as adjunctive therapy, is not more effective than standard therapy in reducing the risk of tracheal intubation in AWS [RR: 0.57, 95% CI: 0.25-1.3, p = 0.15]. It also appears to be less safe than sedative therapy as it significantly increases the risk of bradycardia [RR: 2.68, 95% CI: 1.79-4.16, p = 0.0016]. Hypotension was not significantly different in patients who received dexmedetomidine [RR: 1.5, 95% CI: 0.69-3.49, p = 0.21].

Objective: This study aimed to investigate whether the administration of intrathecal dexmedetomidine as a bupivacaine adjuvant for caesarean section can prolong the duration of analgesia compared with bupivacaine alone. Secondary outcomes included postoperative pain, the time interval to the first analgesic request, the level of sedation, the incidence of adverse effects, and the fetal outcomes., Materials and Methods: A systematic review and meta-analysis were conducted. The study compared the intrathecal administration of bupivacaine plus dexmedetomidine (group BD) to the intrathecal administration of bupivacaine alone (group B) for cesarean sections., Results: Fourteen publications were included. Among patients who underwent spinal anesthesia for a cesarean section, 514 patients received intrathecal bupivacaine alone, and 533 patients received intrathecal bupivacaine plus dexmedetomidine. The onset of sensory and motor block was essentially the same in both groups; the time for sensory and motor block regression was significantly longer in the BD group. Postoperative Visual Analogue Scale (VAS) values were similar in group BD when compared to group B. Postoperative VAS scores remained consistently low in Group BD compared to Group B, starting from 1 hour after surgery. The level of sedation measured at the end of the cesarean section in both groups was almost similar. No difference in terms of safety, adverse events, and neonatal outcomes was found between the two groups., Conclusions: Use of intrathecal dexmedetomidine for spinal anesthesia in cesarean section significantly prolongs sensory and motor block compared to using bupivacaine alone as an adjuvant. It also improves analgesia after 1 hour with no difference in the incidence of maternal and neonatal adverse effects compared to bupivacaine alone. The optimal dose of dexmedetomidine to use remains to be ingested.

Introduction: The management of pain following a burn is extremely complex because of the multifactorial nature of burn pain (nociceptive and neuropathic). In the pre-hospital setting and emergency department (ED), the main goal of acute pain management is to reduce the patient's pain, allowing them to maintain function and to prevent the chronification of pain. Opioids are used as first-line treatment in management of burn pain. The aim of our study was to evaluate the efficacy and adverse effects of intravenous (IV) morphine for burn pain management in the ED and to evaluate pain management in the pre-hospital setting., Methods: In this single-center observational study, patients presenting with second- and third-degree burns were enrolled in our ED. Numerical Rating Scale (NRS) and Burn Specific Pain Anxiety Scale (BSPAS) were performed at ED admission and after 1 h. Pain medications administered before arrival in the ED were reported by the rescue team. All patients received IV acetaminophen every 8 h and IV morphine according NRS., Results: Thirty patients were included in this study. At the time of arrival to the ED, > 90% of the patients reported severe pain; 95.8% of them received IV morphine to achieve pain relief. After 1 h, > 65% of patients had NRS < 3. The total amount of IV morphine was 18.12 ± 4.26 mg in the first hour. No adverse events were recorded. The BSPAS on admission to the ED was 34.8 ± 5.6, indicating severe anxiety. After 1 h, BSPAS was 12.8 ± 4.8, indicating mild anxiety., Conclusion: IV morphine used for burn pain management in the emergency setting significantly improves patient outcomes in terms of pain. IV morphine also reduced anxiety scores at 1 h., (© 2024. The Author(s).)

Objectives: to evaluate the accuracy (completeness of case recording and diagnostic quality) of the Lombardy Mesothelioma Registry (Registro Mesoteliomi Lombardia, RML) through a comparison with the autopsy database of Pavia University (years 2000-2016)., Design: validation study., Setting and Participants: all mesothelioma records with incidence date between 01.01.2000 and 16.09.2016 were extracted from the RML. They were cross-referenced with deaths from any asbestos-related disease subjected to a forensic autopsy extracted from the archive of the Department of Public Health, Experimental and Forensic Medicine of Pavia University., Main Outcomes Measures: using the postmortem diagnosis by Pavia University as the gold standard, RML sensitivity and specificity and their 95% confidence intervals (95%CI) were calculated using the Agresti-Coull formula., Results: based on 141 deaths, the RML showed very good accuracy: specificity was 100% (95%CI 87%-100%; 32/32 deaths) and sensitivity 94% (95%CI 87%-97%; 102/109 deaths). The 7 false negative cases either were missed by the RML (N. 4) or had been wrongly classified as non-mesotheliomas (N. 3) because the diagnosis was made or confirmed only postmortem after a forensic autopsy., Conclusions: RML accuracy (completeness and diagnostic quality) was very high. No false positive was found and the few false negatives were due to lack of notification of mesotheliomas diagnosed postmortem to the registry. Forensic pathologists should be made aware that mesothelioma notification to the regional mesothelioma registry is important and compulsory.

Premise: Leafless, heterotrophic plants are prime examples of organismal modification, the genomic consequences of which have received considerable interest. In particular, plastid genomes (plastomes) are being sequenced at a high rate, allowing continual refinement of conceptual models of reductive evolution in heterotrophs. However, numerous sampling gaps exist, hindering the ability to conduct comprehensive phylogenomic analyses in these plants., Methods: Using floral tissue from an herbarium specimen, we sequenced and analyzed the plastome of Degranvillea dermaptera, a rarely collected, leafless orchid species from South America about which little is known, including its phylogenetic affinities., Results: The plastome is the most reduced of those sequenced among the orchid subfamily Orchidoideae. In Degranvillea, it has lost the majority of genes found in leafy autotrophic species, is structurally rearranged, and has similar gene content to the most reduced plastomes among the orchids. We found strong evidence for the placement of Degranvillea within the subtribe Spiranthinae using models that explicitly account for heterotachy, or lineage-specific evolutionary rate variation over time. We further found evidence of relaxed selection on several genes and of correlations among substitution rates and several other "traits" of the plastome among leafless members of orchid subfamily Orchidoideae., Conclusions: Our findings advance knowledge on the phylogenetic relationships and paths of plastid genome evolution among the orchids, which have experienced more independent transitions to heterotrophy than any other plant family. This study demonstrates the importance of herbarium collections in comparative genomics of poorly known species of conservation concern., (© 2024 Botanical Society of America.)

Hepatorenal Syndrome is a critical complication of liver failure, mainly in cirrhotic patients and rarely in patients with acute liver disease. It is a complex spectrum of conditions that leads to renal dysfunction in the liver cirrhosis population; the pathophysiology is characterized by a specific triad: circulatory dysfunction, nitric oxide (NO) dysfunction and systemic inflammation but a specific kidney damage has never been demonstrated, in a clinicopathological study, kidney biopsies of patients with cirrhosis showed a wide spectrum of kidney damage. In addition, the absence of significant hematuria or proteinuria does not exclude renal damage. It is estimated that 40% of cirrhotic patients will develop hepatorenal syndrome with in-hospital mortality of about one-third of these patients. The burden of the problem is dramatic considering the worldwide prevalence of more than 10 million decompensated cirrhotic patients, and the age-standardized prevalence rate of decompensated cirrhosis has gone through a significant rise between 1990 and 2017. Given the syndrome's poor prognosis, the clinician must know how to manage early treatment and any complications. The widespread adoption of albumin and vasopressors has increased Hepatorenal syndrome-acute kidney injury reversal and may increase overall survival, as previously shown. Further research is needed to define whether the subclassification of patients may allow to find a personalized strategy to treat Hepatorenal Syndrome and to define the role of new molecules and extracorporeal treatment may allow better outcomes with a reduction in treatment-related adverse effects. This review aims to examine both pharmacological and non-pharmacological treatment of hepatorenal syndrome, with a particular focus on managing adverse events caused by treatment.

(1) Background: Infections caused by multidrug-resistant (MDR) bacteria represent one of the major global public health problems of the 21st century. Beta-lactam antibacterial agents are commonly used to treat infections due to Gram-negative pathogens. New β-lactam/β-lactamase inhibitor combinations are urgently needed. Combining relebactam (REL) with imipenem (IMI) and cilastatin (CS) can restore its activity against many imipenem-nonsusceptible Gram-negative pathogens. (2) Methods: we performed a systematic review of the studies reporting on the use of in vivo REAL/IPM/CS. (3) Results: A total of eight studies were included in this review. The primary diagnosis was as follows: complicated urinary tract infection ( n = 234), complicated intra-abdominal infections ( n = 220), hospital-acquired pneumonia ( n = 276), and ventilator-associated pneumonia ( n = 157). Patients with normal renal function received REL/IPM/CS (250 mg/500 mg/500 mg). The most frequently reported AEs occurring in patients treated with imipenem/cilastatin plus REL/IPM/CS were nausea (11.5%), diarrhea (9.8%), vomiting (9.8%), and infusion site disorders (4.0%). Treatment outcomes in these high-risk patients receiving REL/IPM/CS were generally favorable. A total of 70.6% of patients treated with REL/IPM/CS reported a favorable clinical response at follow-up. (4) Conclusions: this review indicates that REL/IPM/CS is active against important MDR Gram-negative organisms.