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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

Competing Interests: Declaration of competing interest The authors declare no conflicts of interest related to this manuscript. The work described in this article was carried out independently, and no funding or financial support was received from external organizations that could influence the content of the manuscript.

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].

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).)

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.

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.

Amyotrophic lateral sclerosis (ALS) is the most frequent neurodegenerative disease of the motor system that affects upper and lower motor neurons, leading to progressive muscle weakness, spasticity, atrophy, and respiratory failure, with a life expectancy of 2-5 years after symptom onset. In addition to motor symptoms, patients with ALS have a multitude of nonmotor symptoms; in fact, it is currently considered a multisystem disease. The purpose of our narrative review is to evaluate the different types of pain, the correlation between pain and the disease's stages, the pain assessment tools in ALS patients, and the available therapies focusing above all on the benefits of cannabis use. Pain is an underestimated and undertreated symptom that, in the last few years, has received more attention from research because it has a strong impact on the quality of life of these patients. The prevalence of pain is between 15% and 85% of ALS patients, and the studies on the type and intensity of pain are controversial. The absence of pain assessment tools validated in the ALS population and the dissimilar study designs influence the knowledge of ALS pain and consequently the pharmacological therapy. Several studies suggest that ALS is associated with changes in the endocannabinoid system, and the use of cannabis could slow the disease progression due to its neuroprotective action and act on pain, spasticity, cramps, sialorrhea, and depression. Our research has shown high patients' satisfaction with the use of cannabis for the treatment of spasticity and related pain. However, especially due to the ethical problems and the lack of interest of pharmaceutical companies, further studies are needed to ensure the most appropriate care for ALS patients., Competing Interests: The authors declare no financial or other conflict of interests., (Copyright © 2024 Vincenzo Pota et al.)

Bickerstaff brainstem encephalitis (BBE) is a rare autoimmune disease characterized by the subacute onset of bilateral external ophthalmoplegia, ataxia, and decreased level of consciousness. BBE is part of a group of rare autoimmune diseases in children that can affect the nervous system at any level. The onset of neurological deficits is often sudden and nonspecific. The diagnosis is based on clinical findings and abnormal findings on cerebrospinal fluid (CSF), electroencephalography (EEG), electromyography (EMG), and magnetic resonance imaging (MRI). BBE is associated with the presence of the antiganglioside antibody, anti-GQ1b and anti-GM1. Intravenous immunoglobulin (IVIg) and plasma exchange are often used as treatments for these patients. We conducted a review on clinical presentation, diagnosis, treatment and outcome of reported cases of BBE. 74 cases are reported in the literature from the first cases described in 1951 to today. The prevalence is unknown while the incidence is higher in males. In 50% of cases, BBE occurs following respiratory or gastrointestinal tract infections. The most frequent initial symptoms were consciousness disturbance, headache, vomiting, diplopia, gait disturbance, dysarthria and fever. During illness course, almost all the patients developed consciousness disturbance, external ophthalmoplegia, and ataxia. Lumbar puncture showed pleocytosis or cytoalbuminological dissociation. Abnormal EEG and MRI studies revealed abnormalities in most cases. Anti-GQ1b antibodies were detected in more than half of the patients; anti-GM1 antibodies were detected in almost 40% of patients. Treatment guidelines are missing. In our analysis, steroids and IVIg were administered alone or in combination; as last option, plasmapheresis was used. BBE has a good prognosis and recovery in childhood is faster than in adulthood; 70% of patients reported no sequelae in our analysis. Future studies need to investigate pathogenesis and possible triggers, and therapeutic possibilities., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Giaccari, Mastria, Barbieri, De Maglio, Madaro, Paiano, Pace, Sansone, Pulito and Mascia.)

Background: Paravertebral block (PVB) is effective in controlling postoperative pain after video-assisted thoracoscopic surgery (VATS) lobectomy but is subject to a high rate of failure because of incorrect site of injection. We compared methylene blue PVB with thoracic epidural anesthesia (TEA) for postoperative pain after VATS lobectomy., Methods: We conducted a prospective randomized trial of patients undergoing VATS lobectomy; 120 patients were randomly assigned to the PVB or TEA group. The end points were postoperative pain at 1 hour, 12 hours, 24 hours, and 48 hours; time to perform TEA and PVB; opioid consumption; and postoperative outcomes., Results: PVB was associated with reduction of local anesthesia time ( P < .0001). In 2 cases, methylene blue showed that the block was not well performed; thus, it was repeated. No significant differences were found in postoperative pain, opioid consumption, and postoperative outcomes., Conclusions: PVB with methylene blue is as effective as TEA for controlling postoperative pain. Methylene blue use could help reduce PVB failure., (© 2024 The Authors.)

Abdominal surgical site infections (SSIs) are infections that occur after abdominal surgery. They can be superficial, involving the skin tissue only, or more profound, involving deeper skin tissues including organs and implanted materials. Currently, SSIs are large global health problem with an incidence that varies significantly depending on the United Nations' Human Development Index. The purpose of this review is to provide a practical update on the latest available literature on SSIs, focusing on causative pathogens and treatment with an overview of the ongoing studies of new therapeutic strategies., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to declare., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Sepsis is caused by dysregulated immune responses due to infection and still presents high mortality rate and limited efficacious therapies, apart from antibiotics. Recent evidence suggests that very high dose proton pump inhibitors might regulate major sepsis mediators' secretion by monocytes, which might attenuate excessive host reactions and improve clinical outcomes. This effect is obtained with doses which are approximately 50 times higher than prophylactic esomeprazole single daily administration and 17 times higher than the cumulative dose of a three day prophylaxis. We aim to perform a randomized trial to investigate if high dose esomeprazole reduces organ dysfunction in patients with sepsis or septic shock., Methods: This study, called PPI-SEPSIS, is a multicenter, randomized, double blind, placebo-controlled clinical trial on critically ill septic patients admitted to the emergency department or intensive care unit. A total of 300 patients will be randomized to receive high dose esomeprazole (80 mg bolus followed by 12 mg/h for 72 h and a second 80 mg bolus 12 h after the first one) or equivolume placebo (sodium chloride 0.9%), with 1:1 allocation. The primary endpoint of the study will be mean daily Sequential Organ Failure Assessment (SOFA) score over 10 days. Secondary outcomes will include antibiotic-free days, single organ failure severity, intensive care unit-free days at day 28, and mortality., Discussion: This trial aims to test the efficacy of high dose esomeprazole to reduce acute organ dysfunction in patients with septic shock., Trial Registration: This trial was registered on ClinicalTrials.gov with the trial identification NCT03452865 in March 2018., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

(1) Background: In the last few years, many randomized controlled trials (RCTs) have compared direct Macintosh laryngoscopy with McGrath videolaryngoscopy in order to assess the potential benefits of the latter; the results were sometimes controversial. (2) Methods: We conducted a comprehensive literature search to identify our articles according to inclusion and exclusion criteria: to be included, each study had to be a prospective randomized trial or comparison between the McGrath videolaryngoscope and the Macintosh laryngoscope in an adult population. We did not include manikin trials or studies involving double-lumen tubes. (3) Results: 10 studies met the inclusion criteria necessary. In total, 655 patients were intubated with the McGrath and 629 with the Macintosh. In total, 1268 of 1284 patients were successfully intubated, showing equivalent results for the two devices: 648 of 655 patients with the McGrath videolaryngoscope and 620 of 629 patients with the Macintosh laryngoscope. No differences were noted in terms of hemodynamic changes or the incidence of adverse events. (4) Conclusions: We can assert that the McGrath videolaryngoscope and Macintosh laryngoscope, even if with equivalent tracheal intubation results, supplement each other.

Background and Objectives : Postoperative non-invasive ventilation (NIV) has been proposed as an attractive strategy to reduce morbidity in obese subjects undergoing general anaesthesia. The increased body mass index (BMI) correlates with loss of perioperative functional residual capacity, expiratory reserve volume, and total lung capacity. The aim of the current study is to evaluate the efficacy of NIV in a post-anaesthesia care unit (PACU) in reducing post-extubation acute respiratory failure (ARF) after biliointestinal bypass (BIBP) in obese patients. Materials and Methods : A retrospective analysis was conducted from January 2019 to December 2020 to compare acute respiratory failure within the first 72 postoperative hours and oximetry values of obese patients who underwent BIBP after postoperative NIV adoption or conventional Venturi mask. Results : In total, 50 patients who received NIV postoperative protocol and 57 patients who received conventional Venturi mask ventilation were included in the study. After 120 min in PACU pH, pCO 2 , pO 2 , and SpO 2 were better in the NIV group vs. control group ( p < 0.001). Seventy-two hours postoperatively, one patient (2%) in the NIV group vs. seven patients (12.2%) in the control group developed acute respiratory failure. Therefore, conventional Venturi mask ventilation resulted in being significantly associated ( p < 0.05) with postoperative ARF with an RR of 0.51 (IC 0.27-0.96). Conclusions : After bariatric surgery, short-term NIV during PACU observation promotes a more rapid recovery of postoperative lung function and oxygenation in obese patients, reducing the necessity for critical care in the days following surgery. Therefore, as day-case surgery becomes more advocated even for morbid obesity, it might be considered a necessary procedure.

(1) Background: Osteoarthritis (OA) is a debilitating joint disease. The are several therapies available for OA. According to current knowledge, the combination of Platelet-Rich Plasma (PRP) and Pulsed Radiofrequency (PRF) can be applied in the treatment of pain of nociceptive origin due to peripheral tissue damage. (2) Methods: We performed a narrative review identifying the articles by searching electronic databases. A retrospective analysis of patients with OA treated with PRF and PRP in "Vito Fazzi" Hospital (Lecce, Italy) was performed. (3) Results: A total of four publications on the use of PRP and PRF in degenerative joint arthritis were included in our review. In our experience, two patients with OA were treated with PRP and PRF after unsuccessful conservative treatment. Patient pain score, daily activity ability, active range of activity, and muscle strength improved after treatment. Patients reported a higher level of satisfaction. No major adverse events were reported. (4) Conclusions: The goal of the combined application of the two treatments is to make full use of the analgesic effect of PRF and the repairing effect of PRP. At present, the therapeutic potential of PRP and PRF in OA remains unmet.

Spiranthes Rich. (Orchidaceae) is a commonly encountered but systematically and nomenclaturally challenging component of the North American orchid flora. Here, the evolutionary history and hybrid origin of the recently described S.sheviakii Hough and Young are critically examined. The available molecular data unambiguously support a hybrid origin of S.cernua (L.) Rich. × S.ochroleuca (Rydb.) Rydb. for S.sheviakii , the same parentage as the priority name S.×kapnosperia M.C. Pace. As hybrid formulas can have only one correct name, S.sheviakii is a synonym of S.×kapnosperia. It is likely that S.×kapnosperia evolved independently at least twice in at least two widely disjunct locations., (Matthew C. Pace.)

Intensive care units (ICU) for various reasons, including the increasing age of admitted patients, comorbidities, and increasingly complex surgical procedures ( e.g., transplants), have become "the epicenter" of nosocomial infections, these are characterized by the presence of multidrug-resistant organisms (MDROs) as the cause of infection. Therefore, the perfect match of fragile patients and MDROs, as the cause of infection, makes ICU mortality very high. Furthermore, carbapenems were considered for years as last-resort antibiotics for the treatment of infections caused by MDROs; unfortunately, nowadays carbapenem resistance, mainly among Gram-negative pathogens, is a matter of the highest concern for worldwide public health. This comprehensive review aims to outline the problem from the intensivist's perspective, focusing on the new definition and epidemiology of the most common carbapenem-resistant MDROs ( Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacterales ) to emphasize the importance of the problem that must be permeating clinicians dealing with these diseases., Competing Interests: Conflict-of-interest statement: The authors have nothing to disclose., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

For thousands of years, medicinal cannabis has been used for pain treatment, but its use for pain management is still controversial. Meta-analysis of the literature has shown contrasting results on the addition of cannabinoids to opioids compared with placebo/other active agents to reduce pain. Clinical studies are mainly focused on medicinal cannabis use in chronic pain management, for which the analgesic effect has been proven in many studies. This review focuses on the potential use of medical cannabis for acute pain management in preclinical studies, studies on healthy subjects and the few pioneering studies in the clinical setting., Competing Interests: Conflict-of-interest statement: All authors declare no conflicts of interest related to this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Duchenne Muscular Dystrophy (DMD) is a very severe X-linked dystrophinopathy. It is due to a mutation in the DMD gene and causes muscular degeneration in conjunction with several secondary co-morbidities, such cardiomyopathy and respiratory failure. DMD is characterized by a chronic inflammatory state, and corticosteroids represent the main therapy for these patients. To contradict drug-related side effects, there is need for novel and more safe therapeutic strategies. Macrophages are immune cells stringently involved in both physiological and pathological inflammatory processes. They express the CB2 receptor, one of the main elements of the endocannabinoid system, and have been proposed as an anti-inflammatory target in several inflammatory and immune diseases. We observed a lower expression of the CB2 receptor in DMD-associated macrophages, hypothesizing its involvement in the pathogenesis of this pathology. Therefore, we analyzed the effect of JWH-133, a CB2 receptor selective agonist, on DMD-associated primary macrophages. Our study describes the beneficial effect of JWH-133 in counteracting inflammation by inhibiting pro-inflammatory cytokines release and by directing macrophages' phenotype toward the M2 anti-inflammatory one., Competing Interests: The authors declare no conflict of interest.

Background: We evaluated the safety and feasibility of one-lung ventilation in obese patients undergoing thoracoscopic lobectomy and whether obesity affected peri- and postoperative outcomes., Methods: This was a retrospective single center study including consecutive patients undergoing thoracoscopic lobectomy between October 2019 and February 2022. Obese patients were statistically compared to a control group to evaluate any differences in relation to one-lung ventilation and peri- and postoperative outcomes., Results: Our study population included 111 patients; of these, 26 (23%) were included in the obese group, while 85 (77%) were included within the nonobese group. To obtain one-lung ventilation in nonobese patients, a double-lumen tube was more frequently used than a single-lumen tube with bronchial blocker (61% vs. 39%; p = 0.02), while in obese patients a single-lumen tube with bronchial blocker was used more than a double-lumen tube (81% vs. 19%, p = 0.001). Intergroup comparison showed that a double-lumen tube was the preferred method in nonobese patients, while a single-lumen tube with bronchial blockers was the strategy of choice in obese patients (p = 0.0002). Intubation time was longer in the obese group than in the nonobese group (94.0 ± 6.1 vs. 85.0 ± 7.0 s; p = 0.0004) and failure rate of first attempt at intubation was higher in the obese group (23% vs. 5%; p = 0.01). Obesity was not associated with increased intra-, peri- and postoperative complications and/or mortality., Conclusions: One-lung ventilation is a feasible and safe procedure also in obese patients and obesity did not negatively affect peri- and postoperative outcomes after lung resection., (© 2022 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: Dexmedetomidine is a highly selective alpha-2 receptor agonist without any effect on the GABA receptor. It provides an excellent sedative and analgesic profile with few side effects. We report our experience with dexmedetomidine use during orthopaedic surgery under locoregional anaesthesia to ensure adequate sedation and optimal postoperative pain control., Methods: In this retrospective analysis, we included 128 patients who underwent orthopaedic surgery between January 2019 and December 2021. All patients received the same local anaesthetic dose of 20 ml of ropivacaine 0.375% + mepivacaine 0.5% for axillary and supraclavicular block and 35 ml of ropivacaine 0.375% + mepivacaine 0.5% for triple nerve block (femoral, obturator and sciatic nerve). The cohort was divided into two groups based on sedation drugs used during surgery (dexmedetomidine, or group D, vs midazolam, or group M). All patients received postoperative 24-h analgesia consisting of 60 mg of ketorolac, 200 mg of tramadol and 4 mg of ondansetron. The primary outcome measured how many patients in the two groups required an analgesic rescue dose of pethidine and the time to first pethidine administration. To reduce confounding, we included patients in two groups with non-statistically different demo-anamnestic parameters and who received the same dose of intraoperative local anaesthetic and postoperative analgesia., Results: The number of patients in group D who did not require a rescue dose of analgesia was significantly greater than in group M (49 vs 11, p < 0.001). Time-to-first postoperative opioid administration did not show a fundamental difference between the two groups under examination (523.75 ± 131.55 min vs 564 ± 117.84 min). Total opioid consumption was higher in the M group than in the D group (3529.8 ± 30.36 μg vs 1864.8 ± 31.59 μg, p 0.075), with a mean opioid consumption significantly higher in the M group than in the D group (26.26 ± 42.8 μg vs 69.21 ± 46.1 μg, p < 0.001): D group received 62.06% less opioid than M group., Conclusions: The continuous infusion of dexmedetomidine during orthopaedic surgery performed under locoregional anaesthesia has been shown to increase the analgesic effect of local anaesthetics and reduce the consumption of major opioids in the postoperative period. Dexmedetomidine offers a unique ability to supply sedation and analgesia without respiratory depression, having a wide safety margin and an excellent sedative capacity. It does not increase the rate of postoperative complications., (© 2022. The Author(s).)

Plazomicin is a next-generation semisynthetic aminoglycoside antibiotic that can be used to treat infections by multi-resistant bacteria. It is effective against many bacteria-producing carbapenemases or other specific hydrolases. This scoping review aims to define the role acquired by plazomicin from its approval by the FDA (US Food and Drug Administration) in 2018 to the present day. Furthermore, we aim to provide a base for a future meta-analysis. This project was conducted following the recommendations presented in the PRISMA extension for scoping reviews and the JBI Manual for Evidence Synthesis. Among 901 potentially engaging citations, 345 duplicates were removed, and only 81 articles were selected for the analysis. According to the data analysis, plazomicin has been used to treat urinary tract infections, bloodstream infections, and ventilation-associated pneumonia. The pathogens killed included multi-resistant E. coli , K. pneumoniae , A. baumannii , P. aeruginosa , and S. aureus . Plazomicin can be a manageable, valid non-beta-lactam alternative for treating multi-resistant bacteria infections.

(1) Background: The aim of this study was to assess the clinical and microbiological characteristics of multidrug-resistant infections in a neuromuscular semi-intensive/sub-intensive care unit; (2) Methods: Retrospective analysis on data from 18 patients with NMD with proven MDRO/XDRO colonisation/infection from August 2021 to March 2022 was carried out; (3) Results: Ten patients were males (55.6%), with a median age of 54 years, and there were fourteen patients (77.8%) with amyotrophic lateral sclerosis. All patients had at least one invasive device. Ten (55.6%) patients developed MDRO/XDRO infection (with a median time of 24 days) while six (33.3%) were colonised. The Charlson comorbidity index was >2 in both groups but higher in the infected compared with the colonised (4.5 vs. 3). Infected patients were mostly females (seven patients) with a median age of 62 years. The most common pathogens were Acinetobacter baumannii and Pseudomonas aeruginosa, infecting four (28.6%) patients each. Of eighteen infectious episodes, nine were pneumonia (hospital-acquired in seven cases). Colistin was the most commonly active antibiotic while carbapenems were largely inactive. Eradication of infection occurred in seven infectious episodes (38.9%). None of those with infection died; (4) Conclusions: MDRO/XDRO infections are common in patients with neuromuscular diseases, with carbapenem-resistant non-fermenting Gram-negative bacilli prevailing. These infections were numerically associated with the female sex, greater age, and comorbidities. Both eradication and infection-related mortality appeared low. We highlight the importance of infection prevention in this vulnerable population.

This comprehensive review of the recently published literature offers an overview of a very topical and complex healthcare problem: secondary peritonitis from multidrug-resistant pathogens, especially carbapenem-resistant Enterobacterales (CRE). Spontaneous secondary peritonitis and postsurgical secondary peritonitis are among the major causes of community- and healthcare- acquired sepsis, respectively. A large number of patients enter ICUs with a diagnosis of secondary peritonitis, and a high number of them reveal infection by CRE, P. aeruginosa or A. baumannii . For this reason, we conceived the idea to create a synthetic report on this topic including updated epidemiology data, a description of CRE resistance patterns, current strategies of antimicrobial treatment, and future perspectives. From this update it is clear that antimicrobial stewardship and precision medicine are becoming essential to fight the emergence of antimicrobial resistance and that even if there are new drugs effective against CRE causing secondary peritonitis, these drugs have to be used carefully especially in empirical therapy.

Introduction: Chemotherapy-induced peripheral neuropathy (CIPN) is a common complication due to treatment with many commonly used anti-cancer agents. CIPN is a mainly sensory neuropathy that can be characterized by the appearance of motor and autonomic alterations. Clinicians may offer duloxetine (DLX) for patients with cancer experiencing CIPN. Our aim was to assess the non-inferiority of the analgesic effect and safety of tapentadol (TP) alone compared to duloxetine plus tapentadol administered to patients with CIPN., Methods: A total of 114 patients were enrolled in the study and randomized to receive tapentadol in a dosage of 50 to 500 mg/day (n = 56) or tapentadol plus duloxetine in a dosage of 60 to 120 mg/day (n = 58) for a period of 4 weeks. We evaluated the analgesia efficacy, defined as a decrease in pain on the NRS between the first administration and 28 days later. Secondary endpoints included analgesia efficacy at 28 and 42 days, defined by a decrease in DN4 and LEPs, decrease in quality of life, and the incidence of any serious or non-serious adverse events after the first administration., Results: In this randomized, double-blind trial comparing TP and TP plus DLX for CIPN management, TP was feasible and non-inferior to the association with DLX as far as the reduction of pain after chemotherapy at 28 days is concerned. Scores on other rating scales evaluating the quality of life, anxiety and depression, and the characteristics of pain revealed similar improvements associated with tapentadol versus duloxetine at these time points., Conclusion: The use of TP is a safe and effective analgesic therapy in patients with CIPN. Positive effects of TP were noted on the patients' quality-of-life assessments.

(1) Background: healthcare-associated infections are one of the most frequent adverse events in healthcare delivery worldwide. Several antibiotic resistance mechanisms have been developed, including those to carbapenemase. Cefiderocol (CFD) is a novel siderophore cephalosporin designed to treat carbapenem-resistant bacteria. (2) Methods: we performed a systematic review of all cases reported in the literature to outline the existing evidence. We evaluated real-world evidence studies of CFD in the treatment of carbapenem-resistant (CR) bacteria. (3) Results: a total of 19 publications treating cases of infection by CR bacteria were included. The three most frequent CR pathogens were Acinetobacter baumannii , Pseudomonas aeruginosa , and Klebsiella pneumoniae . A regimen of 2 g every 8 h was most frequently adopted for CFD with a mean treatment duration of 25.6 days. CFD was generally well tolerated, with fewer side effects. The success rate of CFD therapy was satisfactory and almost 70% of patients showed clinical recovery; of these, nearly half showed negative blood cultures and infection-free status. (4) Conclusions: This review indicates that CFD is active against important GN organisms including Enterobacteriaceae, P. aeruginosa, and A. baumannii . CFD seems to have a safe profile.

In patients with extrinsic tracheal stenosis caused by a mediastinal mass, an airway stent is a palliative measure to relieve airway obstruction. However, the self-expanding force of the stent may be insufficient to force a rigid stenosis. Our goal was to report a simple strategy to indirectly estimate the rigidity of the stenosis and predict airway patency after inserting the stent. Before the procedure, the inspiratory and expiratory flows and their ratio were evaluated under spontaneous breathing and after positive pressure ventilation generated by a facial mask. In patients with stenosis successfully treated with a stent (n = 11), we found significant changes in expiratory (2.3 ± 0.7 vs 2.8 ± 0.7; p = 0.03) and inspiratory (1.5 ± 0.6 vs 2.5 ± 0.9; p = 0.001) flows and a reduction of their ratio (1.4 ± 0.3 vs 1.1 ± 0.2; p = 0.01) whereas no significant changes were observed in patients (n = 2) whose stent failed to force the stenosis. In these cases, a tracheostomy was performed to assure ventilation. Our simple strategy may help physicians predict airway patency after stenting or plan alternative treatments in patients with rigid stenosis difficult to force by stenting., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

All critically ill adult patients in intensive care units (ICU) typically experience pain. Critically ill adults suffer pain of different intensities. It depends on individual characteristics, specific procedural interventions, and underlying diseases. Inadequate management of acute pain is a risk factor for the emergence of chronic pain, where the incidence is up to 33% into the ICU survivor population. For the management of pain, agitation, and delirium, several coexisting clinical practice guidelines have been published. The first problem is that the patient recovered in intensive care unit should not be able to communicate its pain state. Opioids are the analgesic drugs of choice in critically ill patients with non-neuropathic pain. All intravenous opioids have the same effects, respecting the equianalgesic table. Observational research has shown that opioids are the main analgesic treatment in over 80% of mechanically ventilated patients. It is interesting that opioid consumption in an ICU and the memory of painful experience are linked to the development of post-traumatic stress disorder after ICU discharge. In order to reduce the side effects and maintain analgesia, it is useful to associate adjuvant medications with opioids. An opportunity to improve patients' experience in an ICU is to manage pain through multimodal approaches., (© 2022. The Author(s).)

Pain following brain surgery can compromise the result of surgery. Several pharmacological interventions have been used to prevent postoperative pain in adults undergoing brain surgery. Pain following craniotomy is considered to be moderate to severe during the first two post-operative days. Opioids have been historically the mainstay and are the current prominent strategy for pain treatment. They produce analgesia but may alter respiratory, cardiovascular, gastrointestinal, and neuroendocrine functions. All these side effects may affect the normal postoperative course of craniotomy by affecting neurological function and increasing intracranial pressure. Therefore, their use in neurosurgery is limited, and opioids are used in case of strict necessity or as rescue medication. In addition to opioids, drugs with differing mechanisms of actions target pain pathways, resulting in additive and/or synergistic effects. Some of these agents include acetaminophen/non-steroidal anti-inflammatory drugs (NSAIDs), alpha-2 agonists, NMDA receptor antagonists, gabapentinoids, and local anesthesia techniques. Multimodal analgesia should be a balance between adequate analgesia and less drug-induced sedation, respiratory depression, hypercapnia, nausea, and vomiting, which may increase intracranial pressure. Non-opioid analgesics can be an useful pharmacological alternative in multimodal regimes to manage post-craniotomy pain. This narrative review aims to outline the current clinical evidence of multimodal analgesia for post craniotomy pain control.

There has been an increase in surgical interventions in frailer elderly with concomitant chronic diseases. The purpose of this paper was to evaluate the impact of aging and comorbidities on outcomes in patients who underwent surgery for the treatment of colorectal cancer (CRC) in Veneto Region (Northeastern Italy). This is a retrospective cohort study in patients ≥ 40 years who underwent elective or urgent CRC surgical resection between January 2013 and December 2015. Independent variables included: age, sex, and comorbidities. We analyzed variables associated with the surgical procedure, such as stoma creation, hospitalization during the year before the index surgery, the surgical approach used, the American Society of Anesthesiologists (ASA) score, and the Charlson Comorbidity Index score. Eight thousand four hundred and forty-seven patients with CRC underwent surgical resection. Patient age affected both pre- and post-resection LOS as well as the overall survival (OS); however, it did not affect the 30-day readmission and reoperation rates. Multivariate analysis showed that age represented a risk factor for longer preoperative and postoperative LOS as well as for 30-day and 365-day mortality, but it was not associated with an increased risk of 30-day reoperation and 30-day readmission. Chronic Heart Failure increased the 30-day mortality risk by four times, the preoperative LOS by 51%, and the postoperative LOS by 33%. Chronic renal failure was associated with a 74% higher 30-day readmission rate. Advanced age and comorbidities require a careful preoperative evaluation and appropriate perioperative management to improve surgical outcomes in older patients undergoing elective or urgent CRC resection., (© 2021. The Author(s).)

Carbapenem antibiotics are the most effective antimicrobials for the treatment of infections caused by the most resistant bacteria. They belong to the category of β-lactams that include the penicillins, cephalosporins, monobactams and carbapenems. This class of antimicrobials has a broader spectrum of activity than most other beta-lactams antibiotics and are the most effective against Gram-positive and Gram-negative bacteria. All β-lactams antibiotics have a similar molecular structure: the carbapenems together with the β-lactams. This combination gives an extraordinary stability to the molecule against the enzymes inactivating the β-lactams. They are safe to use and therefore widespread use in many countries has given rise to carbapenem resistance which is a major global public health problem. The carbapenem resistance in some species is intrinsic and consists of the capacity to resist the action of antibiotics with several mechanisms: for the absence of a specific target, or an intrinsic difference in the composition of cytoplasmatic membrane or the inability to cross the outer membrane. In addition to intrinsic resistance, bacteria can develop resistance to antibiotics with several mechanisms that can be gathered in three main groups. The first group includes antibiotics with poor penetration into the outer membrane of bacterium or antibiotic efflux. The second includes bacteria that modify the target of the antibiotics through genetic mutations or post-translational modification of the target. The third includes bacteria that act with enzyme-catalyzed modification and this is due to the production of beta-lactamases, that are able to inactivate carbapenems and so called carbapenemases. In this review, we focus on the mode of action of carbapenem and the mechanisms of carbapenem resistance.