The Omics Complexity in Sepsis: The Limits of the Personalized Medicine Approach.

Sepsis is one of the most common causes of morbidity and mortality worldwide. Despite the remarkable advances in modern medicine throughout the last century, the mortality rates associated with sepsis have remained significantly elevated, both in high- and low-income countries. The main difficulty in the diagnosis and treatment of septic patients is the tremendous heterogeneity of this condition. The vast heterogeneity that characterizes sepsis ranges from the clinical presentation to the biological aspects of the disease. Evidence-based medicine approaches sepsis as a homogenous syndrome and does not consider the individual discrepancies between septic patients. This approach may contribute to the poor outcomes of septic patients. In recent years, personalized medicine has gained significant interest. This novel form of medicine underlines the importance of understanding the genetic, epigenetic, and molecular basis of a disease in order to provide a more tailored approach for the patient. The study of "omics", such as cytomics, genomics, epigenomics, transcriptomics, proteomics, and metabolomics, provides a deeper comprehension of the complex interactions between the host, the disease, and the environment. The aim of this review is to summarize the potential role of a personalized approach in sepsis management, considering the interactions between various "omics".

Biodetoxification Using Intravenous Lipid Emulsion, a Rescue Therapy in Life-Threatening Quetiapine and Venlafaxine Poisoning: A Case Report.

The administration of intravenous lipid emulsion (ILE) is a proven antidote used to reverse local anesthetic-related systemic toxicity. Although the capacity of ILE to generate blood tissue partitioning of lipophilic drugs has been previously demonstrated, a clear recommendation for its use as an antidote for other lipophilic drugs is still under debate. Venlafaxine (an antidepressant acting as a serotonin-norepinephrine reuptake inhibitor (SNRI)) and quetiapine (a second-generation atypical antipsychotic) are widely used in the treatment of psychotic disorders. Both are lipophilic drugs known to induce cardiotoxicity and central nervous depression. We report the case of a 33-year-old man with a medical history of schizoaffective disorder who was admitted to the emergency department (ED) after having been found unconscious due to a voluntary ingestion of 12 g of quetiapine and 4.5 g of venlafaxine. Initial assessment revealed a cardiorespiratory stable patient but unresponsive with a GCS of 4 (M2 E1 V1). In the ED, he was intubated, and gastric lavage was performed. Immediately after the admission to the intensive care unit (ICU), his condition quickly deteriorated, developing cardiovascular collapse refractory to crystalloids and vasopressor infusion. Junctional bradycardia occurred, followed by spontaneous conversion to sinus rhythm. Subsequently, frequent ventricular extrasystoles, as well as patterns of bigeminy, trigeminy, and even episodes of non-sustained ventricular tachycardia, occurred. Additionally, generalized tonic-clonic seizures were observed. Alongside supportive therapy, antiarrhythmic and anticonvulsant therapy, intravenous lipid emulsion bolus, and continuous infusion were administered. His condition progressively improved over the following hours, and 24 h later, he was tapered off the vasopressor. On day 2, the patient repeated the cardiovascular collapse and a second dose of ILE was administered. Over the next few days, the patient's clinical condition improved, and he was successfully weaned off ventilator and vasopressor support. ILE has the potential to become a form of rescue therapy in cases of severe lipophilic drug poisoning and should be considered a viable treatment for severe cardiovascular instability that is refractory to supportive therapy.

Postoperative Cognitive Impairment and Pain Perception after Abdominal Surgery-Could Immersive Virtual Reality Bring More? A Clinical Approach.

Background and Objectives: Impaired cognition and pain after surgery contribute to prolonged hospital stays and increased mortality rates. Thus, the development of preemptive algorithms for reducing their impact should be prioritized. The main objectives of the present study were to evaluate the efficiency of using virtual reality (VR) to treat postoperative cognitive decline and pain perception. Materials and Methods: The study was a prospective, monocentric, clinical study that included 51 patients who have undergone major abdominal surgery. The patients were divided into two groups: Control (n = 25) and VR (n = 26). The VR sessions consisted of 5-8 min exposure at 24-48 h after surgery. We considered the outcome variables, the mini-mental state examination, and visual analogue scale at 24-48 h after surgery. The dependent variables were age, social status, educational level, and duration of surgery. Results: We did not observe any differences in postoperative cognition deficit with regard to VR. The VR, however, successfully reduced postoperative pain intensity. Moreover, the patients' age, surgery duration, level of education, and social status influenced the MMSE score at 24-48 h after surgery. Conclusions: Even if using VR does not alleviate short-term postoperative cognitive impairments, it could affect pain perception. Further studies are needed to support the use of VR in perioperative contexts.

Acute Promyelocytic Leukemia and Severe Differentiation Syndrome in Pregnancy-A Management Challenge.

Acute promyelocytic leukemia (APL) is generated by the PML-RARA fusion gene. In patients suffering from APL, the early diagnosis and treatment are essential in the successful management. We reported a case of a 27-year-old 17th-week pregnant patient diagnosed with APL. After an extensive hematological diagnostic panel, the acute promyelocytic leukemia was confirmed, and the patient received all-trans retinoic acid (ATRA), idarubicin (IDA), and dexamethasone, following national guidelines. Due to ATRA-related differentiation syndrome, the therapy was adjusted, and hydroxycarbamide was added with a good outcome. The patient was admitted to the ICU secondary to hypoxemic respiratory failure on the 2nd day after hospital admission. Our patient received an individualized drug combination, adjusted by the clinical response. Furthermore, the drugs used in APL treatment are all teratogenic. Despite various major complications, including severe acute respiratory distress syndrome (ARDS), which needed mechanical ventilation; ICU-acquired myopathy; and spontaneous abortion, the patient had a good outcome and was transferred from the ICU after a total stay of 40 days. APL during pregnancy is a rare entity of intermediate-risk APL. Our study emphasized the need for individualized therapy in a rare case of a pregnant woman diagnosed with a potentially fatal hematologic disease.

Orthotopic Liver Transplantation of a SARS-CoV-2 Negative Recipient from a Positive Donor: The Border between Uncertainty and Necessity in a Pandemic Era- Case Report and Overview of the Literature.

(1) Introduction: Liver transplantation represents the gold-standard therapy in eligible patients with acute liver failure or end-stage liver disease. The COVID-19 pandemic dramatically affected the transplantation landscape by reducing patients' addressability to specialized healthcare facilities. Since evidence-based acceptance guidelines for non-lung solid organ transplantation from SARS-CoV-2 positive donors are lacking, and the risk of bloodstream-related transmission of the disease is debatable, liver transplantation from SARS-CoV-2 positive donors could be lifesaving, even if long-term interactions are unpredictable. The aim of this case report is to highlight the relevance of performing liver transplantation from SARS-CoV-2 positive donors to negative recipients by emphasizing the perioperative care and short-term outcome. (2) Case presentation: A 20-year-old female patient underwent orthotropic liver transplantation for Child-Pugh C liver cirrhosis secondary to overlap syndrome, from a SARS-CoV-2 positive brain death donor. The patient was not infected nor vaccinated against SARS-CoV-2, and the titer of neutralizing antibodies against the spike protein was negative. The liver transplantation was performed with no significant complications. As immunosuppression therapy, the patient received 20 mg basiliximab (Novartis Farmacéutica S.A., Barcelona, Spain) and 500 mg methylprednisolone (Pfizer Manufacturing Belgium N.V, Puurs, Belgium) intraoperatively. Considering the risk of non-aerogene-related SARS-CoV-2 reactivation syndrome, the patient received remdesivir 200 mg (Gilead Sciences Ireland UC, Carrigtohill County Cork, Ireland) in the neo-hepatic stage, which was continued with 100 mg/day for 5 days. The postoperative immunosuppression therapy consisted of tacrolimus (Astellas Ireland Co., Ltd., Killorglin, County Kerry, Ireland) and mycophenolate mofetil (Roche România S.R.L, Bucharest, Romania) according to the local protocol. Despite the persistent negative PCR results for SARS-CoV-2 in the upper airway tract, the blood titer of neutralizing antibodies turned out positive on postoperative day 7. The patient had a favorable outcome, and she was discharged from the ICU facility seven days later. (3) Conclusions: We illustrated a case of liver transplantation of a SARS-CoV-2 negative recipient, whose donor was SARS-CoV-2 positive, performed in a tertiary, university-affiliated national center of liver surgery, with a good outcome, in order to raise the medical community awareness on the acceptance limits in the case of COVID-19 incompatibility for non-lung solid organs transplantation procedures.

The Management of Postoperative Cognitive Dysfunction in Cirrhotic Patients: An Overview of the Literature.

Background and objectives: Postoperative cognitive dysfunction (POCD) represents a decreased cognitive performance in patients undergoing general anesthesia for major surgery. Since liver cirrhosis is associated with high mortality and morbidity rates, cirrhotic patients also assemble many risk factors for POCD. Therefore, preserving cognition after major surgery is a priority, especially in this group of patients. The purpose of this review is to summarize the current knowledge regarding the effectiveness of perioperative therapeutic strategies in terms of cognitive dysfunction reduction. Data Collection: Using medical search engines such as PubMed, Google Scholar, and Cochrane library, we analyzed articles on topics such as: POCD, perioperative management in patients with cirrhosis, hepatic encephalopathy, general anesthesia in patients with liver cirrhosis, depth of anesthesia, virtual reality in perioperative settings. We included 115 relevant original articles, reviews and meta-analyses, and other article types such as case reports, guidelines, editorials, and medical books. Results: According to the reviewed literature, the predictive capacity of the common clinical tools used to quantify cognitive dysfunction in cirrhotic settings is reduced in perioperative settings; however, novel neuropsychological tools could manage to better identify the subclinical forms of perioperative cognitive impairments in cirrhotic patients. Moreover, patients with preoperative hepatic encephalopathy could benefit from specific preventive strategies aimed to reduce the risk of further neurocognitive deterioration. Intraoperatively, the adequate monitoring of the anesthesia depth, appropriate anesthetics use, and an opioid-sparing technique have shown favorable results in terms of POCD. Early recovery after surgery (ERAS) protocols should be implemented in the postoperative setting. Other pharmacological strategies provided conflicting results in reducing POCD in cirrhotic patients. Conclusions: The perioperative management of the cognitive function of cirrhotic patients is challenging for anesthesia providers, with specific and targeted therapies for POCD still sparse. Therefore, the implementation of preventive strategies appears to remain the optimal attitude. Further research is needed for a better understanding of POCD, especially in cirrhotic patients.

Perioperative Care in Patients with Chronic Liver Disease: What Can We Do More?

Chronic liver diseases represent a prevalent pathology that exerts considerable pressure on healthcare providers and various healthcare systems worldwide [...].

Melatonin-Microbiome Two-Sided Interaction in Dysbiosis-Associated Conditions.

Melatonin is a pineal indolamine, allegedly known as a circadian rhythm regulator, and an antioxidative and immunomodulatory molecule. In both experimental and clinical trials, melatonin has been shown to have positive effects in various pathologies, as a modulator of important biochemical pathways including inflammation, oxidative stress, cell injury, apoptosis, and energy metabolism. The gut represents one of melatonin's most abundant extra pineal sources, with a 400-times-higher concentration than the pineal gland. The importance of the gut microbial community-namely, the gut microbiota, in multiple critical functions of the organism- has been extensively studied throughout time, and its imbalance has been associated with a variety of human pathologies. Recent studies highlight a possible gut microbiota-modulating role of melatonin, with possible implications for the treatment of these pathologies. Consequently, melatonin might prove to be a valuable and versatile therapeutic agent, as it is well known to elicit positive functions on the microbiota in many dysbiosis-associated conditions, such as inflammatory bowel disease, chronodisruption-induced dysbiosis, obesity, and neuropsychiatric disorders. This review intends to lay the basis for a deeper comprehension of melatonin, gut microbiota, and host-health subtle interactions.

Novel Biomarkers Predictive of Diabetic Charcot Foot-An Overview of the Literature.

Background: Although Charcot diabetic foot (CDF) is a frequent complication of diabetic neuropathy, less is known about the possibility of its early prevention. Methods: A review of the original articles published in English, using the "biomarkers AND Charcot's foot" criterion, resulted in 33 articles from the PubMed database and seven articles from the Web of Science database. The five duplicates were eliminated, and two independent reviewers selected the most relevant articles, leaving a total of 21 articles. Results: The biomarkers identified are exhaustively described, related to the system of advanced glycation end products (AGEs) and their soluble receptors (sRAGE), inflammatory cascade, osteoclastogenesis, and, respectively, osteoblastic activity. Conclusions: This article highlights the importance of potential early identifiable biomarkers that can lead to microstructural changes in the affected bones.

The Cumulative Detrimental Effect of COVID-19 Pneumonia in a Patient with Myasthenic Crisis: A Case Report and Overview of the Literature.

BACKGROUND: As the COVID-19 pandemic reached its peak, it became unavoidable that patients with other risk factors for severe pulmonary impairment (such as neuromuscular illnesses) would become afflicted. While the subject of myasthenic crisis secondary to COVID-19 pneumonia represents an interesting topic in the literature, we could not find consistent data that include, as a novel therapeutic approach, both intravenous immunoglobulin and plasma exchange therapy for the treatment of these two concurrent diseases. CASE SUMMARY: A 69-year-old man with known seropositive generalized myasthenia gravis, hypertension, ischaemic heart disease, NYHA class II-III heart failure, cerebrovascular disease, and recurrent urinary tract infections, was admitted to the ICU for mixed acute respiratory failure, elevated serum lactate and liver function enzymes, and severe thrombocytopenia. A SARS-CoV-2 PCR test was positive, despite a previous COVID-19 pneumonia episode, 10 months prior to the current one. The patient had a recent ICU admission for a myasthenic crisis, which required non-invasive mechanical ventilation and intravenous immunoglobulin therapy. He received supportive therapy, as well as etiological (intravenous remdesivir, plasmapheresis and intravenous dexamethasone). Fifteen days after admission, the patient was transferred to the neurological ward, whence he left 20 days later, with no apparent sequelae. CONCLUSIONS: Subsequent intravenous immunoglobulins and plasma exchange therapy appear to be effective and safe in patients with simultaneous acute myasthenic episode and COVID-19 pneumonia.

Does a Single Exposure to General Anesthesia Have a Cumulative Effect on the Developing Brain after Mild Perinatal Asphyxia?

BACKGROUND: General anesthesia (GA) in pediatric patients represents a clinical routine. Factors such as increased birth age and maternal chronic conditions cause more infants to experience hypoxic-ischemic encephalopathy, an additional risk for anesthesia. AIM: This study evaluates the effect of one sevoflurane-induced GA episode on the immature brain previously exposed to perinatal asphyxia (PA). METHODS: Postnatal day 6 (PND6) Wistar rats were exposed to a 90-min episode of normoxia/PA and at PND15 to a 120-min episode of normoxia/GA. Four groups were analyzed: Control (C), PA, GA, and PA-GA. Post-exposures, fifteen pups/group were sacrificed and the hippocampi were isolated to assess S-100B and IL-1B protein levels, using ELISA. At maturity, the behavior was assessed by: forced swimming test (FST), and novel object recognition test. RESULTS: Hippocampal S-100B level was increased in PA, GA, and PA-GA groups, while IL-1B was increased in PA, but decreased in PA-GA. The immobility time was increased in PA and PA-GA, in FST. CONCLUSIONS: Both PA and GA contribute to glial activation, however with no cumulative effect. Moreover, PA reduces the rats' mobility, irrespective of GA exposure, while memory evaluated by the novel object recognition test was not influenced.

Near-Infrared Spectroscopy Usefulness in Validation of Hyperventilation Test.

Background: The hyperventilation test is used in clinical practice for diagnosis and therapeutic purposes; however, in the absence of a standardized protocol, the procedure varies significantly, predisposing tested subjects to risks such as cerebral hypoxia and ischemia. Near-infrared spectroscopy (NIRS), a noninvasive technique performed for cerebral oximetry monitoring, was used in the present study to identify the minimum decrease in the end-tidal CO2 (ETCO2) during hyperventilation necessary to induce changes on NIRS. Materials and Methods: We recruited 46 volunteers with no preexisting medical conditions. Each subject was asked to breathe at a baseline rate (8−14 breaths/min) for 2 min and then to hyperventilate at a double respiratory rate for the next 4 min. The parameters recorded during the procedure were the regional cerebral oxyhemoglobin and deoxyhemoglobin concentrations via NIRS, ETCO2, and the respiratory rate. Results: During hyperventilation, ETCO2 values dropped (31.4 ± 12.2%) vs. baseline in all subjects. Changes in cerebral oximetry were observed only in those subjects (n = 30) who registered a decrease (%) in ETCO2 of 37.58 ± 10.34%, but not in the subjects (n = 16) for which the decrease in ETCO2 was 20.31 ± 5.6%. According to AUC-ROC analysis, a cutoff value of ETCO2 decrease >26% was found to predict changes in oximetry (AUC-ROC = 0.93, p < 0.0001). Seven subjects reported symptoms, such as dizziness, vertigo, and numbness, throughout the procedure. Conclusions: The rise in the respiratory rate alone cannot effectively predict the occurrence of a cerebral vasoconstrictor response induced by hyperventilation, and synchronous ETCO2 and cerebral oximetry monitoring could be used to validate this clinical test. NIRS seems to be a useful tool in predicting vasoconstriction following hyperventilation.

Toxic-Induced Nonthyroidal Illness Syndrome Induced by Acute Low-Dose Pesticides Exposure-Preliminary In Vivo Study.

BACKGROUND AND OBJECTIVES: Conditions such as trauma, burns, sepsis, or acute intoxications have considerable consequences on the endocrine status, causing "sick euthyroid syndrome". Organophosphate exposure may induce an increase in acetylcholine levels, thus altering the thyroid's hormonal status. The present study aims to identify the effects of acetylcholinesterase inhibition on thyroid hormones. MATERIAL AND METHODS: A prospective experimental study was conducted on twenty Wistar rats. Blood samples were drawn to set baseline values for thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4). Chlorpyrifos 0.1 mg/kg was administered by oral gavage to induce acetyl-cholinesterase inhibition. After exhibiting cholinergic symptoms, blood samples were collected to assess levels of cholinesterase and thyroid hormones using ELISA. RESULTS: Butyrylcholinesterase levels confirmed major inhibition immediately after intoxication compared to the baseline, certifying the intoxication. A significant increase in T4 levels was noted (p = 0.01) both at 2 h and 48 h after administration of organophosphate in sample rats. Similarly, T3 almost doubled its value 2 h after poisoning (4.2 ng/mL versus 2.5 ng/mL at baseline). Surprisingly, TSH displayed acute elevation with an afterward slow descending trend at 48 h (p = 0.1), reaching baseline value. CONCLUSIONS: This study demonstrated that cholinesterase inhibition caused major alterations in thyroid hormone levels, which may be characterized by a transient hypothyroidism status with an impact on survival prognosis.

Mesenteric Ischemia in a Patient with Essential Thrombocythemia: Does COVID-19 Play Any Role? A Case Report and Overview of the Literature.

INTRODUCTION: Chronic mesenteric ischemia is a rare entity with non-specific symptomatology; combined with rare etiologies, it could lead to unwarranted surgical indication. CASE REPORT: We report the case of an 85-year-old woman, with a history of hypertension, persistent thrombocytosis, atherosclerosis, and recent minor COVID-19 infection, presenting to the hospital with postprandial abdominal pain and nonspecific clinical examination findings; upon abdominal CT, superior mesenteric artery circumferential thrombosis was revealed. A bone marrow biopsy was performed due to suspected essential thrombocythemia, confirming the diagnosis. An endovascular approach was chosen as therapy option and a stent was placed in the occluded area. Dual antiplatelet and cytoreductive therapies were initiated after the intervention. Clinical course was excellent, with no residual stenosis 1 month after stenting. CONCLUSIONS: The therapeutic strategy in elderly patients with exacerbated chronic mesenteric ischemia requires an interdisciplinary approach in solving both the exacerbation and the underlying conditions in order to prevent further thrombotic events. Although the patient presented a thrombotic state, other specific risk factors such as COVID-19 related-coagulopathy and essential thrombocythemia should be considered.

What Is Different in Acute Hematologic Malignancy-Associated ARDS? An Overview of the Literature.

Background and Objectives: Acute hematologic malignancies are a group of heterogeneous blood diseases with a high mortality rate, mostly due to acute respiratory failure (ARF). Acute respiratory distress syndrome (ARDS) is one form of ARF which represents a challenging clinical condition. The paper aims to review current knowledge regarding the variable pathogenic mechanisms, as well as therapeutic options for ARDS in acute hematologic malignancy patients. Data collection: We provide an overview of ARDS in patients with acute hematologic malignancy, from an etiologic perspective. We searched databases such as PubMed or Google Scholar, including articles published until June 2022, using the following keywords: ARDS in hematologic malignancy, pneumonia in hematologic malignancy, drug-induced ARDS, leukostasis, pulmonary leukemic infiltration, pulmonary lysis syndrome, engraftment syndrome, diffuse alveolar hemorrhage, TRALI in hematologic malignancy, hematopoietic stem cell transplant ARDS, radiation pneumonitis. We included relevant research articles, case reports, and reviews published in the last 18 years. Results: The main causes of ARDS in acute hematologic malignancy are: pneumonia-associated ARDS, leukostasis, leukemic infiltration of the lung, pulmonary lysis syndrome, drug-induced ARDS, radiotherapy-induced ARDS, diffuse alveolar hemorrhage, peri-engraftment respiratory distress syndrome, hematopoietic stem cell transplantation-related ARDS, transfusion-related acute lung injury. Conclusions: The short-term prognosis of ARDS in acute hematologic malignancy relies on prompt diagnosis and treatment. Due to its etiological heterogeneity, precision-based strategies should be used to improve overall survival. Future studies should focus on identifying the relevance of such etiologic-based diagnostic strategies in ARDS secondary to acute hematologic malignancy.

The Outcome of Surgical Treatment for the Neuropathic Diabetic Foot Lesions-A Single-Center Study.

The prevalence of diabetic foot complications is continuously increasing as diabetes has become one of the most important "epidemics" of our time. The main objective of this study was to describe the appropriate surgical intervention for the complicated neuropathic diabetic foot; the secondary goal was to find the risk factors associated with minor/major amputation and good or adverse surgical outcomes. This is an observational, retrospective study conducted between 1 January 2018 and 31 December 2019, which included 251 patients from the General Surgery Department at the Dr I. Cantacuzino Clinical Hospital in Bucharest with type II diabetes mellitus and neuropathic diabetic foot complications. The surgical conditions identified at admission were the following: osteitis (38.6%), infected foot ulcer (27.5%), gangrene (20.7%), infected Charcot foot (3.6%), non-healing wound (3.6%), necrosis (3.2%), and granulated wound (2.8%). We found that a minor surgical procedure (transmetatarsal amputation of the toe and debridement) was performed in 85.8% of cases, and only 14.2% needed major amputations. Osteitis was mainly associated with minor surgery (p = 0.001), while the gangrene and the infected Charcot foot were predictable for major amputation, with OR = 2.230, 95% CI (1.024-4.857) and OR = 5.316, 95% CI (1.354-20.877), respectively. Admission anemia and diabetic nephropathy were predictive of a major therapeutical approach, with p = 0.011, OR = 2.975, 95% CI (1.244-8.116) and p = 0.001, OR = 3.565, 95% CI (1.623-7.832), respectively. All the major amputations had a good outcome, while only several minor surgeries were interpreted as the adverse outcome (n = 24). Osteitis (45.8%) and admission anemia (79.2%) were more frequently associated with adverse outcomes, with p = 0.447 and p = 0.054, respectively. The complicated neuropathic diabetic foot requires a surgical procedure mainly associated with a good outcome.

Anti-MDA5 Amyopathic Dermatomyositis-A Diagnostic and Therapeutic Challenge.

Clinically amyopathic Dermatomyositis (CADM) is a rare subtype of idiopathic inflammatory myositis, associated with no muscular manifestations, which is more frequent in Asian women. Anti-melanoma differentiation-associated gene 5 (MDA5) antibodies are a recently discovered type of specific autoantibodies associated with myositis. The anti-MDA5 DM was initially described in Japan and later it was discovered that the target antigen was a protein implicated in the innate immune response against viruses, that is encoded by the melanoma differentiation-associated gene 5. Anti-MDA5 DM is characteristically associated with distinguished mucocutaneus and systemic manifestations, including skin ulcerations, palmar papules, arthritis, and interstitial-lung disease. Patients with anti-MDA5 positivity have a high risk of developing rapid progressive interstitial-lung disease (RP-ILD), with a poor outcome. As a result, despite high mortality, diagnosis is often delayed, necessitating increased awareness of this possible condition. Despite a severe course of lung disease and an increased mortality rate, there is currently no standard treatment. Recent insights based on observational studies and case reports support combined therapy with immunosuppressive drugs and corticotherapy, as soon as the symptoms appear. The aim of this paper is to describe anti-MDA5 DM, focusing on the recent literature about the unique clinical manifestations and therapeutic options, starting from a severe clinical case diagnosed in our Rheumatology Department.

Opioid-Sparing Analgesia Impacts the Perioperative Anesthetic Management in Major Abdominal Surgery.

Background and Objectives: The management of acute postoperative pain (APP) following major abdominal surgery implies various analgetic strategies. Opioids lie at the core of every analgesia protocol, despite their side effect profile. To limit patients' exposure to opioids, considerable effort has been made to define new opioid-sparing anesthesia techniques relying on multimodal analgesia. Our study aims to investigate the role of adjuvant multimodal analgesic agents, such as ketamine, lidocaine, and epidural analgesia in perioperative pain control, the incidence of postoperative cognitive dysfunction (POCD), and the incidence of postoperative nausea and vomiting (PONV) after major abdominal surgery. Materials and Methods: This is a clinical, observational, randomized, monocentric study, in which 80 patients were enrolled and divided into three groups: Standard group, C (n = 32), where patients received perioperative opioids combined with a fixed regimen of metamizole/acetaminophen for pain control; co-analgetic group, Co-A (n = 26), where, in addition to standard therapy, patients received perioperative systemic ketamine and lidocaine; and the epidural group, EA (n = 22), which included patients that received standard perioperative analgetic therapy combined with epidural analgesia. We considered the primary outcome, the postoperative pain intensity, assessed by the visual analogue scale (VAS) at 1 h, 6 h, and 12 h postoperatively. The secondary outcomes were the total intraoperative fentanyl dose, total postoperative morphine dose, maximal intraoperative sevoflurane concentration, confusion assessment method for intensive care units score (CAM-ICU) at 1 h, 6 h, and 12 h postoperatively, and the postoperative dose of ondansetron as a marker for postoperative nausea and vomiting (PONV) severity. Results: We observed a significant decrease in VAS score, as the primary outcome, for both multimodal analgesic regimens, as compared to the control. Moreover, the intraoperative fentanyl and postoperative morphine doses were, consequently, reduced. The maximal sevoflurane concentration and POCD were reduced by EA. No differences were observed between groups concerning PONV severity. Conclusions: Multimodal analgesia concepts should be individualized based on the patient's needs and consent. Efforts should be made to develop strategies that can aid in the reduction of opioid use in a perioperative setting and improve the standard of care.

Impact of COVID-19 Infection on Liver Transplant Recipients: Does It Make Any Difference?

The first case of coronavirus disease 2019 (COVID-19) was diagnosed in December 2019 in Wuhan, China. Since then, this novel infectious disease, caused by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), has grown into a pandemic with over 330 million infected individuals worldwide, many of them with innate or acquired immunosuppression. Liver transplantation (LT) is offered as a curative therapy for end-stage liver disease as well as for acute liver failure cases. Advances in immunosuppressive therapy decreased the rates of acute and chronic graft rejection, significantly improving the quality of life. Liver transplant recipients are considered at particularly high risk for developing critical COVID-19 infection because of their chronic immunosuppressed state. Available data are heterogeneous, and the mortality rate is variably reported in the literature. There is controversy regarding whether their immunosuppressive status is a risk or a protective factor for developing severe respiratory disease. Moreover, the mechanism of action is still unclear. We report the clinical outcome of three liver transplant recipients who had COVID-19 pneumonia at different moments following liver transplantation. All patients received a standard immunosuppression regimen and specific antiviral therapy, requiring no invasive mechanical ventilation. They were discharged from the hospital with no long-term COVID-19 complications.

Epigenetics in inflammatory liver diseases: A clinical perspective (Review).

Inflammatory liver diseases are, nowadays, multifactorial and wide-spread, thus having an important socio-economic impact. Although the therapeutic algorithms are well-known in hepatitis, regardless of etiology, strategies to identify inflammatory hepatic lesions in early stages and to develop new epigenetic therapies should be prioritized. The main entities of inflammatory liver disease are: alcoholic and non-alcoholic fatty liver disease, autoimmune hepatitis, viral hepatitis and Wilson disease. The main epigenetic processes include: DNA methylation/demethylation, which imply changes in DNA tertiary structure; post-translational histone covalent changes (methylation/demethylation, acetylation/deacetylation, ubiquitination), that cause DNA-histone instability; synthesis of small, non-coding RNA molecules, called microRNAs, that modulate translational potential of transcripts (mRNAs) and post-translational modification of polypeptide chains. Consequently, the epigenetic interactions aforementioned, play an important modulatory role in disease progression and response to conventional therapies The present review focused on the main epigenetic changes in inflammatory liver conditions, considering a new perspective: Epigenetic therapy. This approach is more than welcomed, taking into consideration that conventional therapeutic strategies are almost exhausted.