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".

The Hemodynamic Profile and Intraoperative Bleeding Impact on Liver Transplant Patients.

Liver transplantation is the treatment of choice for end-stage liver disease and despite accumulated experience over the years, improved surgical techniques, better immunosuppression and adequate intensive care management, it still represents the greatest challenge for anesthesiologists. The aim of the study was the characterization of the hemodynamic profile of patients with liver cirrhosis undergoing liver transplantation with the help of the PiCCO system during the three surgical stages, the impact of bleeding on hemodynamic status and correlation between the amount of bleeding, lactate levels, severity scores and survival rate and complications. Another focus of this study was the amount of transfused blood products and their impact on postoperative complications. Our study included 70 patients who underwent liver transplantation in our center and were hemodynamically monitored with the PiCCO system. Data were processed using the Python 3.9 programming language. Results: The mean MELD severity score was 18 points. During surgery, significant variations in the hemodynamic parameters occurred. All patients had a decrease in cardiac output in the anhepatic phase, with 50% presenting a decrease of more than 40%. In total, 78% of patients showed a decrease in the global ejection fraction, with a median value of 30%.Overall, 75% of patients had a total blood loss of less than 6000 mL and 31 patients developed immediate postoperative complications with a 50% probability with blood loss exceeding 6500 mL. Seven patients (10%) did not survive after 30 days. An amount of 5 mmol/L of serum neohepatic lactate determines a 50% probability of complications. Conclusions: Surgical technique causes an important decrease in cardiac output. Intraoperative bleeding has a major impact on outcome and the first month represents a critical period after liver transplantation. Statistical tests describe the probability of 30/90-day survival and the occurrence of complications according to variables such as intraoperative bleeding and MELD severity score. Intraoperative transfusion correlates with the occurrence of postoperative complications.

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.

Rotational Thromboelastometry Coagulation Parameters (ROTEM®) May be Discriminative for Active Inflammatory Bowel Disease: A Prospective Observational Study.

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) is associated with increased risk of thromboembolic events. The rotational thromboelastometry (ROTEM®) is a validated integrative assessment of coagulation, but it has never been studied in IBD patients. METHODS: We performed a monocentric prospective observational study in a national tertiary center. Adult IBD patients underwent ROTEM® analysis on admission to our IBD Department. Parameters evaluated with ROTEM® tests (INTEM, EXTEM and FIBTEM) were clotting time (CT), the time of clot formation (CFT), clot firmness amplitude after 5 and 10 minutes (A5 and A10) and maximum clot firmness (MCF). ROC curves were performed in order to evaluate the ability of ROTEM® to predict active IBD. RESULTS: Several ROTEM® parameters were significantly associated with active IBD compared to patients in remission, towards a hypercoagulable status for patients with active disease: CT, CFT, A5, A10, MCF. ROC analysis demonstrated that parameters related to clot robustness showed a very good prediction ability of active IBD (AUC >0.8): A5, A10, MCF in INTEM (p<0.001), in EXTEM (p<0.001) and MCF in FIBTEM (p<0.001). ROTEM® parameters showed high correlations with inflammation markers as C-reactive protein (CRP) and faecal calprotectin (FC). CONCLUSIONS: Our study showed that ROTEM® parameters are modified in patients with active IBD, being correlating with inflammation markers and demonstrating a high prediction ability of active IBD. Future research is needed to validate ROTEM® as a method to discriminate patterns of active IBD and to guide anticoagulant therapy in patients with active IBD.

Less (Transfusion) Is More-Enhancing Recovery through Implementation of Patient Blood Management in Cardiac Surgery: A Retrospective, Single-Centre Study of 1174 Patients.

Introduction: The implementation of Patient Blood Management (PBM) in cardiac surgery has been shown to be effective in reducing blood transfusions and associated complications, as well as improving patient outcomes. Despite the potential benefits of PBM in cardiac surgery, there are several barriers to its successful implementation. Objectives: The main objectives of this study were to ascertain the impact of the national Romanian PBM recommendations on allogeneic blood product transfusion in cardiac surgery and identify predictors of perioperative packed red blood cell transfusion. Methods: As part of the Romanian national pilot programme of PBM, we performed a single-centre, retrospective study in a tertiary centre of cardiovascular surgery, including patients from two time periods, before and after the implementation of the national recommendations. Using coarsened exact matching, from a total of 1174 patients, 157 patients from the before group were matched to 169 patients in the after group. Finally, we built a multivariate regression model from the entire cohort to analyse independent predictors of PRBC transfusion in the perioperative period. Results: Although there was a trend towards a lower proportion of patients requiring PRBC transfusion in the "after" group compared to the "before" group (44.9%vs. 50.3%), it was not statistically significant. There was a significant difference between the "after" group and the "before" group in terms of fresh-frozen plasma (FFP) transfusion rates, with a lower percentage of patients requiring FFP transfusion in the "after" group compared to "before" (14.2%, vs. 22.9%, p = 0.04). This difference was also seen in the total perioperative FFP transfusion (mean transfusion 0.7 units in the "before" group, SD 1.73 vs. 0.38 units in the "after" group, SD 1.05, p = 0.04). In the multivariate regression analysis, age > 64 years (OR 1.652, 95% CI 1.17-2.331, p = 0.004), female sex (OR 2.404, 95% CI 1.655-3.492, p < 0.001), surgery time (OR 1.295, 95% CI 1.126-1.488, p < 0.001), Hb < 13 g/dl (OR 3.611, 95% CI 2.528-5.158, p < 0.001), re-exploration for bleeding (OR 3.988, 95% CI 1.248-12.738, p = 0.020), viscoelastic test use (OR 2.18, 95% CI 1.34-3.544, p < 0.001), FFP transfusion (OR 4.023, 95% CI 2.426-6.671, p < 0.001), and use of a standardized pretransfusion checklist (OR 8.875, 95% CI 5.496-14.332, p < 0.001) remained significantly associated with PRBC transfusion. The use of a preoperative standardized haemostasis questionnaire was independently associated with a decreased risk of perioperative PRBC transfusion (0.565, 95% CI 0.371-0.861, p = 0.008). Conclusions: Implementation of national PBM recommendations led to a reduction in FFP transfusion in a cardiac surgery centre. The use of a preoperative standardized haemostasis questionnaire is an independent predictor of a lower risk for PRBC transfusion in this setting.

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 [...].

Safety and Efficacy of Direct-acting Antiviral Therapies for Chronic HCV Infection in Hemodialysis Patients.

BACKGROUND/AIM: The aim of this study was to determine the safety and efficacy of a direct-acting antiviral treatment, ombitasvir/paritaprevir/ritonavir and dasabuvir, without ribavirin, in a real-life setting. PATIENTS AND METHODS: We performed a prospective observational study including 108 patients undergoing hemodialysis for end-stage kidney disease, referred to our clinic for antiviral therapy for chronic hepatitis C virus infection. Patients received treatment with ombitasvir/paritaprevir/ritonavir and dasabuvir, for 12 weeks. Sustained virologic response (SVR) was defined as undetectable viremia at 12 weeks after the end of therapy. For safety analysis, we monitored serum levels of hemoglobin, albumin, total bilirubin, alanine-aminotransferase and aspartate- aminotransferase at the beginning and end of therapy, as well as at SVR. Verbal Numeric Rating Scale was used to assess the presence of nausea, headaches and fatigue. RESULTS: We noted a high prevalence of diabetic and hypertensive nephropathy as the underlying cause of chronic kidney disease. Most of the patients had F2 and F3 liver fibrosis (32.40% and 34.25%, respectively). The SVR rate was 96.2% (103/107 patients). We recorded an unrelated death after the completion of antiviral therapy. We found increased levels of nausea, headaches and fatigue at the end of therapy compared to at initiation, The presence and degree of symptoms did not correlate with the underlying cause of renal disease (p=0.72) nor with the degree of fibrosis (p=0.08). Minimal increases in transaminases and bilirubin were recorded at the end of treatment, with no statistical significance. CONCLUSION: Oral antiviral therapy with ombitasvir/paritaprevir/ritonavir and dasabuvir can be safely used in hemodialysis patients, with similar response rates compared to the general population.

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.

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.

Reverse Takotsubo Cardiomyopathy after Orthotopic Liver Transplantation. A Case Report.

Introduction: Takotsubo cardiomyopathy is a rare reversible type of heart failure, often precipitated by emotional stress; other risk factors include intracranial bleeding, ischemic stroke, sepsis, major surgery, pheochromocytoma. The clinical, electrical and blood sample analysis features resemble those of a myocardial infarction- however, they occur in the absence of angiographic coronary filling defects. Case presentation: A 61-year-old male patient, 71 kg, 175 cm, underwent liver transplantation for Child-Pugh B cirrhosis secondary to mixed viral hepatitis (B and D). His medical records revealed mild mitral, aortic, and tricuspid insufficiencies and heart failure with preserved ejection fraction. An initially uneventful perioperative stage was succeeded by cardiogenic shock (cardiac index - 1.2 l/min/ sqm), which the patient developed 24 hours after the intervention. Elevated cardiac markers and ECG abnormalities showing ST-T changes in the V2-V5 leads were additionally noted. Transesophageal echocardiography (TEE) revealed an acute onset reduction in the left ventricular systolic function secondary to basal hypokinesia. No coronary obstruction was detected by percutaneous angiography. The above findings lead to the diagnosis of reverseTakotsubo cardiomyopathy. Further, the patient developed acute kidney injury and liver graft failure, succumbing within 48 hours after the surgical procedure. Conclusions: We report a rare case of reverse Takotsubo cardiomyopathy in a male patient after orthotopic liver transplant.

The Impact of Postoperative Complications on Survival after Simultaneous Resection of Colorectal Cancer and Liver Metastases.

BACKGROUND: The aim of this study was to investigate the impact of postoperative complications on the long-term outcomes of patients who had undergone simultaneous resection (SR) of colorectal cancer and synchronous liver metastases (SCLMs). METHODS: We conducted a single-institution survival cohort study in patients with SR, collecting clinical, pathological, and postoperative complication data. The impact of these variables on overall survival (OS) and disease-free survival (DFS) was compared by log rank test. Multivariate Cox regression analysis identified independent prognostic factors. RESULTS: Out of 243 patients, 122 (50.2%) developed postoperative complications: 54 (22.2%) major complications (Clavien-Dindo grade III-V), 86 (35.3%) septic complications, 59 (24.2%) hepatic complications. Median comprehensive complication index (CCI) was 8.70. Twelve (4.9%) patients died postoperatively. The 3- and 5-year OS and DFS rates were 60.7%, 39.5% and 28%, 21.5%, respectively. Neither overall postoperative complications nor major and septic complications or CCI had a significant impact on OS or DFS. Multivariate analysis identified the N2 stage as an independent prognostic of poor OS, while N2 stage and four or more SCLMs were independent predictors for poor DFS. CONCLUSION: N2 stage and four or more SCLMs impacted OS and/or DFS, while CCI, presence, type, or grade of postoperative complications had no significant impact on long-term outcomes.

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.

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.

Outcomes of COVID-19 Critically Ill Extremely Elderly Patients: Analysis of a Large, National, Observational Cohort.

BACKGROUND: During the COVID-19 pandemic, resource allocation became a major problem in globally overwhelmed ICUs. The main goal of this study was to describe the clinical characteristics of the very elderly patients (aged ≥ 80 years) with COVID-19 admitted in Romanian ICUs. The study objectives were to evaluate and determine the factors associated with ICU mortality. METHODS: We designed a national, multicentric, observational platform with prospective enrolment. This study included patients aged ≥ 80 years admitted in Romanian ICUs with SARS-CoV-2 infection from March 2020 to December 2021. RESULTS: We included 1666 patients with a median age of 83 years and 78% ICU mortality. Male sex, dyspnoea, lower Glasgow Coma Scale and lower SpO2 at ICU admission, the need for mechanical ventilation (MV), and corticosteroid use were independently associated with mortality. A total of 886/1666 (53%) elderly patients underwent invasive mechanical ventilation, with a mortality of 97%. The age impact on mortality was confirmed by a 1:1 propensity matching with less elderly ICU patients. CONCLUSION: In extremely elderly patients with COVID-19 admitted in the ICU, mortality is high, particularly when requiring MV. Therapy should be directed towards the optimization of less invasive ventilatory methods and the use of MV and corticosteroids only in highly selected patients.

COVID-19 Pandemic Was Associated with Lower Activity but Not Higher Perioperative Mortality in a Large Eastern European Center.

BACKGROUND Surges of critically ill patients can overwhelm hospitals during pandemic waves and disrupt essential surgical activity. This study aimed to determine whether hospital mortality increased during the COVID-19 pandemic and during pandemic waves. MATERIAL AND METHODS This was a retrospective analysis of a prospective, observational, epidemiological database. All patients who underwent surgery from January 1 to December 31, 2020, were included in the analysis. The setting was a large Eastern European Surgical Center referral center of liver transplant and liver surgery, a major center of abdominal surgery. RESULTS A total of 1078 patients were analyzed, and this number corresponded to a reduction of surgical activity by 30% during the year 2020 compared with 2019. Despite an increase in surgery complexity during the pandemic, perioperative mortality was not different, and this was maintained during the pandemic wave. The pandemic (OR 1.45 [0.65-3.22], P=0.365) and the wave period (OR 0.897 [0.4-2], P=0.79) were not associated with hospital mortality in univariate analysis. In the multivariate model analysis, only the American Society of Anesthesiology (ASA) score (OR 5.815 [2.9-11.67], P<0.0001), emergency surgery (OR 5.066 [2.24-11.48], P<0.0001), and need for surgical reintervention (OR 5.195 [1.78-15.16], P=0.003) were associated with hospital mortality. CONCLUSIONS Despite considerable challenges, in this large retrospective cohort, perioperative mortality was similar to that of pre-pandemic practice. Efforts should be made to optimize personnel issues, while maintaining COVID-19-free surgical pathways, to adequately address patients' surgical needs during the following waves of the pandemic.