Hepatic ischemia-reperfusion syndrome and its effect on the cardiovascular system: The role of treprostinil, a synthetic prostacyclin analog.

Hepatic ischemia-reperfusion syndrome has been the subject of intensive study and experimentation in recent decades since it is responsible for the outcome of several clinical entities, such as major hepatic resections and liver transplantation. In addition to the organ's post reperfusion injury, this syndrome appears to play a central role in the dysfunction of distant tissues and systems. Thus, continuous research should be directed toward finding effective therapeutic options to improve the outcome and reduce the postoperative morbidity and mortality rates. Treprostinil is a synthetic analog of prostaglandin I2, and its experimental administration has shown encouraging results. It has already been approved by the Food and Drug Administration in the United States for pulmonary arterial hypertension and has been used in liver transplantation, where preliminary encouraging results showed its safety and feasibility by using continuous intravenous administration at a dose of 5 ng/kg/min. Treprostinil improves renal and hepatic function, diminishes hepatic oxidative stress and lipid peroxidation, reduces hepatictoll-like receptor 9 and inflammation, inhibits hepatic apoptosis and restores hepatic adenosine triphosphate (ATP) levels and ATP synthases, which is necessary for functional maintenance of mitochondria. Treprostinil exhibits vasodilatory properties and antiplatelet activity and regulates proinflammatory cytokines; therefore, it can potentially minimize ischemia-reperfusion injury. Additionally, it may have beneficial effects on cardiovascular parameters, and much current research interest is concentrated on this compound.

COVID-19-associated pulmonary aspergillosis in patients with severe SARS-CoV-2 infection: A single-center observational study from Greece.

INTRODUCTION: COVID-19-associated pulmonary aspergillosis (CAPA) is a serious complication affecting patients with severe SARS-CoV-2 infection, and is associated with increased mortality. OBJECTIVE: The objective of this study was to investigate potential risk factors, and to estimate the incidence and mortality in patients diagnosed with CAPA. METHODS: A single-center retrospective observational study was conducted on patients admitted to the intensive care unit (ICU) with severe COVID-19 from October 2020 to May 2022. Patients with deterioration of their clinical status were evaluated with serum galactomannan (GM) for probable CAPA. Baseline demographic patient characteristics, vaccination status, and time period during which each patient was infected with SARS-CoV-2 were obtained, and risk stratification according to underlying comorbidities was performed in an effort to assess various risk factors for CAPA. The incidence of CAPA in the entire cohort was measured, and mortality rates in the CAPA and non-CAPA groups were calculated and compared. RESULTS: Of 488 patients admitted to the ICU, 95 (19.4%) had deterioration of their clinical status, which prompted testing with serum GM. Positive serum testing was observed in 39/95 patients, with an overall CAPA incidence in the entire study cohort reaching 7.9% (39/488). The mortality rate was 75% (42/56) in the non-CAPA group that was tested for serum GM, and 87.2% (34/39) in the CAPA group (P = 0.041). Multivariable Cox regression hazard models were tested for 28- and 90-day survival from ICU admission. An invasive pulmonary aspergillosis (IPA) risk-stratified cox regression model corrected for the SARS-CoV-2 variant of the patient identified the diagnosis of probable CAPA and elevated procalcitonin (PCT) levels measured at least 10 days after ICU admission, as significantly associated with death in the IPA-risk subgroup only, with hazard ratio (HR): 3.687 (95% confidence interval [CI], 1.030-13.199, P = 0.045) for the diagnosis of probable CAPA, and HR: 1.022 (95% CI, 1.003-1.042, P = 0.026) for every 1 ng/mL rise in PCT. CONCLUSIONS: Patients in the IPA-risk subgroup that were diagnosed with CAPA had a lower 90-day survival when compared to patients in the same group without a CAPA diagnosis.

Cutaneous lesions in a COVID-19 patient leading to a surprising diagnosis.

Differential diagnosis of skin lesions is broad. Cutaneous metastases should always be considered in the appropriate clinical and laboratory context to ensure accurate diagnosis. https://bit.ly/400Msre.

Enhanced recovery after surgery in liver transplantation: Challenges and feasibility.

BACKGROUND: Enhanced recovery after surgery (ERAS) started a revolution that changed age-old surgical stereotypical practices regarding the overall management of the surgical patient. In the last decade, ERAS has gained significant acceptance in the community of general surgery, in addition to several other surgical specialties, as the evidence of its advantages continues to grow. One of the last remaining fields, given its significant complexity and intricate nature, is liver transplantation (LT). AIM: To investigate the existing efforts at implementing ERAS in LT. METHODS: We conducted a systematic review of the existing studies that evaluate ERAS in orthotopic LT, with a multimodal approach and focusing on measurable clinical primary endpoints, namely length of hospital stay. RESULTS: All studies demonstrated a considerable decrease in length of hospital stay, with no readmission or negative impact of the ERAS protocol applied to the postoperative course. CONCLUSIONS: ERAS is a well-validated multimodal approach for almost all types of surgical procedures, and its future in selected LT patients seems promising, as the preliminary results advocate for the safety and efficacy of ERAS in the field of LT.

Effect of intravenous clarithromycin in patients with sepsis, respiratory and multiple organ dysfunction syndrome: a randomized clinical trial.

BACKGROUND: Clarithromycin may act as immune-regulating treatment in sepsis and acute respiratory dysfunction syndrome. However, clinical evidence remains inconclusive. We aimed to evaluate whether clarithromycin improves 28-day mortality among patients with sepsis, respiratory and multiple organ dysfunction syndrome. METHODS: We conducted a multicenter, randomized, clinical trial in patients with sepsis. Participants with ratio of partial oxygen pressure to fraction of inspired oxygen less than 200 and more than 3 SOFA points from systems other than the respiratory function were enrolled between December 2017 and September 2019. Patients were randomized to receive 1 gr of clarithromycin or placebo intravenously once daily for 4 consecutive days. The primary endpoint was 28-day all-cause mortality. Secondary outcomes were 90-day mortality; sepsis response (defined as at least 25% decrease in SOFA score by day 7); sepsis recurrence; and differences in peripheral blood cell populations and leukocyte transcriptomics. RESULTS: Fifty-five patients were allocated to each arm. By day 28, 27 (49.1%) patients in the clarithromycin and 25 (45.5%) in the placebo group died (risk difference 3.6% [95% confidence interval (CI) - 15.7 to 22.7]; P = 0.703, adjusted OR 1.03 [95%CI 0.35-3.06]; P = 0.959). There were no statistical differences in 90-day mortality and sepsis response. Clarithromycin was associated with lower incidence of sepsis recurrence (OR 0.21 [95%CI 0.06-0.68]; P = 0.012); significant increase in monocyte HLA-DR expression; expansion of non-classical monocytes; and upregulation of genes involved in cholesterol homeostasis. Serious and non-serious adverse events were equally distributed. CONCLUSIONS: Clarithromycin did not reduce mortality among patients with sepsis with respiratory and multiple organ dysfunction. Clarithromycin was associated with lower sepsis recurrence, possibly through a mechanism of immune restoration. Clinical trial registration clinicaltrials.gov identifier NCT03345992 registered 17 November 2017; EudraCT 2017-001056-55.

Changes in molecular epidemiology of carbapenem-resistant Klebsiella pneumoniae in the intensive care units of a Greek hospital, 2018-2021.

The spread of multi-drug resistant (MDR) Gram-negative bacteria, including Klebsiella pneumoniae, constitutes a global threat. The most frequent mechanism of acquired carbapenem resistance is the production of carbapenemases, especially KPC, NDM, VIM, IMP and OXA-48. We analyzed the epidemiological trend of carbapenem resistance genes of carbapenem-resistant K. pneumoniae (CRKP) strains isolated from critically ill patients in a Greek tertiary hospital. The study included 150 CRKP isolates collected from 116 (77.4%) patients hospitalized in the adult ICU and 17 (11.3%) each in the pediatric and the two neonatal ICUs between March 2018 and March 2021. Identification and antimicrobial susceptibility testing were performed using VITEK-2. A multiplex lateral flow immunoassay was used for the detection of carbapenemases, while the detection of bla VIM, bla KPC, bla NDM, bla IMP and bla OXA-48-like genes was achieved by multiplex PCR. The bla NDM was mainly detected in adults (54/116, 46.9%), while in children the most often detected gene was bla KPC (24/34, 70.6%). The predominant carbapenem resistance gene during 2018-2019 was bla KPC alone or in combination with bla VIM, reaching 44.4% in 2019, while during 2020-2021 the detection of bla NDM prevailed significantly, reaching 45.5 and 60.7% for 2020 and 2021, respectively. A shift in the molecular epidemiology of CRKP was seen during 2018-2021, which is probably associated with the recent excessive empiric use of newer antimicrobials. Surveillance studies and proper and strict implementation of infection control measures are highly needed to decrease the spread of MDR bacteria, including CRKP.

Psychological morbidity a year after treatment in intensive care unit.

Several studies have linked treatment in the Intensive Care Unit (ICU) with negative psychological outcomes. This study explores the prevalence of negative psychological outcomes in Greek patients (N=29), a year after treatment in ICU. Percentages of participants with anxiety [41%, 95% CI (22%, 60%)] and Post- Traumatic Stress Disorder (PTSD) [34%, 95% CI (16%, 53%)] symptoms were similar to the related literature. Percentages of participants with depressive [17%, 95% CI (3%, 32%)] symptoms were rather low. Only 10% of participants reported absence of quality of live issues. Anxiety symptoms were related to desire to talk about the ICU experience (p=0.010), duration of propofol administration (p=0.018) and loss of employment (p=0.019) and negatively related to duration of stay in the ICU (p=0.025). PTSD symptoms were related to experiencing other stressors during the year after the ICU stay (p=0.001), social constraint (p=0.003), duration of propofol administration (p=0.004), loss of employment (p=0.020), low income (p=0.022) and negative ICU memories (p=0.029). Depressive symptoms were related to loss of employment (p=0.003), low income (p=0.029) and social constraint (p=0.033). Patients experience elevated levels of psychological symptoms long after they are discharged from the hospital. Several psychosocial factors emerged as important factors to consider for predicting levels of distress.

Forecasting models of infections due to carbapenem-resistant Gram-negative bacteria in an intensive care unit in an endemic area.

OBJECTIVES: The aim of this study was to forecast the monthly incidence rates of infections [infections/1000 bed-days (IBD)] due to carbapenem-resistant Klebsiella pneumoniae (CRKP), carbapenem-resistant Pseudomonas aeruginosa (CRPA), carbapenem-resistant Acinetobacter baumannii (CRAB) and total carbapenem-resistant Gram-negative bacteria (CRGNB) in an endemic intensive care unit (ICU) during the subsequent year (December 2016-December 2017) following the observational period. METHODS: A 52-month observational period (August 2012-November 2016) was used. Two forecasting models, including a simple seasonal model for CRGNB, CRKP and CRPA and Winters' additive model for CRAB infections, were applied. RESULTS: The models predicted the highest infection rates for CRKP, CRAB and CRGNB in January and September 2017 (23.8/23.4, 24.6/28.5 and 46.8/46.7 IBD, respectively) and for CRPA in February and March 2017 (8.3 and 7.9, respectively). The highest observed rates for CRKP, CRAB and CRGNB were indeed in January and September 2017 (25.6/19.0, 34.2/23.8 and 59.8/42.8 IBD, respectively); and for CRPA in February and March of the same year (15.2 and 12.7, respectively). The increased rates may be associated with personnel's annual work programme and behavioural factors. CONCLUSION: Forecasting models in endemic ICUs may assist in implementation strategies for infection control measures.

Comparison of semiquantitative and differential time to positivity methods for the diagnosis of central line-associated bloodstream infections in an intensive care unit.

INTRODUCTION: Central line-associated bloodstream infections (CLABSIs) adversely affect patients' hospitalization. AIM: We compared semiquantitative roll plate (SQRP) and differential time to positivity (DTP) culture methods in diagnosing CLABSIs. METHODOLOGY: A retrospective study was conducted in an intensive care unit (ICU) from January 2013 to August 2014. All ICU patients with suspected CLABSIs were included. Blood cultures were taken, while central venous catheter (CVC) tips were cultured using the roll-tip method. DTP was considered positive if CVC lumen blood cultures became positive at least 2 h prior to concurrently drawn peripheral blood cultures with an identical micro-organism. SQRP method was considered positive when ≥15 c.f.u. of a micro-organism identical to that of blood cultures grew. Measures of diagnostic accuracy were calculated. RESULTS: SQRP displayed high sensitivity (94.7 %), while DTP showed high specificity (82.5 %). SQRP combined with DTP displayed 100  % sensitivity and negative predictive value. CONCLUSION: SQRP and DTP methods should be evaluated in combination.

Molecular Epidemiology of Endemic Carbapenem-Resistant Gram-Negative Bacteria in an Intensive Care Unit.

The molecular epidemiology of endemic carbapenem-resistant Klebsiella pneumoniae (CRKP), carbapenem-resistant Pseudomonas aeruginosa (CRPA), and carbapenem-resistant Acinetobacter baumannii (CRAB) in an intensive care unit located in an endemic area with high rates of resistance was investigated. A CRPA strain producing VIM and KPC concurrently was detected for the first time in an endemic area. CRKP strains producing K. pneumoniae carbapenemase predominated and were mainly assigned to the "hyperepidemic Greek clone." Predominant OXA-23-like producing CRAB strains were assigned to multiple pulsotypes.

Comparison of Oligon catheters and chlorhexidine-impregnated sponges with standard multilumen central venous catheters for prevention of associated colonization and infections in intensive care unit patients: a multicenter, randomized, controlled study.

OBJECTIVE: To evaluate silver-impregnated (Oligon) central venous catheters and chlorhexidine-gluconate-impregnated sponges for reducing catheter-related colonization and infection, nonbacteremic or bacteremic. DESIGN: Multicenter, prospective, randomized, controlled study. SETTING: Five general intensive care units in Greece. PATIENTS: Intensive care unit patients requiring a multilumen central venous catheter between June 2006 and May 2008. INTERVENTIONS: Patients were randomly assigned to receive a standard catheter (standard group), a standard catheter plus chlorhexidine-gluconate-impregnated sponge (chlorhexidine-gluconate-impregnated sponge group), or an Oligon catheter (Oligon group). Catheter colonization was defined as a positive quantitative tip culture (≥10 colony-forming units/mL), catheter-related infection was defined by the previous criterion plus clinical evidence of sepsis, and bacteremia catheter-related infection as catheter-related infection plus a positive peripheral blood culture with the same micro-organism as in the catheter tip. MEASUREMENTS AND MAIN RESULTS: Data were obtained from 465 patients, 156 in the standard-group, 150 in the chlorhexidine-gluconate-impregnated sponge group, and 159 in the Oligon-group. Colonization occurred in 24 (15.4%) standard catheters, 21 (14%) in the chlorhexidine-gluconate-impregnated sponge group, and 25 (15.7%) in the Oligon catheters (p = .35) (20.9, 19.9, 21.8/1000 catheter-days, respectively). Catheter-related infections were recorded in nine (5.8%) standard catheters, six (4%) in the chlorhexidine-gluconate-impregnated sponge group, and seven (4.4%) in the Oligon catheters (p = .58) (7.8/1,000, 5.7/1,000, 6.1/1,000 catheter-days, respectively). No difference was observed between the chlorhexidine- gluconate-impregnated sponge group and the standard group regarding catheter colonization (hazard ratio 1.21; 95% confidence interval 0.56-2.61; p = .64) and catheter-related infections (hazard ratio 0.65; 95% confidence interval 0.23-1.85; p = .42). The Oligon catheter did not reduce colonization or catheter-related infections when compared with the standard catheter (colonization: hazard ratio 1.0; 95% confidence interval 0.46-2.21; p = .98; catheter-related infection: hazard ratio 0.72; 95% confidence interval 0.27-1.95; p = .52). Seven patients (1.5%, 2.09/1,000 catheter-days) presented bacteremic catheter-related infections. Central venous catheters inserted either in the internal jugular or the femoral vein had greater risk to be colonized than catheters inserted in the subclavian vein (internal jugular vs. subclavian: hazard ratio 3.29; 95% confidence interval 1.26-8.61; p = .01; femoral vs. subclavian: hazard ratio 3.36; 95% confidence interval 1.17-9.65; p = .02). Acinetobacter baumannii was the predominant pathogen (37.1% episodes of colonization, 36.4% catheter-related infections, 57.1% bacteremic catheter-related infections). CONCLUSION: For short-term (median duration 7 days) central venous catheters in intensive care units with high prevalence of multiresistant Gram-negative bacteria, chlorhexidine-impregnated sponges and Oligon catheters as single preventive measures did not reduce catheter colonization or catheter-related infections. As a result of the limited amount of events, no conclusion could be reached regarding bacteremic catheter-related infections. The femoral site was the most frequently colonized insertion site in all types of catheters.

Influenza A/H1N1 septic shock in a patient with systemic lupus erythematosus. A case report.

BACKGROUND: Immunocompromised patients, such as systemic lupus erythematosus (SLE) sufferers have an increased risk of mortality, following influenza infection. In the recent pandemic, influenza A H1NI virus caused 18449 deaths, mainly because of adult respiratory distress syndrome or bacterial co-infections. CASE PRESENTATION: In this case report, an SLE patient with viral-induced septic shock, without overt pulmonary involvement, is discussed. The patient was administered oseltamivir and supportive treatment, including wide-spectrum antibiotics, vasopressors and steroids, according to the guidelines proposed for bacterial sepsis and septic shock. She finally survived and experienced a lupus flare soon after intensive care unit (ICU) discharge. CONCLUSIONS: To our knowledge, this is the first case to report severe septic shock from influenza A/H1N1 virus, without overt pulmonary involvement.

Bloodstream infections caused by metallo-ß-lactamase/Klebsiella pneumoniae carbapenemase-producing K. pneumoniae among intensive care unit patients in Greece: risk factors for infection and impact of type of resistance on outcomes.

OBJECTIVE: To determine risk factors for bloodstream infections (BSIs) caused by Klebsiella pneumoniae producing metallo-ß-lactamases (MBLs) or K. pneumoniae carbapenemases (KPCs), as well as risk factors for mortality associated with carbapenem-resistant K. pneumoniae, among intensive care unit (ICU) patients. METHODS: Two case-control studies were conducted in a patient cohort with K. pneumoniae BSIs in an 8-bed ICU in a Greek hospital from January 1, 2007, through December 31, 2008. In study 1, patients with K. pneumoniae BSIs were allocated among 3 groups according to isolate susceptibility profile: (1) carbapenem-susceptible insolates (control group), (2) MBL-producing isolates, or (3) KPC-producing isolates. The MBL and KPC groups were compared with the control group to identify risk factors for development of K. pneumoniae BSI. In study 2, patients with K. pneumoniae BSIs who died were compared with survivors to identify risk factors for mortality. RESULTS: Fifty-nine patients had K. pneumoniae BSIs (22 with carbapenem-susceptible isolates, 18 with MBL-producing isolates, and 19 with KPC-producing isolates). All KPC-producing isolates carried the bla(KPC-2) gene, and 17 of 18 MBL-producing isolates carried bla(VIM-1). Acute Physiology and Chronic Health Evaluation II score (odds ratio, 1.13 [95% confidence interval, 1.03-1.25]; [Formula: see text]) was independently associated with KPC-producing K. pneumoniae BSIs. Nine (41%) of 22 control patients, 8 (44%) of 18 MBL group patients, and 13 (68%) of 19 KPC group patients died in the ICU. Nine (41%) of 22 control patients, 10 (56%) of 18 MBL group patients, and 15 (79%) of 19 KPC group patients died in the hospital. Isolation of KPC-producing K. pneumoniae was an independent predictor of ICU death ([Formula: see text]) and in-hospital death ([Formula: see text]) but not infection-attributable death. CONCLUSIONS: BSIs due to KPC-producing K. pneumoniae resulted in significantly increased mortality. The accurate and rapid detection of these pathogens is necessary for therapeutic considerations and for the implementation of infection control measures to contain them.

The use of central venous catheters during emergency prehospital care: a 2-year experience.

OBJECTIVE: Evaluation of the efficacy and safety of central venous catheter (CVC) use during prehospital emergency care. METHODS: All prehospital patients who underwent CVC positioning by emergency medical services physicians in the greater area of Thessaloniki during a 2-year period were included. A two-lumen indwelling polyurethane 8F catheter was inserted using the Seldinger technique in all cases. Patients' demographics and underlying diseases, site of access, number of attempts, time spent for catheter placement, and insertion-related complications were recorded. RESULTS: Four hundred and ninety-seven CVCs were inserted by emergency medical services physicians during the study period in patients with various underlying diseases [cardiac arrest (35.4%), other cardiac emergencies (16.3%), trauma (30.0%), coma (7.7%)]. Subclavian and internal jugular veins were accessed in 55.3 and 44.15% of patients, respectively. The mean number of attempts was 1.3 and the mean time spent for insertion was 2.0+/-0.5 min. Eleven (2.2%) hematomas at the insertion site of minor clinical importance and five (1.0%) uncomplicated arterial punctures were found. All of the 378 patients referred alive for admission in hospitals after prehospital resuscitation had radiological detection of their CVCs. Catheter malposition occurred in 11 (2.9%) cases. Three pneumothoraces were also detected (0.8%), but only one required chest tube placement. CONCLUSION: Insertion of CVCs during prehospital emergency care is effective in providing intravenous access, thus facilitating the delivery of fluids and medications in unstable patients. It is safe, as associated with a low incidence of complications in experienced hands.

Metastatic liver disease and fulminant hepatic failure: presentation of a case and review of the literature.

Although liver metastases are commonly found in cancer patients, fulminant hepatic failure (FHF) secondary to diffuse liver infiltration is rare. Furthermore, clinical presentation and laboratory findings are obscure and far from being pathognomonic for the disease. We report a case of a patient who died in the intensive care unit of our hospital from multiple organ failure syndrome secondary to FHF, as a result of liver infiltration from poorly differentiated small cell lung carcinoma. We also present the current knowledge about the clinical picture, laboratory findings and physical history of neoplastic liver-metastasis-induced FHF.

Treatment with aerosols in mechanically ventilated patients: is it worthwhile?

Aerosol medications are commonly used in mechanically ventilated patients. Several classes of drugs with different properties and indications may be given by inhalation. In all cases, compared with the systemic route, the inhaled therapy has the main advantage that for a given therapeutic response, the drug dose is several-fold lower, while the systemic absorption is negligible, thus the side effects are greatly minimized. In addition, for some medications the systemic route either causes non-acceptable side effects or results in considerably inferior therapeutic response, rendering the inhaled route the method of choice of drug administration. Bronchodilators, corticosteroids, vasoactive drugs, surfactants, antibiotics, helium and perfluorocarbons are the medications that can be given by inhalation during mechanical ventilation. Some of those represent part of the standard treatment for various groups of mechanically ventilated patients, while the role of others has not been well established yet.