Effect of machine learning-guided haemodynamic optimization on postoperative free flap perfusion in reconstructive maxillofacial surgery: A study protocol.

AIMS: Intraoperative hypotension and liberal fluid haemodynamic therapy are associated with postoperative medical and surgical complications in maxillofacial free flap surgery. The novel haemodynamic parameter hypotension prediction index (HPI) has shown good performance in predicting hypotension by analysing arterial pressure waveform in various types of surgery. HPI-based haemodynamic protocols were able to reduce the duration and depth of hypotension. We will try to determine whether haemodynamic therapy based on HPI can improve postoperative flap perfusion and tissue oxygenation by improving intraoperative mean arterial pressure and reducing fluid infusion. METHODS: We present here a study protocol for a single centre, randomized, controlled trial (n = 42) in maxillofacial patients undergoing free flap surgery. Patients will be randomized into an intervention or a control group. In the intervention, group haemodynamic optimization will be guided by machine learning algorithm and functional haemodynamic parameters presented by the HemoSphere platform (Edwards Lifesciences, Irvine, CA, USA), most importantly, HPI. Tissue oxygen saturation of the free flap will be monitored noninvasively by near-infrared spectroscopy during the first 24 h postoperatively. The primary outcome will be the average value of tissue oxygen saturation in the first 24 h postoperatively.

Hypotension prediction index guided versus conventional goal directed therapy to reduce intraoperative hypotension during thoracic surgery: a randomized trial.

PURPOSE: Intraoperative hypotension is linked to increased incidence of perioperative adverse events such as myocardial and cerebrovascular infarction and acute kidney injury. Hypotension prediction index (HPI) is a novel machine learning guided algorithm which can predict hypotensive events using high fidelity analysis of pulse-wave contour. Goal of this trial is to determine whether use of HPI can reduce the number and duration of hypotensive events in patients undergoing major thoracic procedures. METHODS: Thirty four patients undergoing esophageal or lung resection were randomized into 2 groups -"machine learning algorithm" (AcumenIQ) and "conventional pulse contour analysis" (Flotrac). Analyzed variables were occurrence, severity and duration of hypotensive events (defined as a period of at least one minute of MAP below 65 mmHg), hemodynamic parameters at 9 different timepoints interesting from a hemodynamics viewpoint and laboratory (serum lactate levels, arterial blood gas) and clinical outcomes (duration of mechanical ventilation, ICU and hospital stay, occurrence of adverse events and in-hospital and 28-day mortality). RESULTS: Patients in the AcumenIQ group had significantly lower area below the hypotensive threshold (AUT, 2 vs 16.7 mmHg x minutes) and time-weighted AUT (TWA, 0.01 vs 0.08 mmHg). Also, there were less patients with hypotensive events and cumulative duration of hypotension in the AcumenIQ group. No significant difference between groups was found in terms of laboratory and clinical outcomes. CONCLUSIONS: Hemodynamic optimization guided by machine learning algorithm leads to a significant decrease in number and duration of hypotensive events compared to traditional goal directed therapy using pulse-contour analysis hemodynamic monitoring in patients undergoing major thoracic procedures. Further, larger studies are needed to determine true clinical utility of HPI guided hemodynamic monitoring. TRIAL REGISTRATION: Date of first registration: 14/11/2022 Registration number: 04729481-3a96-4763-a9d5-23fc45fb722d.

OPIOID FREE GENERAL ANESTHESIA IN CLINICAL PRACTICE - A REVIEW ARTICLE.

Currently, enhanced recovery after surgery (ERAS) protocols are multimodal perioperative care pathways with the goal to achieve early patient recovery after surgery with minimal postoperative complications. According to studies, opioid free general anesthesia has many perioperative benefits and should be part of the ERAS protocols in specific surgical and patient indications. Opioid free general anesthesia is a multimodal balanced technique that is based on the concept that opioids are not used preoperatively or intraoperatively until the patient has aroused. The basic concept of opioid free general anesthesia is intravenous administration of several nonopioid drugs that operate at different pharmacological sites blocking surgical stress and sympathetic activation response. Moreover, current studies have shown that opioid free anesthesia is a technique which satisfactorily controls postoperative pain as the fifth vital sign, and has minimal side effects and better patient recovery with the same surgical conditions as general multimodal balanced anesthesia. However, further research is needed.

Epidemiological characteristics, baseline clinical features, and outcomes of critically ill patients treated in a coronavirus disease 2019 tertiary center in continental Croatia.

AIM: To describe epidemiological characteristics and baseline clinical features, laboratory findings at intensive care unit (ICU) admission, and survival rates of critically ill coronavirus disease 2019 (COVID-19) patients treated at a tertiary institution specialized for COVID-19 patients. METHODS: This retrospective study recruited 692 patients (67.1% men). Baseline demographic data, major comorbidities, anthropometric measurements, clinical features, and laboratory findings at admission were compared between survivors and non-survivors. RESULTS: The median age was 72 (64-78) years. The median body mass index was 29.1 kg/m2. The most relevant comorbidities were diabetes mellitus (32.6%), arterial hypertension (71.2%), congestive heart failure (19.1%), chronic kidney disease (12.6%), and hematological disorders (10.3%). The median number of comorbidities was 3 and median Charlson Comorbidity Index (CCI) was 5. A total of 61.8% patients received high-flow nasal oxygen therapy (HFNO) and 80.5% received mechanical ventilation (MV). Median duration of HFNO was 3, and that of MV was 7 days. ICU mortality rate was 72.7%. Survivors had significantly lower age, number of comorbidities, CCI, sequential organ failure assessment score, serum ferritin, C-reactive protein, D-dimer, and procalcitonin, interleukin-6, lactate, white blood cell, and neutrophil counts. They also had higher lymphocyte counts, PaO2/FiO2 ratio, and glomerular filtration rate at admission. Length of ICU stay was 9 days. The median survival was 11 days for mechanically ventilated patients, and 24 days for patients who were not mechanically ventilated. CONCLUSION: The parameters that differentiate survivors from non-survivors are in agreement with published data. Further multivariate analyses are warranted to identify individual mortality risk factors.

HIGH-FLOW NASAL CANNULA COMBINED WITH PRONE POSITIONING AS AN INTUBATION ALTERNATIVE IN COVID-19: A CASE REPORT AND REVIEW OF THE LITERATURE.

The use of high-flow nasal cannula (HFNC) in COVID-19 patients is a controversial topic due to the benefits and risks which may occur in patients and healthcare workers. The goal of this treatment modality is potential avoidance of invasive mechanical ventilation, but generation of aerosol and increased healthcare professional infection risk must be considered. We present a case of a SARS-CoV-2-positive 71-year-old male with acute hypoxemic respiratory failure, who was successfully treated with HFNC combined with prone positioning. Furthermore, we discuss recent literature concerning potential issues of HFNC treatment in COVID-19 patients.

Influence of different PEEP levels on electrical impedance tomography findings in patients under general anesthesia ventilated in the lateral decubitus position.

To determine the effect of various PEEP levels on electrical impedance tomography (EIT) measured differences in regional ventilation, hemodynamics, lung mechanics and parameters of alveolar gas exchange. Thirty three patients scheduled for elective urologic surgery in general anesthesia in lateral decubitus position were randomized into three groups-PEEP 0, 5 and 10 mbar. EIT recording, arterial blood gas analysis and hemodynamic parameters were captured at three timepoints-before induction (T0), 5 min after lateral positioning (T1) and 90 min after positioning (T2). Dynamic compliance (Cdyn) was measured at T1 and T2. Offline EIT data analysis was performed to calculate EIT derived parameters of ventilation distribution. Patients ventilated with PEEP of 10 mbar had a significantly lower A-a (alveolo arterial) gradient over measurements and symmetrical distribution of ventilation measured by EIT. There was no significant difference in Cdyn, center of ventilation indices and inhomogeneity index between groups. There was no difference of mean arterial pressure, cardiac index and heart rate between groups. Patients with 5 mbar of PEEP had higher stroke volume index compared to 0 and 10 mbar at baseline and over measurements. Nondependent/dependent TV ratio as well as global inhomogeneity index were correlated with A-a gradient. Dynamic compliance showed no correlation to A-a gradient. In our study, a PEEP level of 10 mbar improved alveolar gas exchange without compromising hemodynamic stability in patients mechanically ventilated in the lateral decubitus position. EIT measured parameters may be used to determine optimal ventilation parameters in these patients with inhomogeneous lung mechanics. Further studies are needed in patients with various lung pathologies.

Cardiopulmonary resuscitation performed by trained providers and shorter time to emergency medical team arrival increased patients' survival rates in Istra County, Croatia: a retrospective study.

AIM: To assess the effect of the time for emergency medical services (EMS) arrival on resuscitation outcome in the transition period of the EMS system in Istra County. METHODS: This retrospective study analyzed the data from 1440 patients resuscitated between 2011 and 2017. The effect of demographic data, period of the year, time for EMS arrival, initial cardiopulmonary resuscitation (CPR) provider, initial cardiac rhythm, and airway management method on CPR outcome was assessed with multivariate logistic regression. RESULTS: Survivors were younger than non-survivors (median of 66 vs 70 years, P<0.001) and had shorter time for EMS arrival (median of 6 vs 8 min, P<0.001). The proportion of non-survivors was significantly higher when initial basic life support (BLS) was performed by bystanders without training (83.8%) or when no CPR was performed before EMS team arrival (87.3%) than when BLS was performed by medical professionals (66.8%) (P<0.001). Sex, airway management, and tourist season had no effect on CPR outcome. CONCLUSION: Since the time for arrival and level of CPR provider training showed a significant effect on CPR outcome, further organizational effort should be made to reduce the time for EMS arrival and increase the number of individuals trained in BLS.

Are Dentists Hypocrites? Oral Self-care Habits and Self-reported Oral Health Status among Dentists and Non-dentists in Croatia.

Objectives: Dentists provide dental care to their patients and educate them on their oral hygiene and how to maintain oral health. This paper aimed to determine whether dentists are hypocritical when advising their patients on oral hygiene procedures and dental treatments because they do not apply to themselves what they recommend to others. Material and methods: This is a self-reported study conducted through an online survey questionnaire completed by 1001 participants, of whom 551 were non-dentists and 450 dentists. This is the first study on oral hygiene habits and oral status among dentists in Croatia. This research included almost 10% of the total number of working dentists in Croatia. Results: In terms of dental hygiene habits, dentists brushed, flossed and used interdental brushes more frequently, and they also changed toothbrushes more frequently, whereas they attended check-ups less frequently. Dentists also reported a smaller number of teeth with cavities, a greater number of teeth with fillings, a greater number of extracted teeth, and a greater number of dental crowns, but a smaller number of healthy teeth compared to general population. However, dentists had a much higher proportion of participants over 30 years of age, and when sub-analysis of participants over 30 years of age was performed, dentists had a greater number of healthy teeth compared to the general population. Conclusions: The results showed that dentists are aware of the importance of their oral health and that they do not pay attention only to their oral hygiene habits, but also apply advice they give their patients. Therefore, they cannot be considered hypocritical.

ABO Blood Type and Urinary Bladder Cancer: Phenotype, Genotype, Allelic Association with a Clinical or Histological Stage and Recurrence Rate.

Background Previous research on connection between the ABO blood group and bladder cancer has been based on determining the ABO phenotype. This specific research is extended to the molecular level, providing more information about particular ABO alleles. Aim To investigate the impact of the ABO blood group genotype or phenotype as a risk factor for urinary bladder cancer. Materials and Methods In the case-control study, we included 74 patients who underwent surgery for a urinary bladder tumor at the Urology Clinic, Clinical Hospital Centre Zagreb, in 2021 and 2022. The control group comprised 142 asymptomatic and healthy blood donors. ABO genotyping to five basic alleles was done using a polymerase chain reaction with sequence-specific primers. We compared ABO phenotypes, genotypes, and alleles between patients and the healthy controls and investigated their distribution according to the clinical and histological stage and recurrence rate. Results No statistically significant difference was found among the groups, nor for the observed disease stages in terms of the phenotype and genotype. At the allele level, the results show a significantly lower proportion of malignancy in O1 ( p < 0.001), A1 ( p < 0.001), and B ( p = 0.013), and a lower proportion of metastatic disease in A2 (0%, p = 0.024). We also found significantly higher proportions of high-grade tumors in patients with O1 (71.4%, p < 0.001), A1 (70.1%, p = 0.019), of nonmuscle invasive tumors in patients with O1 (55.1%, p < 0.001), O2 (100%, p = 0.045), and recurrent tumors in patients with O1 (70.2%, p < 0.001) and A1 (74.2%, p = 0.007) alleles. Conclusion We did not find an association between the ABO blood group genotype or phenotype as a genetic risk factor for urinary bladder cancer. However, an analysis at the allelic level revealed a statistically significant association between certain alleles of the ABO blood group system and urinary bladder tumors, clinical or histological stage, and recurrence rate, respectively.

POStoperative INTELLiVENT-adaptive support VEntilation in cardiac surgery patients (POSITiVE) II-study protocol of a randomized clinical trial.

BACKGROUND: One single-center randomized clinical trial showed that INTELLiVENT-adaptive support ventilation (ASV) is superior to conventional ventilation with respect to the quality of ventilation in post-cardiac surgery patients. Other studies showed that this automated ventilation mode reduces the number of manual interventions at the ventilator in various types of critically ill patients. In this multicenter study in patients post-cardiac surgery, we test the hypothesis that INTELLiVENT-ASV is superior to conventional ventilation with respect to the quality of ventilation. METHODS: "POStoperative INTELLiVENT-adaptive support VEntilation in cardiac surgery patients II (POSITiVE II)" is an international, multicenter, two-group randomized clinical superiority trial. In total, 328 cardiac surgery patients will be randomized. Investigators screen patients aged > 18 years of age, scheduled for elective cardiac surgery, and expected to receive postoperative ventilation in the ICU for longer than 2 h. Patients either receive automated ventilation by means of INTELLiVENT-ASV or ventilation that is not automated by means of a conventional ventilation mode. The primary endpoint is quality of ventilation, defined as the proportion of postoperative ventilation time characterized by exposure to predefined optimal, acceptable, and critical (injurious) ventilatory parameters in the first two postoperative hours. One major secondary endpoint is ICU team staff workload, captured by the ventilator software collecting manual settings on alarms. Patient-centered endpoints include duration of postoperative ventilation and length of stay in ICU. DISCUSSION: POSITiVE II is the first international, multicenter, randomized clinical trial designed to confirm that POStoperative INTELLiVENT-ASV is superior to non-automated conventional ventilation and secondary to determine if this closed-loop ventilation mode reduces ICU team staff workload. The results of POSITiVE II will support intensive care teams in their choices regarding the use of automated ventilation in postoperative care of uncomplicated cardiac surgery patients. TRIAL REGISTRATION: Clinicaltrials.gov NCT06178510 . Registered on December 4, 2023.

Evaluation of Contrast-Enhanced Mammography and Development of Flowchart for BI-RADS Classification of Breast Lesions.

This study aimed to evaluate contrast-enhanced mammography (CEM) and to compare breast lesions on CEM and breast magnetic resonance imaging (MRI) using 5 features. We propose a flowchart for BI-RADS classification of breast lesions on CEM based on the Kaiser score (KS) flowchart for breast MRI. Sixty-eight subjects (women and men; median age 61.4 ± 11.6 years) who were suspected of having a malignant process in the breast based on digital mammography (MG) findings were included in the study. The patients underwent breast ultrasound (US), CEM, MRI and biopsy of the suspicious lesion. There were 47 patients with malignant lesions confirmed by biopsy and 21 patients with benign lesions, for each of which a KS was calculated. In the patients with malignant lesions, the MRI-derived KS was 9 (IQR 8-9); its CEM equivalent was 9 (IQR 8-9); and BI-RADS was 5 (IQR 4-5). In patients with benign lesions, MRI-derived KS was 3 (IQR 2-3); its CEM equivalent was 3 (IQR 1.7-5); and BI-RADS was 3 (IQR 0-4). There was no significant difference between the ROC-AUC of CEM and MRI (p = 0.749). In conclusion, there were no significant differences in KS results between CEM and breast MRI. The KS flowchart is useful for evaluating breast lesions on CEM.

The size distribution of SARS-CoV-2 genetic material in airborne particles sampled in hospital and home care environments occupied by COVID-19 positive subjects.

Characterizing the size distribution of airborne particles carrying SARS-CoV-2 virus is essential for understanding and predicting airborne transmission and spreading of COVID-19 disease in hospitals as well as public and home indoor settings. Nonetheless, few data are currently available on virus-laden particle size distribution. Thus, the aim of this study is reporting the total concentrations and size distributions of SARS-CoV-2- genetic material in airborne particles sampled in hospital and home environments. A nanoMOUDI R122 cascade impactor (TSI, USA) was used to collect size-segregated aerosol down to the sub-micron range in home and in three different hospital environments in presence of infected patients in order to provide the concentration of airborne SARS-CoV-2 genetic material for each particle size range at different sampling locations. Providing one of the largest datasets of detailed size-fractionated airborne SARS-CoV-2 RNA to date, we found that 45.2 % of the total sub- and super-micrometric fractions were positive for SARS-CoV-2 with its genetic material being present in 17.7 % of sub-micrometric (0.18-1 µm) and 81.9 % of super-micrometric (>1 µm) fractions. The highest concentration of SARS-CoV-2 genetic material in total suspended particles (5.6 ± 3.4 RNA copies m-3) was detected in the room occupied with patients with more severe COVID-19 symptoms collected during the patients' high flow nasal oxygen therapy. The highest concentration at certain particle size fraction strongly depends on the sampling environment. However, the contribution of SARS-CoV-2 genetic material was in favour of super-micrometric compared to sub-micrometric particle size range. The evaluation of the individual risk of infection was carried out on the basis of the obtained data considering a hypothetical exposure scenario. The obtained results indicate the necessity of the protective masks in presence of infected subjects, especially while staying for longer period of time in the hospital environments.

Effects of epidurally administered dexmedetomidine and dexamethasone on postoperative pain, analgesic requirements, inflammation, and oxidative stress in thoracic surgery.

The aim of this study was to compare the effects of dexmedetomidine and dexamethasone as adjuvants to preoperative epidural administration of local anesthetic (ropivacaine) in thoracic surgery on the postoperative level of pain, use of analgesics, inflammation, and oxidative stress. The study enrolled 42 patients who underwent elective thoracic surgery in a one-year period at the University Hospital Dubrava (Zagreb, Croatia). Based on a computer-generated randomization list the patients were assigned to the dexmedetomidine (n = 18) or dexamethasone (n = 24) group. Postoperatively, patients of dexmedetomidine group reported lower pain (VAS value 1 h post surgery, 3.4 ± 2.7 vs. 5.4 ± 1.8, dexmedetomidine vs. dexamethasone, p < 0.01) and had lower anal-gesic requirements in comparison with dexamethasone group. Thus, dexmedetomidine in comparison with dexamethasone was more efficient in lowering pain and analgesia requirements 24 h after the surgery. On the contrary, dexamethasone had better anti-inflammatory properties (CRP level 24 h post surgery, 131.9 ± 90.7 vs. 26.0 ± 55.2 mg L-1, dexmedetomidine vs. dexamethasone, p < 0.01). Both dexmedetomidine and dexamethasone exhibited antioxidant effects, however, their antioxidant properties should be further explored. The results of this study improve current knowledge of pain control in thoracic surgery.

Inflammatory Biomarkers Affecting Survival Prognosis in Patients Receiving Veno-Venous ECMO for Severe COVID-19 Pneumonia.

Severe COVID-19 pneumonia in which mechanical ventilation is unable to achieve adequate gas exchange can be treated with veno-venous ECMO, eliminating the need for aggressive mechanical ventilation which might promote ventilator-induced lung injury and increase mortality. In this retrospective observational study, 18 critically ill COVID-19 patients who were treated using V-V ECMO during an 11-month period in a tertiary COVID-19 hospital were analyzed. Biomarkers of inflammation and clinical features were compared between survivors and non-survivors. Survival rates were compared between patients receiving ECMO and propensity matched mechanically ventilated controls. There were 7 survivors and 11 non-survivors. The survivors were significantly younger, with a higher proportion of females, higher serum procalcitonin at ICU admission, and before initiation of ECMO they had significantly lower Murray scores, PaCO2, WBC counts, serum ferritin levels, and higher glomerular filtration rates. No significant difference in mortality was found between patients treated with ECMO compared to patients treated using conventional lung protective ventilation. Hypercapnia, leukocytosis, reduced glomerular filtration rate, and increased serum ferritin levels prior to initiation of V-V ECMO in patients with severe COVID-19 pneumonia may be early warning signs of reduced chance of survival. Further multicentric studies are needed to confirm these findings.

Clinical and laboratory predictors at ICU admission affecting course of illness and mortality rates in a tertiary COVID-19 center.

BACKGROUND: Survival rates of critically ill COVID-19 patients are affected by various clinical features and laboratory parameters at ICU admission. Some of these predictors are universal but others may be population specific. OBJECTIVE: To determine utility of baseline clinical and laboratory parameters in a multivariate regression model to predict outcomes in critically ill COVID-19 patients in a tertiary hospital in Croatia. METHODS: 692 critically ill COVID-19 patients treated during a 10-month period were included in this retrospective observational trial to assess the risk factors determining mortality rates. Various anthropometric features, comorbidities, laboratory parameters, clinical features and therapeutic interventions were included in the analysis. ICU mortality rates and length of ICU stay were primary endpoints analyzed in this study. RESULTS: After multivariate adjustment, only the SOFA score, PaO2/FiO2 and history of arterial hypertension had an effect on ICU mortality, as well as the need to initiate invasive mechanical ventilation. Increase in PaO2/FiO2 over the first 7 days was present in survivors, while reverse applied to SOFA. Length of ICU stay was 9 (4-14) days. Factors affecting survival times were admission from wards, congestive heart failure, invasive mechanical ventilation, bacterial superinfections, age > 75 years, SOFA score, and serum ferritin, CRP and IL-6 values at ICU admission. CONCLUSION: Elevated inflammatory biomarkers and SOFA score at ICU admission were detected as significant predictors of ICU mortality in this cohort, while initiation of invasive mechanical ventilation is the most relevant interventional mortality risk factor in critically ill COVID-19 patients.

Distribution of Pathogens and Predictive Values of Biomarkers of Inflammatory Response at ICU Admission on Outcomes of Critically Ill COVID-19 Patients with Bacterial Superinfections-Observations from National COVID-19 Hospital in Croatia.

BACKGROUND: Superinfections contribute to mortality and length of stay in critically ill COVID-19 patients. The aim of this study was to determine the incidence and pathogen distribution of bacterial and fungal superinfections of the lower respiratory tract (LRTI), urinary tract (UTI) and bloodstream (BSI) and to determine the predictive value of biomarkers of inflammatory response on their ICU survival rates. METHODS: A retrospective observational study that included critically ill COVID-19 patients treated during an 11-month period in a Croatian national COVID-19 hospital was performed. Clinical and diagnostic data were analyzed according to the origin of superinfection, and multivariate regression analysis was performed to determine the predictive values of biomarkers of inflammation on their survival rates. RESULTS: 55.3% critically ill COVID-19 patients developed bacterial or fungal superinfections, and LRTI were most common, followed by BSI and UTI. Multidrug-resistant pathogens were the most common causes of LRTI and BSI, while Enterococcus faecalis was the most common pathogen causing UTI. Serum ferritin and neutrophil count were associated with decreased chances of survival in patients with LRTI, and patients with multidrug-resistant isolates had significantly higher mortality rates, coupled with longer ICU stays. CONCLUSION: The incidence of superinfections in critically ill COVID-19 patients was 55.3%, and multidrug-resistant pathogens were dominant. Elevated ferritin levels and neutrophilia at ICU admission were associated with increased ICU mortality in patients with positive LRTI.

The Dark Side of the Heart: Cardiovascular Manifestation of Ochronosis.

Alkaptonuria is rare genetic disorder of tyrosine metabolism manifesting with signs of tissue pigmentation, dark urine, and ochronotic arthropathies. Commonly undiscovered by late adulthood, alkaptonuria can manifest as cardiac ochronosis with cardiovascular disorders such as valvulopathies, but rarely coronary artery disease. This case report describes 2 patients with aortic stenosis and coronary artery disease in whom alkaptonuria was diagnosed during open heart surgery.