Impact of fluid balance and opioid-sparing anesthesia within enchanced recovery pathway on postoperative morbidity after transthoracic esophagectomy for cancer

BackgroundEnhanced Recovery After Surgery (ERAS) protocol for esophagectomy may reduce the high incidence of postoperative morbidity and mortality. The aim of this study was to assess the impact of properly conducted ERAS protocol with specific emphasis on fluid balance and opioid-sparing anesthesia (OSA) on postoperative major morbidity and mortality after esophagectomy.MethodsPatients undergoing elective esophagectomy for esophageal cancer at the Hospital for Digestive Surgery, University Clinical Center of Serbia, from December 2017 to March 2021, were included in this retrospective observational study. Patients were divided into two groups: the ERAS group (OSA, intraoperative goal-directed therapy, and postoperative “near-zero” fluid balance) and the control group (opioid-based anesthesia, maintenance mean blood pressure ≥ 65 mmHg, and liberal postoperative fluid management). The primary outcome was major morbidity within 30 days from surgery and 30-day and 90-day mortality. Multivariable analysis was used to examine the effect of the ERAS protocol.ResultsA total of 121 patients were divided into the ERAS group (69 patients) and the control group (52 patients). Patients in the ERAS group was received less fentanyl, median 300 (interquartile range (IQR), 200–1,550) mcg than in control group, median 1,100 (IQR, 650–1750) mcg, p < 0.001. Median intraoperative total infusion was lower in the ERAS group, 2000 (IQR, 1000–3,750) mL compared to control group, 3,500 (IQR, 2000–5,500) mL, p < 0.001. However, intraoperative norepinephrine infusion was more administered in the ERAS group (52.2% vs. 7.7%, p < 0.001). On postoperative day 1, median cumulative fluid balance was 2,215 (IQR, −150-5880) mL in the ERAS group vs. 4692.5 (IQR, 1770–10,060) mL in the control group, p = 0.002. After the implementation of the ERAS protocol, major morbidity was less frequent in the ERAS group than in the control group (18.8% vs. 75%, p < 0.001). There was no statistical significant difference in 30-day and 90-day mortality (p = 0.07 and p = 0.119, respectively). The probability of postoperative major morbidity and interstitial pulmonary edema were higher in control group (OR 5.637; CI95%:1.178–10.98; p = 0.030 and OR 5.955; CI95% 1.702–9.084; p < 0.001, respectively).ConclusionA major morbidity and interstitial pulmonary edema after esophagectomy were decreased after the implementation of the ERAS protocol, without impact on overall mortality

Is Increased Susceptibility to Balkan Endemic Nephropathy in Carriers of Common GSTA1 (*A/*B) Polymorphism Linked with the Catalytic Role of GSTA1 in Ochratoxin A Biotransformation? Serbian Case Control Study and In Silico Analysis

Although recent data suggest aristolochic acid as a putative cause of Balkan endemic nephropathy (BEN), evidence also exists in favor of ochratoxin A (OTA) exposure as risk factor for the disease. The potential role of xenobiotic metabolizing enzymes, such as the glutathione transferases (GSTs), in OTA biotransformation is based on OTA glutathione adducts (OTHQ-SG and OTB-SG) in blood and urine of BEN patients. We aimed to analyze the association between common GSTA1, GSTM1, GSTT1, and GSTP1 polymorphisms and BEN susceptibility, and thereafter performed an in silico simulation of particular GST enzymes potentially involved in OTA transformations. GSTA1, GSTM1, GSTT1 and GSTP1 genotypes were determined in 207 BEN patients and 138 non-BEN healthy individuals from endemic regions by polymerase chain reaction (PCR). Molecular modeling in silico was performed for GSTA1 protein. Among the GST polymorphisms tested, only GSTA1 was significantly associated with a higher risk of BEN. Namely, carriers of the GSTA1*B gene variant, associated with lower transcriptional activation, were at a 1.6-fold higher BEN risk than those carrying the homozygous GSTA1*A/*A genotype (OR = 1.6; p = 0.037). In in silico modeling, we found four structures, two OTB-SG and two OTHQ-SG, bound in a GSTA1 monomer. We found that GSTA1 polymorphism was associated with increased risk of BEN, and suggested, according to the in silico simulation, that GSTA1-1 might be involved in catalyzing the formation of OTHQ-SG and OTB-SG conjugates

The <i>GSTO2</i> (rs156697) Polymorphism Modifies Diabetic Nephropathy Risk

Background and Objectives: In the development of type 2 diabetes mellitus (T2DM) and its complications, genetic and environmental factors play important roles. Diabetic nephropathy (DN), one of the major microangiopathic chronic diabetic complications, is associated with an increased risk of major cardiovascular events and all-cause mortality. The present study was designed to investigate the possible modifying effect of glutathione transferase polymorphisms (GSTM1, GSTT1, GSTP1 rs1138272/rs1695, GSTO1 rs4925 and GSTO2 rs156697) in the susceptibility to T2DM and diabetic nephropathy. Materials and Methods: GSTM1 and GSTT1 deletion polymorphisms were determined by multiplex PCR, whereas GSTO1, GSTO2, and GSTP1 polymorphisms were determined by the real-time PCR in 160 T2DM patients and 248 age- and gender-matched controls. Advanced glycation end products (AGEs) were measured by ELISA. Results: Among six investigated GST polymorphisms, a significant association between the GST genotypes and susceptibility for development of diabetes mellitus was found for the GSTM1, GSTT1, GSTP1 (rs1138272) and GSTO1 polymorphisms. When the GST genotypes’ distribution in diabetes patients was assessed in the subgroups with and without diabetic nephropathy, a significant association was found only for the GSTO2 rs156697 polymorphism. Diabetic patients, carriers of the GSTM1 null, GSTT1 null and variant GSTO1*AA genotypes, had significantly increased levels of AGEs in comparison with carriers of the GSTM1 active, GSTT1 active and referent GSTO1*CC genotypes (p p p = 0.004, respectively). Conclusions: The present study supports the hypothesis that GST polymorphisms modulate the risk of diabetes and diabetic nephropathy and influence the AGEs concentration, suggesting the potential regulatory role of these enzymes in redox homeostasis disturbances

Dilemmas in the Choice of Adequate Therapeutic Treatment in Patients with Acute Pulmonary Embolism—From Modern Recommendations to Clinical Application

Pulmonary thromboembolism is a very common cardiovascular disease, with a high mortality rate. Despite the clear guidelines, this disease still represents a great challenge both in diagnosis and treatment. The heterogeneous clinical picture, often without pathognomonic signs and symptoms, represents a huge differential diagnostic problem even for experienced doctors. The decisions surrounding this therapeutic regimen also represent a major dilemma in the group of patients who are hemodynamically stable at initial presentation and have signs of right ventricular (RV) dysfunction proven by echocardiography and positive biomarker values (pulmonary embolism of intermediate–high risk). Studies have shown conflicting results about the benefit of using fibrinolytic therapy in this group of patients until hemodynamic decompensation, due to the risk of major bleeding. The latest recommendations give preference to new oral anticoagulants (NOACs) compared to vitamin K antagonists (VKA), except for certain categories of patients (patients with antiphospholipid syndrome, mechanical valves, pregnancy). When using oral anticoagulant therapy, special attention should be paid to drug–drug interactions, which can lead to many complications, even to the death of the patient. Special population groups such as pregnant women, obese patients, patients with antiphospholipid syndrome and the incidence of cancer represent a great therapeutic challenge in the application of anticoagulant therapy. In these patients, not only must the effectiveness of the drugs be taken into account, but great attention must be paid to their safety and possible side effects, which is why a multidisciplinary approach is emphasized in order to provide the best therapeutic option

Acute Coronary Syndrome in the COVID-19 Era—Differences and Dilemmas Compared to the Pre-COVID-19 Era

The COVID-19 pandemic has led to numerous negative implications for all aspects of society. Although COVID-19 is a predominant lung disease, in 10–30% of cases, it is associated with cardiovascular disease (CVD). The presence of myocardial injury in COVID-19 patients occurs with a frequency between 7–36%. There is growing evidence of the incidence of acute coronary syndrome (ACS) in COVID-19, both due to coronary artery thrombosis and insufficient oxygen supply to the myocardium in conditions of an increased need. The diagnosis and treatment of patients with COVID-19 and acute myocardial infarction (AMI) is a major challenge for physicians. Often the presence of mixed symptoms, due to the combined presence of COVID-19 and ACS, as well as possible other diseases, nonspecific changes in the electrocardiogram (ECG), and often elevated serum troponin (cTn), create dilemmas in diagnosing ACS in COVID-19. Given the often-high ischemic risk, as well as the risk of bleeding, in these patients and analyzing the benefit/risk ratio, the treatment of patients with AMI and COVID-19 is often associated with dilemmas and difficult decisions. Due to delays in the application of the therapeutic regimen, complications of AMI are more common, and the mortality rate is higher

Use of Anticoagulant Therapy in Patients with Acute Myocardial Infarction and Atrial Fibrillation

The incidence of atrial fibrillation (AF) in acute coronary syndrome (ACS) ranges from 2.3–23%. This difference in the incidence of AF is explained by the different ages of the patients in different studies and the different times of application of both reperfusion and drug therapies in acute myocardial infarction (AMI). About 6–8% of patients who underwent percutaneous intervention within AMI have an indication for oral anticoagulant therapy with vitamin K antagonists or new oral anticoagulants (NOAC).The use of oral anticoagulant therapy should be consistent with individual risk of bleeding as well as ischemic risk. Both HAS-BLED and CHA2DS2VASc scores are most commonly used for risk assessment. Except in patients with mechanical valves and antiphospholipid syndrome, NOACs have an advantage over vitamin K antagonists (VKAs). One of the advantages of NOACs is the use of fixed doses, where there is no need for successive INR controls, which increases the patient’s compliance in taking these drugs. The use of triple therapy in ACS is indicated in the case of patients with AF, mechanical valves as well as venous thromboembolism. The results of the studies showed that when choosing a P2Y12 receptor blocker, less potent P2Y12 blockers such as Clopidogrel should be chosen, due to the lower risk of bleeding. It has been proven that the presence of AF within AMI is associated with a higher degree of reinfarction, more frequent stroke, high incidence of heart failure, and there is a correlation with an increased risk of sudden cardiac death. With the appearance of AF in ACS, its rapid conversion into sinus rhythm is necessary, and in the last resort, good control of heart rate in order to avoid the occurrence of adverse clinical events