Perioperative management of a double valve replacement and coronary artery bypass graft in a patient with carcinoid syndrome; a case report and literature review.

INTRODUCTION: Carcinoid tumors are rare neuroendocrine tumors; about 5% of patients develop the carcinoid syndrome. We present the case of a patient with carcinoid syndrome undergoing cardiac surgery. CASE REPORT: A 74-year-old patient with carcinoid heart disease and hepatic metastases underwent double valve replacement and CABG. The patient was on octreotide therapy and antihypertensive medication. An octreotide infusion was commenced perioperatively. Pharmaceutical agents that could potentially precipitate histamine release or exacerbate catecholamine secretion and carcinoid crises were avoided. Postoperatively, recovery was complicated by atrial fibrillation, chest infection, pleural effusions, acute kidney injury and delirium. DISCUSSION: Hepatic metastases cause systemic hormones' secretion, which cause a carcinoid crisis. Perioperative administration of octreotide is used, while vigilance is required to differentiate between hemodynamic effects related to the operation or disease specific factors. CONCLUSION: No carcinoid crisis was evident perioperatively. High vigilance with appropriate monitoring, aggressive management combined with meticulous choice of pharmaceutical agents led to this outcome.

The Efficacy of the Combination of Continuous Femoral Nerve Block and Intravenous Parecoxib on Rehabilitation in Patients Undergoing Total Knee Arthroplasty: A Double-Blind, Randomized Clinical Trial.

BACKGROUND AND AIM: The optimal strategy for the management of postoperative pain after total knee arthroplasty (TKA) remains challenging, while its treatment is crucial to increase patients' outcomes. This study aimed to investigate the effects of parecoxib as add-on therapy, in a standard postoperative pain management protocol, represented by the continuous femoral nervous block. We studied its influence on rehabilitation indices and pain scores in patients undergoing TKA. MATERIAL AND METHODS: This is a single-center, prospective, double-blind, randomized, placebo-controlled trial. All patients were operated with the use of subarachnoid anesthesia, and divided into two groups for postoperative analgesia. Both groups received a continuous femoral nerve block. One of the groups received intravenous parecoxib, while the other received a placebo. The primary investigated outcome was the range of motion (ROM). Recordings were noted at different times postoperatively. Bromage score (BS), visual analog scale (VAS), and the State-Trait Anxiety Inventory (STAI) were also studied. RESULTS: A total of 90 patients were included and analyzed. ROM was significantly better (p<0.001) and pain scores were significantly lower (p=0.007) in the parecoxib group. No statistically significant difference was found with regard to BS between the two groups. A significant correlation was found between ROM and VAS pain scores at 12 hours (p=0.02), while ROM was inversely correlated with STAI postoperatively. CONCLUSIONS: The use of intravenous parecoxib is effective in improving rehabilitation indices and provides decreased postoperative pain scores after TKA.

Individualized heparin monitoring and management reduces protamine requirements in cardiac surgery on minimal invasive extracorporeal circulation; A prospective randomized study.

INTRODUCTION: Individualized heparin and protamine management is increasingly used as a strategy to reduce coagulation activation and bleeding complications. While it is associated with increased heparin requirements during Cardiopulmonary Bypass (CPB), the impact on protamine administration remains controversial. We aim to investigate the effect of heparin level-guided monitoring on protamine dosing during cardiac surgery where low-anticoagulation protocols are implemented. METHODS: This is a prospective, randomized, controlled trial. A total of 132 patients undergoing elective full-spectrum cardiac surgery with Minimal Invasive Extracorporeal Circulation (MiECC) were recruited. All patients were managed by the same anaesthetic, surgical and perfusion team. Patients were randomly allocated in two groups; the individualized heparin-protamine titration (IHPT) group and the conventional heparinization and reversal group by using ACT (cACT) with a 0.75:1, protamine: heparin ratio. Titration was accomplished with the Hepcon HMS Plus (Medtronic, Minneapolis, MN) system. The primary outcome of the study was the total protamine dose used. Secondary outcomes comprised of the total heparin dose, the percentage of patients achieving target ACT, 24-h transfusion requirements, postoperative bleeding, duration of mechanical ventilation, major morbidity and length of hospital stay. Patients in each group were divided in two subgroups according to the target ACT; those operated for coronary artery bypass grafting (CABG) using a target ACT >300 s and the rest (non-CABG) patients operated with a target ACT >400 s, respectively. RESULTS: Protamine requirements were significantly reduced when IHPT was implemented; CABG (118 ± 24 mg vs 163 ± 61 mg; p < 0.001) and non-CABG cases (151 ± 46 mg vs 197 ± 45 mg; p < 0.001). Moreover, heparin requirements were significantly higher in the non-CABG subgroup managed with IHPT (34,539 ± 7658 IU vs 29,893 ± 9037 IU; p = 0.02). In overall, no significant differences were detected with respect to postoperative bleeding, transfusion of RBC or other blood products. CONCLUSIONS: Individualized heparin monitoring and management reduces protamine requirements in cardiac surgery with MiECC implementing reduced anticoagulation strategy. TRIAL REGISTRATION: clinicaltrials.gov; NCT04215588.

Monitoring the Cerebral Oximetry Index Along With In-line Cardiopulmonary Bypass Parameters in a High-Risk Patient Undergoing Cardiac Surgery: A Case Report.

The quest to minimize the morbidity and mortality of patients undergoing cardiac surgery is ongoing. Impaired cerebral autoregulation and tissue malperfusion are linked with neurological complications. The cerebral oximetry index (COx) has been introduced as an index of cerebral autoregulation, while in-line monitoring enables the detection and prevention of metabolic disturbances during cardiopulmonary bypass (CPB). This report presents the case of a 58-year-old female patient scheduled for aortic valve replacement under minimally invasive extracorporeal circulation (MiECC). Her medical history consisted of epilepsy, multiple ischemic strokes, heavy smoking, and brachiocephalic artery stenosis. We sought to investigate the limits of autoregulation and the role of metabolic indices of perfusion on COx. Mean arterial blood pressure (ABP), cerebral oximetry (rSO2), and in-line perfusion data during CPB were recorded at 10s intervals. The lower limit of autoregulation was 44mmHg on both sides and the upper limit was 98mmHg on the right and 107mmHg on the left side. A multiple linear regression analysis was performed to identify any potential predictors of COx values. Hemoglobin (Hb), PCO2, flow, DO2 index (DO2i), Ο2 extraction ratio (O2ER), and perfusion ratio (PR) were included in the analysis. Significant equations were found on both sides. Predicted COx left was equal to 5.8 - 11.04O2ER - 0.04Hb (p=0.001, R2= 0.15). Predicted COx right was equal to 3.06 - 0.3flow - 6.8O2ER -0.03Hb + 0.02PCO2 + 0.004DO2i(p=0.03, R2=0.13). Targeting physiological perfusion and monitoring perfusion during CPB may have an additional impact on cerebral autoregulation and should be studied further.

The feasibility and effect of intraperitoneal administration of regorafenib on peritoneal carcinomatosis from colorectal cancer in the rat.

AIM: Our goal was to investigate the potential use and efficacy of regorafenib for IPEC in an animal model of colorectal derived peritoneal metastases. Twenty four male rats were included. Carcinogenesis was induced in all rats through intraperitoneal injection of cancer. MATERIAL AND METHODS: Cells at T0. At T1(Day 28) they were randomly allocated 1:1:1:1 into 4 groups and underwent median laparotomy and the corresponding intervention. Specifically, Group A: no other intervention; Group B: cytoreductive surgery; Group C: intraperitoneal chemotherapy with regorafenib; and Group D: cytoreductive surgery and intraperitoneal chemotherapy with regorafenib. At T2 (Day 56) rats were euthanized and laparotomy was performed for further investigation. The primary outcome was the experimental Peritoneal Cancer Index (ePCI) at T2. Secondary outcomes include relative change of body weight between T1 and T2, weight of the ascites, anastomotic leak/peritonitis and death. RESULTS: The ePCI was significantly lower in Group D as opposed to all other groups. Comparing Group C versus Group A we found a trend towards lesser tumor progression, but no significant difference. Growth of rats in Group D was significantly least affected compared to all other groups. Animals undergoing CRS in Group B developed less ascites than Group A and C. Less ascites was found in Group D compared to Group A and C. CONCLUSIONS: Intraperitoneal chemotherapy with regorafenib combined with cytoreductive surgery may impair metastases' progression. KEY WORDS: Regorafenib, Chemotherapy, Cytoreductive surgery, Colorectal cancer, Intraperitoneal injection.

Breakthrough infections after COVID-19 vaccination: Insights, perspectives and challenges.

Vaccination programs against SARS-CoV-2 constitute the mainstay of public health interventions against the global COVID-19 pandemic. Currently available vaccines have shown 90% or better rates of protection against severe disease and mortality. Barely a year after vaccines became available, the Omicron variant and its unprecedented speed of transmission has posed a new challenge. Overall, Omicron presents increased immune escape, transmissibility, and decreased pathogenicity. Vaccines do not offer a full protection against SARS-CoV-2 acquisition, since "breakthrough" infections may occur in fully vaccinated individuals, who may in turn spread the virus to others. Breakthrough infections may be causally related to the viral profile (viral variant and load, incubation period, transmissibility, pathogenicity, immune evasion), immunity characteristics (mucosal versus systemic immunity, duration of immunity, etc.), host determinants (age, comorbidities, immune status, immunosuppressive drugs) and vaccination properties (platform, antigen dose, dose number, dose interval, route of administration). Determining the rate of breakthrough infections may be challenging and necessitates the conduction of population-based studies regarding vaccine effectiveness as well as neutralizing antibody testing, a surrogate of immune protection. In this review, we analyze the causes of breakthrough infections, their clinical consequences (severity of infection and transmission), methods of determining their incidence as well as challenges and perspectives. Long COVID as well as multi-inflammatory syndrome in adolescents may be significantly reduced in breakthrough infections. The need for universal pancoranavirus vaccines that would aim at protecting against a plethora of SARS-CoV-2 variants as well as emerging variants is discussed. Finally, novel vaccine strategies, such as nasal vaccines, may confer robust mucosal and systemic protection, reducing efficiently transmission.

Minimal invasive extracorporeal circulation preserves coagulation integrity.

INTRODUCTION: Coagulopathy after cardiac surgery is a serious multifactorial complication that results in postoperative bleeding requiring transfusion of red blood cells and procoagulant products. Use of cardiopulmonary bypass represents the major contributing factor affecting coagulation. We sought to prospectively investigate the effect of contemporary minimal invasive extracorporeal circulation (MiECC) on coagulation parameters using point-of-care (POC) rotational thromboelastometry and the relation to postoperative bleeding. METHODS: Patients undergoing elective cardiac surgery on MiECC were prospectively recruited. Anticoagulation strategy was based on individualized heparin management and heparin level-guided protamine titration. Rotational thromboelastometry testing was performed before induction of anesthesia and after aortic cross-clamp release. A strict POC-guided transfusion protocol was implemented. The primary endpoint was the assessment of viscoelastic properties of the coagulating blood at the end of surgery compared to preoperative values and the relation to postoperative bleeding and 24-hour transfusion requirements. RESULTS: Fifty patients were included in the study with a significant proportion having complex surgery. Thirteen patients (26%) required blood transfusion (mean rate: 0.5 ± 1 units per patient), 5/50 (10%) received coagulation factors while no patient received fresh frozen plasma, platelets or fibrinogen. Thromboelastometry analysis showed that the major derangement was CT EXTEM > 100 seconds in 28/50 (56%) and A10 EXTEM < 40 mm in one (2%) patient without clinical significance. Platelet function was preserved throughout surgery. A10-FIBTEM was found predictive of postoperative bleeding at 12 hours. CONCLUSIONS: MiECC preserves clot quality throughout surgery acting in both key determinants of clot strength; fibrinogen and platelets. This is clinically translated into minimal postoperative bleeding and restricted use of blood products and coagulation factors.

Effect of N-acetyl-L-cysteine on inflammation after intraperitoneal mesh placement in a potentially contaminated environment: An experimental study in the rat.

BACKGROUND: The use of prosthetic meshes in abdominal wall reconstruction is a well-established approach; however, in certain cases where a bowel resection coexists its application is disputed. Any underlying inflammatory process may augment adhesion formation which is a major postoperative complication. In this animal study, our aim was to investigate the effect of N-acetyl-l-cysteine (NAC) on adhesion formation and the expression of inflammatory markers when a mesh was used in a clean or a potentially contaminated environment. METHODS: Sixty male Wistar rats were randomly and equally allocated in 3 groups: A, B and C. Animals in all groups underwent laparotomy, a prosthetic mesh was placed and chemoprophylaxis with ciprofloxacin was administered. In groups B and C an enterectomy was also performed. NAC was injected intraperitoneally in group C. Adhesion formation, IL-1a, IL-6, TNF-a and histological data including fibrosis, neutrophils' infiltration and neovascularization were assessed. Mesh samples were sent for cultivation. RESULTS: Adhesion formation was significantly less and inflammation markers were also lower in group C compared to group B (p<0.05). Histological findings were significant for greater fibrosis, neutrophils' infiltration and neovascularization in group B compared to both group A and C. Regarding mesh cultures, more specimens were tested positive in group B (p <0.05). Outcomes between group A and C did not differ. CONCLUSION: NAC effectively ameliorated adhesion formation and inflammation in a potentially septic environment where a prosthetic mesh was placed.

Giant Adrenocortical Carcinoma: A Case Report and Review of the Relevant Literature.

BACKGROUND Adrenocortical carcinomas are rare and aggressive tumors often diagnosed as incidentalomas. The malignancy can present with abnormal hormone secretion or the tumor may be non-functioning and present as a palpable mass causing discomfort. Here, we present a case of an adrenal cortical carcinoma originally identified as an incidentaloma. CASE REPORT A 63-year-old woman presented with abdominal pain and discomfort. A large abdominal mass, occupying the left upper and lower quadrant, was palpated. Imaging revealed a mass occupying the left abdomen between the stomach and the spleen, applying pressure on the pylorus, duodenum, splenic vessels, and pancreas. The mass size was 21.2×13×14.6 cm. Hormonal investigations were normal. Surgical exploration was performed, and the tumor was excised. Pathological analysis revealed an adrenocortical carcinoma and the patient underwent adjuvant chemotherapy. Twelve months later, the carcinoma recurred. The patient underwent a second operation in which the recurrent mass was excised along with the tail of the pancreas and a small part of the left lobe of the liver. The postoperative period was uneventful, and the patient was discharged home on the 7th postoperative day. No further adjuvant therapy was applied. The patient remains disease-free 18 months after the reoperation. CONCLUSIONS Giant adrenocortical carcinomas, although rare, pose a challenge to the surgical team both diagnostically and therapeutically. Surgical excision with the appropriate oncologic support can guarantee excellent outcomes.

Metalloproteinase expression after desflurane preconditioning in hepatectomies: A randomized clinical trial.

BACKGROUND: Hepatectomy with inflow occlusion results in ischemia-reperfusion injury; however, pharmacological preconditioning can prevent such injury and optimize the postoperative recovery of hepatectomized patients. The normal inflammatory response after a hepatectomy involves increased expression of metalloproteinases, which may signal pathologic hepatic tissue reformation. AIM: To investigate the effect of desflurane preconditioning on these inflammatory indices in patients with inflow occlusion undergoing hepatectomy. METHODS: This is a single-center, prospective, randomized controlled trial conducted at the 4th Department of Surgery of the Medical School of Aristotle University of Thessaloniki, between August 2016 and December 2017. Forty-six patients were randomized to either the desflurane treatment group for pharmacological preconditioning (by replacement of propofol with desflurane, administered 30 min before induction of ischemia) or the control group for standard intravenous propofol. The primary endpoint of expression levels of matrix metalloproteinases and their inhibitors was determined preoperatively and at 30 min posthepatic reperfusion. The secondary endpoints of neutrophil infiltration, coagulation profile, activity of antithrombin III (AT III), protein C (PC), protein S and biochemical markers of liver function were determined for 5 d postoperatively and compared between the groups. RESULTS: The desflurane treatment group showed significantly increased levels of tissue inhibitor of metalloproteinases 1 and 2, significantly decreased levels of matrix metalloproteinases 2 and 9, decreased neutrophil infiltration, and less profound changes in the coagulation profile.  During the 5-d postoperative period, all patients showed significantly decreased activity of AT III, PC and protein S (vs baseline values, P < 0.05). The activity of AT III and PC differed significantly between the two groups from postoperative day 1 to postoperative day 5 (P < 0.05), showing a moderate drop in activity of AT III and PC in the desflurane treatment group and a dramatic drop in the control group. Compared to the control group, the desflurane treatment group also had significantly lower international normalized ratio values on all postoperative days (P < 0.005) and lower serum glutamic oxaloacetic transaminase and serum glutamic pyruvic transaminase values on postoperative days 2 and 3 (P < 0.05).   Total length of stay was significantly less in the desflurane group (P = 0.009). CONCLUSION: Desflurane preconditioning can lessen the inflammatory response related to ischemia-reperfusion injury and may shorten length of hospitalization.

Blood and fluid management during scoliosis surgery: a single-center retrospective analysis.

AIM: In the present retrospective study in scoliosis surgery, we hypothesized that application of a protocol for blood and fluid management, based on goal-directed fluid therapy, cell salvage and tranexamic acid, could lead to reduced allogeneic red blood cells transfusion. METHODS AND MATERIAL: Thirty-five patients, with American Society of Anesthesiologists physical status I/III, between 14 and 18 years scheduled for elective orthopedic surgery of scoliosis, with a planned intensive care unit admission, were enrolled in a retrospective observational study. Patients were divided in two groups. Patients in no-protocol group (Group noPro, n = 18) received a liberal intraoperative fluid therapy and patients in protocol group (Group Pro, n = 17) received fluid therapy managed according to a stroke volume variation-based protocol. The protocol included fluid therapy according to SVV monitor, permissive hypotension, tranexamic acid infusion, restrictive RBC trigger and use of perioperative cell savage. STATISTICAL ANALYSIS USED: Student's t test (2-tailed), Mann-Whitney test, Chi square test were used for statistical analysis of the data. RESULTS: There were no significant differences between the two groups in demographic data and clinical characteristics. Infused crystalloids (p = .003) and transfused allogeneic red blood cells (p = .015) were lesser in Group Pro compared to Group noPro. On the other hand, diuresis (p < .001) and vasopressors administration (p = .042) were higher in Group Pro than in Group noPro. CONCLUSION: The application of a protocol for blood and fluid management, based on goal-directed fluid therapy, cell salvage and tranexamic acid, was associated with less crystalloid fluid administration, less perioperative RBC transfusions and significantly better diuresis than patients in the no-protocol group in scoliosis surgery. REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT03814239.

Minimal invasive extracorporeal circulation preserves platelet function after cardiac surgery: a prospective observational study.

INTRODUCTION: Cardiac surgery on conventional cardiopulmonary bypass induces a combination of thrombocytopenia and platelet dysfunction which is strongly related to postoperative bleeding. Minimal invasive extracorporeal circulation has been shown to preserve coagulation integrity, though effect on platelet function remains unclear. We aimed to prospectively investigate perioperative platelet function in a series of patients undergoing cardiac surgery on minimal invasive extracorporeal circulation using point-of-care testing. METHODS: A total of 57 patients undergoing elective cardiac surgery on minimal invasive extracorporeal circulation were prospectively recruited. Anticoagulation strategy was based on individualized heparin management and heparin level-guided protamine titration performed in all patients with a specialized point-of-care device (Hemostasis Management System - HMS Plus; Medtronic, Minneapolis, MN, USA). Platelet function was evaluated with impedance aggregometry using the ROTEM platelet (TEM International GmbH, Munich, Germany). ADPtest and TRAPtest values were assessed before surgery and after cardiopulmonary bypass. RESULTS: ADPtest value was preserved during surgery on minimal invasive extracorporeal circulation (58.2 ± 20 U vs. 53.6 ± 21 U; p = 0.1), while TRAPtest was found significantly increased (90 ± 27 U vs. 103 ± 38 U; p = 0.03). Postoperative ADPtest and TRAPtest values were inversely related to postoperative bleeding (correlation coefficient: -0.29; p = 0.03 for ADPtest and correlation coefficient: -0.28; p = 0.04 for TRAPtest). The preoperative use of P2Y12 inhibitors was identified as the only independent predictor of a low postoperative ADPtest value (OR = 15.3; p = 0.02). CONCLUSION: Cardiac surgery on minimal invasive extracorporeal circulation is a platelet preservation strategy, which contributes to the beneficial effect of minimal invasive extracorporeal circulation in coagulation integrity.

The aberrant right subclavian artery: cadaveric study and literature review.

PURPOSE: Taking into consideration that the aberrant right subclavian artery (ARSA) is the commonest congenital aortic arch anomaly (prevalence 0.16-4.4%), our goal was to investigate its incidence in Greeks, with respect to location, course, and relationship to trachea and esophagus. Gender dimorphism, coexisting neural, and vascular variations were also examined. The clinical impact and embryological background of the variation are discussed. METHODS: Two hundred and sixty-seven (126 male and 141 female) formalin-embalmed Greek cadavers (mean age 59 ± 13 years) were examined. RESULTS: The ARSA was detected in 6 cadavers (2.2%), 4 females (2.8%) and 2 males (1.6%). The artery followed a retroesophageal course in 83%, an interesophageotracheal course in 16.7%, while no pretracheal ARSA was detected. The ARSA coexisted with a bicarotid trunk, a Kommerell diverticulum, and a combination of them in one cadaver. Α combination of the ARSA with a thyroidea ima artery and a bilateral abnormal origin of the internal mammary artery was also detected in one case (17%), while no other associated anomaly was detected in a single case (17%). All ARSAs were accompanied with a right non-recurrent laryngeal nerve. CONCLUSION: The ARSA has a relative high incidence in Greeks and a female predominance. The aberrant vessel follows a retroesophageal course in most cases and only one case with a location between trachea and esophagus was detected. The retroesophageal ARSA justifies the wide variety of clinical manifestations and complications occurred.