Retinal microvascular complexity as a putative biomarker of biological age: a pilot study.

Physiological changes associated with aging increase the risk for the development of age-related diseases. This increase is non-specific to the type of age-related disease, although each disease develops through a unique pathophysiologic mechanism. People who age at a faster rate develop age-related diseases earlier in their life. They have an older "biological age" compared to their "chronological age". Early detection of individuals with accelerated aging would allow timely intervention to postpone the onset of age-related diseases. This would increase their life expectancy and their length of good quality life. The goal of this study was to investigate whether retinal microvascular complexity could be used as a biomarker of biological age. Retinal images of 68 participants ages ranging from 19 to 82 years were collected in an observational cross-sectional study. Twenty of the old participants had age-related diseases such as hypertension, type 2 diabetes, and/or Alzheimer's dementia. The rest of the participants were healthy. Retinal images were captured by a hand-held, non-mydriatic fundus camera and quantification of the microvascular complexity was performed by using Sholl's, box-counting fractal, and lacunarity analysis. In the healthy subjects, increasing chronological age was associated with lower retinal microvascular complexity measured by Sholl's analysis. Decreased box-counting fractal dimension was present in old patients, and this decrease was 2.1 times faster in participants who had age-related diseases (p = 0.047). Retinal microvascular complexity could be a promising new biomarker of biological age. The data from this study is the first of this kind collected in Montenegro. It is freely available for use.

Impact of Perioperatively Administered Amino Acids, Lidocaine, and Magnesium on Inflammatory Response and Pain Associated with Abdominal Surgery: A Prospective Clinical Study.

BACKGROUND Abdominal surgery is associated with a systemic inflammatory response which facilitates postoperative complications through immune imbalance and hypercatabolism. The aim of the study was to evaluate the effect of the combined perioperative lidocaine, magnesium, and amino acids on postoperative inflammation and pain. MATERIAL AND METHODS This prospective, randomized, double-blind study included 2 groups of patients undergoing abdominal surgery: Group 1 - receiving the aforementioned substances; and Group 2 - control (undergoing conventional general anesthesia). The following parameters were evaluated intraoperatively: arterial blood pressure, end-tidal CO2 level, urine output, bispectral index, base excess, oxygen saturation, operating room temperature and body temperature (BT), opioid use, and surgery duration; and postoperatively: total leukocyte (WBC), neutrophil, lymphocyte and platelet count; fibrinogen, C-reactive protein (CRP), procalcitonin (PCT) and interleukin (IL)-6 levels; numeric rating scale (NRS) pain level, first flatus and bowel movement, and postoperative complications. The postoperative parameters were evaluated 2 h and 6 h postoperatively, as well as on postoperative days (POD) 1, 2, 3, and 5. RESULTS Group 1 showed lower counts of WBC, neutrophils, and lymphocytes and lower fibrinogen, CRP, PCT, IL-6, and BT in the first 5 POD, as well as NRS scores and time to first flatus/bowel movement. The groups did not differ significantly regarding postoperative complications. CONCLUSIONS The isolated effects of lidocaine, magnesium, and amino acids in surgery have been described previously. To the best of our knowledge, this is the first study to show the anti-inflammatory and analgesic effects of simultaneous use of these substances in abdominal surgery.

HSP60, SP110 and TNF-α expression in Chlamydia pneumoniae-positive versus Chlamydia pneumoniae-negative atherosclerotic plaques.

Traditionally recognized risk factors for atherosclerosis are not presented in 50% of patients with ischemic heart disease. Chronic inflammation with low pathogenic agents with slightly, or no signs of inflammation is the mainstay of atherosclerosis and could be triggered by an infectious agent, most commonly by Chlamydia pneumoniae. Immunostaning of 33 Chlamydia pneumoniae-positive and 30 Chlamydia pneumoniae- negative quadriple arterial sets were examined for protective Sp110, and atherogenic HSP60 markers, as well as for TNF-α which is inflammatory marker affected by both of them. The Chlamydia pneumoniae-negative deceased subjects were statistically significantly older and their BMI was significantly lower. The results showed that age, hypercholesterolemia, diabetes, arterial hypertension and BMI were negatively correlated with Chlamydia pneumoniae-positivity, while no significant relationship was found between Chlamydia pneumoniae-positivity and a positive family history of cardiovascular diseases, as well as smoking. Significantly higher presence of Sp110 in Chlamydia pneumoniae-negative group versus significantly higer presence od HSP60 in Chlamydia pneumoniae-positive group. Chlamydia pneumoniae-negative plaques showed higher TNF-α expression; difference is present for all arteries examined except the Willis circle. This study may provide a model for further understanding the mechanisms of Chlamydia pneumoniae atherogenesis and evaluating chlamydial intervention strategies for preventing the advancement of atherosclerotic lesions enhanced by bacterial infections.

First case of drug-induced liver injury associated with the use of tocilizumab in a patient with COVID-19.

BACKGROUND AND AIMS: Tocilizumab (TCZ; interleukine-6 receptor antagonist) has been proposed to treat severe forms of Coronavirus disease-19 (COVID-19) because interleukine-6 plays an important role in COVID-19-induced cytokine storm. Several clinical studies have shown very good effects of TCZ in patients with COVID-19, with a few minor side effects reported. Only eight serious liver injuries caused by TCZ were reported before being used in the treatment of patients with COVID-19. Considering the significantly increased use of TCZ for the treatment of COVID-19, we would like to warn of its rare but possible serious hepatotoxicity, especially when used together with other hepatotoxic drugs. METHODS: We describe a patient with COVID-19-induced cytokine storm who developed drug-induced liver injury associated with the use of TCZ. RESULTS: One day after TCZ administration, serum transaminase levels increased 40-fold. Nevertheless, TCZ had a positive effect on clinical and laboratory parameters in cytokine storm, with transaminases values normalizing in 10 days. CONCLUSIONS: This is the first reported case of DILI caused by TCZ in a COVID-19 patient. Intensive liver function monitoring is imperative in COVID-19 patients, because of frequent polypharmacy with potentially hepatotoxic drugs.

The pterygopalatine fossa: morphometric CT study with clinical implications.

PURPOSE: The pterygopalatine fossa is a deep viscerocranial space containing the maxillary artery and nerve, the pterygopalatine ganglion, and the nerve of the pterygoid canal (vidian nerve). The endoscopic approach to this area relies on adequate preoperative imaging, such as computed tomography (CT). The aim was to determine the morphometric characteristics of the pterygopalatine fossa and its communications, including several previously unpublished measurements. METHODS: 100 CT scans (56 male and 44 female patients) were analyzed. The axial, coronal, and sagittal slices, together with the three-dimensional reconstructions, were used in the study. RESULTS: The central diameter and the length of the foramen rotundum, the vertical diameter and the length of the pterygoid (vidian) canal, and the diameter of the sphenopalatine foramen were significantly larger in men. The central diameters of the foramen rotundum and the vidian canal were significantly smaller than their anterior and posterior transverse diameters. The vidian canal length of 12.1 mm indicates the presence of the type 3 VC with a sensitivity of 83% and a specificity of 85%. CONCLUSION: Several new descriptions of the pterygopalatine fossa are presented here (such as the angle between the sphenopalatine foramen and the vidian canal, a new aspect in the understanding of the FR, and the distance between the posterior wall of the maxillary sinus to the vidian canal and the foramen rotundum), which might prove useful in the comprehension of the anatomy of the pterygopalatine fossa.

The Quality of Life of Patients with Surgically Treated Mandibular Fractures and the Relationship of the Posttraumatic Pain and Trismus with the Postoperative Complications: A Prospective Study.

Background and objectives: Due to the fact that the mandible is the only movable bone in the face, it is often exposed to the influence of external forces. The incidence of trismus and posttraumatic pain in unilateral mandibular corpus fractures may be related to the occurrence of complications. There is a decrease in the quality of life of these patients. The aim was to study the relationship of the preoperative pain and trismus with the incidence of complications, as well as to investigate the quality of life. Materials and Methods: A prospective study on 60 patients with isolated mandibular fractures was performed, with a follow-up period of six months. The level of preoperative pain was measured on a 0-10 scale, while the mouth opening was measured with a caliper. All patients were treated surgically on the third day after the fracture. The University of Washington Quality of Life (UW-QOL v4) questionnaire was used to analyze the quality of life. Results: The most common types of complications were the occlusal derangement and facial asymmetry. The majority of complications were treated with counseling and physical therapy. The degree of preoperative pain was significantly positively related to the onset of complications (rs = 0.782, p = 0.004). The interincisal distance showed a significant inverse relation with the incidence of complications (rs = -0.722, p < 0.001). The patients regarded the pain, appearance and mood issues as the most important issues during the first postoperative month. Conclusions: The degree of inflammatory symptoms may be positively related to the onset of complications occurring after the rigid fixation of mandibular fractures. The postoperative health-related and overall quality of life was unsatisfactory in nearly half of the patients.

Asymmetry of the greater cornua of the hyoid bone and the superior thyroid cornua: a case report.

The hyoid bone consists of a body and two pairs of processes: the greater cornua (GC) and the lesser cornua. The GC is connected to the superior thyroid cornu (STC) by the lateral thyrohyoid ligament. The GC and the STC share a common embryological origin from the third pharyngeal arch. During anatomical dissection of a male cadaver of 56 years of age, a combined variation of the GC and the STC was found. The left GC was 27.7 mm long, and the right GC was 30 mm long. The left GC axis was in the same plane as the hyoid body, while an angle of 33° was between the right GC axis and the hyoid body plane. The left STC was 17.6 mm long, and the right STC was 25.8 mm long. The angle of left STC medial inclination was 70°, while the right STC was perpendicular to the horizontal plane of the larynx. Anatomical variations of the hyoid bone and the laryngeal cartilages have possible clinical implications, such as Eagle syndrome and the STC syndrome. The case we described may inspire the anatomists to research the occurrence of combined variations of the larynx and the hyoid bone.

Duplication of the middle cerebral artery in a neonate: case report.

The middle cerebral artery, a terminal branch of the internal carotid artery, participates greatly in the blood supply of the cerebral cortex and basal nuclei. The aim of this paper is to present a case of middle cerebral artery duplication in a 3-day-old neonate. A brief literature overview in this paper serves to summarize the research on the middle cerebral artery duplication. Also, possible etiology of this anatomical variation will be discussed, together with the embryology of the middle cerebral artery. The arteries of the circle of Willis are affected by numerous neurovascular diseases and the knowledge of these anatomical variations is important in the diagnostic and therapeutic interventions in this field.

The assessment of airbag deployment and seatbelt use in preventing facial injuries.

This study aimed to determine the effectiveness of airbags and seatbelts in the prevention of facial fractures and slight facial injuries in relation to the speed and kinetic energy experienced in frontal collisions. All cases of vehicle occupants who had been in frontal collisions and had subsequently been examined in the Institute for Emergency Medical Assistance and the Clinical Center of Montenegro in 2017 were analyzed. There were 29 cases of facial fractures (Group 1), 35 cases of slight facial injuries (including nondisplaced nasal fractures) (Group 2), and 26 cases of occupants who had suffered no facial injuries (control Group 3). In all assessed cases all of the subjects had been wearing a seatbelt and the airbag had deployed at the time of impact. A frontal collision is defined as a collision in which the principal force acts within a range of 90° from the longitudinal axis of the vehicle. Using the mass and the speed of the vehicles, the total kinetic energy (KE) of all frontal collisions being analyzed was calculated. The cut-off value of total KE in frontal collisions that were associated with either facial fractures or slight facial injury was estimated using a receiver operating characteristic (ROC) curve. The cut-off amounts of KE were then used to calculate the barrier equivalent velocity (BEV). The BEV for a vehicle of average mass was estimated to be 55.7 km/h (34.6 mph) in Group 1, and 49.2 km/h (30.6 mph) in Group 2. Airbags and seatbelts are effective in preventing facial injuries in vehicles of average mass that are traveling at speeds under 49.2 km/h (30.6 mph) at the point of impact, but they do not protect from facial fractures when the vehicle speed exceeds 55.7 km/h (34.6 mph).

Obstructive jaundice treatment during the COVID-19 pandemic: retrospective cohort study at a single tertiary care center in Serbia.

OBJECTIVE: We aimed to compare mortality and complication rates in patients treated for obstructive jaundice before and during the COVID-19 pandemic in a tertiary care center in Serbia. METHODS: We conducted a retrospective cohort study among a first group of patients treated between 1 January 2017 and 1 January 2019. The second group was treated between 1 March 2020 and 1 March 2022. RESULTS: The first group comprised 35 patients, and the second group (in which all patients were SARS-CoV-2 positive) included 18 patients; 37 and 16 patients were treated for malignant and benign diseases, respectively. The groups did not differ significantly regarding the diagnoses and treatment received. The second group showed significantly higher aspartate aminotransferase levels and lower white blood cell, C-reactive protein, and interleukin 6 levels. Mortality and complication rates did not differ significantly between groups. All deceased patients in the second group had significant radiologic findings associated with COVID-19 pneumonia. CONCLUSIONS: COVID-19 infection is a risk factor in treating obstructive jaundice. This study illustrates the potential influence of COVID-19 on mortality after obstructive jaundice treatment. COVID-19 pneumonia may be a significant risk factor for mortality in patients treated for obstructive jaundice.

The role of miRNA in colorectal cancer diagnosis: A pilot study.

Despite recent advances in diagnosis and treatment, colorectal cancer (CRC) remains the third most common cancer worldwide, and has both a poor prognosis and a high recurrence rate, thus indicating the need for new, sensitive and specific biomarkers. MicroRNAs (miRNAs/miRs) are important regulators of gene expression, which are involved in numerous biological processes implicated in tumorigenesis. The objective of the present study was to investigate the expression of miRNAs in plasma and tissue samples from patients with CRC, and to examine their potential as CRC biomarkers. Using reverse transcription-quantitative PCR, it was revealed that miR-29a, miR-101, miR-125b, miR-146a and miR-155 were dysregulated in the formalin-fixed paraffin-embedded tissues of patients with CRC, compared with the surrounding healthy tissue, and these miRNAs were associated with several pathological features of the tumor. Bioinformatics analysis of overlapping target genes identified AGE-RAGE signaling as a putative joint regulatory pathway. miR-146a was also upregulated in the plasma of patients with CRC, compared with the healthy control group, and had a fair discriminatory power (area under the curve, 0.7006), with 66.7% sensitivity and 77.8% specificity. To the best of our knowledge, this distinct five-miRNA deregulation pattern in tumor tissue, and upregulation of plasma miR-146a, were shown for the first time in patients with CRC; however, studies on larger patient cohorts are warranted to confirm their potential to be used as CRC diagnostic biomarkers.

Attitudes Toward Organ Donation and Transplantation Among Transplant-Related Health Care Workers and the Local Population of Montenegro.

OBJECTIVES: The aim of this research was to determine the attitudes of transplant-related health care workers and the local population of Montenegro toward organ donation and transplantation. MATERIALS AND METHODS: Our study included 200 transplant-related health care professionals (from the Clinical Center of Montenegro, the only transplant hospital in the country) and 200 volunteers from Podgorica (the capital of Montenegro). Their attitudes were evaluated using an anonymous, self-administered, multiple-choice questionnaire. RESULTS: Most health care workers would donate their organs only on specific occasions (43.6%), whereas the general population was divided between willingness to donate only on specific occasions and the need to consider the decision of donating (34.6% each). Both groups of respondents predominantly claimed that they would donate their organs to any potential recipient, regardless of sensory or physical disability. A positive opinion regarding the promotion of organ donation, as well as the need for legal regulation of the transplant process, was noted in both groups of responders. CONCLUSIONS: There is a need to increase the generosity of the Montenegrin population and its health care workers regarding organ donation at all times and not exclusively on specific occasions.

Renal aspergillosis in a liver transplant patient: A case report and review of literature.

BACKGROUND: Aspergillosis is a frequent invasive fungal infection in liver recipients (affecting 1%-9.2% of all patients), second only to candidiasis. Significant risk factors for invasive aspergillosis in liver recipients include corticosteroid therapy, neutropenia, T-cell dysfunction, renal failure and requirement for renal replacement therapy. Aspergillus infection usually affects the lungs of liver recipients, with hematogenous dissemination occurring in 50%-60% of cases. Renal involvement is rare and is considered to occur in 0.4% of all cases of invasive aspergillosis. CASE SUMMARY: This paper describes a case of a liver recipient presenting with a newly formed renal mass a year after liver transplantation. The patient underwent liver transplantation due to alcoholic liver cirrhosis, with preoperative corticosteroid therapy and postoperative immunosuppressants (tacrolimus and mycophenolate mofetil). His 1-year follow-up was uneventful, with a satisfying graft function and lack of any symptoms. During a routine follow-up abdominal ultrasound, he was diagnosed with a renal tumor. The renal imaging findings were inconclusive (with a differential diagnosis to renal cell carcinoma), while the computed tomography (CT) of the chest showed scar tissue in the lungs suggestive of previous inflammation. The patient underwent radical nephrectomy, with histopathological analysis showing renal aspergilloma, yielding postoperative treatment with voriconazole. His follow up was uneventful, and the chest CT did not show any change in pulmonary lesions. This case illustrates the possibility of aspergillosis affecting the lungs of liver recipients, subsequently affecting the kidney and forming an aspergilloma. CONCLUSION: Clinicians should be aware of aspergilloma mimicking solid organ tumors in organ recipients.

Clinical significance of understanding lateral and medial circumflex femoral artery origin variability.

The common femoral artery (CFA) divides into the superficial femoral artery (SFA) and deep femoral artery (DFA). The lateral circumflex femoral artery (LCFA) and medial circumflex femoral artery (MCFA) are most often branches of the DFA, although a large number of different variations in their origin has been described. We performed microdissection on both lower limbs of 30 fetuses, gestational age from 7 to 10 lunar months. Our results show that the LCFA and MCFA usually arise from the DFA. In 78.3% of cases, the MCFA originated from the DFA. In 11.7% of cases, the MCFA originated from the CFA, and in 5% of cases from the SFA. One case showed a common trunk with the DFA. Also, the MCFA was missing in one case, and it had a common trunk with the LCFA in one case. In 83.3% of cases, the LCFA arose from the DFA and in 6.7% of cases from the CFA. In one case, it had a common trunk with the DFA, and in one case with the MCFA. In 3.3% of cases, the LCFA was missing. In 66.7% of cases, both arteries originated from the DFA, in 15% of cases one originated from the DFA and the other from the CFA or SFA. Our results are in accordance with some published studies but also differ from the outcomes of other studies. Comprehensive knowledge of different variation types is imperative in order to prevent complications during surgical and orthopedic interventions.

Superficial palmar branch of the radial artery: A study of occurrence and diameter.

The superficial palmar branch (SPB) of the radial artery (RA) is an important blood vessel in plastic surgery procedures of the hand. It is used as the axial artery in a free flap used for finger reconstruction. The occurrence of this arterial branch is variable, as well as its diameter and course. The aim of this study was to determine the occurrence and measure the external diameter of the SPB, as well as the external circumference of the RA. All results were analyzed with the intent to determine a possible correlation between RA and SPB size, as well as between SPB occurrence and the cadavers' sex and height. The study was conducted on both upper extremities of 60 cadavers (31 male and 29 female), of 35-55 years of age (average age was 46.5 years). A radial artery sample was taken at the level of the wrist, together with its superficial palmar branch. The samples were preserved in 4% formaldehyde for four weeks. After the fixation, the external circumference of the radial artery and the external diameter of the superficial palmar branch were measured with a Vernier caliper and an operating microscope. Bilateral SPB absence was the most common variant of SPB occurrence in our material. There was no linear correlation between the size of the RA and the SPB, nor was there any relationship between SPB occurrence and the cadavers' age and height. Also, the correlation between the cadavers' height and the size of both blood vessels was not linear. We conclude that the SPB diameter and occurrence are independent of the other factors described in this study.