Medicina, Volume 60, Issue 6 (June 2024) – 97 articles

Background and Objectives: Options for treatment-resistant bipolar depression (TRBPD) are limited. Electroconvulsive therapy (ECT) has shown efficacy in TRBPD. However, the cognitive deficits and memory concerns associated with ECT are problematic for a significant number of patients. It remains unclear what the next step is for patients with TRBPD who fail ECT. Materials and Methods: In this case report, we present a patient with TRBPD who sequentially received 12 sessions of brief-pulse right unilateral ECT, 22 sessions of ketamine infusion at 0.5–0.75 mg/kg for 40 min, and 39 sessions of deep repetitive transcranial magnetic stimulation (dTMS). Results: The patient had some benefit from ECT, but declined continuation of ECT due to memory concerns. The patient tolerated ketamine infusion well but had limited benefit. However, the patient responded well to acute treatment with dTMS and maintained relative stability for more than 2 years. Conclusions: This case suggests that patients with TRBPD who fail ECT and/or ketamine infusion might benefit from dTMS. Full article

Background and Objectives: The aim of the present work was to compare the characteristics of delta and omicron variants of COVID-19 infection in pregnant women, the association of infection with comorbidity, clinical manifestation of the disease, type of delivery, and pregnancy outcome. Material and Methods: The study was designed as an observational, retrospective study of a single center. The analysis included the cohort of women who had SARS-CoV-2 infection during pregnancy and/or childbirth in the period from 1 March 2020 to 30 June 2023. Results: Out of a total of 675 pregnant women with SARS-CoV-2 infection, 130 gave birth with the delta and 253 with the omicron variant. In our retrospective analysis, pregnant women with both SARS-CoV-2 variants had a mild clinical history in most cases. In the omicron period, a significantly lower incidence of pregnancy loss (p < 0.01) and premature birth (p = 0.62) admission of mothers and newborns to the intensive care unit (p < 0.05) was recorded. Conclusions: In our retrospective analysis, pregnant women with COVID-19 infection generally exhibited a milder clinical manifestation with both variants (delta and omicron) of the viral infection. During the delta-dominant period, ten percent of affected pregnant women experienced a severe clinical history. However, during the omicron-dominant period infection, a significantly lower incidence of complications, pregnancy loss, preterm delivery, and admission of mothers and neonates to the intensive care unit was recorded. This can be partly explained by the greater presence of pregnant women with natural or induced vaccine immunity. Full article

I propose that a deficiency of essential fatty acids (EFAs) and an alteration in their (EFAs) metabolism could be a major factor in the pathogenesis of sepsis and sepsis-related mortality. The failure of corticosteroids, anti-TNF-α, and anti-interleukin-6 monoclonal antibodies can be attributed to this altered EFA metabolism in sepsis. Vitamin C; folic acid; and vitamin B1, B6, and B12 serve as co-factors necessary for the activity of desaturase enzymes that are the rate-limiting steps in the metabolism of EFAs. The altered metabolism of EFAs results in an imbalance in the production and activities of pro- and anti-inflammatory eicosanoids and cytokines resulting in both hyperimmune and hypoimmune responses seen in sepsis. This implies that restoring the metabolism of EFAs to normal may form a newer therapeutic approach both in the prevention and management of sepsis and other critical illnesses. Full article

Background and Objective: Colorectal cancer (CRC) is among the most common types of cancer. Although the disease is treatable in its early stages, five-year survival falls below 20% in the later stages. CEA and CA19-9 are tumor markers used in the diagnosis and follow-up of the disease in clinical practice; however, their diagnostic effectiveness is insufficient. Therefore, the identification of biomarkers that can be easily studied from serum and can diagnose CRC and determine its severity is highly important. In this context, dickkopf1 (DKK1) and cytoskeleton-associated protein 4 (CKAP4) are both promising biomarkers. Materials and Methods: Serum DKK1 and CKAP4 levels were measured in 55 patients with CRC and 40 healthy controls. The patients with CRC were divided into groups based on pathological stages and histological differentiation. The serum levels of both proteins in patients with CRC were measured preoperatively and 10 and 30 days postoperatively. Results: Serum DKK1 and CKAP4 were significantly higher in the CRC group than in the healthy controls (p < 0.05). Serum levels of both proteins rose in line with the disease stage and grade but decreased following surgical resection. A positive correlation was observed between tumor diameter and protein blood levels. The diagnostic efficacy of DKK1 and CKAP4 in CRC (approximately 95%) was higher than that of markers such as CEA and CA19-9. Conclusions: The DKK1 and CKAP4 serum values of patients with CRC are promising biomarkers. They can potentially be used in CRC management, namely, in the diagnosis and treatment of tumor response access and in tumor aggressiveness prediction. Full article

Background and Objectives: Microsurgical resection with intraoperative neuromonitoring is the gold standard for acoustic neurinomas (ANs) which are classified as T3 or T4 tumors according to the Hannover Classification. Microscope-based augmented reality (AR) can be beneficial in cerebellopontine angle and lateral skull base surgery, since these are small areas packed with anatomical structures and the use of this technology enables automatic 3D building of a model without the need for a surgeon to mentally perform this task of transferring 2D images seen on the microscope into imaginary 3D images, which then reduces the possibility of error and provides better orientation in the operative field. Materials and Methods: All patients who underwent surgery for resection of ANs in our department were included in this study. Clinical outcomes in terms of postoperative neurological deficits and complications were evaluated, as well as neuroradiological outcomes for tumor remnants and recurrence. Results: A total of 43 consecutive patients (25 female, median age 60.5 ± 16 years) who underwent resection of ANs via retrosigmoid osteoclastic craniotomy with the use of intraoperative neuromonitoring (22 right-sided, 14 giant tumors, 10 cystic, 7 with hydrocephalus) by a single surgeon were included in this study, with a median follow up of 41.2 ± 32.2 months. A total of 18 patients underwent subtotal resection, 1 patient partial resection and 24 patients gross total resection. A total of 27 patients underwent resection in sitting position and the rest in semi-sitting position. Out of 37 patients who had no facial nerve deficit prior to surgery, 19 patients were intact following surgery, 7 patients had House Brackmann (HB) Grade II paresis, 3 patients HB III, 7 patients HB IV and 1 patient HB V. Wound healing deficit with cerebrospinal fluid (CSF) leak occurred in 8 patients (18.6%). Operative time was 317.3 ± 99 min. One patient which had recurrence and one further patient with partial resection underwent radiotherapy following surgery. A total of 16 patients (37.2%) underwent resection using fiducial-based navigation and microscope-based AR, all in sitting position. Segmented objects of interest in AR were the sigmoid and transverse sinus, tumor outline, cranial nerves (CN) VII, VIII and V, petrous vein, cochlea and semicircular canals and brain stem. Operative time and clinical outcome did not differ between the AR and the non-AR group. However, use of AR improved orientation in the operative field for craniotomy planning and microsurgical resection by identification of important neurovascular structures. Conclusions: The single-center experience of resection of ANs showed a high rate of gross total (GTR) and subtotal resection (STR) with low recurrence. Use of AR improves intraoperative orientation and facilitates craniotomy planning and AN resection through early improved identification of important anatomical relations to structures of the inner auditory canal, venous sinuses, petrous vein, brain stem and the course of cranial nerves. Full article

Background and Objectives: The COVID-19 pandemic has had a significant global impact, necessitating a comprehensive understanding of its spatiotemporal patterns. The objective of this study is to explore the spatial and temporal patterns of COVID-19 infections among five age groups (<1, 1–4, 5–9, 10–14, and 15–19 years) in 72 districts of Slovakia on a quarterly basis from March 2020 to July 2022. Material and Methods: During the study period, a total of 393,429 confirmed PCR cases of COVID-19 or positive antigen tests were recorded across all studied age groups. The analysis examined the spatiotemporal spread of COVID infections per quarter, from September 2021 to May 2022. Additionally, data on hospitalizations, intensive care unit (ICU) admissions, pulmonary ventilation (PV), and death cases were analyzed. Results: The highest number of COVID-19 infections occurred between September 2021 and May 2022, particularly in the 10–14-year-old group (68,695 cases), followed by the 15–19-year-old group (62,232 cases), while the lowest incidence was observed in the <1-year-old group (1235 cases). Out of the total confirmed PCR cases, 18,886 individuals required hospitalization, 456 needed ICU admission, 402 received pulmonary ventilation, and only 16 died. The analysis of total daily confirmed PCR cases for all regions showed two major peaks on 12 December 2021 (6114 cases) and 1 February 2022 (3889 cases). Spatial mapping revealed that during December 2021 to February 2022, the highest number of infections in all age groups were concentrated mainly in Bratislava. Moreover, temporal trends of infections within each age group, considering monthly and yearly variations, exhibited distinct spatial patterns, indicating localized outbreaks in specific regions. Conclusions: The spatial and temporal patterns of COVID-19 infections among different age groups in Slovakia showed a higher number of infections in the 10–14-year-old age group, mainly occurring in urban districts. The temporal pattern of the spread of the virus to neighboring urban and rural districts reflected the movement of infected individuals. Hospitalizations, ICU and PV admissions, and deaths were relatively low. The study highlights the need for more proactive measures to contain outbreaks promptly and ensure the resilience of healthcare systems against future pandemics. Full article

Background and Objectives: This study aimed to elucidate the cytologic characteristics and diagnostic usefulness of endoscopic ultrasonography–fine needle aspiration cytology (EUS-FNAC) by comparing it with liquid-based preparation (LBP) and conventional smear (CS) in pancreas. Methods: The diagnostic categories (I through VII) were classified according to the World Health Organization Reporting System for Pancreaticobiliary Cytopathology. Ten cytologic features, including nuclear and additional features, were evaluated in 53 cases subjected to EUS-FNAC. Nuclear features comprised irregular nuclear contours, nuclear enlargement, hypochromatic nuclei with parachromatin clearing, and nucleoli. Additional cellular features included isolated atypical cells, mucinous cytoplasm, drunken honeycomb architecture, mitosis, necrotic background, and cellularity. A decision tree analysis was conducted to assess diagnostic efficacy. Results: The diagnostic concordance rate between LBP and CS was 49.1% (26 out of 53 cases). No significant differences in nuclear features were observed between categories III (atypical), VI (suspicious for malignancy), and VII (malignant). The decision tree analysis of LBP indicated that cases with moderate or high cellularity and mitosis could be considered diagnostic for those exhibiting nuclear atypia. Furthermore, in CS, mitosis, isolated atypical cells, and necrotic background exerted a more significant impact on the diagnosis of EUS-FNAC. Conclusions: Significant parameters for interpreting EUS-FNAC may differ between LBP and CS. While nuclear atypia did not influence the diagnosis of categories III, VI, and VII, other cytopathologic features, such as cellularity, mitosis, and necrotic background, may present challenges in diagnosing EUS-FNAC. Full article

Background and Objectives: The prolonged infusion of meropenem is recommended by guidelines for the treatment of sepsis. However, studies provide controversial data on the advantages of prolonged infusions over intermittent ones. In our opinion, this can be related to age, which possibly distorts the final data, as older people have age-related characteristics. In our study, we analyzed the ventilatory status, laboratory tests and vital signs of the patient and carried out microbiological cultures. Materials and Methods: This was a prospective single-center case series investigation conducted from June 2022 to June 2023. The objective of this study was to evaluate the effectiveness of continuous infusion in elderly patients with severe infectious complications after orthopedic interventions. The primary endpoints were 28-day survival and the emergence of new multidrug-resistant strains. Secondary endpoints were long-term mortality and length of stay in the ICU. Results: Three patients (median age 65, 100% female) received a continuous infusion of meropenem. Two patients were alive at hospital discharge, and one patient died on the 105th day of hospitalization. Multi-resistant bacteria were observed in one patient. Conclusions: The use of a continuous meropenem infusion in the complex treatment of purulent-septic complications in elderly patients with periprosthetic infection and anemia probably led to clinical improvement in these case reports. However, the emergence of new pan-resistant strains and overall mortality using this infusion technique remains unclear. Further, high-quality RCTs for the elderly are needed. Full article

Background and Objectives: This study aimed to determine the relationship between non-simultaneous contralateral hip fractures, urban and rural differences, fracture localization, time between fractures, physiotherapy applications, comorbidity, and the second fracture outcomes. Materials and Methods: We retrospectively analyzed 107 patients aged 65 and older with proximal femur fractures (PFFs) who underwent surgery at Düzce University Medical Faculty between January 2010 and December 2022. High-energy fractures, pathological fractures, and patients with a history of old fractures were excluded. Results: The study included 66 females (61.7%) and 41 males (38.3%), with a mean age of 83.76 years. The mean interval between two fractures was 28.3 months. There was no statistical difference between the localization of the first and second fractures (p = 0.107). However, there was a significant difference in the first PFF localizations of patients living in rural areas (p = 0.023). Patients with heart failure, respiratory failure, osteoporosis, and cognitive impairment had shorter intervals between fractures (p < 0.001). Conclusions: This study shows that age, female gender, place of residence, comorbid diseases, and whether physical therapy is received after the first fracture are significant risk factors for a second hip fracture in patients over 65 years of age. Full article

Background and Objectives: Although the growing literature is now focusing on the long-term effects of Deep Brain Stimulation (DBS) in Parkinson’s disease (PD), there is still a large gap of knowledge about its long-term implications in rehabilitation. Therefore, this study aimed at investigating the effects of rehabilitation in PD patients years after DBS implantation. Materials and Methods: This retrospective case–control study analyzed records from Moriggia-Pelascini Hospital, Italy from September 2022 to January 2024. Data of PD patients (n = 47) with (DBS group, n = 22) and without (control group, n = 25) DBS were considered. All study participants underwent a daily rehabilitation program lasting four weeks, including warm-up, aerobic exercises, strength training, postural exercises, and proprioceptive activities. The outcomes assessed were the Unified Parkinson’s Disease Rating Scale (UPDRS), Berg Balance Scale (BBS), Timed Up and Go (TUG), 6 Min Walk Test (6MWT), and Self-Assessment Parkinson Disease Scale (SPDDS). Results: DBS group showed significant improvements in terms of all outcome measures after the rehabilitation intervention (UPDRS III: −7.0 (−11.5 to −1.0); p = 0.001; UPDRS I II IV: −12.0 (−19.0 to −4.5); p = 0.001; BBS: 7.0 (3.8 to 10.3); p < 0.001; TUG (s): −2.8 (−5.7 to −1.1); p < 0.001; SPDDS: −8 (−13.0 to −4.0); p < 0.001; 6MWT (m): 81 (37.3 to 132.3); p < 0.001). No differences were reported in the between-group analysis (p: NS). Conclusions: This study emphasizes positive rehabilitation effects on PD patients irrespective of DBS status. Further research is essential to elucidate long-term effects of DBS on rehabilitation outcomes of PD patients. Full article

Background and Objectives: Radicalization, a complex and multifaceted phenomenon, has been a subject of increasing concern in recent years, particularly due to its potential connection to acts of mass violence and terrorism. This systematic review examines the intricate link between radicalization and psychotic disorders, utilizing various sources such as observational studies, case reports, and series. It aims to highlight the prevalence of schizophrenia spectrum and other psychotic disorders among radicalized individuals and to define the role of mental health professionals in dealing with this issue, contributing to the development of prevention and treatment strategies. Materials and Methods: The methodology involved an extensive literature search across PubMed, Scopus, and APA PsycINFO up to 1 February 2024, adhering to PRISMA guidelines. The study focused on radicalization and psychotic disorders as defined by DSM-5 criteria, excluding other mental disorders. A population sample of 41 radicalized individuals diagnosed with psychotic disorders was selected, among which schizophrenia was identified as the predominant condition. Results: It was observed that 24% of these individuals passed away soon after committing their crimes, leading the researchers to rely on retrospective data for their diagnoses. The use of diverse assessment tools for psychiatric diagnosis and the lack of a standardized method for diagnosing or assessing involvement in the radicalization process were also noted. Despite limitations like reliance on observational studies and case reports, which result in low evidence quality and varied methodologies, our work provides a valuable contribution to clarifying the relationship between radicalization and psychotic disorders. However, further clinical studies are needed to delve deeper into these aspects. Conclusions: In conclusion, our review points out that individuals with psychotic disorders do not have a higher crime rate than the general population and warns against associating crimes with mental illness due to the stigma it creates. The lack of uniform psychiatric diagnostic tools and radicalization assessment highlights the need for more standardized risk assessment tools and validated scales in psychiatric diagnosis to better understand the relationship between radicalization and psychotic disorders and to develop integrated protocols. Full article

Background and Objectives: The focus on mild cognitive dysfunction in adults is of great interest, given the risk of worsening and conversion to dementia. Cognitive dysfunctions are characterized by a decrease in the weight and volume of the brain, due to cortical atrophy, with a widening of the grooves and flattening of the convolutions. Brain atrophy that mainly involves the hippocampus is related to the progression of cognitive impairment and the conversion from mild cognitive dysfunction to dementia. Currently, there is no treatment for MCI. Results from a trial on Alzheimer’s disease (ASCOMALVA trial) suggest that a sustained cholinergic challenge can slow the progression of brain atrophy typical of Alzheimer’s disease associated with vascular damage. This study intends to evaluate the efficacy of choline alphoscerate in patients with mild cognitive impairment (MCI) and associated vascular damage, in stabilizing and/or slowing brain atrophy typical of adult-onset cognitive dysfunction, and in improving and/or slowing the progression of cognitive and behavioral symptoms associated with MCI. Materials and Methods: This randomized controlled trial will recruit 60 patients that will be evaluated and randomized in a 1:1 ratio to receive choline alphoscerate (1200 mg/day) or placebo, for 12 months. Analyses will be carried out using SPSS vesion No 26 the Statistician in charge of this study, with the statistical significance level chosen as 0.05. Discussion: This trial may provide evidence about the efficacy of treatment with the cholinergic precursor choline alphoscerate in patients with mild cognitive dysfunction. The results of this study will be published in peer-reviewed journals. Registration: EudraCT number: 2020-000576-38 Full article

Background and Objectives: Secretory carcinoma of the breast is an uncommon histological subtype of breast cancer. There is little research on this entity and only a few larger studies, which lack consensus. We aim to report a particular apocrine differentiation in this subtype and ponder upon the clinical outcome of this case. Case presentation: We report the case of a 72-year-old female patient who presented to our hospital with a suspicious breast tumor. Core biopsy and mastectomy showed a low-grade breast carcinoma, a secretory subtype with apocrine differentiation. Immunohistochemistry confirmed both the secretory nature and the apocrine nature of the tumor cells. Surgical excision was considered curative and the patient is under long-term surveillance for any recurrences. Conclusions: There is very little research on the clinical behavior of secretory carcinomas with apocrine differentiation. The clinical outcome is unknown and, unfortunately, besides surgery, no other adjuvant treatments have shown efficacy. Further studies on long-term clinical progression are required for this rare entity. Full article

Background and Objectives: Unhealthy nutrition can contribute to the development or progression of various alimentary-dependent diseases, including obesity, type 2 diabetes mellitus, metabolic syndrome, anaemia, and arterial hypertension. Young-old and old-old individuals often have diets deficient in essential vitamins, minerals, and macronutrients, characterized by high consumption of carbohydrate-rich foods and insufficient intake of plant-based products like vegetables and fruits. This study aims to identify key parameters of nutritional status among the young-old (aged 60–74 years) and old-old (aged 75–90 years) populations in central Kazakhstan, particularly in relation to specific alimentary-dependent diseases. Materials and Methods: The study involved 300 participants aged 60−90 years. The study incorporated a dietary questionnaire, food consumption records (such as 24 h recalls), and measurements of anthropometric indicators including weight and skinfold measurements. Results: Residents in the surveyed regions typically consumed food 3–4 times daily, with breakfast, lunch, and dinner being eaten at consistent times. A significant proportion of individuals, especially older adults, followed this meal schedule. About one-third ate before bedtime, and more than half believed they adhere to a specific diet. The mean BMI for men aged 60–74 years was 28.3 (95% CI: 20.1–43.2) and, for those aged 75–90 years, it was 29.0 (95% CI: 22.1–40.8). Caloric intake among individuals aged 60–74 was higher compared to those aged 75–90, with males consuming an average of 2372.7 kcal and females consuming 2236.78 kcal versus 2101.5 kcal for males and 2099.9 kcal for females in the older age group. Conclusions: The dietary patterns observed among old-old individuals were marked by excessive calorie intakes and imbalances in macronutrient composition, with a predominant emphasis on high-carbohydrate foods at the expense of essential nutrients like proteins, fats, and key vitamins (such as C, E, B vitamins) and minerals (such as potassium, calcium, and iron). Full article

Background and Objectives: Human papillomavirus (HPV) infection and its etiological role in the development of cervical cancer are well established. The cervical cancer mortality rate in Serbia is one of the highest among European countries, and this cancer is the second-leading cause of death in Serbian women aged from 15 to 44. Materials and Methods: This retrospective study was conducted at the Institute of Public Health of Vojvodina. A total of 10,062 cervical specimens from Serbian women were collected and HPV tested in ten years. The study patients were divided into five age groups. HPV genotype testing was performed using a commercial kit to detect 14 high-risk (HR) HPV genotypes. Additionally, cervix cytology data have been available for patients tested in 2022 and 2023. Results: An overall positive rate was found in 43.3% of patients (4356/10,062). A single HPV infection (62.1%) was the main infection pattern. The most frequent HR HPV genotypes were HPV 16, 31, 52, 56, 39, and 51, comprising 62.3% of the detected genotypes, including multiple infections. A significant difference was noted in the HPV prevalence across the different age groups, with a bimodal distribution of HPV infection. The highest prevalence was recorded in the age group ≤ 30 and those after 61 years. Women diagnosed with high-grade squamous intraepithelial lesions (HSIL) were significantly older compared to others. HR HPV is the most prevalent in patients with HSIL cytological findings (76.5%). The most common type, according to age-specific distribution and cytological findings, was HR HPV 16. Conclusions: This study provides comprehensive data on HR HPV distribution among Serbian women, which can serve as a basis for subsequent monitoring of genotypic distribution. It is particularly significant considering they are missing in the updated ICO/IARC Report for Serbia, and the cervical cancer mortality rate in Serbia is one of the highest among European countries. Full article

Background and Objectives: Lateral ankle injuries are commonly encountered injuries, and the open modified Broström operation (OMBO) is the primary treatment option. Recently, an arthroscopic modification of the Broström operation (AMBO) was developed; many studies have shown that there are no significant differences in clinical and radiological outcomes between the two surgical methods. However, no studies have been conducted comparing the two surgical methods in terms of return to play (RTP) time. This study assesses the time to RTP and the functional clinical outcomes. Materials and Methods: Sixty patients were enrolled from January 2012 to July 2014. They were segregated into two cohorts: the AMBO group comprised 30 patients, while the OMBO group comprised another 30 patients. Each participant underwent standardized treatment and rehabilitation regimens and RTP time was measured using seven questions that explored the times to return of painless walking, running, jumping, squatting, climbing stairs, and rising up on the heels and toes. We compared the time intervals from the onset of instability to the date of surgery. Clinical outcomes were evaluated before the surgery, 6 weeks after surgery, and 6 months after surgery. The assessments included the American Orthopedic Foot & Ankle Society (AOFAS) ankle–hindfoot score, the pain visual analog scale (VAS) score, subjective satisfaction with rehabilitation, and activity level. Results: In terms of RTP, AMBO was associated with a shorter interval to walking without pain (7.07 ± 2.96 weeks) relative to OMBO (11.03 ± 8.58 weeks). No disparities were observed in the time to return to play (RTP) between OMBO and AMBO. While there were no discrepancies in the 6-month postoperative AOFAS or VAS scores, the 6-week postoperative VAS score was notably lower in the AMBO group compared to the OMBO group. AMBO provided a faster RTP in terms of two of the seven questions in a group exhibiting high-level physical activity. The rate of subjective satisfaction with rehabilitation was higher for AMBO than for OMBO. Conclusions: Aside from walking, the duration to return to play and the clinical outcomes were similar between AMBO and OMBO treatments for lateral ankle instability. AMBO is a good treatment option and should be carefully considered for athletes with lateral ankle instability. AMBO demonstrated positive outcomes in a group with higher activity levels compared to others, particularly in terms of time to RTP, subjective satisfaction, and postoperative pain. Full article

Background and Objectives: Mucin has been implicated via various mechanisms in the development and growth of tumour cells. However, mucin expression studies in salivary gland tumours are limited, especially with samples from minor salivary glands. This study aims to investigate and compare mucin expression in benign and malignant salivary gland tumours of minor and major salivary gland origins. Materials and Methods: Special stains were used to stain neutral mucin (Periodic acid Schiff), sialomucin (Alcian Blue) and sulfomucin (Aldehyde Fuschin) within tissues from six normal salivary glands and 73 salivary gland tumours including 31 pleomorphic adenomas, 27 mucoepidermoid carcinomas, and 15 adenoid cystic carcinomas. A semi-quantitative approach was used to evaluate mucin expression within ductal lumens. Sialomucin was the most expressed mucin in all salivary gland tumours, regardless of origin. Results: A significant difference was observed in the mucin expression between benign and malignant salivary gland tumours, as pleomorphic adenoma showed three times significantly higher expression of sialomucin compared to mucoepidermoid carcinoma and adenoid cystic carcinoma (p = 0.028). Pleomorphic adenomas of major glands showed 42 times significantly higher expression of sialomucin compared to those of minor glands (p = 0.000). Conclusions: Sialomucin content in pleomorphic adenomas of major glands was vastly increased compared to that in minor glands. Differential sialomucin expression in benign and malignant salivary gland tumours suggests a role in diagnosing of borderline salivary gland tumours. Full article

Background and Objectives: Ketogenic diet therapy (KDT) has been used as a non-pharmacological treatment for childhood refractory epilepsy. Its efficacy and safety have been described in numerous studies and reviews. However, there have been fewer studies evaluating the challenges experienced by patients and their family members when starting KDT. When implementing a new treatment method, challenges arise for both the healthcare professionals and patients, making it important to summarize the initial results and compare them with the experiences of other centers. To analyze and evaluate the efficacy and safety of KDT in children with epilepsy, as well as to consider the challenges faced by their parents/caregivers. Materials and Methods: A retrospective analysis of patients’ data (N = 30) and an analysis of the completed questionnaires of the parents/caregivers (N = 22) occurred. Results: In the study group, 66.7% of the patients had a >50% decrease in seizure frequency, and 2/3 of them had a >90% decrease in seizure frequency or were seizure-free, which enabled reducing the anti-seizure medications in 36.4% of the patients, as well as reducing the hospital visits. Cognitive improvement and better alertness were subjectively reported by 59.1% of the parents/caregivers. No dangerous long-term adverse effects of KDT have been observed in the study group. The patients with generalized epilepsy experienced significantly more adverse events. Most of the adverse effects of KDT were related to the digestive system, but usually they were temporary and controllable. The challenges of the parents/caregivers were mostly related to social life issues and financial difficulties; the medical-related challenges were minimal. Conclusions: KDT is an effective and safe treatment option for children with drug-resistant epilepsy, and the challenges faced by families are resolvable. In order to ensure effective KDT, a multidisciplinary team is required. This would ensure smooth and comprehensive care and the timely resolution of emerging problems. The cooperation of the families undergoing KDT is also important, enabling them to share their experiences. Full article

Introduction: The ongoing concern of the medical profession regarding chronic medication is related to increasing patient adherence and compliance to treatment and reducing medication side effects. In this respect, drugs represented by fixed-dose combinations of active substances within the same tablet have emerged. Such a principle can be extrapolated by following the potential beneficial effects that a chronic medication can have on chronic pathologies affecting different systems. Materials and Methods: The study included 48 female Albino Wistar rats, aged 16–18 months, which were divided into two groups: ovariectomized and non-ovariectomized rats. One batch of 12 non-ovariectomized rats received no treatment, becoming a control batch (NOVX-M). The ovariectomized (OVX) group was divided into 3 batches of 12 rats each: no treatment, control (OVX-M), fenofibrate-treated (OVX-F) and statin-treated (OVX-S) rats. At 12 weeks after ovariectomy, a femoral fracture occurred in the right hind limb of all animals included in the experiment To reveal the changes, at intervals of 2, 4, 6 and 8 weeks post-fracture, the proximal part of the femur was evaluated by NMR diffusiometry, which allows random motion of proton molecules expressed by self-diffusion coefficients, D, thus allowing analysis of the size and complexity of microscopic order cavities within biological structures, such as pores inside bones. Results: The effects of hypolipidemic medication in the absence of estrogen were evidenced, proving the beneficial effect that fenofibrate can have in preserving healthy tissue exposed to osteoporotic risk during the menopausal period. The effects of lipid-lowering medication are also influenced by the duration of administration. Conclusions: Osteoporosis and heart disease are two chronic pathologies that affect mainly female population in the second half of life, and proving the dual therapeutic potential of lipid-lowering medication may also have positive effects by increasing adherence and compliance to treatment. Full article

Chronic diffuse sclerosing osteomyelitis is a very rare condition, described as a non-suppurative, inflammatory disease of the bone and characterized by a proliferative endosteal reaction, which clinically reveals itself with cyclic pain of the jaw and swelling. We reported two clinical cases, where patients suffered recurrent swelling and pain at the mandible irradiating to the preauricular area, denying any previous trauma or significant medical history. Odontogenic causes were excluded. An initial treatment with antibiotics and NSAIDs temporarily relieved the symptoms without complete resolution, prompting further investigations. After a comprehensive array of diagnostic tools (X-rays, CT scans, scintigraphy, bone biopsy, serum markers), both patients were diagnosed with chronic diffuse sclerosing osteomyelitis of the mandible. Bisphosphonates (clodronate and zolendronate) with different treatment schemes were used to treat the condition, until a full recovery from symptoms was reported. Bisphosphonates could therefore represent an effective option in managing this rare but impactful condition. Further research is warranted to better understand the underlying mechanisms of the disease and to optimize treatment strategies. Full article

Abstract: Hepatobiliary ascariasis is caused by the entry of the nematode A. lumbricoides from the duodenum into the biliary duct. We report a case of an Ascaris-induced extrahepatic biliary tract obstruction in a pediatric patient admitted to the hospital due to a wide spectrum of symptoms of biliary disease, which included abdominal pain in the upper abdominal quadrants, vomiting, and jaundice. Imaging tests—including ultrasound, magnetic resonance cholangiopancreatography (MRCP), and endoscopic retrograde cholangiopancreatography (ERCP)—were performed to confirm the diagnosis of biliary ascariasis. The tests did, in fact, demonstrate signs of this disease. Nevertheless, during the ERCP, only the remains of Ascaris parasites in the form of tissue fragments were extracted. We also aim to discuss the prevalence of ascariasis in children, the causes of migration of Ascaris parasites into the bile ducts, together with its clinical manifestations, as well as the diagnostic and treatment methods of this disease. Full article

Background and Objectives: Hepatocellular carcinoma (HCC) is a prevalent form of malignancy that is characterized by high mortality rates and prognosis that remain suboptimal, largely due to treatment resistance mechanisms. Recent studies have implicated cancer stem cells (CSCs), particularly those expressing epithelial cell adhesion molecule (EpCAM), in HCC progression and resistance. In the present study, we sought to assess EpCAM expression in HCC patients and its correlation with various clinicopathological parameters. Materials and Methods: Tissue samples from 42 HCC patients were subjected to immunohistochemical staining to evaluate EpCAM expression. Clinicopathological data were obtained including the size, grade and stage of tumors, vascular invasion status, alpha-fetoprotein levels, and cirrhosis status. The Chi square and Fisher’s exact tests were employed to assess the association between categorical groups. Independent Student-t test or Mann–Whitney U test was used to investigate the association between continuous patient characteristics and survival. Results: Immunohistochemical analysis revealed EpCAM expression in 52.5% of HCC cases. EpCAM-positive tumors exhibited characteristics indicative of aggressive disease, including larger tumor sizes (p = 0.006), greater tumor multiplicity (p = 0.004), higher grades (p = 0.002), more advanced stages (p = 0.003), vascular invasion (p = 0.023), elevated alpha-fetoprotein levels (p = 0.013), and cirrhosis (p=0.052). Survival analysis demonstrated that EpCAM expression was significantly associated with lower overall rates of survival and higher rates of recurrence in HCC patients. Conclusions: Our findings suggest that EpCAM expression may serve as a prognostic biomarker for HCC with a potential role in patient management. Targeting EpCAM-positive CSCs may represent a promising approach to overcome treatment resistance and improve clinical outcomes in HCC. However, further investigation into the molecular mechanisms underlying EpCAM’s role in HCC progression is warranted to facilitate the development of personalized therapeutic interventions. Full article

Background and objectives: Paragangliomas of the head and neck are rare, slow-growing neuroendocrine tumors, benign in their vast majority, but with a possibility of developing distant metastases. They show great inheritable character, and their behavior has proven to be unpredictable; therefore, they are considered malignant. Material and methods: This article aims to offer a more comprehensive presentation of the pathogenesis, epidemiology, diagnostic methods, imaging development, and treatment guidelines. We tried to bring together all the necessary data that, in our opinion, a head and neck practitioner should know when managing this type of tumor. Our main focus is on the most recent studies, with the purpose of a homogenous presentation of all current guidelines and approaches to this pathology. Results: Paragangliomas of the head and neck are still a disputed topic. One of the main reasons for that is their low incidence of 0.3 to 1 per 100.000 every year. The most frequent locations are the carotid body, the temporal bone, the jugular and mastoid foramen, and the vagal nerve. Their clinical presentation usually involves a painless lateral mass associated with symptoms such as hoarseness, hearing loss, tinnitus, and cranial nerve deficits. Up to 40% of them are inherited, mostly linked with mutations of succinate dehydrogenase complex. Imaging evaluation consists of CT and MRI, and new functional explorations such as ¹⁸F-FDA and ¹⁸F-FDG PET/CT, ¹⁸F-DOPA PET, ¹²³I-MIBG, and ⁶⁸Ga-DOTATE PET/CT. Measuring the catecholamine levels in the plasma and urine is mandatory, even though paragangliomas of the head and neck rarely display secretory behavior. Treatment mainly consists of surgery, with different approaches and techniques, but conservative management methods such as wait and scan, radiotherapy, proton therapy, and chemotherapy have proven their efficiency. The therapeutical decision lacks consensus, and current studies tend to recommend an individualized approach. Guidelines regarding long-term follow-up are still a matter of debate. Full article

Background and Objective: Understanding whether cranial nerve palsy (CNP) acts as an independent risk factor for kidney cancer could have important implications for patient care, early detection, and potentially the development of preventive strategies for this type of cancer in individuals with CNP. This study aimed to examine the risk of kidney cancer following the onset of ocular motor CNP and assess whether CNP could be considered an independent risk factor for kidney cancer. Materials and Methods: A population-based cohort study was conducted using data from the National Sample Cohort (NSC) database of Korea’s National Health Insurance Service which was collected from 2010 to 2017. Follow-up was until kidney cancer development, death, or 31 December 2018. Cox proportional hazard regression analysis was performed to determine hazard ratios (HRs) for kidney cancer according to CNP status. Participants aged 20 years or more diagnosed with CNP from 2010 to 2017 were included. Exclusions comprised individuals with specific pre-existing conditions, inability to match a control group, and missing data, among others. CNP patients were age–sex matched in a 1:5 ratio with control cases. The primary outcome was incidence of kidney cancer during the follow-up period. Results: This study comprised 118,686 participants: 19,781 in the CNP group, and 98,905 in the control group. Compared to the control group, participants with CNP had a higher risk of kidney cancer (adjusted HR in model 4, 1.599 [95% CI, 1.116–2.29]). After a 3-year lag period, the CNP group had a significantly higher risk (adjusted HR in model 4, 1.987 [95% CI, 1.252–3.154]). Conclusions: Ocular motor CNP may be an independent risk factor for kidney cancer, as indicated by a higher incidence of kidney cancer in CNP patients. Further research is needed to elucidate the underlying mechanisms and explore potential preventive measures for kidney cancer in patients with ocular motor CNP. Full article

Over the last few years, given the increase in the incidence and prevalence of both type 2 diabetes mellitus (T2DM) and heart failure (HF), it became crucial to develop guidelines for the optimal preventive and treatment strategies for individuals facing these coexisting conditions. In patients aged over 65, HF hospitalization stands out as the predominant reason for hospital admissions, with their prognosis being associated with the presence or absence of T2DM. Historically, certain classes of glucose-lowering drugs, such as thiazolidinediones (rosiglitazone), raised concerns due to an observed increased risk of myocardial infarction (MI) and cardiovascular (CV)-related mortality. In response to these concerns, regulatory agencies started requiring CV outcome trials for all novel antidiabetic agents [i.e., dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and sodium-glucose cotransporter-2 inhibitors (SGLT2is)] with the aim to assess the CV safety of these drugs beyond glycemic control. This narrative review aims to address the current knowledge about the impact of glucose-lowering agents used in T2DM on HF prevention, prognosis, and outcome. Full article

Lower limb amputation is a common surgical procedure performed worldwide. Many individuals require amputation due to various circumstances, with amputations occurring above or below the knee. Surgeons rely on published research to determine the most appropriate technique based on intraoperative and postoperative outcomes. The Gritti–Stokes amputation (GSA) procedure, introduced in 1857, has shown positive results in terms of primary wound healing, reduced mortality rates during and after surgery, and accelerated healing and mobility. However, due to the need for highly trained surgeons and limitations in functional and cosmetic prosthesis fitting, concerns have been raised regarding its utility. Additionally, the procedure is underutilized in cases where it could potentially yield better results. This article provides a comprehensive review of the documented benefits of GSA, suitable candidate selection, limitations, various modifications, and a comparison with traditional approaches to lower limb amputation. The review is focused on evidence published in the last 100 years. Full article

Background and Objectives: Dementia is increasing worldwide. This study aimed to examine the impact of comorbidity burden and frailty on dementia prognosis in patients with dementia. Materials and Methods: This retrospective cohort study was conducted with 47 patients with dementia who were followed for up to two years. The Modified Charlson Comorbidity Index (MCCI), Mini-Mental State Examination (MMSE-E), and Edmonton Fragility Scale were used besides laboratory and clinical findings. Results: The mean age of the 47 patients was 78.77 ± 12.44 years. During the follow-up period, MMSE-E scores were observed to improve in 50% of the patients. Initial MMSE-E scores were found to be lowest in men and patients with coronary artery disease or depression, while final MMSE-E scores were observed to be lowest in patients with depression and low vitamin B12 or vitamin D levels. The rates of decrease in MMSE-E scores in non-, moderately and severely frail patients were 21.4%, 55.6%, and 70.6%, respectively. There was a moderate negative correlation between MMSE-E scores and both comorbidity burden and frailty scores. The mediation analysis revealed that frailty was a complete mediator, and that comorbidity burden led to an increase in frailty and a decrease in MMSE-E scores. During the follow-up period, patients with moderate frailty, hypertension, diabetes mellitus, alcohol and tobacco use, low B12 levels, or hypothyroidism showed an increased risk of decrease in cognitive functions. Conclusions: There was a significant association between dementia prognosis and both frailty and biological deficits. We recommend the adoption of a syndemic approach in the follow-up of dementia, as we believe that the prevention of frailty and associated biological deficits will contribute to slowing dementia’s clinical course. Full article

Background and Objectives: Our aim was to perform a retrospective analysis of the volume of cervical screening tests, the number of patients treated with an excision method, and the incidence of invasive and non-invasive cervical during a pandemic and pre-pandemic period of 24 months. Materials and Methods: The study compared 404 patients who underwent cervical cone biopsy for cervical cancer. The study examined patients’ specimens based on histopathological characteristics and categorized cervical lesions based on pap smear. Results: There was a statistically significant age difference between the two study periods. The mean difference was 32 years before the pandemic and 35 years during the pandemic (p-value > 0.05). The biggest patient loss ratio identified by age group was in the 50–59-year group, with a 14.53% loss in the pre-pandemic period and a 9.1% loss in the pandemic period. In the pandemic period, patients from rural areas presented in the clinical trial with a lower rate of 39.52% (83 patients) vs. 60.47% (127 patients) in urban areas. A higher percentage of patients experiencing cervicorrhagia as a clinical manifestation in the pandemic period vs. the pre-pandemic period, with an increase in more severe lesions in the pandemic period, had a statistical significance of 8% more newly diagnosed compared to the pre-pandemic period. Conclusions: The addressability of the patients during the COVID period was not affected in a drastic way in our study. We encountered a decrease in appointments in the age group of 50–59 years and a decrease in patients with rural residence. In our study, we found an increase in cervical bleeding as a reason for consultation in the pandemic period with a higher lesion degree, both on a pap smear and on a cervical biopsy. Full article

Background and Objectives: The rise in global diabetes cases, reaching a staggering 529 million in 2021 from 108 million in 1980, underscores the urgency of addressing its complications, notably macrovascular ones like coronary artery, cerebrovascular, and peripheral artery diseases, which contribute to over 50% of diabetes mortality. Atherosclerosis, linked to hyperglycemia-induced endothelial dysfunction, is pivotal in cardiovascular disease development. Cytokines, including pentraxin 3 (PTX3), copeptin, lipoprotein(a) [Lp(a)], and matrix metalloproteinase-9 (MMP-9), influence atherosclerosis progression and plaque vulnerability. Inhibiting atherosclerosis progression is crucial, especially in diabetic individuals. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs), increasingly used for type 2 diabetes, show promise in reducing the cardiovascular risk, sparking interest in their effects on atherogenesis. This study sought to examine the effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on biomarkers that indicate the instability of atherosclerotic plaques. These biomarkers include pentraxin 3 (PTX3), copeptin (CPC), matrix metalloproteinase-9 (MMP-9), and lipoprotein(a) [Lp(a)]. Materials and Methods: A total of 34 participants, ranging in age from 41 to 81 years (with an average age of 61), who had been diagnosed with type 2 diabetes mellitus (with a median HbA1c level of 8.8%), dyslipidemia, and verified atherosclerosis using B-mode ultrasonography, were included in the study. All subjects were eligible to initiate treatment with a GLP-1 RA—dulaglutide. Results: Significant reductions in anthropometric parameters, blood pressure, fasting glucose levels, and HbA1c levels were observed posttreatment. Moreover, a notable decrease in biochemical markers associated with atherosclerotic plaque instability, particularly PTX3 and MMP-9 (p < 0.001), as well as Lp(a) (p < 0.05), was evident following the GLP-1 RA intervention. Conclusions: These findings underscore the potential of GLP-1 RAs in mitigating atherosclerosis progression and plaque vulnerability, thus enhancing cardiovascular outcomes in individuals with type 2 diabetes mellitus. Full article

Background and Objectives: Cardiogenic shock (CS) is a potentially severe complication following acute myocardial infarction (AMI). The use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) in these patients has risen significantly over the past two decades, especially when conventional treatments fail. Our aim is to provide an overview of the role of VA-ECMO in CS complicating AMI, with the most recent literature highlights. Materials and Methods: We have reviewed the current VA-ECMO practices with a particular focus on CS complicating AMI. The largest studies reporting the most significant results, i.e., overall clinical outcomes and management of the weaning process, were identified in the PubMed database from 2019 to 2024. Results: The literature about the use of VA-ECMO in CS complicating AMI primarily has consisted of observational studies until 2019, generating the need for randomized controlled trials. The EURO-SHOCK trial showed a lower 30-day all-cause mortality rate in patients receiving VA-ECMO compared to those receiving standard therapy. The ECMO-CS trial compared immediate VA-ECMO implementation with early conservative therapy, with a similar mortality rate between the two groups. The ECLS-SHOCK trial, the largest randomized controlled trial in this field, found no significant difference in mortality at 30 days between the ECMO group and the control group. Recent studies suggest the potential benefits of combining left ventricular unloading devices with VA-ECMO, but they also highlight the increased complication rate, such as bleeding and vascular issues. The routine use of VA-ECMO in AMI complicated by CS cannot be universally supported due to limited evidence and associated risks. Ongoing trials like the Danger Shock, Anchor, and Recover IV trials aim to provide further insights into the management of AMI complicated by CS. Conclusions: Standardizing the timing and indications for initiating mechanical circulatory support (MCS) is crucial and should guide future trials. Multidisciplinary approaches tailored to individual patient needs are essential to minimize complications from unnecessary MCS device initiation. Full article