Medicina, Volume 60, Issue 5 (May 2024) – 114 articles

Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL) and Breast Implant-Associated Squamous Cell Carcinoma (BIA-SCC) are emerging neoplastic complications related to breast implants. While BIA-ALCL is often linked to macrotextured implants, current evidence does not suggest an implant-type association for BIA-SCC. Chronic inflammation and genetics have been hypothesized as key pathogenetic players, although for both conditions, the exact mechanisms and specific risks related to breast implants are yet to be established. While the genetic alterations in BIA-SCC are still unknown, JAK-STAT pathway activation has been outlined as a dominant signature of BIA-ALCL. Recent genetic investigation has uncovered various molecular players, including MEK-ERK, PI3K/AKT, CDK4-6, and PDL1. The clinical presentation of BIA-ALCL and BIA-SCC overlaps, including most commonly late seroma and breast swelling, warranting ultrasound and cytological examinations, which are the first recommended steps as part of the diagnostic work-up. While the role of mammography is still limited, MRI and CT-PET are recommended according to the clinical presentation and for disease staging. To date, the mainstay of treatment for BIA-ALCL and BIA-SCC is implant removal with en-bloc capsulectomy. Chemotherapy and radiation therapy have also been used for advanced-stage BIA-ALCL and BIA-SCC. In-depth characterization of the tumor genetics is key for the development of novel therapeutic strategies, especially for advanced stage BIA-ALCL and BIA-SCC, which show a more aggressive course and poor prognosis. Full article

Background and Objectives: Breastmilk is the safest and most suitable food for an infant, playing the role of their first vaccine and containing all the essential nutrients for the first months of life. The World Health Organisation recommends exclusive breastfeeding for the first 6 months of life and continued breastfeeding while introducing a child to complementary foods until 2 years and beyond. According to Latvian statistics from 2022, only 27.4% of babies were breastfed for 12 months. The aim of this study was to determine the socio-economic factors and factors related to pregnancy, childbirth and postpartum that influence breastfeeding for more than 6 months in Latvia. Materials and Methods: Data were used from the cross-sectional survey “Research on factors and behaviours affecting the sexual and reproductive health of the population of Latvia”, which was conducted in 2023. A study sample was randomised and stratified by gender and five age groups. The analyses in this study are based on a sample of women who had given birth at least once (n = 1407), and the dependent variable was the duration of breastfeeding their last child. Binary logistic regression was conducted to identify the associated factors. Results: The point prevalence of longer duration of breastfeeding for the last child was 47.9% (n = 674). The odds of longer breastfeeding duration were higher among mothers who did not smoke during pregnancy (vs. smokers, aOR 2.1, p < 0.001), of Latvian nationality (vs. Russian, aOR 1.3, p = 0.03), who had two childbirth (vs. one, aOR 1.5, p = 0.003), who had the highest level of education (vs. primary education, aOR 2.0, p = 0.03), started breastfeeding immediately after the birth (vs. later than the first day, aOR 1.7, p = 0.01) or on the first day (vs. later, aOR 1.6, p = 0.01). Conclusions: We documented socio-demographic pregnancy and childbirth factors associated with longer breastfeeding durations. Efforts to promote breastfeeding practices should target mothers from the most vulnerable groups. Full article

Background and Objectives: Long-term outcomes of immediately postoperative rotational malreduction in the axial plane after operative treatment of supracondylar humeral fractures (SCHF) are unknown. This study aimed to investigate the long-term clinical outcomes and associated factors for immediately postoperative rotational malreduction of SCHF. Materials and methods: In this retrospective case–control study, 88 patients who underwent surgery for Gratland type III SCHF were enrolled between January 2012 and January 2020. Among them, 49 patients had immediately postoperative malrotational reduction (rotational malreduction group) and 39 patients had no rotational deformity (control group). To evaluate the associated factors for immediately postoperative rotational malreduction, demographic data, fracture patterns, physical examination signs, and preoperative radiological parameters were analyzed. To compare the clinical outcomes, operation time, range of motion of the elbow, time from operation to full range of motion, and Flynn criteria were evaluated. The Oxford elbow score was used to investigate long-term clinical outcomes for patients five years after operation. Results: The mean age was 5.7 ± 2.3 years and mean follow-up period was 15.7 ± 4.0 months. The rotational malreduction group had significantly more patients with oblique fracture pattern (p = 0.031) and Pucker sign (p = 0.016) and showed a significantly longer operative time (p = 0.029) than the control group. Although there was no significant difference in the range of elbow motion and the Flynn criteria, the Kaplan–Meier survival curve showed a longer time to recover the full range of elbow motion in the rotational malreduction group (p = 0.040). There were no significant differences in the long-term clinical outcomes assessed using the Oxford elbow score (p = 0.684). Conclusions: Oblique fracture pattern and Pucker sign may be associated with immediately postoperative rotational malreduction in the axial plane. Although patients with immediately postoperative rotational malreduction showed favorable results of long-term clinical outcomes, they required more weeks to recover the full range of elbow motion. Full article

Background and Objectives: Despite the promise of phage therapy (PT), its efficacy in prosthetic joint infection (PJI) management is unknown. Much of the current literature is largely limited to case reports and series. Materials and Methods: In order to help inform power calculations for future clinical trials and comparative analyses, we performed a systematic review and proportional meta-analysis of early PT outcomes to provide a preliminary assessment of early phage therapy treatment outcomes for cases of PJI. Results: In a search of available literature across MEDLINE (Ovid, Wolters Kluwer, Alphen aan den Rijn, The Netherlands), Embase (Elsevier, Amsterdam, The Netherlands), the Web of Science Core Collection (Clarivate, London, UK), and Cochrane Central (Wiley, Hoboken, NJ, USA) up to 23 September 2023, we identified 37 patients with PJIs receiving adjunctive PT. Patients most frequently reported Staphylococcal species infection (95%) and intraarticular phage delivery (73%). Phage cocktail (65%) and antibiotic co-administration (97%) were common. A random-effects proportional meta-analysis suggested infection remission in 78% of patients (95% CI: 39%, 95%) (I² = 55%, p = 0.08) and 83% with a minimum 12-month follow-up (95% CI: 53%, 95%) (I² = 26%, p = 0.26). Conclusions: Our study provides a preliminary estimate of PT’s efficacy in PJIs and informs future comparative studies. Full article

Background and Objectives: Patella baja is a common complication after operative treatment for patellar fracture. This study aimed to investigate (1) the serial changes in patellar height and (2) the potential predictive factors for patellar height changes after tension band wiring (TBW) for patellar fractures. Materials and Methods: Forty-one patients who underwent TBW for patellar fracture between March 2019 and September 2022 were enrolled. To identify serial changes in patellar height, modified Blackburne–Peel index (mBPI) was assessed at just after surgery, at 3 months, at 6 months, at 1 year and at the final follow-up. Multiple regression analysis was conducted to identify factors correlated with mBPI difference between the contralateral side (considered as preoperative status) and injured side. Results: The postoperative mBPI exhibited a decline over time (mean mBPI immediately post operation/3 months/6 months/1 year/final follow-up: 0.69/0.63/0.63/0.62/0.61) Specifically, mBPI showed a significant reduction immediately post operation to 3 months (p < 0.001), although comparisons at other time points did not reveal significant differences. A lower position of the fracture was associated with a decrease in patellar height after surgery. Conclusions: Patellar height was mainly decreased from immediately post operation to 3 months. A fracture in a lower position of associated with decreased patellar height after the TBW of the transverse patellar fracture. Full article

Background and Objectives: During the COVID-19 pandemic, there was an increased number of hospitalized COVID-19-positive patients suffering from type 2 diabetes mellitus (T2DM). The objective of this research study was to explore factors associated with the length of hospitalization of patients with T2DM and the mild form of COVID-19. Material and Methods: This retrospective cohort study involved all patients who tested positive for COVID-19 and those who were treated in the dedicated COVID-19 department of the University Clinical Center (UCC) in Nis between 10 September 2021 and 31 December 2021. Upon admission, patients underwent blood tests for biochemical analysis, including blood count, kidney and liver function parameters (C-reactive protein (CRP), creatinine kinase, and D-dimer), and glycemia and HbA1c assessments. Additionally, all patients underwent lung radiography. Univariate and multivariate regression analyses were employed to assess the impact of specific factors on the length of hospitalization among patients with T2DM. Results: Out of a total of 549 treated COVID-19-positive patients, 124 (21.0%) had T2DM, while 470 (79.0%) did not have diabetes. Among patients with T2DM, men were significantly younger than women (60.6 ± 16.8 vs. 64.2 ± 15.3, p < 0.01). The average hospitalization length of patients with diabetes was 20.2 ± 9.6 (5 to 54 days), and it was significantly longer than for patients without diabetes, at 15.0 ± 3.4, which ranged from 3 days to 39 (t-test ≈ 5.86, p < 0.05). According to the results of the univariate regression analysis, each year of age is associated with an increase in the length of hospital stay of 0.06 days (95% CI: 0.024 to 0.128, p = 0.004). Patients who received oxygen therapy were treated for 2.8 days longer than those who did not receive oxygen treatment (95% CI: 0.687 to 4988, p = 0.010), and each one-unit increase in CRP level was associated with a 0.02-day reduction in the length of hospitalization (95% CI: 0.004 to 0.029, p = 0.008). Based on the results of the multivariate regression analysis, each year of age is associated with an increase in the length of hospitalization by 0.07 days (95% CI: 0.022 to 0.110, p = 0.003). Patients who received oxygen therapy were treated for 3.2 days longer than those who did not receive oxygen therapy (95% CI: 0.653 to 5726, p = 0.014), and each unit increase in CRP level was associated with a 0.02-day reduction in the length of hospitalization (95% CI: 0.005 to 0.028, p = 0.004). Conclusions: Based on the presented results, COVID-19-positive patients with diabetes had, on average, longer hospitalizations than COVID-19 patients without diabetes. The hospital treatment of patients with T2DM and a milder form of COVID-19 was associated with older age, the use of oxygen therapy, and elevated CRP values. Patients who received oxygen therapy were treated approximately 3 days longer than those who did not receive this therapy. Full article

Background and Objectives: Stem cell-based regeneration strategies have shown therapeutic efficacy in various fields of regenerative medicine. These include bone healing after bone augmentation, often complicated by pain, which is managed by using nonsteroidal anti-inflammatory drugs (NSAIDs). However, information is limited about how NSAIDs affect the therapeutic potential of stem cells. Materials and Methods: We investigated the effects of ibuprofen and diclofenac on the characteristics, morphology, and immunophenotype of human mesenchymal stromal cells isolated from the dental pulp (DPSCs) and cultured in vitro, as well as their effects on the expression of angiogenic growth factors (VEGFA and HGF) and selected genes in apoptosis signalling pathways (BAX, BAK, CASP3, CASP9, and BCL2). Results: Ibuprofen and diclofenac significantly reduced the viability of DPSCs, while the expression of mesenchymal stem cell surface markers was unaffected. Both ibuprofen and diclofenac treatment significantly upregulated the expression of HGF, while the expression of VEGFA remained unchanged. Ibuprofen significantly altered the expression of several apoptosis-related genes, including the upregulation of CASP9 and BCL2, with decreased CASP3 expression. BAK, CASP3, CASP9, and BCL2 expressions were significantly increased in the diclofenac-treated DPSCs, while no difference was demonstrated in BAX expression. Conclusions: Our results suggest that concomitant use of the NSAIDs ibuprofen or diclofenac with stem cell therapy may negatively impact cell viability and alter the expression of apoptosis-related genes, affecting the efficacy of stem cell therapy. Full article

Background and Objectives: The aim of the study was to evaluate the health status of professional athletes after recovering from COVID-19 and the impact that SARS-CoV-2 had on their overall cardiorespiratory fitness, which was done by conducting cardiopulmonary exercise testing (CPET). Materials and Methods: A total of twenty-seven professional basketball players (Euroleague Basketball and the ABA League) participated in the study. CPET was performed before (as part of their regular preparticipation exam, during the pre-season period), as well as after SARS-CoV-2 infection (after two weeks of home isolation, during the competitive part of the season). CPET was performed on a treadmill, while cardiovascular, respiratory, and metabolic functions were evaluated by using a breath-by-breath analysis technique (Quark CPET system manufactured by Cosmed, Rome, Italy). Results: Maximal oxygen consumption and aerobic efficiency were significantly reduced after SARS-CoV-2 infection (p = 0.000). An obvious decrease in oxygen pulse was observed during CPET after recovering from COVID-19 (p = 0.001), as was deterioration of ventilatory efficiency. Internal respiration was the most negatively affected. An early transition from aerobic to anaerobic mechanisms of creating energy for work and intensive metabolic fatigue were obvious after SARS-CoV-2 infection. Conclusions: Although it was believed that SARS-CoV-2 only affects the cardiopulmonary status of the elderly population and people with associated comorbidities, it is clear from this research that professional athletes can also be at certain risk. Even though no pathological cardiovascular and respiratory changes were found in athletes after COVID-19, results showed significantly decreased cardiorespiratory fitness, with an emphasis on internal respiration. Full article

Background and Objectives: Thrombosis is a serious complication experienced by some hospitalized patients. While concurrent placement of two catheters (CVCs) in the same central vein offers several benefits in clinical settings, we aimed to investigate the role of this procedure in relation to the risk of thrombosis. Materials and Methods: Over a two-year retrospective analysis, we examined 114 patients with septic shock caused by a pulmonary infection, who underwent the insertion of one or more central lines into a central vein during their ICU stay. Logistic regression models were employed to assess the correlation between the Caprini risk score, the placement of two CVCs in the same vein, COVID-19 infection and the risk of venous thromboembolism (VTE). Results: In total, 53% of the patients underwent the concurrent insertion of two CVCs. The placement of two CVCs in the same vein appears to elevate the VTE risk by 2.5 times (95% CI: 1.03–6.12). Logistic regression analysis indicated that hemodialysis catheters amplify the VTE risk by nearly five times, even when accounting for a series of factors (95% CI: 1.86–12.31). Conclusions: Our study suggests that the elevated risk of VTE is likely associated with the insertion of the hemodialysis catheters rather than solely the presence of two concurrent catheters. Full article

Background and Objectives: mortality and morbidity due to cardiovascular causes are frequently experienced in amputees. Research on the effects of chronic exercise on biomarkers and cardiac damage indicators in these individuals is limited. The aim of this study was to investigate the effects of a core training program on brain natriuretic-related peptide, as well as hematological and biochemical parameters in amputee soccer players. Materials and Methods: The participants were randomly allocated to the following two groups: a core exercise group (CEG) and a control group (CG). While the CG continued routine soccer training, the CEG group was included in a core exercise program different from this group. During the study, routine hemogram parameters of the participants, various biochemical markers, and the concentration of brain natriuretic-related peptide (NT-pro-BNP) were analyzed. Results: after the training period, notable improvements in various hematological parameters were observed in both groups. In the CEG, there were significant enhancements in red blood cell count (RBC), hematocrit (HCT), mean corpuscular hemoglobin concentration (MCHC), and mean corpuscular hemoglobin (MCH) values. Similarly, the CG also showed substantial improvements in RBC, HCT, mean corpuscular volume (MCV), MCHC, MCH, red cell distribution width-standard deviation (RDW-SD), platelet-to-lymphocyte ratio (PLCR), mean platelet volume (MPV), and platelet distribution width (PDW). Moreover, in the CEG, serum triglycerides (TG) and maximal oxygen uptake (MaxVO₂) exhibited significant increases. Conversely, TG levels decreased in the CG, while high-density lipoprotein (HDL), low-density lipoprotein (LDL), and MaxVO₂ levels demonstrated substantial elevations. Notably, the N-terminal pro-brain natriuretic peptide (BNP) levels did not undergo significant changes in either the CEG or the CG following the core exercise program (p > 0.05). However, in the CEG, a meaningful positive correlation was observed between NT-pro-BNP and creatine kinase (CK) levels before and after the core exercise program. Conclusions: the findings emphasized the potential benefits of core training in enhancing specific physiological aspects, such as erythrocyte-related parameters and lipid metabolism, as well as aerobic capacity. Furthermore, the observed correlation between NT-pro-BNP and CK levels in the CEG provides intriguing insights into the unique physiological adaptations of amputee athletes. Full article

Background and Objectives: Erdosteine (Erd) is an antioxidant and anti-inflammatory drug. Vitamin B has been reported to exert anti-inflammatory and antioxidant effects. In this study, we investigated the effect of erdosteine and vitamin B complex on a liver ischemia/reperfusion (I/R) model. Materials and Methods: Thirty-two Wistar Albino male rats weighing 350–400 g were used. The animals were randomly selected and divided into four groups. The groups are as follows: first group (Sham), second group (I/R), third group (I/R + vit B), and fourth group (I/R + vit B + Erd). Rats were subjected to 45 min of hepatic ischemia, followed by a 45 min reperfusion period in the I/R and Vitamin B + Erd groups. An amount of 150 mg/kg/day of erdosteine was given orally for 2 days, and 0.05 mL/kg of i.p. vitamin B complex was given 30 min before the reperfusion. Serum biochemical parameters were measured. Serum Total Antioxidant Status (TAS) and Total Oxidant Status (TOS) were measured, and the Oxidative Stress Index (OSI) was calculated. Hepatic tissue samples were taken for the evaluation of histopathological features. Results: In terms of all histopathological parameters, there were significant differences in the I/R + vit B group and I/R + vit B + Erd group compared with the I/R group (p < 0.01). In terms of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), TNF-alpha, and IL-6 levels, there were significant differences between the I/R group and treatment groups (p < 0.01). The lowest TOS and OSI levels were obtained in the treatment groups, and these groups had statistically significantly higher TAS levels compared with the sham and I/R groups (p < 0.01). Conclusions: As a preliminary experimental study, our study suggests that these agents may have potential diagnostic and therapeutic implications for both ischemic conditions and liver-related diseases. These results suggest that the combination of vit B + Erd may be used to protect against the devastating effects of I/R injury. Our study needs to be confirmed by clinical studies with large participation. Full article

Background and Objectives: Predominantly antibody deficiencies (PAD) represent the most common type of primary immunodeficiencies in humans, characterized by a wide variation in disease onset, clinical manifestations, and outcome. Considering that the prevalence of PAD in Greece is unknown, and there is limited knowledge on the clinical and laboratory characteristics of affected patients, we conducted a nationwide study. Materials and Methods: 153 patients (male/female: 66/87; median age: 43.0 years; range: 7.0–77.0) diagnosed, and followed-up between August 1979 to September 2023. Furthermore, we classified our cohort into five groups according to their medical history, immunoglobulin levels, and CTLA4-mutational status: 123 had common variable immunodeficiency (CVID), 12 patients with “secondary” hypogammaglobulinemia due to a previous B-cell depletion immunotherapy for autoimmune or malignant disease several years ago (median: 9 years, range 6–14) displaying a typical CVID phenotype, 7 with combined IgA and IgG subclass deficiencies, 5 patients with CVID-like disease due to CTLA4-mediated immune dysregulation syndrome, and 6 patients with unclassified hypogammaglobulinemia. Results: We demonstrated a remarkable delay in PAD diagnosis, several years after the onset of related symptoms (median: 9.0 years, range: 0–43.0). A family history of PAD was only present in 11.8%, with the majority of patients considered sporadic cases. Most patients were diagnosed in the context of a diagnostic work-up for recurrent infections, or recurrent/resistant autoimmune cytopenias. Interestingly, 10 patients (5.6%) had no history of infection, diagnosed due to either recurrent/resistant autoimmunity, or during a work-up of their medical/family history. Remarkable findings included an increased prevalence of lymphoproliferation (60.1%), while 39 patients (25.5%) developed bronchiectasis, and 16 (10.5%) granulomatous disease. Cancer was a common complication in our cohort (25 patients, 16.3%), with B-cell malignancies representing the most common neoplasms (56.7%). Conclusion: Our findings indicate the necessity of awareness about PAD and their complications, aiming for early diagnosis and the appropriate management of affected patients. Full article

Background and Objectives: Cellulite, or edemato-fibro-sclerotic panniculopathy (EFP), is characterized by dermal and hypodermal changes leading to adipose tissue accumulation and compromised venous circulation. This study investigates the efficacy of a hypertonic cream containing concentrated sodium chloride (Jovita Osmocell^®) in addressing water retention and structural alterations in adipose tissue, aiming to interrupt the cellulite formation process. Materials and Methods: A 12-week, prospective, monocentric, double-blind, placebo-controlled study enrolled 30 female subjects with grade II or III cellulite. Patients were randomized to receive hypertonic cream or a placebo. Thigh circumference, ultrasound evaluations, and standardized photographs were collected at baseline, intermediate, and endpoint visits. Adverse events were monitored. Results: After 84 days, the hypertonic cream group exhibited a significant reduction in thigh circumference compared to the placebo group (p = 0.0037). B-mode ultrasound examinations revealed significant changes in the parameters studied, such as the thickness of the subcutaneous tissue. No statistically significant changes were noticed in the placebo group. Volunteers reported the investigational product’s pleasantness and good anti-cellulite activity, with no reported adverse events. Conclusions: The hypertonic cream demonstrated efficacy in reducing thigh circumference, addressing water retention and structural alterations in adipose tissue. The proposed mechanism involves osmosis, releasing accumulated fluids between fat cells, supporting drainage, and reducing inflammation. This study supports the efficacy and safety of hypertonic sodium chloride emulsions in cellulite treatment and confirms safety and user satisfaction. Full article

Background and Objectives: Connexin 43 (Cx43) is involved in the transfer of small signaling molecules between neighboring cells, thereby exerting a major influence on the initiation and progression of tumorigenesis. However, there is a lack of systematic research on Cx43 expression and its predictive role in clinical diagnosis and prognosis in pan-cancer. Materials and Methods: Several biological databases were used to evaluate the expression levels of GJA1 (encoding Cx43) and its diagnostic and prognostic significance in pan-cancer. We targeted kidney renal clear cell carcinoma (KIRC) and investigated the relationship between GJA1 expression and different clinical features of KIRC patients. Then, we performed cell-based experiments to partially confirm our results and predicted several proteins that were functionally related to Cx43. Results: The expression of GJA1 has a high level of accuracy in predicting KIRC. High GJA1 expression was remarkably correlated with a favorable prognosis, and this expression was reduced in groups with poor clinical features in KIRC. Cell experiments confirmed the inhibitory effects of increased GJA1 expression on the migratory capacity of human renal cancer (RCC) cell lines, and protein–protein interaction (PPI) analysis predicted that CDH1 and CTNNB1 were closely related to Cx43. Conclusions: GJA1 could be a promising independent favorable prognostic factor for KIRC, and upregulation of GJA1 expression could inhibit the migratory capacity of renal cancer cells. Full article

Background and Objectives: Bone age determination is a valuable method for forensic and disaster identifications of unknown human remains, as well as for medical and surgical procedural purposes. This retrospective research study aimed to determine the age based on epiphyseal fusion stages and investigate differences related to gender. Materials and Methods: X-rays of the knee were collected from medical imaging centers in hospitals in the south of Jordan and examined by two observers who determined the bone epiphyseal phase of closure for the femur, tibia, and fibula bone ends close to the knee based on a three-stage classification. Results: The main results revealed that females showed earlier epiphyseal union (Stage II) at the lower end of the femur and the upper ends of the tibia and fibula compared to males. In males, the start of complete union (Stage III) at knee bones was seen at the age of 17–18 years, while in females, it was seen at the age of 16–17 years. Additionally, knee bones showed complete union in 100% of males and females in the age groups 21–22 years and 20–21 years, respectively. Although females showed an earlier start and end of epiphyseal complete union than males, analysis of collected data showed no significant age differences between males and females at the three stages of epiphyseal union of the knee bones. Conclusions: Findings of the radiographic analysis of bone epiphyseal fusion at the knee joint are a helpful method for chronological age determination. This study supports the gender and ethnicity variation among different geographical locations. Studies with a high sample number would be needed to validate our findings. Full article

Background and Objectives: Primary malignant bone tumors are rare lesions, and their complex treatment can lead to functional impairment. It is important to have a postoperative assessment tool for patients’ functional outcomes to be evaluated and to consequently adapt future treatments in the pursuit of a continuous improvement of their quality of life. The Musculoskeletal Tumor Society Score (MSTS) is a validated specific system score that is used frequently in the follow-up of these patients. We found no information about a valid translated Romanian version of this score neither for the upper limb nor for the lower limb. We proposed in this study to translate the original version of the MSTS Score into Romanian and to perform validation analysis of the Romanian-language MSTS Score. Materials and Methods: We selected 48 patients who underwent limb-salvage surgery after resection of bone sarcomas. Patients were interrogated twice according to the translated Romanian version of the MSTS Score during their follow-up. The translation was performed according to the recommended guidelines. A total number of 96 questionnaires were valid for statistical analysis. Results: Internal consistency and reliability were good for both sets of questionnaires’ analytic measurements, with Cronbach’s alpha values of 0.848 (test) and 0.802 (retest). The test-retest evaluation proved to be statistically strong for reproducibility and validity with Spearman’s rho = 0.9 (p < 0.01, 95% CI). Conclusions: This study permitted the translation of this score and the validation of psychometric data. Our results showed that the Romanian version of the MSTS is a reliable means of assessment of the functional outcome of patients who received limb-salvage surgery for the upper and lower extremities. Full article

Background and Objectives: Lower extremity arterial disease is one of the most prevalent manifestations of atherosclerosis. The results from numerous studies regarding the best revascularization method of an occluded superficial femoral artery have been conflicting. The aim of this study was to compare the patency of transvenous endovascular with open femoropopliteal bypass, both with vein and prosthetic grafts. To our knowledge, a direct patency comparison between transvenous endovascular and open femoropopliteal bypass has not been published. This could help elucidate which method is preferable and in which cases. Materials and Methods: Patients with complex TASC-C and D SFA lesions were offered endovascular transvenous or open bypass. A total of 384 consecutive patients with PAD requiring surgical treatment were evaluated for inclusion in this study. Three-year follow-up data were collected for 52 endovascular procedures, 80 prosthetic grafts, and 44 venous bypass surgeries. Bypass patency was investigated by Duplex US every 6 months. Kaplan–Meier plots were used to analyze primary, primary-assisted, and secondary patency for endovascular transvenous, autovenous, and prosthetic bypasses. Results: Primary, primary-assisted, and secondary patency in venous group at 3 years was 70.5%, 77.3%, and 77.3%, respectively. In the endovascular transvenous group, primary, primary-assisted, and secondary patency at 3 years was 46.2%, 69.2%, and 76.9%, respectively. The lowest patency rates at 3 years were noted in the prosthetic graft group with 22.5% primary, 26.6% primary-assisted, and 28.2% secondary patency. Conclusions: The saphenous vein is the best graft to perform in above-the-knee femoropopliteal bypass. Transvenous endovascular bypass is a viable option with comparable primary-assisted and secondary patency. Primary patency is substantially lower for endovascular transvenous compared to venous bypass. Patients treated with endovascular transvenous bypass will require a significant number of secondary procedures to provide optimal patency. Prosthetic grafts should only be used if no other option for bypass is available. Full article

Background and Objectives: A deficiency in serum 25-hydroxyvitamin D levels is associated with a number of cardiovascular situations, such as high blood pressure, heart failure, atherosclerotic heart disease, and peripheral artery disease. The frontal QRS-T angle has recently been proposed as a marker of ventricular repolarization. A wider frontal QRS-T angle has been positively correlated with adverse cardiac events. The objective of our study was to examine the association between serum 25-hydroxyvitamin D level and the frontal QRS-T angle. Materials and Methods: A total of 173 consecutive patients aged 18–60 years undergoing routine cardiology check-up evaluation, and not receiving concurrent vitamin D treatment were included in the study. Patients were classified in three groups, depending on their vitamin D levels, and categorized as follows: Group 1—deficient (<20 ng/mL), Group 2—insufficient (20–29 ng/mL), or Group 3—optimal (≥30 ng/mL). The frontal QRS-T angle was determined using the automated reports generated by the electrocardiography machine. Results: The average age of participants was 45.8 (±12.2) years, and 55.5% of participants were female (p < 0.001). Individuals with low vitamin D concentrations exhibited a wider frontal QRS-T angle. It was determined that vitamin D level is an independent predictive factor for the frontal QRS-T angle. Conclusions: As the levels of 25-hydroxyvitamin D decrease, repolarization time assessed by frontal QRS-T angle is widened. Our findings indicate that lower concentrations of vitamin D may increase the susceptibility to ventricular arrhythmia. Full article

Background and Objectives: Screening for type 2 diabetes mellitus (DM2) aims to identify asymptomatic individuals who may be at a higher risk, allowing proactive interventions. The objective of this study was to predict the incidence of DM2 and prediabetes in the Saudi population over the next five years. Materials and Methods: The study was conducted in the Aseer region through August 2023 using a cross-sectional survey for data collection. A multistage stratified random sampling technique was adopted, and data were collected through face-to-face interviews using the validated Arabic version of the Australian Type 2 Diabetes Risk Assessment Tool (AUSDRISK). Results: In total, 652 individuals were included in the study. Their mean age was 32.0 ± 12.0 years; 53.8% were male, 89.6% were from urban areas, and 55.8% were single. There were statistically significant differences between males and females in AUSDRISK items, including age, history of high blood glucose, use of medications for high blood pressure, smoking, physical activity, and measurements of waist circumference (p < 0.05). Based on AUSDRISK scores, 46.2% of the included participants were predicted to develop impaired glucose tolerance within the coming five years (65.8% among females vs. 23.6%), and 21.9% were predicted to develop DM2 (35.6% among males vs. 6.0% among females); this difference was statistically significant (p = 0.0001). Conclusions: Urgent public health action is required to prevent the increasing epidemic of DM2 in Saudi Arabia. Full article

Background and Objective: Menopause can be associated with many clinical manifestations: vasomotor symptoms, urogenital problems, and additional psychological disturbances, such as anxiety, mood changes, and sleep alterations. The prolonged lack of hormones also increases the risk of long-term consequences. Hormone Replacement Treatment (HRT) in menopause consists of the administration of estrogen, alone or associated to progesterone, to relieve these uncomfortable disturbances and to prevent the onset of other pathologic conditions. The aim of this study is to examine the prevalence of HRT use in a sample of menopausal women and their experience with menopause and HRT. This study also investigates the knowledge of general practitioners (GPs) and gynecologists about HRT and its prescription. Materials and Methods: We conducted a cross-sectional population survey on 126 women of 50–59 years in an industrial city in the North of Italy, Vercelli (Novara), in Eastern Piedmont. We also presented a questionnaire on the topic to 54 medical doctors (GPs and gynecologists) of the same area. Results: The prevalence of HRT use in our sample was 11.9%. In total, a good percentage of the users affirmed to be satisfied with HRT. Additionally, a minority of women reported being ideally against the use of replacement hormones, were advised against using HRT by doctors, and did not use it because of the fear of side effects. We found a positive association between patient education, health care attitude, and HRT usage. A significant number of women knew about HRT from the media, and most of them were not informed by a health professional. Despite this, the interviewed doctors considered their knowledge about HRT as ‘good’ and would recommend HRT: only 5.6% would not prescribe it. Conclusions: Our results highlight the need for information about HRT among patients and health professionals, along with the need for more effective communication, evaluation, and suggestion of treatment. Full article

The regeneration of periodontal bone defects continues to be an essential therapeutic concern in dental biomaterials. Numerous biomaterials have been utilized in this sector so far. However, the immune response and vascularity in defect regions may be disregarded when evaluating the effectiveness of biomaterials for bone repair. Among several regenerative treatments, the most recent technique of in situ tissue engineering stands out for its ability to replicate endogenous restorative processes by combining scaffold with particular growth factors. Regenerative medicine solutions that combine biomaterials/scaffolds, cells, and bioactive substances have attracted significant interest, particularly for bone repair and regeneration. Dental stem cells (DSCs) share the same progenitor and immunomodulatory properties as other types of MSCs, and because they are easily isolable, they are regarded as desirable therapeutic agents in regenerative dentistry. Recent research has demonstrated that DSCs sown on newly designed synthetic bio-material scaffolds preserve their proliferative capacity while exhibiting increased differentiation and immuno-suppressive capabilities. As researchers discovered how short peptide sequences modify the adhesion and proliferative capacities of scaffolds by activating or inhibiting conventional osteogenic pathways, the scaffolds became more effective at priming MSCs. In this review, the many components of tissue engineering applied to bone engineering will be examined, and the impact of biomaterials on periodontal regeneration and bone cellular biology/molecular genetics will be addressed and updated. Full article

Background and Objectives: The safe zone in total hip replacement was introduced many years ago. Its aim was to provide guidelines for orthopedic surgeons in order to avoid complications such as instability. With the growing interest in spinopelvic alignment, some new insights suggest that the safe zone is an obsolete concept. This study aims to show that, even outside the safe zone, the effect of total hip replacement can be satisfactory. This could be used as preliminary study for an analysis of a larger group. Materials and Methods: Fifty-nine consecutive patients with end-stage osteoarthritis treated by total hip replacement were enrolled into the study and divided into two groups: inside the safe zone and outside the safe zone. A physical examination during postoperative visits was performed; the range of movement was measured using a goniometer; and the HHS and VAS were taken to measure functional outcomes and pain, respectively. An analysis of the radiological outcomes was performed. Results: There was no significant difference in regard to changes in total offset, pain, HHS and other complications. There were no signs of instability among patients during the follow-up. Conclusions: The results of this study show that the “safe zone” is a more complicated term that was previously thought. A proper soft tissue balance and spinopelvic alignment could be factors that change the “safe zone” for each patient and make it more individual. Full article

Background and Objectives: Assess the quality of life of children aged 2–10 with mild to moderate bronchial asthma. To evaluate the general health condition of children with mild and moderate severity bronchial asthma. To determine health changes in children with mild- and moderate-severity bronchial asthma as they grow older. To evaluate the impact of mild- and moderate-severity bronchial asthma on children’s daily and social activities, physical health, emotional state, and general well-being. Materials and Methods: A comparative cross-sectional study was conducted in March–June 2020. Parents or guardians of 2–10-year-old children without bronchial asthma and children with mild to moderate bronchial asthma were interviewed after receiving their written informed consent. The questionnaire was based on the standardized quality-of-life quiz SF-36. A total of 248 questionnaires were collected—106 from the parents or guardians of children with bronchial asthma and 142 from parents/guardians of children without bronchial asthma. For further analysis, 106 children without bronchial asthma and with no chronic conditions were selected. Quantitative variables were compared using the Mann–Whitney U test and qualitative data using the chi-square (χ²) criteria. Quantitative data were described by giving means, medians, and standard deviations (SD); qualitative features by giving relative frequencies. Statistical data were analyzed using SPSS and Excel 2020. Results: Children with mild and moderate asthma exhibit poorer health compared to their healthy counterparts. Only 20.7% of respondents with asthma reported excellent or very good health, contrasting with 64.1% of healthy children (p < 0.001). As children with asthma age, their general condition improves, with 46.2% showing improvement in the past year, while 42.5% of healthy children had a stable condition (p < 0.05). In various activities, children with asthma face more constraints than healthy children (p < 0.05), including energetic activities (sick—59.5%; healthy—10.3%), moderate activities (sick—24.5%; healthy—4.7%), climbing stairs (sick—22.7%; healthy—3.8%), and walking over 100 m (sick—9.4%; healthy—0%). Children with asthma are more likely to experience exhaustion, anxiety, tiredness, lack of energy, and restraint in public activities (p < 0.05). Conclusions: Parents/caregivers of children with mild to moderate bronchial asthma rate their health worse than those of healthy children do. As children with mild to moderate bronchial asthma grow, the disease impact on their overall well-being decreases. Children with mild to moderate bronchial asthma, compared to healthy children, experience more limitations in vigorous or moderate activities; face more difficulties climbing stairs or walking more than 100 m; frequently feel exhaustion, anxiety, fatigue, or lack of energy; and encounter restrictions in social activities. Full article

The COVID-19 pandemic has affected the lifestyles of people of all ages, conditions and occupations. Social distance, remote working, changes in diet and a lack of physical activity have directly and indirectly affected many aspects of mental and physical health, particularly in patients with many comorbidities and non-communicable diseases (NCDs). In our paper, we analyzed COVID-19 hospitalized and non-hospitalized cases according to comorbidities to assess the average monthly percentage change (AMPC) and monthly percentage change (MPC) using open access data from the Chilean Ministry of Science, Technology, Knowledge and Innovation. As expected, the infection mainly affected patients with comorbidities, including cardiovascular risk factors. The hospitalized cases with obesity and chronic lung disease increased throughout the period of June 2020–August 2021 (AMPC = ↑20.8 and ↑19.4%, respectively, p < 0.05), as did all the non-hospitalized cases with comorbidities throughout the period (AMPC = ↑15.6 to ↑30.3 [p < 0.05]). The increases in hospitalizations and non-hospitalizations with comorbidities may be associated with physical inactivity. A healthy lifestyle with regular physical activity may have had a protective effect on the COVID-19 severity and related events in the post-pandemic period, especially for the NCD population. Full article

Background and Objectives: The ki67 nuclear protein is a tool for diagnosis and prognosis in oncology that is used to evaluate cell proliferation. Differentiated thyroid carcinoma is usually a slow-growing neoplasm, the most common type being the papillary form. Some clinical and pathological aspects may predict aggressive behaviour. There are reported cases of recurrence without clinico-pathological findings of aggressiveness. To obtain better predictions of the disease outcome in thyroid carcinoma, many immunohistochemical markers have been studied. The aim of this narrative literature review is to identify the benefits that ki67 may add to the management of patients with differentiated thyroid carcinoma, according to the latest evidence. Materials and Methods: We performed a search on the PubMed and Google Scholar databases using controlled vocabulary and keywords to find the most suitable published articles. A total number of sixty-eight items were identified, and five other articles were selected from other sources. After refining the selection, the inclusion criteria and exclusion criteria were applied, and a total number of twenty-nine articles were included in this literature review. Results and Discussion: The studies consist of retrospective studies (89.66%), case reports (6.9%) and literature reviews (3.45%), evaluating the role, implications and other parameters of ki67 as a diagnostic and/or prognostic tool. The statistical correlations between ki67 and other features were systematized as qualitative results of this review in order to improve the treatment strategies presented in the included articles. Conclusions: The included studies present converging data regarding most of the aspects concerning ki67. The ki67 proliferation index is a diagnostic/prognostic tool of interest in differentiated thyroid carcinoma and a good predictor of disease-free survival, disease recurrence and metastatic development. Prospective studies on large cohorts may add value for ki67 as a specific tool in the management strategy of differentiated thyroid carcinoma. Full article

Background and objectives: while acute ischemic stroke is the leading cause of epilepsy in the elderly population, data about its risk factors have been conflicting. Therefore, the aim of our study is to determine the association of early and late epileptic seizures after acute ischemic stroke with cerebral cortical involvement and electroencephalographic changes. Materials and methods: a prospective cohort study in the Hospital of the Lithuanian University of Health Sciences Kaunas Clinics Department of Neurology was conducted and enrolled 376 acute ischemic stroke patients. Data about the demographical, clinical, radiological, and encephalographic changes was gathered. Patients were followed for 1 year after stroke and assessed for late ES. Results: the incidence of ES was 4.5%, the incidence of early ES was 2.7% and the incidence of late ES was 2.4%. The occurrence of early ES increased the probability of developing late ES. There was no association between acute cerebral cortical damage and the occurrence of ES, including both early and late ES. However, interictal epileptiform discharges were associated with the occurrence of ES, including both early and late ES. Full article

PTEN Hamartoma Tumour Syndrome (PHTS) encompasses diverse clinical phenotypes, including Cowden syndrome (CS), Bannayan–Riley–Ruvalcaba syndrome (BRRS), Proteus syndrome (PS), and Proteus-like syndrome. This autosomal dominant genetic predisposition with high penetrance arises from heterozygous germline variants in the PTEN tumour suppressor gene, leading to dysregulation of the PI3K/AKT/mTOR signalling pathway, which promotes the overgrowth of multiple and heterogenous tissue types. Clinical presentations of CS range from benign and malignant disorders, affecting nearly every system within the human body. CS is the most diagnosed syndrome among the PHTS group, notwithstanding its weak incidence (1:200,000), for which it is considered rare, and its precise incidence remains unknown among other important factors. The literature is notably inconsistent in reporting the frequencies and occurrences of these disorders, adding an element of bias and uncertainty when looking back at the available research. In this review, we aimed to highlight the significant disparities found in various studies concerning CS and to review the clinical manifestations encountered in CS patients. Furthermore, we intended to emphasize the great significance of early diagnosis as patients will benefit from a longer lifespan while being unceasingly advised and supported by a multidisciplinary team. Full article

Background and Objectives: Treatment of chronic plantar fasciitis is challenging given that there are various of available treatment options with no clear gold standard. The aim of the study was to examine the dose-escalation effect of rESWT on the biomechanical parameters of the plantar fascia and pain ailments. Materials and Methods: In the experimental group (n = 30), the intensity of the shock wave was increased every two subsequent treatment sessions. In the control group (n = 32), the treatment parameters were not changed. In both groups, six treatments were performed, with two treatment sessions a week. In order to assess the biomechanical parameters of the plantar fascia, myotonometric measurements were performed. The pain intensity was assessed using the Visual Analog Scale (VAS). Results: The tension of the plantar fascia attachment in the experimental group decreased from 27.69 ± 2.06 [Hz] before treatment to 26.29 ± 1.69 [Hz] after treatment (p = 0.009) and to 26.03 ± 2.15 [Hz] 1 month after the beginning of treatment (p = 0.003). In the control group, the frequency results did not change significantly (p > 0.05). Flexibility increased in both groups. The test results before treatment and 1 month after the beginning of the treatment showed statistical significance in the experimental group (p = 0.001) vs. (p = 0.002) in the control group. The differences were not statistically significant between groups (p > 0.05). The assessment of pain intensity carried out 1 month after the end of treatment in the experimental group amounted to 3.14 ± 2.28 points, which was statistically significantly lower compared to that in the control group, where it amounted to 5.14 ± 1.92 points. (p < 0.001). Conclusions: The use of rESWT performed with an increasing intensity of impact during subsequent treatment procedures demonstrated greater effectiveness in improving the biomechanical parameters of the plantar fascia and was also more effective in reducing the pain ailments. Our results are encouraging. The dose escalation in the treatment cycle is worth considering. To prove that this method of treatment is more effective, a randomized controlled trial should be carried out on a representative sample. Full article

Background and Objectives: The modified Duke index derived from coronary computed tomography angiography (CCTA) was designed to predict cardiovascular outcomes based on the severity of coronary stenosis. However, it does not take into consideration the presence or severity of peri-coronary inflammation. The peri-coronary fat attenuation index (FAI) is a novel imaging marker determined by CCTA which reflects the degree of inflammation in the coronary tree in patients with coronary artery disease. To assess the association between the modified Duke index assessed by CCTA, cardiovascular risk factors, and peri-coronary inflammation in the coronary arteries of patients with coronary artery disease. Materials and Methods: One hundred seventy-two patients who underwent CCTA for typical angina were assigned into two groups based on the modified Duke index: group 1—patients with low index, ≤3 (n = 107), and group 2—patients with high index, >3 (n = 65). Demographic, clinical, and CCTA data were collected for all patients, and FAI analysis of coronary inflammation was performed. Results: Patients with increased values of the modified Duke index were significantly older compared to those with a low index (61.83 ± 9.89 vs. 64.78 ± 8.9; p = 0.002). No differences were found between the two groups in terms of gender distribution, hypertension, hypercholesterolemia, or smoking history (all p > 0.5). The FAI score was significantly higher in patients from group 2, who presented a significantly higher score of inflammation compared to the patients in group 1, especially at the level of the right coronary artery (FAI score, 20.85 ± 15.80 vs. 14.61 ± 16.66; p = 0.01 for the right coronary artery, 13.85 ± 8.04 vs. 10.91 ± 6.5; p = 0.01 for the circumflex artery, 13.26 ± 10.18 vs. 11.37 ± 8.84; p = 0.2 for the left anterior descending artery). CaRi-Heart^® analysis identified a significantly higher risk of future events among patients with a high modified Duke index (34.84% ± 25.86% vs. 16.87% ± 15.80%; p < 0.0001). ROC analysis identified a cut-off value of 12.1% of the CaRi-Heart^® risk score for predicting a high severity of coronary lesions, with an AUC of 0.69. Conclusions: The CT-derived modified Duke index correlates well with local perilesional inflammation as assessed using the FAI score at different levels of the coronary circulation. Full article

Background: Mental capacity is a fundamental aspect that enables patients to fully participate in various healthcare procedures. To assist healthcare professionals (HCPs) in assessing patients’ capacity, especially in the mental health field, several standardized tools have been developed. These tools include the MacArthur Competence Assessment Tool for Treatment (MacCAT-T), the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR), and the Competence Assessment Tool for Psychiatric Advance Directives (CAT-PAD). The core dimensions explored by these tools include Understanding, Appreciation, Reasoning, and Expression of a choice. Objective: This meta-analysis aimed to investigate potential differences in decision-making capacity within the healthcare context among groups of patients with bipolar disorders (BD) and schizophrenia spectrum disorders (SSD). Methods: A systematic search was conducted on Medline/Pubmed, and Scopus. Additionally, Google Scholar was manually inspected, and a manual search of emerging reviews and reference lists of the retrieved papers was performed. Eligible studies were specifically cross-sectional, utilizing standardized assessment tools, and involving patients diagnosed with BD and SSD. Data from the studies were independently extracted and pooled using random-effect models. Hedges’ g was used as a measure for outcomes. Results: Six studies were identified, with three studies using the MacCAT-CR, two studies the MacCAT-T, and one the CAT-PAD. The participants included 189 individuals with BD and 324 individuals with SSD. The meta-analysis revealed that patients with BD performed slightly better compared to patients with SSD, with the difference being statistically significant in the domain of Appreciation (ES = 0.23, 95% CI: 0.01 to 0.04, p = 0.037). There was no statistically significant difference between the two groups for Understanding (ES = 0.09, 95% CI:−0.10 to 0.27, p = 0.352), Reasoning (ES = 0.18, 95% CI: −0.12 to 0.47, p = 0.074), and Expression of a choice (ES = 0.23, 95% CI: −0.01 to 0.48, p = 0.60). In the sensitivity analysis, furthermore, when considering only studies involving patients in symptomatic remission, the difference for Appreciation also resulted in non-significant (ES = 0.21, 95% CI: −0.04 to 0.46, p = 0.102). Conclusions: These findings indicate that there are no significant differences between patients with BD and SSD during remission phases, while differences are minimal during acute phases. The usefulness of standardized assessment of capacity at any stage of the illness should be considered, both for diagnostic-therapeutic phases and for research and advance directives. Further studies are necessary to understand the reasons for the overlap in capacity between the two diagnostic categories compared in this study. Full article