INTRODUCTION:The postmenopausal bone health reflects the influence of various factors that have been in effect throughout life and hormonal regulation is among them. The aim of the current study is to investigate the effect of pregnancies and other factors related to female reproductive health on bone mineral density and the incidence of fractures in the postmenopausal period. MATERIAL AND METHODS:We performed a case-control retrospective analysis in a group of 977 postmenopausal women from the RACOST-POL cohort. RESULTS:In the study group, there were 894 (91.5%) women who had at least one delivery and breastfeeding was reported by 845 (86.5%) women. Bone mineral density (FN T-score) was not related to pregnancies and history of lactation, but correlated positively with age at menopause and with time of reproductive period. Low-energy fractures were reported by 286 women, which consists 29.3% of the study group. There was no difference in fracture prevalence between women who delivered (29.4%) or not (27.7%). Also the breastfeeding status was not related to fracture prevalence (28.9% in the subgroup declaring lactation and 31.8% in the others). Women with fractures had earlier age of menopause and shorter time of reproductive period in comparison to subjects without fractures (48.3 ± 5.2 vs. 49.5 ± 4.7 ys.; p < 0.001; OR 0.95 (95% CI: 0.93 - 0.98), and 34.1 ± 5.5 vs. 35.5 ± 4.9 ys.; p < 0.001; OR 0.95 (95% CI: 0.93 - 0.98), respectively). Additionally, fracture prevalence in the 'early menopause' (below 45 ys) subgroup was significantly higher (39.1%) than in all the others (27.8%) with OR 1.66 (95% CI: 1.13 - 2.42). CONCLUSIONS:Our study did not show a significant association between history of pregnancies or lactation and the skeletal status in the postmenopausal period. However, a shortened period between menarche and menopause and an earlier age at menopause may have a negative impact on bone health in later life. Presented results complement the knowledge on a wide and diverse spectrum of factors modifying bone health in postmenopausal women.

The PD-1/PD-L1 axis is crucial for immune regulation and homeostasis, but cancer cells can exploit this pathway to evade immune surveillance. PD-1, a key immune checkpoint receptor, interacts with its ligands PD-L1 and PD-L2 to modulate immune responses within the tumor microenvironment. We hypothesized that single nucleotide polymorphisms (SNPs) in the PDCD1 and CD274 genes, encoding PD-1 and PD-L1, are associated with clinicopathological features, PD-L1 immunohistochemical expression, and clinical outcomes in clear cell renal cell carcinoma (ccRCC). We analyzed four SNPs using TaqMan allelic discrimination assays in 238 ccRCC cases: rs11568821 and rs7603052 (PDCD1), and rs4143815 and rs17718883 (CD274). The rs7603052 polymorphism in PDCD1 and rs17718883 in CD274 were significantly associated (p = 0.033 and p = 0.043 respectively) with PD-L1 expression in tumor-infiltrating immune cells (TIICs). Specifically, the C allele of rs7603052 and the CC genotype of rs17718883 correlated with PD-L1 positivity in TIICs. Additionally, the C allele of rs4143815 in CD274 was associated with PD-L1 positivity in tumor cells (p = 0.039). Notably, rs17718883 in CD274 was associated with ccRCC patient prognosis: carriers of the T allele, particularly those with the CT genotype, demonstrated improved overall survival compared to CC genotype carriers (p < 0.001). These findings suggest that PDCD1 and CD274 polymorphisms may serve as potential predictive and prognostic biomarkers in ccRCC.

The study presents osteoporotic fracture risk in postmenopausal women established by FRAX, Garvan and POL-RISK algorithms for next 10 years. In studied group, a relatively high level of fracture risk was shown. These findings emphasize the importance of increasing treatment to reduce the expected rise in fracture rate in the future. The aim of the study was to assess the 10-year osteoporotic fracture risk of postmenopausal women using the FRAX, Garvan, and POL-RISK algorithms and to compare those tools in terms of identification of high-risk subjects. The study group consisted of 508 consecutive postmenopausal women recruited in three osteoporotic outpatient clinics. Mean age was 69.8 ± 7.5 years. Data on clinical risk factors were collected. Bone status was assessed at the hip using a Lunar Prodigy device. Fracture risk was established by FRAX, Garvan, and POL-RISK algorithms for the next 10 years. Mean risk for major fractures for FRAX was 8.85 ± 5.43

Introduction: Renal cell carcinoma (RCC) accounts for 2% of all cancers worldwide and causes 2% of cancer deaths. There are three types of RCC: clear cell (ccRCC), papillary (pRCC), and chromophobe (chRCC). The most common symptoms are hematuria (often periodic), pain in the lumbar region, weight loss, weakness, and periodic fever with night sweats. Often, in advanced stages, there is an abdominal tumor, enlargement of the cervical and supraclavicular lymph nodes, swelling of the lower limbs, and varicose veins. Material and methods: 249 patients with RCC were enrolled in the study, including 203 (81.5%) with ccRCC, 32 (12.9%) with pRCC, and 14 (5.6%) with chRCC. We focused on a comparison of the surgical treatment outcomes between radical nephrectomy (RN) and nephron-sparing surgery (NSS) in terms of qualitative and quantitative characteristics. Results: It was estimated that factors such as the maximum tumor size, age at the day of surgery and sarcomatic transformation had the greatest impact on survival. Also, important factors are the cancer type, cancer stage, WHO grading, embolism, vascular invasion, nerve invasion, fat capsule infiltration and fibrous capsule infiltration. Conclusions: The results suggest that the above factors should be taken into account when choosing the appropriate treatment method as it allows the patient’s life to be extended and the number of postoperative complications to be reduced.

Background: Fine needle aspiration (FNA) cytology for salivary gland lesions is sensitive and specific for diagnosing and treating salivary gland pathologies. The objective of the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) is to organize the diagnostic information from the FNA into a uniform reporting terminology. Aims: The study was conducted retrospectively to reclassify previous diagnoses into the MSRSGC categories to determine the cytohistological concordance and assess the risk stratification by calculating the risk of malignancy (ROM) for different categories. Materials and Methods: A total of 248 FNA cases of salivary gland lesions were analyzed and reclassified according to the second edition of the MSRSGC. The histological diagnosis was considered the gold standard. The ROM for each category was calculated based on 101 histopathologic follow-up cases. Results: Of the 248 patients, 1.2% were classified as nondiagnostic, 37.9% as nonneoplastic, 1.2% as atypia of undetermined significance (AUS), 52.8% as benign neoplasm, 0.4% as uncertain malignant potential (SUMP), 0.4% as suspicious of malignancy (SFM), and 6.1% as malignant neoplasm. Histopathological correlation was available in 101 cases. The ROM was 0% for nonneoplastic lesions and benign neoplasms, and 100% for AUS, SUMP, SFM, and malignant categories. The sensitivity, specificity, positive predictive value, and negative predictive value of FNA cytology in diagnosing salivary gland lesions using MSRSGC were found to be 76.5%, 100%, 100%, and 95.3%, respectively. Conclusion: The use of the MSRSGC helps in triaging patients with salivary gland lesions, increases the effectiveness of communication between clinicians and pathologists, and thus facilitates individualized patient management.

Background/Objectives: Lung carcinoma is the leading cause of cancer-related deaths globally, with lung adenocarcinoma being the most prevalent subtype. This study aims to review the clinical data and survival outcomes of patients diagnosed with lung adenocarcinoma who underwent surgical treatment. Methods: We retrospectively analyzed 471 patients (mean age 65.9 ± 7.81 years, range 38–86; 53.5% women) with histopathologically confirmed lung adenocarcinoma who underwent a lobectomy, bilobectomy, or pneumonectomy between May 2012 and December 2022. All patients were followed for up to five years post-surgery. Their medical histories, including previous neoplasms, comorbidities, tumor characteristics, and symptoms, were thoroughly reviewed. We calculated the overall survival rate and evaluated the impact of tumor grading and spread through air spaces (STAS) on patient outcomes. Results: The survival rate for the entire cohort was 76.23%. No significant survival differences emerged between G1 and G2 tumors, whereas both showed markedly better survival rates than G3 tumors. When these findings were applied to a simplified two-tier grading system (low grade vs. high grade), survival analyses showed a clear stratification of prognosis. Patients with STAS had a lower survival rate than those without STAS. Conclusions: Our findings indicate that a simplified grading system may improve prognostic evaluations for lung adenocarcinoma patients. Furthermore, STAS is a crucial factor affecting survival rates and should be considered in future treatment strategies. Expanding research in this area is essential to enhance treatment approaches for lung adenocarcinoma patients.

INTRODUCTION:Osteoporosis is one of the most common diseases in elderly subjects. Accurate assessment of fracture risk is essential in the management of osteoporotic patients. The aim of the study was to present the optimal manner of using a method designed for fracture risk prediction, e.g. POL-RISK, in daily practice. MATERIAL AND METHODS:Methods for fracture prediction were presented, especially those which allow easy and quick online assessment. In addition to true medical aspect, e.g. the ability to accurately detect high fracture risk patients who need therapy, the economic aspects were also presented. Due to the enormous number of osteoporotic patients the therapy should be indicated mainly in patients with high fracture risk. The optimal threshold of fracture risk for the initiation of reimbursed therapy should be established as a compromise of prior established medical threshold and economic aspects. The expected endpoint is the reduction of new fractures noted in longitudinal observation. CONCLUSION:Implementation of the described scenario should enable the development of the optimal model of care in osteoporotic subjects. Broad use of fracture risk thresholds to initiate reimbursed therapy, encompassing both true medical and economic aspects, should result in the reduction of osteoporotic fractures and decrease overall osteoporosis-related costs to the healthcare system.

INTRODUCTION:In daily practice the diagnostic process for osteoporosis in elderly patients should also include physical assessment. The aim of the study was to verify the hypothesis that height loss (HL) predicts fracture incidence.MATERIAL AND METHODS:The study was performed in an epidemiological sample of postmenopausal women recruited in the RAC-OST-POL study. At baseline, data were collected in 978 postmenopausal women at a mean age of 66.48±7.6 years, and at 10-year follow-up 640 patients remained, with a mean age of 75.04 ± 6.95 years. Current height and HL were established in regard to maximal life height. Data on fracture incidence were gathered throughout the period of observation.RESULTS:During the follow-up period 190 osteoporotic fractures were noted. Ninety-one women had one fracture, and in 38 women, multiple fractures occurred. In the fractured and unfractured subgroups, HL was 5.45 ± 3.28 and 4.8 ± 3.56 cm, respectively, and differed significantly (p < 0.05). HL in subjects without fracture did not differ from those with one fracture (HL 4.8 ± 3.56 vs. 4.8 ± 2.66 cm, respectively). For patients with more than one fracture HL was 7.03 ± 4.06 cm and was significantly higher than in subjects with one or without any fracture (p < 0.01). Based on receiver operating characteristic (ROC) analysis, HL of 6 cm was identified as the cut-off point for high risk of multiple fractures.CONCLUSION:HL of at least 6 cm is the predictor of multiple fractures in a prospective observation of a representative epidemiological female sample. Therefore, the measurement of HL should always be included in patients' assessments.

Introduction: The aim of the study was presentation of the data on falls in a cohort of postmenopausal women in a 10-year prospective longitudinal observation. Material and methods: 640 postmenopausal women at baseline age above 55 years were included. The cohort was randomly selected from the population of the whole Racib & oacute;rz district. Data on falls and fracture incidence were gathered yearly. Results: 256 (40%) women had no falls, and in 384 (60%) subjects at least one fall was noted. The number of women with 1, 2, and 3 or more falls were 115, 62, and 207, respectively. The total number of falls was 1988. Mean baseline age in those who noted falls was 65.7 +/- 7.02 years, and it was significantly higher than in the rest of the patients (64.1 +/- 6.75; p<0.01). Duringfollow-up 190 osteoporotic fractures were noted in 129 patients. Falls were proven to have a strong, significant relationship with fracture (chi-square test = 80.5; p < 0.0001). Among potential clinical factors only diabetes type 1 (chi-square test = 5.80; p < 0.05) and depression (chi-square test = 3.82; p < 0.05) influenced falls incidence. The risk of falls was increased in cases of greater numbers of clinical risk factors (chi-square test = 28.4 df = 5; p < 0.0001). Conclusions: In long-term follow-up in postmenopausal women, falls were frequently observed, and their occurrence increased the frac- ture rate. Diabetes type 1 and depression increase the fall rate, which suggests the necessity of implementation of some preventive procedures. (Endokrynol Pol 2024; 75 (5): 543-547)

Introduction: The aim of the study was to present data on risk factors for fractures in various parts of the skeleton in a cohort of postmenopausal women during a 10-year prospective observation period. It can be hypothesised that fracture risk factors should be different for spine, hip, and peripheral fractures. Material and methods: 640 postmenopausal women at mean baseline age was 65.0 +/- 6.9 years were enrolled into the study. The cohort was randomly selected from the population of the entire Racib & oacute;rz district. Data on the incidence of fractures and falls were updated annually during the 10-year follow-up period. Information on clinical risk factors for fractures was collected at baseline. Results: During the observation period, 190 low-traumatic fractures were recorded in 129 patients. The following number of fractures was observed: hip 15, spine 30, non-hip fractures other than spine 145 (including 81 forearm fractures). The effect of falls was insignificant in the case of spine fractures (chi-square test: 3.64; p = 0.06). For all other skeletal sites, the incidence of fractures was significantly increased by falls, with the greatest effect observed for forearm fractures and non-spine and non-hip fractures (chi-square test for hip, forearm, and all non-spine, non-hip fractures was 6.43, p < 0.05; 42.7, p < 0.0001 and 66.7, p < 0.0001, respectively). To determine the factors having a significant impact on the incidence of fractures during the observation period, logistic regression was used separately in subgroups. The following risk factors were taken into account: age, height, body weight, bone mineral density (BMD) at the femoral neck as expressed by T-score, rheumatoid arthritis, steroid use, falls reported at baseline, and the total number of risk factors. Spine fractures depended only on T-score, odds ratio (OR) = 0.42 (0.23-0.76); hip fractures depended only on age, OR = 1.15 (1.07-1.24); forearm fractures depended only on age T-score, OR = 0.69 (0.51-0.92); and non-hip, non-spine on fall rate, OR = 1.86 (1.20-2.87). Conclusions: Fractures at various skeletal sites recorded in long-term follow-up in postmenopausal women were dependent on various risk factors. Multivariate analysis identified a single, dominant risk factor for each fracture location analysed.

Background: Periodontitis preceded by gingivitis is the most common form of periodontal disease and occurs due to the interaction of microorganisms present in the complex bacterial aggregates of dental plaque biofilm and their metabolism products with periodontal tissues. Histamine is a heterocyclic biogenic amine acting via four types of receptors. Histamine H3 receptors act as presynaptic auto/heteroreceptors to regulate the release of histamine and other neurotransmitters. Aim: Since the nervous system is able to regulate the progression of the inflammatory process and bone metabolism, the aim of this study was to investigate the effects of DL76, which acts as an antagonist/inverse agonist of H3 receptors, on the course of experimental periodontitis. Materials and methods: This study was conducted in 24 mature male Wistar rats weighing 245–360 g, aged 6–8 weeks. A silk ligature was placed on the second maxillary molar of the right maxilla under general anesthesia. From the day of ligating, DL76 and 0.9% NaCl solutions were administered subcutaneously for 28 days in the experimental and control groups, respectively. After the experiment, histopathological, immunohistochemical and radiological examinations were performed. Results: Ligation led to the development of the inflammatory process with lymphocytic infiltration, increased epithelial RANKL and OPG expression as well as bone resorption. DL76 evoked a reduction in (1) lymphocytic infiltration, (2) RANKL and OPG expression as well as (3) bone resorption since the medians of the mesial and distal interdental spaces in the molars with induced periodontitis were 3.56-fold and 10-fold lower compared to the corresponding values in saline-treated animals with periodontitis. Conclusion: DL76 is able to inhibit the progression of experimental periodontitis in rats, as demonstrated by a reduction in the inflammatory cell infiltration, a decrease in the RANKL/RANK OPG pathway expression and a reduction in the alveolar bone resorption.

In the longitudinal, retrospective study, the ability of the FRAX, Garvan, and POL-RISK algorithms to predict osteoporotic fractures was compared in a group of 457 women. Using the rigid threshold of 10

PD-L1 is one of the two programmed cell death 1 (PD-1) ligands and a part of an immune checkpoint system (PD-1/PD-L1) with widespread clinical application. The aim of this study was to investigate PD-L1 expression and its association with clinicopathological and prognostic significance in non-clear cell renal cell carcinoma (non-ccRCC) patients. A total of 41 papillary (pRCC) and 20 chromophobe (chRCC) RCC tumors were examined for PD-L1 expression by immunohistochemistry in the cancer cells and tumor-infiltrating mononuclear cells (TIMCs). PD-L1 positivity was detected in 36.6% pRCC and 85.0% chRCC cancer cells, while PD-L1 positivity was observed in 73.2% pRCC and 50.0% chRCC TIMCs. PD-L1 positivity in both pRCC and chRCC tumor cells was not correlated with any of the examined clinicopathological features, while PD-L1 positivity in TIMCs was associated with the age of patients with pRCC. During follow-up, the death was documented among 6 patients with pRCC. Papillary RCC patients with PD-L1-positive tumor cells were significantly associated with an increased risk of death compared with patients with PD-L1-negative cancer cells. A similar trend was observed when comparing PD-L1 expression in TIMCs. However, no differences in overall survival for PD-L1-positive pRCC patients with compared to PD-L1-negative patients were observed in tumor cells or TIMCs.

CD44, MMP-2, and MMP-9 are new potential molecular prognostic markers in renal cell carcinoma (RCC). The aim of the study was to analyze whether the expression of CD44, MMP-2, and MMP-9 in association with the histopathological subtype of RCC affects the survival of patients with renal cancer. The study population included 243 clear cell RCC (ccRCC) and 59 non-ccRCC cases. A total of 302 tumors were examined for CD44, MMP2, and MMP9 expression by immunohistochemistry. The expression levels of the proteins were scored by semi-quantitative methods, and the correlation with overall patient survival was verified. We found no significant differences in CD44 expression levels between cc-RCC and non-ccRCC cases; however, significant differences existed in the degree of MMP-2 and MMP-9 expression between cc-RCC and non-ccRCC cases. There was significantly higher MMP expression in non-ccRCC than in ccRCC cases. Univariate Cox regression analysis showed that increased CD44 expression and histopathological subtype of ccRCC were predictors of shorter overall survival. Moreover, MMP-2 overexpression slightly reduced the risk of patient death, while MMP-9 expression did not show an association with patients’ survival. However, on multivariate analysis, only the histopathological subtypes of ccRCC and CD44 expression were independent risk factors for patient death.

BACKGROUND Current evidence suggests that nevoid basal cell carcinoma syndrome (NBCCS)-associated odontogenic keratocysts (OKCs) exhibit more aggressive clinical behavior and a higher tendency to relapse. The prognostic efficacy of various markers in sporadic and syndromic OKCs is unclear, and so are the results of studies on the usefulness of immunohistochemistry in distinguishing syndromic from sporadic OKCs. OBJECTIVES This retrospective study aimed to compare the prognostic relevance of various clinicoradiological and histopathological features, as well as the immunoexpression of COX-2, Bcl-2, proliferating cell nuclear antigen (PCNA), p53, Ki-67, osteoprotegerin (OPG), receptor activator of nuclear factor κ B (RANK) and receptor activator of nuclear factor κ B ligand (RANKL), as well as RANKL/OPG balance between sporadic and syndromic OKCs, and to test their utility in distinguishing the 2 types of OKC. MATERIAL AND METHODS We compared the immunoexpression of the aforementioned markers between 31 sporadic and 12 syndromic OKCs, and tested clinicopathological findings and levels of immunostaining against recurrence. RESULTS We found a significant association between NBCCS and OKC recurrence. There were significant differences in PCNA, p53 and OPG immunoexpression between sporadic and syndromic OKCs. We also found that recurrent sporadic OKCs were significantly larger and markedly more often associated with cortical perforation. Recurrent sporadic OKCs exhibited COX-2 upregulation, but we failed to demonstrate its prognostic relevance. Recurrent syndromic OKCs showed a markedly higher RANKL > OPG ratio. CONCLUSIONS The NBCCS-associated OKCs are significantly more prone to recur than their sporadic counterparts. Larger size and radiological signs of cortical perforation in sporadic OKCs may indicate a higher risk of recurrence. The COX-2 is upregulated in recurrent sporadic OKCs, whereas recurrent syndromic OKCs exhibit higher RANKL and lower OPG expression; however, these findings have no prognostic relevance. The immunoexpression of p53, PCNA and OPG may help to distinguish syndromic from sporadic OKCs.

Renal cell carcinoma (RCC) is a common malignant tumor of the urinary system. The von Hippel-Lindau (VHL) tumor suppressor gene play an essential role in the tumorigenic pathway of clear cell RCC (ccRCC). This study was aimed to clarify the influence of VHL polymorphisms on ccRCC susceptibility and survival in Central European population. We genotyped 2 single-nucleotide polymorphisms (SNPs) rs779805 and rs1642742 in VHL gene and assessed their associations with ccRCC risk, clinicopathologic parameters, and prognosis in 171 cases. The selected SNPs were genotyped by ROCHE LifeCycler 96 using tumor tissue-derived DNA. Both SNPs do not directly influence ccRCC susceptibility and overall survival. A significant associations were found between allele G and genotypes AG and GG of rs779805 in the VHL tumor suppressor gene and increased tumor size, as well as high nuclear grade. Furthermore, a statistically significant association was observed between rs1642742 of VHL gene and low pathological tumor stage and between rs779805 of VHL gene and high pathological tumor stage. Both investigated SNPs can be important prognostic indicators of RCC in the Central European population, because statistically significant associations were observed between evaluated VHL polymorphisms and the best known factors with proven prognostic significance in kidney cancer.