The role of vitamin D in shoulder health: a comprehensive review of its impact on rotator cuff tears and surgical results.

Vitamin D deficiency is highly prevalent in the general population and is associated with various chronic health conditions. In addition to its role in bone mineralization, Vitamin D has various physiological effects that may impact the pathogenesis of shoulder pathologies. Vitamin D deficiency may also affect outcomes after shoulder surgeries, such as rotator cuff repair and total shoulder arthroplasty. Vitamin D plays a role in tissue healing, bone growth, and maintenance of homeostasis in skeletal muscle cells. Vitamin D also has anti-inflammatory effects that are important to rotator cuff health. Vitamin D deficiency is highly prevalent in patients with rotator cuff tears, suggesting its role as a potential risk factor. Vitamin D deficiency has been associated with decreased preoperative shoulder strength as well as increased re-tear rates, postoperative stiffness, and the need for revision surgery in patients who underwent rotator cuff repair. Studies have also demonstrated a potential association between vitamin D deficiency and increased risk of revision after total shoulder arthroplasty. Further research is necessary to elucidate the direct role of vitamin D in the pathogenesis of rotator cuff tears and its impact on clinical outcomes after rotator cuff surgery and total shoulder arthroplasty.

Unlocking Hope: Anti-VEGFR inhibitors and their potential in glioblastoma treatment.

PURPOSE: This systematic review summarizes evidence of VEGFR gene mutations and VEGF/VEGFR protein expression in glioblastoma multiforme (GBM) patients, alongside the efficacy and safety of anti-VEGFR tyrosine kinase inhibitors (TKIs) for GBM treatment. METHODS: A comprehensive literature review was conducted using PubMed up to August 2023. Boolean operators and MeSH term "glioma," along with specific VEGFR-related keywords, were utilized following thorough examination of existing literature. RESULTS: VEGFR correlates with glioma grade and GBM progression, presenting a viable therapeutic target. Regorafenib and axitinib show promise among studied TKIs. Other multi-targeted TKIs (MTKI) and combination therapies exhibit potential, albeit limited by blood-brain barrier penetration and toxicity. Combining treatments like radiotherapy and enhancing BBB penetration may benefit patients. Further research is warranted in patient quality of life and biomarker-guided selection. CONCLUSION: While certain therapies hold promise for GBM, future research should prioritize personalized medicine and innovative strategies for improved treatment outcomes.

Tyrosine kinase inhibitors in osteosarcoma: Adapting treatment strategiesa.

Osteosarcoma (OS) is an aggressive primary bone malignancy that metastasizes rapidly. The standard of care has changed little over the previous four decades, and survival rates have plateaued. In this context, tyrosine kinase inhibitors (TKIs) emerge as potential treatments. A literature search was conducted to collect data related to receptor tyrosine kinase genetic alterations and expression in OS specimens. Gene amplification and protein expression of these receptors were linked to prognosis and tumor behavior. Relevant TKIs were evaluated as monotherapies and as parts of combination therapies. Certain TKIs, such as apatinib, regorafenib, and cabozantinib, present a potential therapeutic avenue for OS patients, especially when combined with chemotherapy. Producing long-lasting responses and enhancing quality of life remain key goals in OS treatment. To this effect, optimizing the use of TKIs by identifying biomarkers predictive of response and assessing promising TKIs in larger-scale trials to validate the efficacy and safety outcomes relative to these drugs reported in phase II clinical trials. To this effect, it is necessary to identify biomarkers predictive of response to TKIs in larger-scale trials and to validate the efficacy and safety of these drugs reported in phase II clinical trials.

Acquired resistance mechanisms to osimertinib: The constant battle.

Lung cancer is the leading cause of cancer-related mortality worldwide. Detectable driver mutations have now changed the course of lung cancer treatment with the emergence of targeted therapy as a novel strategy that widely improved lung cancer prognosis, especially in metastatic patients. Osimertinib (AZD9291) is an irreversible third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) used to treat stage IV EGFR-mutated non-small-cell lung cancer. It was initially designed to target both EGFR-activating mutations and the EGFR T790M mutation as well, which is the most common resistance mechanism to first- and second-generation EGFR-TKIs. Following the FLAURA trial, osimertinib is now widely used in the first-line setting. However, resistance to osimertinib inevitably develops, with numerous mechanisms leading to its resistance, classified into two main categories: EGFR-dependent and EGFR-independent mechanisms. While EGFR-dependent mechanisms consist mainly of the C797S EGFR mutation, EGFR-independent mechanisms include bypass pathways, oncogenic fusions, and phenotypic transformation, among others. This review summarizes the molecular resistance mechanisms to osimertinib, with the aim of identifying novel therapeutic approaches to overcome osimertinib resistance and improve patient outcome.

BRCAness in biliary tract cancer: a new prognostic and predictive biomarker?

Cholangiocarcinoma (CCA) is a rare malignancy with a very poor prognosis. Considering that most cases of CCA are diagnosed at a locally advanced stage and the standard of care for advanced CCA remains suboptimal, new prognostic and predictive biomarkers must be developed to improve the management and survival of patients diagnosed with CCA regardless of disease stage. According to recent studies, 20% of biliary tract cancers exhibit the BRCAness phenotype, meaning that these tumors do not have germline mutations in BRCA but share phenotypic traits with tumors that possess hereditary BRCA mutations. Therefore, screening for these mutations in CCA patients is beneficial to predict tumor sensitivity and response to DNA-damaging chemotherapy such as platinum agents.

Association Between Personality Traits/Dimensions and Fear of No Mobile Phone Connectivity (nomophobia): Results of a Lebanese National Study.

Objective: To study nomophobia in a large sample of Lebanese adults and its relationship with personality traits and other sociodemographic factors that may contribute to the diagnosis such as sex, parental status, and smoking.Methods: This cross-sectional study was conducted between January and July 2019. A total of 2,260 residents randomly selected from districts in Lebanon completed a questionnaire about sociodemographic characteristic and smoking. Respondents also completed the Nomophobia Questionnaire, Personality Inventory for DSM-5, and NEO Five-Factor Inventory.Results: The results of a linear regression, taking the nomophobia score as the dependent variable, showed that higher neuroticism (B = 0.648), number of waterpipes smoked per week (B = 0.749), and disinhibition (B = 0.706) were significantly associated with higher nomophobia, whereas more agreeableness (B = -0.535) and detachment (B = -0.594) were significantly associated with lower nomophobia.Conclusions: This study assessed the variation of inherent personality traits using 2 validated personality questionnaires and their association with nomophobia. As digital use becomes more prevalent within personal and professional aspects of life, nomophobia might become an anxiety risk. Future studies should focus on preventive and treatment measures in the form of awareness campaigns.

Nomophobia and temperaments in Lebanon: Results of a national study.

OBJECTIVES: Assess the association between nomophobia and temperaments in the Lebanese population. METHODS: The cross-sectional study was conducted between January and July 2019 (N = 2260). RESULTS: A total of 1089 of the participants (48.3%) appeared to have moderate nomophobia while 349 (15.5%) were found to exhibit severe nomophobia. Multivariable analysis showed that higher hyperthymic temperament (ß = -0.34) was associated with less nomophobia, whereas higher irritable temperament (ß = 0.43) was associated with more nomophobia. PRACTICAL IMPLICATIONS: The findings obtained from our study showed that a more irritable temperament was significantly associated with a more severe nomophobia, while hyperthymic temperament was associated with less nomophobia. They open up new perspectives for the evaluation of the temperaments among nomophobics with a better focus on the personality model and how they can predict nomophobia.

Nomophobia in Lebanon: Scale validation and association with psychological aspects.

OBJECTIVES: Nomophobia, an abbreviation of "No mobile phone phobia", is characterized by the illogical fear of being detached from the mobile phone or unable to use it. Research have provided evidence of an association between increased cellular phone use and multiple health issues, such as anxiety, depression, insomnia, and others. To our knowledge, there are no Lebanese studies about nomophobia, despite the high incorporation rate of mobile phones in Lebanon and the likelihood of suffering from anxiety, depression, and other conditions due to nomophobic attitudes. The study objectives were to validate and confirm psychometric properties of the Nomophobia Questionnaire (NMP-Q) and examine the associations between particular psychological conditions (anxiety, depression, stress, insomnia and impulsivity) and nomophobia among a representative sample of Lebanese people. METHODS: This cross-sectional study was carried out between January and July 2019. It enrolled 2260 residents of the community randomly selected from Lebanon's Mohafazat. Two villages per sub-district and households from each village were chosen using a random sampling technique. A questionnaire was distributed randomly to the households. SPSS version 25 was used to perform the statistical analysis. A multinomial regression was computed taking the nomophobia categories as the dependent variable (and taking the absence of nomophobia as the reference category) and all variables that showed a significant association in the bivariate analysis as independent variables. RESULTS: A total of 2260 (80.71%) out of 2800 questionnaires distributed was collected back. The mean age of the participants was 27.98 ± 9.66 years (58.8% females). Moreover, the mean nomophobia score was 71.56 ± 26.92 (median = 71; minimum = 14; maximum = 140). The results showed that 46 (2.0%) had no nomophobia, 769 (34.1%) mild nomophobia [95% CI 0.322-0.361], 1089 (48.3%) moderate nomophobia [95% CI 0.463-0.504] and 349 (15.5%) severe nomophobia [95% CI 0.140-0.170]. Items of the nomophobia scale converged over a solution of three factors that had an Eigenvalue over 1 (Factor 1 = emotions associated to losing connectedness, Factor 2 = not being able to communicate, Factor 3 = not being able to access information; total variance explained = 66.65%, and Cronbach's alpha = 0.948). The results of a multinomial regression, taking the nomophobia score as the dependent variable, showed that higher age was significantly associated with lower odds of having mild (aOR = 0.97), moderate (aOR = 0.93) and severe (aOR = 0.97) nomophobia respectively. Higher anxiety (aOR = 1.09) and higher insomnia (aOR = 1.04) were significantly associated with higher odds of having severe nomophobia. CONCLUSION: The results suggest a positive correlation between nomophobia and psychological conditions. There is a need for longitudinal and prospective studies that furnish information with regards of the impact of time on the variables measured, in order to better understand the nature, causes, and attributes of nomophobia.

11-Beta Dehydrogenase Type 2 Activity Is Not Reduced in Treatment Resistant Hypertension.

BACKGROUND AND OBJECTIVE: Decreased renal 11-beta dehydrogenase type 2 (11ß-HSD2) activity, as reflected by an increased urinary free cortisol to cortisone ratio (UFF/UFE), is associated with having hypertension (HTN). The current study was conducted to determine if reduced 11ß-HSD2 activity is also associated with having resistant HTN. METHOD: We evaluated 55 consecutive patients with RHTN, defined as blood pressure (BP) ≥140/90 mm Hg despite using ≥3 antihypertensive medications including a diuretic, and 38 patients whose BP was controlled on ≤3 medications to serve as a non-RHTN comparator group. All patients underwent biochemical evaluation, including measurement of 24-hour urinary UFF/UFE. RESULTS: The 2 study groups had similar demographic characteristics. Systolic, diastolic BP, and number of antihypertensive medications were greater in patients with uncontrolled RHTN vs. the control group (167.5 ± 28.2/91.2 ± 18.8 vs. 126.6 ± 11.4/77.8 ± 8.65 mm Hg and 4.31 ± 1.23 vs. 2.74 ± 0.6, respectively). The 24-hour UFF was 13.6 ± 11.8 vs. 14.3 ± 10.7 µg/24 h and UFE was 64.9 ± 36.3 vs. 76.1 ± 44 µg/24 h such that the UFF/UFE was 0.22 ± 0.16 vs. 0.19 ± 0.09 in RHTN vs. the control group. This ratio was not associated to age, race, gender, and body mass index. CONCLUSION: An elevated UFF/UFE was not present in this large cohort of patients with uncontrolled RHTN. This suggests that reduced conversion of cortisol to cortisone does not contribute to the development of RHTN.