Differential Utilization Patterns of Total Ankle Arthroplasty vs Arthrodesis: A United States National Ambulatory Database Analysis.

Background: End-stage ankle osteoarthritis is a condition that can be treated with ankle arthrodesis (AA) or total ankle arthroplasty (TAA). The goal of this study is to estimate the 2016-2017 United States' utilization of TAA and AA in specific ambulatory settings and delineate patient and hospital factors associated with the selection of TAA vs AA for treatment of ankle osteoarthritis. Methods: TAA and AA procedures performed for ankle osteoarthritis were identified in the 2016-2017 Nationwide Ambulatory Surgery Sample (NASS) Database. Notably, the NASS database only examines instances of ambulatory surgery encounters at hospital-owned facilities. As such, instances of TAA and AA performed at privately owned or freestanding ambulatory surgical centers or those performed inpatient are excluded from this analysis. Cases were weighted using nationally representative discharge weights. Univariate analyses and a combined multiple logistic regression model were used to compare demographic, hospital-related, and socioeconomic factors associated with TAA vs AA. Results: In total, 6577 cases were identified, which represents 9072 cases after weighting. Of these, TAA was performed for 2233 (24.6%). Based on the logistic regression model, several factors were associated with increased utilization of TAA vs AA. With regard to patient factors, older patients were more likely to undergo TAA, as well as females. Conversely, patients with a higher comorbidity burden were less likely to receive TAA over AA.With regard to socioeconomic factors, urban teaching and urban nonteaching hospitals were significantly more likely to use TAA compared to rural hospitals. Similarly, privately insured patients and those with a median household income of $71 000 or more were also more likely to receive TAA over AA. Private hospitals ("not-for-profit" and "investor-owned") were significantly more likely to offer TAA over AA. Conclusion: Using a large nationally representative cohort, the current data revealed that during 2016-2017, 24.6% of operatively treated cases of end-stage ankle osteoarthritis in the ambulatory setting are treated with TAA. Associations between socioeconomic and hospital-level factors with TAA utilization suggest that nonclinical factors may influence surgical treatment choice for ankle osteoarthritis. Level of Evidence: Level III, retrospective cohort study.

Metformin alone and in combination with sitagliptin induces depression and impairs quality of life in type 2 diabetes mellitus patients: An observational study.

BACKGROUND: Various studies have reported the association of cognition and depression with diabetes. Literature suggests that metformin and sitagliptin used to control hyperglycemia in type 2 diabetes mellitus (T2DM) possess a beneficial effect on neurological symptoms associated with diabetes. However, there are scarce data in the clinical setting. Thus, this study aims to compare depression, cognitive impairment, and quality of life (QoL) of newly diagnosed T2DM patients with those of healthy individuals. Further, the impact of metformin alone or in combination with dipeptidyl peptidase-4 inhibitors on cognition, depression, and QoL of T2DM patients was also compared with newly diagnosed T2DM patients. MATERIALS AND METHODS: This was a prospective observational study in 120 subjects. The subjects were equally divided into four groups: healthy controls, newly diagnosed T2DM patients, and T2DM patients taking either metformin alone or in combination with sitagliptin. We assessed cognition using Mini-Mental State Examinations (MMSE), depression using Hamilton Depression Rating Scale (HAM-D), and health status using Short-Form Health Survey-36 (SF-36). RESULTS: No significant change in MMSE score was observed among the groups. However, a significant increase in the HAM-D score of newly diagnosed patients (p < 0.001), T2DM patients receiving metformin alone (p < 0.05), and in combination with sitagliptin (p < 0.001) was observed as compared to healthy controls (p < 0.001). Also, a statistically significant increase in HAM-D score was observed in patients receiving sitagliptin in combination with metformin as compared to metformin alone (p < 0.01). A decrease in SF-36 scores was observed in all groups as compared to healthy controls. CONCLUSION: To conclude, this preliminary study indicates that T2DM patients are most likely to suffer from depression and impaired QoL. Moreover, both the conventional and recent antidiabetic agents might lead to neurobehavioral complications and adverse impact on the QoL of these patients. Thus, we warrant the assessment of cognitive functions, depression, and QoL in patients receiving metformin and sitagliptin.

Saudi medical students' views on obstetrics and gynecology as a future career specialty.

BACKGROUND: The specialty of obstetrics and gynecology is showing a widening gap between the vacant positions and the number of applicants as reported by the Saudi Commission for Health Specialties (SCFHS). This study was conducted to explore the medical students' views on obstetrics and gynecology as a future career and identify factors influencing these views. METHODS: An observational survey was conducted on 148 medical students in years 5 and 6 at Jazan University between June 2019 and July 2019. Participants completed a self-report online questionnaire covering their sociodemographic details, interest in obstetrics and gynecology, and views on the specialty. RESULTS: Overall, obstetrics and gynecology was selected as the first specialty choice by 8.8% and second choice by 17.6%. Intention to take a career in obstetrics and gynecology was associated with female sex (P = 0.01). While over half of the participants emphasized the merits of obstetrics and gynecology as exciting, interesting, and challenging, over 40% viewed the specialty as stressful, over one-third described it as demanding, and over one-quarter appreciated its riskiness. CONCLUSION: This study showed that 8.8% of the respondents chose obstetrics and gynecology as their first career choice. Sex was the only factor influencing the views of medical students on the specialty, with more females favoring the specialty than males. To improve its appeal, students should be supplied with more information about the specialty and its training opportunities, as well as exposure to areas of special interest.

Molecular Analysis of Factor VIII and Factor IX Genes in Hemophilia Patients: Identification of Novel Mutations and Molecular Dynamics Studies.

BACKGROUND: Hemophilias A and B are X-linked bleeding disorders caused by mutations in the factor VIII and factor IX genes, respectively. Our objective was to identify the spectrum of mutations of the factor VIII and factor IX genes in Saudi Arabian population and determine the genotype and phenotype correlations by molecular dynamics (MD) simulation. METHODS: For genotyping, blood samples from Saudi Arabian patients were collected, and the genomic DNA was amplified, and then sequenced by Sanger method. For molecular simulations, we have used softwares such as CHARMM (Chemistry at Harvard Macromolecular Mechanics; http://www.charmm-gui.org) and GROMACS. In addition, the secondary structure was determined based on the solvent accessibility for the confirmation of the protein stability at the site of mutation. RESULTS: Six mutations (three novel and three known) were identified in factor VIII gene, and six mutations (one novel and five known) were identified in factor IX gene. The factor VIII novel mutations identified were c.99G>T, p. (W33C) in exon 1, c.2138 DelA, p. (N713Tfs*9) in eon14, also a novel mutation at splicing acceptor site of exon 23 c.6430 - 1G>A. In factor IX, we found a novel mutation c.855G>C, p. (E285D) in exon 8. These novel mutations were not reported in any factor VIII or factor IX databases previously. The deleterious effects of these novel mutations were confirmed by PolyPhen2 and SIFT programs. CONCLUSION: The protein functional and structural studies and the models built in this work would be appropriate for predicting the effects of deleterious amino acid substitutions causing these genetic disorders. These findings are useful for genetic counseling in the case of consanguineous marriages which is more common in the Saudi Arabia.

The impact of oral Polypodium leucotomos extract on ultraviolet B response: A human clinical study.

BACKGROUND: There is a rationale for adding systemic photoprotective agents to the current photoprotection regimen. OBJECTIVE: This study was designed to objectively evaluate the molecular and photobiologic effects of oral administration of Polypodium leucotomos extract (PLE). METHODS: In all, 22 subjects with Fitzpatrick skin phototype I to III were enrolled. On day 1, subjects were irradiated with visible light, ultraviolet (UV) A1, and UVB (using 308-nm excimer laser). Evaluation was done immediately and 24 hours after irradiation. On days 3 and 4, irradiation and evaluation process was repeated after ingestion of PLE. RESULTS: Clinical assessments and colorimetry data showed a decrease in UVB-induced changes in 17 of 22 subjects post-PLE administration; histology findings demonstrated such a decrease in all 22 subjects. LIMITATIONS: Only 2 doses of PLE were given. Furthermore, subjects with skin phototypes I to III only were studied. CONCLUSION: The results suggest that PLE can potentially be used as an adjunctive agent to lessen the negative photobiologic effects of UVB.

Impact of comorbidity on initial treatment and overall survival in elderly head and neck cancer patients.

BACKGROUND: Comorbidity is a determinant of treatment selection and survival in various cancers including head and neck cancer (HNC) and is often associated with a higher utilization of non-curative intent treatment. PATIENTS AND METHODS: In this retrospective study we analyzed 182 consecutively treated HNC patients >65 years old at the Dallas Veterans Affairs Medical Center from January 2000-June 2007. Comorbidity was assessed with the Charlson Comorbidity Index (CCI). Treatment was classified as curative vs. non-curative intent. RESULTS: Median overall survival was 883 days. Patients with a CCI score 0-2 had non-significant higher rate of curative intent treatment than patients with CCI score >2 (83.8% vs. 74.6%, p=0.13). In multivariate analysis, only stage had significant prognostic importance (hazard ratio (HR) 1.66; 95% confidence interval (CI) 1.29-2.14; p<0.0005). In separate multivariate analyses of patients treated with surgery or chemoradiation, CCI was not a significant predictor of survival with HR of 0.88 (95% CI 0.69-1.11; p=0.29) and 1.13 (95% CI 0.83-1.53; p=0.44), respectively. CONCLUSION: In our elderly HNC population, CCI was not an independent predictor of selection of curative intent treatment or overall survival.

Gli1 protein regulates the S-phase checkpoint in tumor cells via Bid protein, and its inhibition sensitizes to DNA topoisomerase 1 inhibitors.

Aberrant expression of hedgehog molecules, particularly Gli1, is common in cancers of many tissues and is responsible for their aggressive behavior and chemoresistance. Here we demonstrate a novel and tumor-specific role for aberrant Gli1 in the regulation of the S-phase checkpoint that suppresses replication stress and resistance to chemotherapy. Inhibition of Gli1 in tumor cells induced replication stress-mediated DNA damage response, attenuated their clonogenic potential, abrogated camptothecin (CPT)-induced Chk1 phosphorylation, and potentiated its cytotoxicity. However, in normal fibroblasts, Gli1 siRNAs showed no significant changes in CPT-induced Chk1 phosphorylation. Further analysis of ataxia telangiectasia and Rad3-related protein (ATR)/Chk1 signaling cascade genes in tumor cells revealed an unexpected mechanism whereby Gli1 regulates ATR-mediated Chk1 phosphorylation by transcriptional regulation of the BH3-only protein Bid. Consistent with its role in DNA damage response, Bid down-regulation in tumor cells abolished CPT-induced Chk1 phosphorylation and sensitized them to CPT. Correspondingly, Gli1 inhibition affected the expression of Bid and the association of replication protein A (RPA) with the ATR- interacting protein (ATRIP)-ATR complex, and this compromised the S-phase checkpoint. Conversely, complementation of Bid in Gli1-deficient cells restored CPT-induced Chk1 phosphorylation. An in silico analysis of the Bid promoter identified a putative Gli1 binding site, and further studies using luciferase reporter assays confirmed Gli1-dependent promoter activity. Collectively, our studies established a novel connection between aberrant Gli1 and Bid in the survival of tumor cells and their response to chemotherapy, at least in part, by regulating the S-phase checkpoint. Importantly, our data suggest a novel drug combination of Gli1 and Top1 inhibitors as an effective therapeutic strategy in treating tumors that expresses Gli1.

Topical tazarotene chemoprevention reduces Basal cell carcinoma number and size in Ptch1+/- mice exposed to ultraviolet or ionizing radiation.

Oral retinoids can reduce basal cell carcinoma (BCC) incidence in genetically susceptible patients, and one topical retinoid, tazarotene, has been reported to cure some sporadic BCCs. Therefore, we have tested whether this agent would affect BCCs in Ptch1+/- mice in a controlled chemoprevention trial. We found that topical tazarotene dramatically inhibits the formation of BCCs induced with either UV or ionizing radiation. The ability of tazarotene to inhibit BCC formation in this mouse model provides encouragement for the use of tazarotene in skin cancer chemoprevention trials in humans.