Rationale and design of the Kidney Precision Medicine Project

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Oral cancer prediction by noninvasive genetic screening

Oral squamous cell carcinomas (OSCCs) develop in genetically altered epithelium in the mucosal lining, also coined as fields, which are mostly not visible but occasionally present as white oral leukoplakia (OL) lesions. We developed a noninvasive genetic assay using next-generation sequencing (NGS) on brushed cells to detect the presence of genetically altered fields, including those that are not macroscopically visible. The assay demonstrated high accuracy in OL patients when brush samples were compared with biopsies as gold standard. In a cohort of Fanconi anemia patients, detection of mutations in prospectively collected oral brushes predicted oral cancer also when visible abnormalities were absent. We further provide insight in the molecular landscape of OL with frequent changes of TP53, FAT1 and NOTCH1. NGS analysis of noninvasively collected samples offers a highly accurate method to detect genetically altered fields in the oral cavity, and predicts development of OSCC in high-risk individuals. Noninvasive genetic screening can be employed to screen high-risk populations for cancer and precancer, map the extension of OL lesions beyond what is visible, map the oral cavity for precancerous changes even when visible abnormalities are absent, test accuracy of promising imaging modalities, monitor interventions and determine genetic progression as well as the natural history of the disease in the human patient.     

Sexual Dysfunctions are Predicted by Childhood Sexual Abuse in Women with Opioid Use Disorder

Background: Studies on sexual functioning of populations with substance use disorders (SUDs) are mostly conducted with male substance users. We have very limited information about the sexuality and related factors in women with opioid use disorder (OUD). Objectives: We aimed to evaluate the relationship between childhood traumatic experiences (CTEs) and sexual dysfunctions (SDs) of women with OUD and to compare it with a sample of women who do not have SUD. Methods: Participants included 51 outpatient women with OUD who were on opioid maintenance treatment (OMT) with Buprenorphine/Naloxone and 48 women without SUD. Participants were evaluated by a semi-structured sociodemographic form, the Golombok-Rust Inventory of Sexual Satisfaction (GRISS), the Childhood Trauma Questionnaire (CTQ-28), the Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory (STAI). Results: In women with OUD; CTQ-28, BDI, STAI, and GRISS scores were significantly higher. In the partial correlation analysis, sexual abuse was found to be significantly correlated with nonsensuality, avoidance and total GRISS score. In stepwise regression model, sexual abuse was found to predict SDs together with depression. Conclusions: CTE, SD, depression, and anxiety rates were higher in the women with OUD. Especially childhood sexual abuse was associated with SDs in this group. Sexual abuse was predicting SDs together with depression. Further investigation of different characteristics of women with SUD may give an opportunity to clinicians to have a better understanding for adaptable treatment strategies.     

Clinical evaluation of medications on oral and dental health

OBJECTIVE: To evaluate the effect of medications on oral and dental health on a group of dental patients taking drugs regularly. METHODS: The study comprised two groups, the medication group included 328 dental patients regularly taking medication and the control group of 201 dental patients who took no medication. The patients were questioned about occurrence of self-reported oral dryness and were evaluated for the occurrence of any oral mucosal lesions, gingival recession, bleeding and enlargement, alveolar bone resorption, dental caries, any restorations and missing teeth were recorded. Data were statistically analysed with chi-square and Fisher's exact tests. RESULTS: There was no statistically significant difference (p > 0.05) between medication and control groups for oral mucosal lesions, gingival recession and enlargement but a statistically significant difference (p < 0.05) was found between the groups for oral dryness and gingival bleeding. Statistically significant differences (p < 0.05) were found between the groups for dental caries, amalgam, fixed and removable prosthetic restorations and missing teeth. CONCLUSIONS: There was a statistically significant difference for self-reported oral dryness and gingival bleeding and these factors may have been influenced by the increased rate of missing teeth and prosthetic restorations in the medication group.     

An adult case of temporomandibular joint osteoarthritis treated with splint therapy and the subsequent orthodontic occlusal reconstruction

Herein we report treatment for a 19-year-old female patient with severe osteoarthritis of the temporomandibular joint. The patient had severe open bite with a Class II molar relationship. She had limited mouth opening and pain. Clinical examination and magnetic resonance imaging revealed that she had anterior disc displacement without reduction. By splint therapy, limited mouth opening and pain was eliminated, but an anterior open bite developed after the treatment. By orthodontic treatment, an acceptable occlusion was achieved with a Class I molar relationship.     

Comparison of 2 retentive systems for implant-supported overdentures: soft tissue management and evaluation of patient satisfaction

BACKGROUND: The aim of the present study was to compare the peri-implant soft tissue health status of implants supporting overdentures with bar attachments or ball attachments in the mandible, as well as patient satisfaction with these attachment types. METHODS: The study included a Dolder bar group with 18 cases (43 implants) and a ball attachment group with 18 cases (51 implants). The mean function period in the Dolder bar group was 49 months (range: 12 to 72 months) and in the ball attachment group, the mean was 23 months (range: 12 to 40 months). Implants were clinically evaluated by using a modified plaque index (mPI), modified sulcus bleeding index (mSBI), and probing depths. Patient satisfaction with the treatment was recorded using a questionnaire. RESULTS: mPI, probing depth, and mSBI did not statistically differ between groups (Mann-Whitney U test, P > 0.05). Patient satisfaction was similar with both retentive systems. CONCLUSION: Within the limits of this study, we concluded that there was no significant difference between the 2 attachment types used for implant-supported overdentures with respect to the soft tissue health status or patient satisfaction.     

The effect of repetitive transcranial magnetic stimulation on refractory neuropathic pain in spinal cord injury

Objective

To investigate the analgesic effect of repetitive transcranial magnetic stimulation (rTMS) on intractable neuropathic pain in patients with spinal cord injury (SCI).

Design

A single center, prospective, randomized, double-blinded, controlled study.

Setting

SCI rehabilitation unit of university rehabilitation center.

Participants

Seventeen patients with SCI and chronic neuropathic pain who met the inclusion criteria recruited between April 2010 and January 2012.

Interventions

Ten daily treatment sessions of real or sham rTMS (30 trains of 10-Hz stimuli for a duration of 5 seconds; a total of 1500 pulses at intensity equal to 110% of the resting motor threshold) was applied over vertex using a figure-of-8-shaped coil.

Outcome measures

Pain was assessed with visual analog scale (VAS) at baseline and 10 days, 6 weeks and 6 months after the treatment. Patients’ satisfactions obtained using a 5-point Likert scale at 6 months.

Results

Both real and sham rTMS provided a significant reduction in the VAS scores (real rTMS group, P = 0.004; sham rTMS group, P = 0.020). Post hoc analysis revealed the significant difference was at 10 days and 6 weeks compared to baseline in the real rTMS group and only at 10 days compared to baseline in the sham rTMS group. Comparison of VAS scores and patient satisfaction did not show any significant difference at each assessment point (P > 0.05).

Conclusion

Our results demonstrated analgesic effect of rTMS on intractable neuropathic pain in SCI was not superior to placebo. However, middle-term (over 6 weeks) pain relief by rTMS is encouraging and suggests the need for future studies with a larger sample size.