Associations of Adolescent Exposure to Severe Violence with Substance Use From Adolescence into Adulthood: Direct Versus Indirect Exposures.

BACKGROUND: While previous research has documented the impact of violence on substance use, none has looked longitudinally across the lifespan to measure independent effects of direct and indirect violence exposure. OBJECTIVE: To examine independent associations between adolescent experiences of violence and subsequent substance use in adolescence and adulthood in the United States. METHOD: Using the National Longitudinal Study of Adolescent to Adult Health (N = 12,288), we examined being shot or stabbed ("experienced"), being threatened with a knife or gun ("threatened"), and seeing someone either shot or stabbed ("witnessed") during adolescence (Wave I) as correlates of substance use in adolescence and adulthood (Wave IV) via logistic regression. RESULTS: Violence exposure was a significant correlate of drug use in adolescence and several associations remained significant in adulthood. Witnessing violence had the highest point estimates in the adjusted models in adolescence for each substance use outcome (e.g., Cocaine-Adjusted Odds Ratios [AOR] = 2.59, 95% confidence interval [CI] = 1.21, 5.54). However, the point estimates for threatened with violence or experienced violence were highest in three out of the four drug outcomes in adulthood (e.g., Threatened with violence: Binge drinking-AOR = 1.41, 95% CI = 1.08, 1.83). Conclusion/Importance: Adolescent exposure to witnessing violence had stronger effects on substance use in adolescence, while experiencing and being threatened with violence in adolescence had stronger effects on substance use in adulthood. Violence prevention efforts targeted toward adolescents may lead to a reduction in substance use throughout the life-course, and clinicians and policy makers should be aware of the downstream effects of violence experienced in adolescence.

Electroacupuncture Promotes Central Nervous System-Dependent Release of Mesenchymal Stem Cells.

Electroacupuncture (EA) performed in rats and humans using limb acupuncture sites, LI-4 and LI-11, and GV-14 and GV-20 (humans) and Bai-hui (rats) increased functional connectivity between the anterior hypothalamus and the amygdala and mobilized mesenchymal stem cells (MSCs) into the systemic circulation. In human subjects, the source of the MSC was found to be primarily adipose tissue, whereas in rodents the tissue sources were considered more heterogeneous. Pharmacological disinhibition of rat hypothalamus enhanced sympathetic nervous system (SNS) activation and similarly resulted in a release of MSC into the circulation. EA-mediated SNS activation was further supported by browning of white adipose tissue in rats. EA treatment of rats undergoing partial rupture of the Achilles tendon resulted in reduced mechanical hyperalgesia, increased serum interleukin-10 levels and tendon remodeling, effects blocked in propranolol-treated rodents. To distinguish the afferent role of the peripheral nervous system, phosphoinositide-interacting regulator of transient receptor potential channels (Pirt)-GCaMP3 (genetically encoded calcium sensor) mice were treated with EA acupuncture points, ST-36 and LIV-3, and GV-14 and Bai-hui and resulted in a rapid activation of primary sensory neurons. EA activated sensory ganglia and SNS centers to mediate the release of MSC that can enhance tissue repair, increase anti-inflammatory cytokine production and provide pronounced analgesic relief. Stem Cells 2017;35:1303-1315.

Child Sexual Abuse and HIV-Related Substance Use and Sexual Risk Across the Life Course Among Males and Females.

Child sexual abuse is associated with substance use and sexual risk behaviors during adolescence and adulthood, but no known studies have documented associations across the life course in a nationally representative U.S. SAMPLE: We used the National Longitudinal Study of Adolescent to Adult Health to measure associations between child sexual abuse and substance use and sexual risk behaviors during adolescence, young adulthood, and adulthood among males and females (n = 11,820). Approximately 10% of females and 7% of males reported child sexual abuse. Associations with substance use were strongest during adolescence and lessened over time. Increased odds of sexual risk among those with a history of child sexual abuse remained consistent through the life course. Significant gender differences existed for some associations (e.g., adulthood multiple partners: males adjusted odds ratio (AOR) = 1.73, 95%CI:1.18, 2.53; females AOR = 1.11, 95%CI:0.79, 1.56). Trauma-informed prevention interventions should address child sexual abuse among both males and females to prevent substance use and sexual risk behavior throughout the life course.

Relationship of maxillary 3-dimensional posterior occlusal plane to mandibular spatial position and morphology.

INTRODUCTION: The purpose of this study was to examine the relationship of the 3-dimensional (3D) posterior occlusal plane (POP) and the mandibular 3D spatial position. The relationship of the POP to mandibular morphology was also investigated. METHODS: Retrospective data from a convenience sample of pretreatment diagnostic cone-beam computed tomography scans were rendered using InVivo software (Anatomage, San Jose, Calif). The sample consisted of 111 subjects (51 male, 60 female) and included growing and nongrowing subjects of different races and ethnicities. The 3D maxillary POP was defined by selecting the cusp tips of the second premolars and the second molars on the rendered images of the subjects. The angles made by this plane, in reference to the Frankfort horizontal plane, were measured against variables that described the mandibular position in the coronal, sagittal, and axial views. The POP was also compared with bilateral variables that described mandibular morphology. RESULTS: There were significant differences of the POP among the different skeletal malocclusions (P <0.0001). The POP showed significant correlations with mandibular position in the sagittal (P <0.0001), coronal (P <0.05), and axial (P <0.05) planes. The POP also showed a significant correlation with mandibular morphology (P <0.0001). CONCLUSIONS: These findings suggest that there is a distinct and significant relationship between the 3D POP and the mandibular spatial position and its morphology.

CNS inflammation and bone marrow neuropathy in type 1 diabetes.

By using pseudorabies virus expressing green fluorescence protein, we found that efferent bone marrow-neural connections trace to sympathetic centers of the central nervous system in normal mice. However, this was markedly reduced in type 1 diabetes, suggesting a significant loss of bone marrow innervation. This loss of innervation was associated with a change in hematopoiesis toward generation of more monocytes and an altered diurnal release of monocytes in rodents and patients with type 1 diabetes. In the hypothalamus and granular insular cortex of mice with type 1 diabetes, bone marrow-derived microglia/macrophages were activated and found at a greater density than in controls. Infiltration of CD45(+)/CCR2(+)/GR-1(+)/Iba-1(+) bone marrow-derived monocytes into the hypothalamus could be mitigated by treatment with minocycline, an anti-inflammatory agent capable of crossing the blood-brain barrier. Our studies suggest that targeting central inflammation may facilitate management of microvascular complications.

Variables affecting orthodontic tooth movement with clear aligners.

INTRODUCTION: In this study, we examined the impacts of age, sex, root length, bone levels, and bone quality on orthodontic tooth movement. METHODS: Clear aligners were programmed to move 1 central incisor 1 mm over the course of 8 weeks. Thirty subjects, ages 19 to 64, were enrolled, and measurements were made on digital models (percentage of tooth movement goal achieved). Morphometric features and bone quality were assessed with cone-beam computed tomography. Data from this study were combined with data from 2 similar studies to increase the power for some analyses. RESULTS: The mean percentage of tooth movement goal achieved was 57% overall. Linear regression modeling indicated a cubic relationship between age and tooth movement, with a decreasing rate of movement from ages 18 to 35 years, a slightly increasing rate from ages 35 to 50, and a decreasing rate from ages 50 to 70. The final decreasing trend was not apparent for women. As would be expected, the correlation was significant between the percentage of the goal achieved and the cone-beam computed tomography superimposed linear measures of tooth movement. A significant negative correlation was found between tooth movement and the measurement apex to the center of rotation, but bone quality, as measured by fractal dimension, was not correlated with movement. CONCLUSIONS: The relationship between age and tooth movement is complex and might differ for male and female patients. Limited correlations with cone-beam computed tomography morphology and rate of tooth movement were detected.

Monitoring uterine activity during labor: a comparison of 3 methods.

OBJECTIVE: Tocodynamometry (Toco; strain gauge technology) provides contraction frequency and approximate duration of labor contractions but suffers frequent signal dropout, necessitating repositioning by a nurse, and may fail in obese patients. The alternative invasive intrauterine pressure catheter (IUPC) is more reliable and adds contraction pressure information but requires ruptured membranes and introduces small risks of infection and abruption. Electrohysterography (EHG) reports the electrical activity of the uterus through electrodes placed on the maternal abdomen. This study compared all 3 methods of contraction detection simultaneously in laboring women. STUDY DESIGN: Upon consent, laboring women were monitored simultaneously with Toco, EHG, and IUPC. Contraction curves were generated in real-time for the EHG, and all 3 curves were stored electronically. A contraction detection algorithm was used to compare frequency and timing between methods. Seventy-three subjects were enrolled in the study; 14 were excluded due to hardware failure of 1 or more of the devices (n = 12) or inadequate data collection duration (n = 2). RESULTS: In comparison with the gold-standard IUPC, EHG performed significantly better than Toco with regard to the Contractions Consistency Index (CCI). The mean CCI for EHG was 0.88 ± 0.17 compared with 0.69 ± 0.27 for Toco (P < .0001). In contrast to Toco, EHG was not significantly affected by obesity. CONCLUSION: Toco does not correlate well with the gold-standard IUPC and fails more frequently in obese patients. EHG provides a reliable noninvasive alternative, regardless of body habitus.

Oral adherence monitoring using a breath test to supplement highly active antiretroviral therapy.

A breath-based adherence system to document ingestion of oral medications (e.g., HAART) was investigated. Specifically, the food additive 2-butanol, which can be easily packaged with a drug, is converted via alcohol dehydrogenase to the volatile metabolite 2-butanone that rapidly appears in breath, indicating adherence. In healthy adults using a portable sensor and GC-MS, the following experiments were performed: yield of 2-butanone in breath following ingestion of 2-butanol, adherence system accuracy, and potential interference of the adherence system by food or misplacement of 2-butanol on the tongue. During feasibility testing, every subject exhaled 2-butanone with 6.6 ± 1.5 min to peak concentrations of 548 ± 235 ppb following ingestion of 2-butanol (40 mg). ROC areas at 5 and 10 min were 0.95 (0.86-1.00) and 1.00 (1.00-1.00). Food did not interfere. Tongue application resulted in large concentrations of 2-butanol, but not 2-butanone. A breath test to provide definitive evidence of oral medication adherence appears technically feasible.

Trends in incidence of oral and pharyngeal carcinoma in Florida: 1981-2008.

OBJECTIVE: While the overall incidence rates of oral and pharyngeal squamous cell carcinoma (SCC) have decreased in the United States, there is evidence of increasing incidence at selected anatomic sites, particularly among younger adults. The objective of this study was to examine trends in incidence rates of oral and pharyngeal cancers in Florida. METHODS: Using data from the Florida Cancer Data System, we examined the incidence of oral and pharyngeal carcinomas in Florida from 1981 through 2008. Factors of interest included sex, race, and trends over time. Percent change (PC) and annual percent change (APC) were computed to characterize trends over time. RESULTS: A total of 53,648 cases of oral or pharyngeal cancer were identified from 1981 through 2008. Significant increasing trends were observed only for pharyngeal cancers in males, with significant decreasing trends for pharyngeal cancer in females and oral cancer for both sexes. For tonsil and base of tongue cancers, increasing trends were detected for white males only. Further investigation among white males showed that, except for base of tongue cancer in the 20-44 age group, the incidence of both cancers increased across all age groups, with the largest increase for both sites found in the 45-64 age group. CONCLUSIONS: This study supports the finding of increasing incidence of SCC of the tonsil and base of tongue in males, in contrast to decreasing trends for most oral and pharyngeal carcinomas. However, we observed that this increase occurred in white males only and the most dramatic increase occurred in the 45-64 age group.

Intrarater agreement about the etiology of Class II malocclusion and treatment approach.

INTRODUCTION: The management of patients with Class II malocclusion has been an ongoing discussion in orthodontics. The aim of this study was to determine whether orthodontists agree among themselves and with each other about the etiology, timing, and difficulty of treating subjects with Class II malocclusion. METHODS: The initial records of 159 Class II subjects were sent to 8 orthodontists. In this sample, duplicate records of 18 subjects were dispersed. A questionnaire was sent with the records. RESULTS: The intrarater consistency values were 65% when determining the type of malocclusion, 60% when deciding which arch was at fault, and 81% when determining the need for immediate treatment. Consistency values were 33% regarding case difficulty and 77% regarding phase 2 treatment need. There was a significant negative correlation between the consistency of the orthodontists' responses and the peer assessment rating score. CONCLUSIONS: We found that practitioners had only moderate agreement among themselves when diagnosing a patient's type of malocclusion and which arch was at fault when a skeletal discrepancy was noted. Intrarater agreement improved as the peer assessment rating score increased, but the correlation was weak, and this was not consistent for all examiners. Because of insufficient intrarater agreement, interrater agreement was not examined.

A randomized, placebo-controlled clinical trial on the effects of recombinant human relaxin on tooth movement and short-term stability.

INTRODUCTION: Moving teeth rapidly and avoiding posttreatment relapse are fundamental goals of orthodontic treatment. In-vitro and animal studies suggest that the human hormone relaxin might increase the rate of movement and the stability through its effect on the periodontal ligament. The purpose of this study was to compare relaxin and a placebo with regard to tooth movement and stability in human subjects. METHODS: A single-center, blinded, placebo-controlled, randomized clinical trial was used to examine the effect of relaxin on tooth movement and stability. Forty subjects were randomized 1:1 and received weekly injections of 50 µg of relaxin or a placebo for 8 weeks. Aligners programmed to move a target tooth 2 mm during treatment were dispensed at weeks 0, 2, 4, and 6. Movement was measured weekly on polyvinyl siloxane impressions that were scanned and digitized. The subjects were followed through week 12 to assess relapse. RESULTS: Tooth movement over the 8-week treatment period did not differ by treatment group (P = 0.995). By using an intent-to-treat analysis, we found that the mean tooth movement for both groups was 0.83 mm (SE, 0.08 for relaxin and 0.09 for the placebo). Relapse from weeks 8 to 12 was the same in both groups (P = 0.986), and the mean was -0.75 (SE, 0.07 for relaxin and 0.08 for theplacebo). CONCLUSIONS: No differences in tooth movement over 8 weeks of treatment or relapse at 4 weeks posttreatment were detected when comparing subjects who received weekly injections of relaxin with those who received a placebo. In both groups, an average of less than half of the programmed tooth movement was obtained after 8 weeks of treatment. The local doses of relaxin might have been too low to affect tooth movement or short-term relapse.

Informed consent process in Alpha-1 testing of at-risk children: views of parents and adults tested as children.

Targeted testing programs are identifying increasing numbers of adults affected by Alpha-1 Antitrypsin Deficiency (Alpha-1) who are making decisions about genetic testing for their at-risk children. Although there are possible benefits, there are also potential risks. The purpose of this pilot study was to explore attitudes toward testing at-risk children from the first hand perspective of those involved, identify the benefits and risks experienced therein, and compare the views of parents and adults tested as children (ATC). The results of this pilot study suggest that ATC were significantly more favorable to including children in testing decisions than parents. ATC strongly indicated that they want to be involved in the testing decision and give permission prior to testing (p = 0.007). While the majority of ATC and parents were in favor of newborn screening for Alpha-1, parents had more extreme views, both positive and negative (p = 0.04). Both ATC and parents expressed significantly higher likelihoods of possible risks and benefits following Alpha-1 testing than they actually experienced. Results do not reveal serious harms from testing at-risk children. The two groups indicated that they want information regarding access to insurance, inheritance and expression, impact on anxiety, association with smoking, and usefulness in future planning prior to a decision to test or not to test at risk children. From the resulting data and ethical analysis we recommend that parents and children have relevant information prior to testing for Alpha-1 and that at risk children are directly involved in the decision-making process prior to testing.

Otologic and audiologic outcomes with the Furlow and von Langenbeck with intravelar veloplasty palatoplasties in unilateral cleft lip and palate.

OBJECTIVE: Cleft palate increases the risk of chronic middle ear disease and hearing loss. The goal of this report was to determine which of two palate surgeries and which timing of palate surgery were associated with better otologic and audiologic outcomes in children with unilateral cleft lip and palate at 5 to 6 years of age. DESIGN: Subjects were randomly assigned to the von Langenbeck with intravelar veloplasty or Furlow palate repair, to palate surgery at 9 to 12 months or 15 to 18 months of age, and to the Spina or Millard lip repair. SETTING: Centralized, tertiary care craniofacial treatment center. PATIENTS: A total of 673 infants with unilateral cleft lip and palate. INTERVENTIONS: Palate and lip were repaired using established techniques. Serial otoscopic and audiometric evaluations were performed. MAIN OUTCOME MEASURES: Hearing and otoscopic findings at 5 to 6 years old. RESULTS: There were 370 children available for analysis. Hearing and need for tympanostomy tube placement did not differ by palatoplasty, age at palatoplasty, cheiloplasty, or surgeon. Risk of developing cholesteatoma or perforation was higher with Millard cheiloplasty (odds ratio  =  5.1, 95% confidence interval  =  1.44 to 18.11, p  =  .012). Type and age at palatoplasty were not significantly associated with either the rate of developing these sequelae or the rate of achieving bilaterally normal hearing and ear examinations. CONCLUSIONS: Type of palatoplasty did not influence otologic and audiologic outcomes in 5- to 6-year-olds with unilateral cleft lip and palate. The potential influence of lip repair on otologic outcomes warrants further investigation.

Effect of early Class II treatment on the incidence of incisor trauma.

INTRODUCTION: Many researchers have examined the prevalence of dental injuries in children and adolescents. The purpose of this study was to examine the prevalence and incidence of incisor trauma in subjects who participated in a randomized clinical trial designed to investigate early growth modifications in the treatment of Class II malocclusion. METHODS: The subjects were randomized to 3 treatment groups during the initial phase of the study: (1) headgear or biteplane, (2) bionator, and (3) observation (no treatment). All 3 groups underwent phase 2 treatment with fixed appliances. Incisor injury was scored at every data collection point with the Ellis index by a blinded examiner using dental casts, intraoral photos, and panoramic and periapical x-rays. RESULTS: Twenty-five percent of the subjects had incisor trauma at the baseline examination, and 28% experienced new or worsening maxillary incisor injury during the study. No significant differences were found with regard to sex and prevalence of injury at baseline. No differences in incidence of trauma were found between the 3 treatment groups throughout the study (P = 0.19); however, boys were more likely to experience maxillary incisor injury (odds ratio estimate, 2.37; 95% CI, 1.33, 4.21), and those with an injury at baseline were more likely to experience an additional injury (odds ratio estimate, 1.81; 95% CI, 1.03, 3.17). CONCLUSIONS: Early orthodontic treatment did not affect the incidence of incisor injury. The majority of the injuries before and during treatment were minor; therefore, the cost-benefit ratio of orthodontic treatment primarily to prevent incisor trauma is unfavorable.

Effects of analgesics on orthodontic pain.

INTRODUCTION: Our objective was too assess the effectiveness of 3 analgesics (ibuprofen, naproxen sodium, and acetaminophen) and a placebo administered before and after the placement of separators in reducing the severity of postseparator placement pain. We also examined the impact of treatment on chewing efficiency at 24 hours after separator placement. METHODS: Twenty-four subjects participated in the study. Each subject received 3 of 4 treatments: ibuprofen, naproxen sodium, acetaminophen, or placebo in random order at monthly intervals. The dosing times were 1 hour before separator placement and 3 and 7 hours after separator placement. Before placement, the subjects completed a masticatory efficiency test and a visual analog scale (VAS) for expected pain and pain experienced. A VAS pain diary was kept for 24 hours. Subjects returned to the clinic after 1 week for separator removal. RESULTS: VAS pain summary scores after separator placement were significantly affected by the administration of ibuprofen (P = 0.0298) and the time after separator placement (P <0.0001). Administering ibuprofen before and after separator placement significantly reduced pain compared with the placebo. The analgesic effects diminished by day 2, resulting in peak pain levels and decreased chewing efficiency. The expected pain after separator placement also played a role in experienced pain; subjects expecting more pain experienced more pain. CONCLUSIONS: Ibuprofen was superior to the placebo in relieving postseparator pain as measured by the VAS pain summary scores, whereas acetaminophen and naproxen sodium did not significantly differ from the placebo.

An intravascular ultrasound analysis in women experiencing chest pain in the absence of obstructive coronary artery disease: a substudy from the National Heart, Lung and Blood Institute-Sponsored Women's Ischemia Syndrome Evaluation (WISE).

AIMS: Using intravascular ultrasound (IVUS), we sought to characterize coronary morphology in women with chest pain without major epicardial obstructive coronary artery disease (CAD). We have previously observed an unexpectedly high rate of adverse outcomes among women with chest pain and normal or insignificant obstructive CAD. Information about the presence and characteristics of coronary atherosclerosis in these women could provide insight into the mechanisms related to increased risk, as well as improved diagnosis, prevention, and treatment. METHODS: Women (n = 100) with suspected ischemia without obstructive CAD (>50% stenosis) underwent IVUS of a left coronary segment with measurements by a core lab masked to clinical and angiographic findings. RESULTS: Angiograhic core lab analysis found 69.6% of patients had no (≤20%) and 30.4% had minimal (20-<50%) CAD. IVUS segmental images were interpretable by the core lab in 92 women, with 19 (21%) having no atherosclerosis (intimal-medial thickness <0.5 mm). In the remaining 73 women (79%), percent atheroma volume was 27 ± 8% and mean maximum plaque thickness was 0.53 ± 0.22 mm. Thirty-eight women with atherosclerosis (53%) had ≥30% of interrogated vessel involved. The average vessel involvement was 40%, and the maximum plaque thickness was 1.27 mm. The number of risk factors strongly correlated with percent atheroma volume (r = 0.53, P < 0.0001) and percent vessel involvement (r = 0.51, P < 0.0001), with the strongest independent predictor of both being age. Remodeling was assessed in 59/73 women (81%), and 73% had evidence of positive remodeling. CONCLUSIONS: In symptomatic women without significant luminal obstructive CAD, we observed a high prevalence of atherosclerosis with positive remodeling and preserved lumen size. These findings may help explain increased risk and emphasize need for improved diagnostic and treatment options for women with concealed CAD.

Comparison of arch dimension changes in 1-phase vs 2-phase treatment of Class II malocclusion.

INTRODUCTION: We compared arch dimension changes in 1-phase and 2-phase treatment of Class II malocclusion. This was a prospective randomized clinical trial conducted in the Department of Orthodontics at the University of Florida between 1990 and 2003. METHODS: During phase 1 treatment, 86 subjects were treated with a bionator, 93 were treated with headgear/biteplane, and 81 served as the observation group. For phase 2, all subjects were then treated with full orthodontic appliances. Arch dimensions were followed; maxillary and mandibular alginate impressions were taken at baseline, end of early Class II treatment or observation, beginning of fixed appliance treatment, end of orthodontic treatment, and approximately 3 years posttreatment. Alginate impressions were taken of each dental arch at each data collection point. These were poured in orthodontic stone, trimmed, and photocopied from the occlusal aspect. These images were then scanned and measured. RESULTS: Although differences between the treatment groups were found in both the maxillary and mandibular arches after phase 1, these differences were no longer evident by the end of full orthodontic treatment or after posttreatment retention. CONCLUSIONS: There were no differences in arch dimensions after 1-phase or 2-phase treatment of Class II malocclusion.

Effects of preoperative ibuprofen on pain after separator placement.

INTRODUCTION: Many patients experience pain with orthodontics, but there is no widely accepted standard of care for controlling orthodontic pain. Previous studies were inconclusive as to the most effective way to manage orthodontic pain. The purpose of this study was to assess the effectiveness in reducing pain of preemptive ibuprofen added to an ibuprofen regimen administered after separator placement. We also examined the contributions of psychological factors and sex to the experience of pain. METHODS: The subjects were randomly assigned to group A, 400 mg of ibuprofen 1 hour before separator placement (D1), 3 hours after placement (D2), and 7 hours after placement (D3); group B, placebo at D1, 400 mg of ibuprofen at D2 and D3; or group C, placebo at D1, D2, and D3. Before separator placement, the subjects completed 2 psychological surveys, a masticatory efficiency test, and a visual analog scale for expected pain and experienced pain during the masticatory efficiency test. After placement, the subjects recorded their actual pain, kept a pain diary for 24 hours after separator placement, and performed a 24-hour follow-up masticatory efficiency test. RESULTS: Group A, receiving ibuprofen before and after separator placement, experienced significantly less pain (P <0.05) at 6 hours, at bedtime, and at awakening on the second day. No contributions to pain were found for psychological factors or sex. CONCLUSIONS: Preemptive administration of analgesics should be recommended to orthodontic patients before separator placement.

A multi-center retrospective analysis of the effect of DPP4 inhibitors on progression-free survival in advanced airway and colorectal cancers.

Cluster of differentiation 26 (CD26), also known as dipeptidyl peptidase IV (DPP4), is a cell surface protein with exopeptidase activity and is expressed by most cell types. CD26/DPP4 is a multifunctional molecule with diverse biological effects, including regulatory effects on tumor growth, invasion and metastasis, and is a potential novel therapeutic target for selected cancers. In this study, we retrospectively analyzed diabetic patients with concurrent advanced airway or colorectal cancer to examine the effect of DPP4-inhibitors on progression-free survival (PFS). We performed a multi-center retrospective review of patients with advanced colorectal or airway (lung, head and neck) cancer and a concurrent diagnosis of diabetes. The control group included patients on metformin and a sulfonylurea, and the study group included patients on metformin and a DPP4 inhibitor. Ninety-six patients were eligible for the study. The cancers progressed in 23.7% of patients treated with DPP4 inhibitors compared to 50.9% of patients in the control group with an odds ratio of 0.303 [95% confidence interval (CI): 0.106-0.809] and P=0.010. There was a statistically significant improvement in PFS in the study group as compared to the control group, hazard ratio=0.42 (95% CI: 0.21-0.84) and P=0.014. There was a trend toward improvement in overall survival, although this effect was not statistically significant (P=0.11). Exposure to DPP4 inhibitors in the study group led to higher PFS in patients with advanced colorectal and airway cancers. Additional investigations with larger patient cohorts are needed to validate the relationship between DPP4 inhibition and the clinical outcome of selected malignancies.

Minimally invasive interval cytoreductive surgery in ovarian cancer: systematic review and meta-analysis.

The introduction of minimally invasive surgery in other gynecologic cancers has shown benefits with similar oncologic outcomes. However, the biology and complexity of surgery for ovarian cancer may preclude this approach for ovarian cancer patients. Our objective is to assess feasibility to achieve complete cytoreductive surgery after neoadjuvant chemotherapy for stage IIIC-IV ovarian cancer patients via minimally invasive surgery. Our data sources include PubMed, Embase, Scopus, Biosis, Clinicaltrials.gov, and the Cochrane Library. Meta-analysis was performed using the random-effects model with DerSimonian and Laird estimator for the amount of heterogeneity to estimate the pooled outcomes. A funnel plot and Egger's regression test were used to test publication bias. The Newcastle-Ottawa Quality Assessment Scale was used to assess the quality of the studies. There were 6 studies (3 prospective, 3 retrospective) that met the criteria for meta-analysis with a total of 3231 patients, 567 were in the minimally invasive group and 2664 in the laparotomy group. Both groups were similar in stage and serous histology. Complete cytoreductive surgery was achieved in 74.50% (95% CI 40.41-97.65%) and 53.10% (95% CI 4.88-97.75%) of patients in the minimally invasive and laparotomy groups, respectively. There was no statistical significant difference between these 2 pooled proportions (p = 0.52). Three studies compared minimally invasive surgery vs laparotomy. No significant difference was observed between the 2 groups in obtaining complete cytoreductive surgery [OR = 0.90 (95% CI 0.70-1.16; p = 0.43)]. A symmetrical funnel plot indicated no publication bias. The pooled proportion for grade > 2 postoperative complications was not significant among the laparoscopy group [3.11% (95% CI 0.00-10.24%; p = 0.15)]. Complete cytoreductive surgery appears feasible and safe with minimally invasive surgery in selected advanced ovarian cancer patients after neoadjuvant chemotherapy.