Growth rates and histopathological outcomes of small (6-9 mm) colorectal polyps based on CT colonography surveillance and endoscopic removal.

BACKGROUND AND AIMS: The natural history of small polyps is not well established and rests on limited evidence from barium enema studies decades ago. Patients with one or two small polyps (6-9 mm) at screening CT colonography (CTC) are offered CTC surveillance at 3 years but may elect immediate colonoscopy. This practice allows direct observation of the growth of subcentimetre polyps, with histopathological correlation in patients undergoing subsequent polypectomy. DESIGN: Of 11 165 asymptomatic patients screened by CTC over a period of 16.4 years, 1067 had one or two 6-9 mm polyps detected (with no polyps ≥10 mm). Of these, 314 (mean age, 57.4 years; M:F, 141:173; 375 total polyps) elected immediate colonoscopic polypectomy, and 382 (mean age 57.0 years; M:F, 217:165; 481 total polyps) elected CTC surveillance over a mean of 4.7 years. Volumetric polyp growth was analysed, with histopathological correlation for resected polyps. Polyp growth and regression were defined as volume change of ±20% per year, with rapid growth defined as +100% per year (annual volume doubling). Regression analysis was performed to evaluate predictors of advanced histology, defined as the presence of cancer, high-grade dysplasia (HGD) or villous components. RESULTS: Of the 314 patients who underwent immediate polypectomy, 67.8% (213/314) harboured adenomas, 2.2% (7/314) with advanced histology; no polyps contained cancer or HGD. Of 382 patients who underwent CTC surveillance, 24.9% (95/382) had polyps that grew, while 62.0% (237/382) remained stable and 13.1% (50/382) regressed in size. Of the 58.6% (224/382) CTC surveillance patients who ultimately underwent colonoscopic resection, 87.1% (195/224) harboured adenomas, 12.9% (29/224) with advanced histology. Of CTC surveillance patients with growing polyps who underwent resection, 23.2% (19/82) harboured advanced histology vs 7.0% (10/142) with stable or regressing polyps (OR: 4.0; p<0.001), with even greater risk of advanced histology in those with rapid growth (63.6%, 14/22, OR: 25.4; p<0.001). Polyp growth, but not patient age/sex or polyp morphology/location were significant predictors of advanced histology. CONCLUSION: Small 6-9 mm polyps present overall low risk to patients, with polyp growth strongly associated with higher risk lesions. Most patients (75%) with small 6-9 mm polyps will see polyp stability or regression, with advanced histology seen in only 7%. The minority of patients (25%) with small polyps that do grow have a 3-fold increased risk of advanced histology.

Ejaculatory Preserving Holmium Laser Enucleation of the Median Lobe: Preserving Sexual Function While Improving Urinary Outcomes.

OBJECTIVE: To evaluate perioperative outcomes related to sexual and urinary function in patients who underwent a holmium laser enucleation of the prostate (HoLEP) with selective laser enucleation of the median lobe. MATERIALS AND METHODS: We retrospectively reviewed the first 450 HoLEP cases by a single surgeon from April 2019 to March 2022. Fifty-five patients with intravesical-prostatic protrusion or high bladder neck without obstructing lateral lobes underwent selective enucleation of the median lobe of the prostate. Patients were asked to comment on whether they had retrograde ejaculation during their follow-up appointment. Urinary function was assessed using the American Urological Association Symptom Score and subjective evaluation of urinary incontinence. RESULTS: Median age of the cohort was 65 years (range: 44-91). Compared to preoperative, there was significant improvement in mean postoperative American Urological Association Symptom Score (22.5 vs 6.9, P < .001), mean postoperative quality of life scores (4 vs 1.2, P < .001), and mean postoperative post void residual volumes (244.1 vs 69.3 cc, P < .001). No patients reported stress urinary incontinence. Of the 55 patients who underwent selective enucleation of the median lobe, 40 were sexually active. Of those men, 35 reported normal ejaculation, 3 had retrograde ejaculation that was unchanged from pre-op, and 2 had new ejaculatory dysfunction. CONCLUSION: In this case series of selective laser enucleation of the median lobe, urinary function significantly improved in short-term follow-up with preservation of ejaculation in approximately 90% of men.

Parent Perspectives on Exclusive Enteral Nutrition for the Treatment of Pediatric Crohn Disease.

OBJECTIVES: Exclusive enteral nutrition (EEN) is infrequently used in the United States but is an effective treatment for pediatric Crohn disease (CD). Limited data exists regarding patient and parent perspectives on this treatment modality. The aim of this study was to determine parent and provider perspectives regarding EEN and understand parent-cited barriers to its use. METHODS: We surveyed the parents/guardians of children ages 1 through 17 with CD in our institution regarding EEN. Healthcare provider perspectives regarding reason for stopping EEN and those cited by survey respondents were compared using retrospective chart review. RESULTS: One hundred fifteen (62.5%) out of 184 recipients responded to the survey. Ninety percentage of respondents had heard of EEN but of these, 26% had not discussed it with their gastroenterologist. Thirty-eight patients (33%) were treated in the past and 15 (13%) were currently on EEN. Common barriers cited by current EEN users were cost/finances and difficult social situations. Of the children who stopped EEN, most did so as parents felt it was not working (n = 14, 37%). In these cases, their primary gastroenterologist cited treatment failure for 4 cases and nonadherence for 6. CONCLUSIONS: Despite the efficacy of EEN and interest in dietary treatments by patients with CD, there are many barriers surrounding effective communication and successful implementation of dietary therapies. Future research is needed regarding patient-physician communication, cost mitigation, and coping with the social limitations of dietary therapies.

Effectiveness of nutritional countermeasures in microgravity and its ground-based analogues to ameliorate musculoskeletal and cardiopulmonary deconditioning-A Systematic Review.

A systematic review was performed to evaluate the effectiveness of nutrition as a standalone countermeasure to ameliorate the physiological adaptations of the musculoskeletal and cardiopulmonary systems associated with prolonged exposure to microgravity. A search strategy was developed to find all astronaut or human space flight bed rest simulation studies that compared individual nutritional countermeasures with non-intervention control groups. This systematic review followed the guidelines of the Cochrane Handbook for Systematic Reviews and tools created by the Aerospace Medicine Systematic Review Group for data extraction, quality assessment of studies and effect size. To ensure adequate reporting this systematic review followed the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analyses. A structured search was performed to screen for relevant articles. The initial search yielded 4031 studies of which 10 studies were eligible for final inclusion. Overall, the effect of nutritional countermeasure interventions on the investigated outcomes revealed that only one outcome was in favor of the intervention group, whereas six outcomes were in favor of the control group, and 43 outcomes showed no meaningful effect of nutritional countermeasure interventions at all. The main findings of this study were: (1) the heterogeneity of reported outcomes across studies, (2) the inconsistency of the methodology of the included studies (3) an absence of meaningful effects of standalone nutritional countermeasure interventions on musculoskeletal and cardiovascular outcomes, with a tendency towards detrimental effects on specific muscle outcomes associated with power in the lower extremities. This systematic review highlights the limited amount of studies investigating the effect of nutrition as a standalone countermeasure on operationally relevant outcome parameters. Therefore, based on the data available from the included studies in this systematic review, it cannot be expected that nutrition alone will be effective in maintaining musculoskeletal and cardiopulmonary integrity during space flight and bed rest.

The Current State of Opioid Prescribing and Drug Enforcement Agency (DEA) Action Against Physicians: An Analysis of DEA Database 2004-2017.

BACKGROUND: Prescribing opioids has become a challenge. The US Drug Enforcement Agency (DEA) and Centers for Disease Control and Prevention (CDC) have become more involved, culminating in the March 2016 release of the CDC's "Guidelines for Prescribing Opioids for Chronic Pain." OBJECTIVES: Given the new guidelines, we wanted to see if there have been any changes in the numbers, demographics, physician risk factors, charges, and sanctions involving the DEA against physicians who prescribe opioids, when compared to a previous DEA database review from 1998 to 2006. STUDY DESIGN: This study involved an analysis of the DEA database from 2004 to 2017. SETTING: The review was conducted at the Henry Ford Health System Division of Pain Medicine. METHOD: After institutional review board approval at Henry Ford Health System, an analysis of the DEA database of criminal prosecutions of physician registrants from 2004-2017 was performed. The database was reviewed for demographic information such as age, gender, type of degree (doctor of medicine [MD] or doctor of osteopathic medicine [DO]), years of practice, state, charges, and outcome of prosecution (probation, sentencing, and length of sentencing). An internet-based search was performed on each registrant to obtain demographic data on specialty, years of practice, type of medical school (US vs foreign), board certification, and type of employment (private vs employed). RESULTS: Between 2004 and 2017, Pain Medicine (PM) had the highest percentage of in-specialty action at 0.11% (n = 5). There was an average of 18 prosecutions per year vs 14 in the previous review. Demographic risk factors for prosecution demonstrated the significance of the type of degree (MD vs. DO), gender, type of employment (private vs. employed), and board certification status for rates of prosecution. Having a DO degree and being male were associated with significantly higher risk as well as being in private practice and not having board certification (P < .001). In terms of type of criminal charges as a percent of cases, possession with intent to distribute (n = 90) was most prevalent, representing 52.3% of charges, with new charges being prescribing without medical purpose outside the usual course of practice (n = 71) representing 41.3% of charges. Comparison of US graduates (MD/DO) vs. foreign graduates showed higher rates of DEA action for foreign graduates but this was of borderline significance (P = .072). LIMITATIONS: State-by-state comparisons could not be made. Specialty type was sometimes self-reported, and information on all opioid prosecutions could not be obtained. The previous study by Goldenbaum et al included data beyond DEA prosecution, so direct comparisons may be limited. CONCLUSION: The overall risk of DEA action as a percentage of total physicians is small but not insignificant. The overall rates of DEA prosecution have increased. New risk factors include type of degree (DO vs. MD) and being in private practice with a subtle trend toward foreign graduates at higher risk. With the trend toward less prescribing by previously high-risk specialties such as Family Medicine, there has been an increase in the relative risk of DEA action for specialties treating patients with pain such as PM, Physical Medicine and Rehabilitation, neurology, and neurosurgery bearing the brunt of prosecutions. New, more subtle charges have been added involving interpretation of the medical purpose of opioids and standard of care for their use. KEY WORDS: Certification, CDC, criminal, DEA, opioid, prescribing, prosecution, sanctions.

Niacin protects against abdominal aortic aneurysm formation via GPR109A independent mechanisms: role of NAD+/nicotinamide.

AIMS: Chronic adventitial and medial infiltration of immune cells play an important role in the pathogenesis of abdominal aortic aneurysms (AAAs). Nicotinic acid (niacin) was shown to inhibit atherosclerosis by activating the anti-inflammatory G protein-coupled receptor GPR109A [also known as hydroxycarboxylic acid receptor 2 (HCA2)] expressed on immune cells, blunting immune activation and adventitial inflammatory cell infiltration. Here, we investigated the role of niacin and GPR109A in regulating AAA formation. METHODS AND RESULTS: Mice were supplemented with niacin or nicotinamide, and AAA was induced by angiotensin II (AngII) infusion or calcium chloride (CaCl2) application. Niacin markedly reduced AAA formation in both AngII and CaCl2 models, diminishing adventitial immune cell infiltration, concomitant inflammatory responses, and matrix degradation. Unexpectedly, GPR109A gene deletion did not abrogate the protective effects of niacin against AAA formation, suggesting GPR109A-independent mechanisms. Interestingly, nicotinamide, which does not activate GPR109A, also inhibited AAA formation and phenocopied the effects of niacin. Mechanistically, both niacin and nicotinamide supplementation increased nicotinamide adenine dinucleotide (NAD+) levels and NAD+-dependent Sirt1 activity, which were reduced in AAA tissues. Furthermore, pharmacological inhibition of Sirt1 abrogated the protective effect of nicotinamide against AAA formation. CONCLUSION: Niacin protects against AAA formation independent of GPR109A, most likely by serving as an NAD+ precursor. Supplementation of NAD+ using nicotinamide-related biomolecules may represent an effective and well-tolerated approach to preventing or treating AAA.

Transarterial Chemoembolization in Treatment-Naïve and Recurrent Hepatocellular Carcinoma: A Propensity-Matched Outcome Analysis.

OBJECTIVES: Transarterial chemoembolization (TACE) improves the survival of patients with hepatocellular carcinoma (HCC); however, TACE treatment outcomes of patients with treatment-naïve HCC (TN-HCC) and those with recurrent HCC after curative resection (R-HCC) have not yet been compared. METHODS: We recruited 448 patients with TN-HCC, and 275 patients with R-HCC treated with TACE as first-line anti-cancer treatment. RESULTS: At first TACE, patients with TN-HCC showed a significantly lower proportion of male gender (74.9% vs. 84.3%), higher proportion of liver cirrhosis (61.9% vs. 49.3%), higher aspartate aminotransferase (median 48 vs. 31 IU/L), alanine aminotransferase (median 38 vs. 26 IU/L), alpha-fetoprotein (AFP) (median 96.6 vs. 7.7 ng/mL), and total bilirubin (mean 1.0 vs. 0.8 mg/dL) levels, longer prothrombin time (median 1.05 vs. 1.01 international normalized ratio), higher tumor number (mean 2.1 vs. 1.7), larger tumor size (median 3.1 vs. 1.6 cm), and lower proportion of Barcelona Clinic Liver Cancer stage 0-A (55.6% vs. 71.9%) than patients with R-HCC (all P < 0.05). Multivariate analysis showed that TACE for TN-HCC (vs. R-HCC) was an independent predictor of mortality (hazard ratio, 1.328; P = 0.024) with AFP level and tumor number (all P < 0.05). However, treatment outcomes between TN-HCC and R-HCC became statistically similar after propensity score-matched (PSM) analysis using liver cirrhosis, tumor size, and multiple tumors (P < 0.05). CONCLUSIONS: Based on the similar TACE treatment outcomes observed with the PSM analysis, the current TACE treatment guideline for patients with TN-HCC might similarly be applied for patients with R-HCC.

Multi-sensory Gamma Stimulation Ameliorates Alzheimer's-Associated Pathology and Improves Cognition.

We previously reported that inducing gamma oscillations with a non-invasive light flicker (gamma entrainment using sensory stimulus or GENUS) impacted pathology in the visual cortex of Alzheimer's disease mouse models. Here, we designed auditory tone stimulation that drove gamma frequency neural activity in auditory cortex (AC) and hippocampal CA1. Seven days of auditory GENUS improved spatial and recognition memory and reduced amyloid in AC and hippocampus of 5XFAD mice. Changes in activation responses were evident in microglia, astrocytes, and vasculature. Auditory GENUS also reduced phosphorylated tau in the P301S tauopathy model. Furthermore, combined auditory and visual GENUS, but not either alone, produced microglial-clustering responses, and decreased amyloid in medial prefrontal cortex. Whole brain analysis using SHIELD revealed widespread reduction of amyloid plaques throughout neocortex after multi-sensory GENUS. Thus, GENUS can be achieved through multiple sensory modalities with wide-ranging effects across multiple brain areas to improve cognitive function.

A large scale high-throughput screen identifies chemical inhibitors of phosphatidylinositol 4-kinase type II alpha.

The minor phospholipid, phosphatidylinositol 4-phosphate (PI4P), is emerging as a key regulator of lipid transfer in ER-membrane contact sites. Four different phosphatidylinositol 4-kinase (PI4K) enzymes generate PI4P in different membrane compartments supporting distinct cellular processes, many of which are crucial for the maintenance of cellular integrity but also hijacked by intracellular pathogens. While type III PI4Ks have been targeted by small molecular inhibitors, thus helping decipher their importance in cellular physiology, no inhibitors are available for the type II PI4Ks, which hinders investigations into their cellular functions. Here, we describe the identification of small molecular inhibitors of PI4K type II alpha (PI4K2A) by implementing a large scale small molecule high-throughput screening. A novel assay was developed that allows testing of selected inhibitors against PI4K2A in intact cells using a bioluminescence resonance energy transfer approach adapted to plate readers. The compounds disclosed here will pave the way to the optimization of PI4K2A inhibitors that can be used in cellular and animal studies to better understand the role of this enzyme in both normal and pathological states.

Effects of Auricular Acupressure on Pain Management: A Systematic Review.

OBJECTIVE: Nearly half of hospitalized patients in the United States have reported experiencing pain even while undergoing treatment for pain. Analgesic use is the most common type of treatment for pain management. Many patients who experience pain seek nonpharmacologic interventions to manage their pain, including forms of complementary or alternative medicine such as auricular acupressure (AA). DESIGN: This study conducted the first systematic review of the studies that have evaluated the effect of AA as an adjunct on pain management. DATA SOURCES: We searched PubMed, CINAHL, Embase, Google Scholar, and Wiley for randomized controlled trials on AA. REVIEW/ANALYSIS METHODS: The pain outcomes were pain severity and analgesic consumption. Methodologic quality was also evaluated. Fifteen randomized controlled trials were included in this analysis. RESULTS: Twelve studies reported statistically significant improvement in the pain outcomes of AA treatment compared with the sham or standard care groups. When methodologic quality was assessed, the selected studies had medium quality, but there was a lack of high quality. This supports that the use of AA for patients may enhance self-management for their pain. However, the small number of studies and the lack of consistent rigorous methodology across the studies preclude definitive statements regarding the effectiveness of AA. CONCLUSION: The nursing implications based on this review is that education about AA and complementary or alternative medicine therapies for health care providers may assist them in providing pain control for their patients. In addition, we need to continue research to build on evidence on the effect of AA on pain management.

ACR Appropriateness Criteria® Colorectal Cancer Screening.

This review summarizes the relevant literature regarding colorectal screening with imaging. For individuals at average or moderate risk for colorectal cancer, CT colonography is usually appropriate for colorectal cancer screening. After positive results on a fecal occult blood test or immunohistochemical test, CT colonography is usually appropriate for colorectal cancer detection. For individuals at high risk for colorectal cancer (eg, hereditary nonpolyposis colorectal cancer, ulcerative colitis, or Crohn colitis), optical colonoscopy is preferred because of its ability to obtain biopsies to detect dysplasia. After incomplete colonoscopy, CT colonography is usually appropriate for colorectal cancer screening for individuals at average, moderate, or high risk. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

New Metrics for Economic Evaluation in the Presence of Heterogeneity: Focusing on Evaluating Policy Alternatives Rather than Treatment Alternatives.

BACKGROUND: Cost-effectiveness analysis (CEA) methods fail to acknowledge that where cost-effectiveness differs across subgroups, there may be differential adoption of technology. Also, current CEA methods are not amenable to incorporating the impact of policy alternatives that potentially influence the adoption behavior. Unless CEA methods are extended to allow for a comparison of policies rather than simply treatments, their usefulness to decision makers may be limited. METHODS: We conceptualize new metrics, which estimate the realized value of technology from policy alternatives, through introducing subgroup-specific adoption parameters into existing metrics, incremental cost-effectiveness ratios (ICERs) and Incremental Net Monetary Benefits (NMBs). We also provide the Loss with respect to Efficient Diffusion (LED) metrics, which link with existing value of information metrics but take a policy evaluation perspective. We illustrate these metrics using policies on treatment with combination therapy with a statin plus a fibrate v. statin monotherapy for patients with diabetes and mixed dyslipidemia. RESULTS: Under the traditional approach, the population-level ICER of combination v. monotherapy was $46,000/QALY. However, after accounting for differential rates of adoption of the combination therapy (7.2% among males and 4.3% among females), the modified ICER was $41,733/QALY, due to the higher rate of adoption in the more cost-effective subgroup (male). The LED metrics showed that an education program to increase the uptake of combination therapy among males would provide the largest economic returns due to the significant underutilization of the combination therapy among males under the current policy. CONCLUSION: This framework may have the potential to improve the decision-making process by producing metrics that are better aligned with the specific policy decisions under consideration for a specific technology.

Intraoperative Low-frequency Electroacupuncture under General Anesthesia Improves Postoperative Recovery in a Randomized Trial.

Neuronal stimulation improves physiological responses to infection and trauma, but the clinical potential of this strategy is unknown. We hypothesized that transdermal neural stimulation through low-frequency electroacupuncture might control the immune responses to surgical trauma and expedite the postoperative recovery. However, the efficiency of electroacupuncture is questioned due to the placebo effect. Here, electroacupuncture was performed on anesthetized patients to avoid any placebo. This is a prospective double-blinded pilot trial to determine whether intraoperative electroacupuncture on anesthetized patients improves postoperative recovery. Patients with electroacupuncture required 60% less postoperative analgesic, even they had pain scores similar to those in the control patients. Electroacupuncture prevented postoperative hyperglycemia and attenuated serum adrenocorticotropic hormone in the older and heavier group of patients. From an immunological perspective, electroacupuncture did not affect the protective immune responses to surgical trauma, including the induction of interleukin-6 and interleukin-10. The most significant immunological effect of electroacupuncture was enhancing transforming growth factor-ß1 production during surgery in the older and lighter group of patients. These results suggest that intraoperative electroacupuncture on anesthetized patients can reduce postoperative use of analgesics and improve immune and stress responses to surgery.

ACR Appropriateness Criteria colorectal cancer screening.

Colorectal cancer is the third leading cause of cancer deaths in the United States. Most colorectal cancers can be prevented by detecting and removing the precursor adenomatous polyp. Individual risk factors for the development of colorectal cancer will influence the particular choice of screening tool. CT colonography (CTC) is the primary imaging test for colorectal cancer screening in average-risk individuals, whereas the double-contrast barium enema (DCBE) is now considered to be a test that may be appropriate, particularly in settings where CTC is unavailable. Single-contrast barium enema has a lower performance profile and is indicated for screening only when CTC and DCBE are not available. CTC is also the preferred test for colon evaluation following an incomplete colonoscopy. Imaging tests including CTC and DCBE are not indicated for colorectal cancer screening in high-risk patients with polyposis syndromes or inflammatory bowel disease. This paper presents the updated colorectal cancer imaging test ratings and is the result of evidence-based consensus by the ACR Appropriateness Criteria Expert Panel on Gastrointestinal Imaging. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

Reassessing the effects of histone deacetylase inhibitors on hippocampal memory and cognitive aging.

Converging results link histone acetylation dynamics to hippocampus-dependent memory, including evidence that histone deacetylase inhibitor (HDACi) administration enhances long-term memory. Previously, we demonstrated that aging disrupts the coordinated epigenetic response to recent experience observed in the young adult hippocampus. Here, we extended that work to test the cognitive effects of a novel, brain-penetrant HDACi (EVX001688; EVX) that we confirmed yields robust, relatively long lasting dose-dependent increases in histone acetylation in the hippocampus. In young rats, acute systemic EVX administration, scheduled to yield elevated histone acetylation levels during training in a contextual fear conditioning (CFC) task, had no effect on memory retention at 24 h at any dose examined (10, 30, or 60 mg/kg). Pretraining injection of another HDACi, sodium butyrate, also failed to affect fear memory, and CFC training itself had no influence on hippocampal histone acetylation at 1 hour in mice or two strains of rats. EVX administration before water maze training in young rats yielded a modest effect such that the middle dose produced marginally better 24-h retention than either the low or high dose, but only a small numerical benefit relative to vehicle. Guided by those findings, a final experiment tested the influence of pretraining EVX treatment on age-related spatial memory impairment. The results, revealing no effect on performance, are consistent with the idea that effective procognitive HDACi treatments in aging may require intervention aimed at restoring coordinated epigenetic regulation rather than bulk increases in hippocampal histone acetylation.

Growth factor-mediated vertical mandibular ridge augmentation: a case report.

Posterior vertical alveolar ridge deficiencies are challenging defects to treat predictably and often require autogenous bone-harvesting procedures. Traditional treatment modalities, eg, guided bone regeneration, distraction osteogenesis, and autogenous grafts, present with a number of potential complications and limited success when used to restore vertical ridge height. Recent advances in recombinant growth factor technology may provide viable, alternative therapies for the treatment of significant alveolar ridge deficiencies. This proof-of-principle case report examines the utility and effectiveness of using a composite graft of freeze-dried bone allograft and recombinant human platelet-derived growth factor BB in conjunction with an overlying titanium mesh to regenerate well-vascularized bone in a significant posterior mandibular ridge defect prior to implant placement. The important role of the overlying periosteum as a possible key source of osteogenic cells during growth factor-enhanced regenerative procedures is emphasized.